The Official Parent's Sourcebook on Neuroblastoma: A Revised and Updated Directory for the Internet Age

THE OFFICIAL PARENT’S SOURCEBOOK on NEUROBLASTOMA J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS...

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THE OFFICIAL PARENT’S SOURCEBOOK

on

NEUROBLASTOMA

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your child’s physician. All matters regarding your child’s health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before administering any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The Official Parent’s Sourcebook on Neuroblastoma: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83356-7 1. Neuroblastoma-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for parent use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of neuroblastoma.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to neuroblastoma. All of the Official Parent’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Parent’s Sourcebook series published by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Parent’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to neuroblastoma, Official Parent’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Childhood Acute Lymphoblastic Leukemia

·

The Official Patient's Sourcebook on Childhood Acute Myeloid Leukemia - Other Myeloid Malignancies

·

The Official Patient's Sourcebook on Childhood Hodgkin's Disease

·

The Official Patient's Sourcebook on Childhood Liver Cancer

·

The Official Patient's Sourcebook on Childhood Non-hodgkin's Lymphoma

·

The Official Patient's Sourcebook on Childhood Rhabdomyosarcoma

·

The Official Patient's Sourcebook on Childhood Soft Tissue Sarcoma

·

The Official Patient's Sourcebook on Retinoblastoma

·

The Official Patient's Sourcebook on Unusual Childhood Cancers

·

The Official Patient's Sourcebook on Wilm's Tumor and Other Childhood Kidney Tumors

To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

Contents vii

Table of Contents INTRODUCTION...................................................................................... 1

Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4

PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON NEUROBLASTOMA: GUIDELINES .... 9

Overview............................................................................................................... 9 What Is Neuroblastoma? .................................................................................... 11 Stage Information ............................................................................................... 12 Treatment Option Overview .............................................................................. 13 Treatment by Stage............................................................................................. 15 To Learn More .................................................................................................... 17 About PDQ......................................................................................................... 18 More Guideline Sources ..................................................................................... 20 Vocabulary Builder............................................................................................. 25

CHAPTER 2. SEEKING GUIDANCE ....................................................... 29

Overview............................................................................................................. 29 Associations and Neuroblastoma........................................................................ 29 Finding More Associations................................................................................. 33 Cancer Support Groups...................................................................................... 34 The Cancer Information Service ......................................................................... 36 Finding Cancer Resources in Your Community................................................ 39 Finding Doctors Who Specialize in Cancer Care ............................................... 42 Selecting Your Child’s Doctor............................................................................ 44 Working with Your Child’s Doctor.................................................................... 46 Getting a Second Opinion .................................................................................. 46 Finding a Cancer Treatment Facility ................................................................. 47 Questions and Answers about Children’s Cancer Centers ................................ 49 Additional Cancer Support Information ............................................................ 51 Vocabulary Builder............................................................................................. 52

CHAPTER 3. CLINICAL TRIALS AND NEUROBLASTOMA ..................... 53

Overview............................................................................................................. 53 Recent Trials on Neuroblastoma ........................................................................ 56 Benefits and Risks............................................................................................... 80 Clinical Trials and Insurance Coverage ............................................................. 82 Increasing the Likelihood of Insurance Coverage for Trials ............................... 85 If Your Insurance Claim Is Denied after the Trial Has Begun .......................... 87 Government Initiatives to Expand Insurance Coverage for Trials .................... 90 Keeping Current on Clinical Trials.................................................................... 91

viii Contents

General References.............................................................................................. 92 Vocabulary Builder............................................................................................. 93

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 99 CHAPTER 4. STUDIES ON NEUROBLASTOMA .................................... 101

Overview........................................................................................................... 101 The Combined Health Information Database ................................................... 101 Federally-Funded Research on Neuroblastoma ................................................ 105 E-Journals: PubMed Central ............................................................................ 120 The National Library of Medicine: PubMed .................................................... 125 Vocabulary Builder........................................................................................... 145

CHAPTER 5. PATENTS ON NEUROBLASTOMA ................................... 155

Overview........................................................................................................... 155 Patents on Neuroblastoma................................................................................ 156 Patent Applications on Neuroblastoma............................................................ 157 Keeping Current ............................................................................................... 157 Vocabulary Builder........................................................................................... 157

CHAPTER 6. BOOKS ON NEUROBLASTOMA ...................................... 159

Overview........................................................................................................... 159 Book Summaries: Federal Agencies .................................................................. 159 The National Library of Medicine Book Index ................................................. 161 Chapters on Neuroblastoma ............................................................................. 165 General Home References ................................................................................. 168 Vocabulary Builder........................................................................................... 169

CHAPTER 7. MULTIMEDIA ON NEUROBLASTOMA ............................ 173

Overview........................................................................................................... 173 Bibliography: Multimedia on Neuroblastoma .................................................. 173 Vocabulary Builder........................................................................................... 174

CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES ................... 175

Overview........................................................................................................... 175 NIH Guidelines................................................................................................. 175 What Is Neuroblastoma? .................................................................................. 176 Cellular Classification ...................................................................................... 183 Stage Information ............................................................................................. 184 Treatment Option Overview ............................................................................ 187 Neuroblastoma Risk-Based Treatment Plan..................................................... 187 Localized Resectable Neuroblastoma ................................................................ 190 Localized Unresectable Neuroblastoma ............................................................ 192 Low-Risk Localized Unresectable Neuroblastoma............................................ 193 High Risk Localized Unresectable Neuroblastoma........................................... 194 Regional Neuroblastoma................................................................................... 194 Low Risk Regional Neuroblastoma................................................................... 196

Contents

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Intermediate Risk Regional Neuroblastoma ..................................................... 197 High Risk Regional Neuroblastoma ................................................................. 198 Disseminated Neuroblastoma........................................................................... 198 Intermediate Risk Disseminated Neuroblastoma ............................................. 202 High Risk Disseminated Neuroblastoma.......................................................... 202 Treatment Options for Stage 4S Neuroblastoma ............................................. 203 Low Risk Stage 4S Neuroblastoma................................................................... 204 Intermediate Risk Stage 4S Neuroblastoma ..................................................... 205 High Risk Stage 4S Neuroblastoma ................................................................. 205 Recurrent Neuroblastoma................................................................................. 206 Recurrent Neuroblastoma in Patients Initially Classified as Low Risk........... 207 Recurrent Neuroblastoma in Patients Initially Classified as Intermediate Risk .......................................................................................................................... 209 Recurrent Neuroblastoma in Patients Initially Classified as High Risk.......... 209 NIH Databases.................................................................................................. 210 Other Commercial Databases ........................................................................... 214 The Genome Project and Neuroblastoma ......................................................... 214 Specialized References....................................................................................... 218 Vocabulary Builder........................................................................................... 220

CHAPTER 9. DISSERTATIONS ON NEUROBLASTOMA ........................ 223

Overview........................................................................................................... 223 Dissertations on Neuroblastoma ...................................................................... 223 Keeping Current ............................................................................................... 224 Vocabulary Builder........................................................................................... 225

PART III. APPENDICES .................................................. 227 APPENDIX A. RESEARCHING YOUR CHILD’S MEDICATIONS ........... 229

Overview........................................................................................................... 229 Your Child’s Medications: The Basics.............................................................. 230 Learning More about Your Child’s Medications ............................................. 231 Commercial Databases...................................................................................... 234 Drug Development and Approval .................................................................... 235 Understanding the Approval Process for New Cancer Drugs......................... 236 The Role of the Federal Drug Administration (FDA)...................................... 237 Getting Drugs to Patients Who Need Them .................................................... 241 Contraindications and Interactions (Hidden Dangers) ................................... 243 A Final Warning .............................................................................................. 244 General References............................................................................................ 244 Vocabulary Builder........................................................................................... 245

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 247

Overview........................................................................................................... 247 What Is CAM? ................................................................................................. 248 What Are the Domains of Alternative Medicine?............................................ 249 Finding CAM References on Neuroblastoma................................................... 254

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Contents

Additional Web Resources................................................................................ 264 General References............................................................................................ 266 Vocabulary Builder........................................................................................... 267

APPENDIX C. RESEARCHING NUTRITION ......................................... 269

Overview........................................................................................................... 269 Food and Nutrition: General Principles........................................................... 270 Finding Studies on Neuroblastoma .................................................................. 274 Federal Resources on Nutrition........................................................................ 278 Additional Web Resources................................................................................ 279 Vocabulary Builder........................................................................................... 279

APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 281

Overview........................................................................................................... 281 Preparation ....................................................................................................... 281 Finding a Local Medical Library ...................................................................... 282 Medical Libraries Open to the Public............................................................... 282

APPENDIX E. YOUR CHILD’S RIGHTS AND INSURANCE ................... 289

Overview........................................................................................................... 289 Your Child’s Rights as a Patient ...................................................................... 289 Parent Responsibilities ..................................................................................... 293 Choosing an Insurance Plan............................................................................. 294 Medicaid ........................................................................................................... 296 Financial Assistance for Cancer Care............................................................... 297 NORD’s Medication Assistance Programs ..................................................... 300 Additional Resources ........................................................................................ 300

APPENDIX F. TALKING WITH YOUR CHILD ABOUT CANCER ........... 303

Overview........................................................................................................... 303 Why Should I Tell My Child? .......................................................................... 304 Parent’s Questions ........................................................................................... 304 What Should My Child Be Told? ..................................................................... 305 Questions Children May Ask ........................................................................... 307 Talking to Your Child with Late-Stage Cancer................................................ 308

ONLINE GLOSSARIES.................................................... 311 Online Dictionary Directories.......................................................................... 318

NEUROBLASTOMA GLOSSARY ................................. 319 General Dictionaries and Glossaries ................................................................ 343

INDEX................................................................................... 345

Introduction

1

INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that all parents incorporate education into the treatment process. According to the AHRQ: Finding out more about your [child’s] condition is a good place to start. By contacting groups that support your [child’s] condition, visiting your local library, and searching on the Internet, you can find good information to help guide your decisions for your [child’s] treatment. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist parents in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3 Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 Adapted from the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

2

Neuroblastoma

Since the late 1990s, physicians have seen a general increase in parent Internet usage rates. Parents frequently enter their children’s doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding children through sound therapies. The Official Parent’s Sourcebook on Neuroblastoma has been created for parents who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to neuroblastoma, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on neuroblastoma. Given parents’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on neuroblastoma should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your child’s best option. This sourcebook is no exception. Each child is unique. Deciding on

Introduction

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appropriate options is always up to parents in consultation with their children’s physicians and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching neuroblastoma (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other parent networks dedicated to neuroblastoma. It also gives you sources of information that can help you find a doctor in your local area specializing in treating neuroblastoma. Collectively, the material presented in Part I is a complete primer on basic research topics for neuroblastoma. Part II moves on to advanced research dedicated to neuroblastoma. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on neuroblastoma. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading covering neuroblastoma or related disorders. The appendices are dedicated to more pragmatic issues facing parents. Accessing materials via medical libraries may be the only option for some parents, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing children with neuroblastoma and their families.

Scope While this sourcebook covers neuroblastoma, doctors, research publications, and specialists may refer to your child’s condition using a variety of terms. Therefore, you should understand that neuroblastoma is often considered a synonym or a condition closely related to the following: ·

Neuroblastoma Child

4

Neuroblastoma

In addition to synonyms and related conditions, physicians may refer to neuroblastoma using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for neuroblastoma:4 ·

171.8 malignant pelvo-abdominal neoplasm

·

173.4 cervical neoplasm

·

194.0 malignant neoplasm of adrenal medulla

·

195.1 thoracic neoplasm

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to neuroblastoma. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by parents, patients, or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? When their child has been diagnosed with neuroblastoma, parents will often log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly 4 This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

Introduction

5

irrelevant or redundant. Parents are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with neuroblastoma is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of neuroblastoma, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find parent groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you and your child the most options in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your child’s treatment plan. The Editors

7

PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on neuroblastoma. The essentials typically include a definition or description of the condition, a discussion of who it affects, the signs or symptoms, tests or diagnostic procedures, and treatments for the disease. Your child’s doctor or healthcare provider may have already explained the essentials of neuroblastoma to you or even given you a pamphlet or brochure describing the condition. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what the doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

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CHAPTER 1. THE ESSENTIALS ON NEUROBLASTOMA: GUIDELINES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines on neuroblastoma. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the parent in mind. Since new guidelines on neuroblastoma can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current guidelines and fact sheets on neuroblastoma. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

5

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Neuroblastoma

There is no guarantee that any one Institute will have a guideline on a specific medical condition, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare disorders. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with neuroblastoma and associated conditions: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Cancer Institute (NCI); guidelines available at http://cancernet.nci.nih.gov/pdq/pdq_treatment.shtml

Among the above, the National Cancer Institute (NCI) is particularly noteworthy. The NCI coordinates the National Cancer Program, which conducts and supports research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients.6 Specifically, the Institute: ·

Supports and coordinates research projects conducted by universities, hospitals, research foundations, and businesses throughout this country and abroad through research grants and cooperative agreements.

·

Conducts research in its own laboratories and clinics.

·

Supports education and training in fundamental sciences and clinical disciplines for participation in basic and clinical research programs and treatment programs relating to cancer through career awards, training grants, and fellowships.

·

Supports research projects in cancer control.

·

Supports a national network of cancer centers.

·

Collaborates with voluntary organizations and other national and foreign institutions engaged in cancer research and training activities.

·

Encourages and coordinates cancer research by industrial concerns where such concerns evidence a particular capability for programmatic research.

·

Collects and disseminates information on cancer.

This paragraph has been adapted from the NCI: http://www.nci.nih.gov/. “Adapted” signifies that a passage has been reproduced exactly or slightly edited for this book. 6

Guidelines 11

·

Supports construction of laboratories, clinics, and related facilities necessary for cancer research through the award of construction grants.

The NCI, established under the National Cancer Act of 1937, is the Federal Government’s principal agency for cancer research and training. The National Cancer Act of 1971 broadened the scope and responsibilities of the NCI and created the National Cancer Program. Over the years, legislative amendments have maintained the NCI authorities and responsibilities and added new information dissemination mandates as well as a requirement to assess the incorporation of state-of-the-art cancer treatments into clinical practice. Information dissemination is made possible through the NCI Online at www.cancer.gov. Cancer.gov offers to the public and physicians up-to-date information on the latest cancer research, current and upcoming clinical trials, statistics, research programs, and research funding. The following guideline was recently published by the NCI on neuroblastoma.

What Is Neuroblastoma?7 Neuroblastoma is a solid cancerous tumor that begins in nerve tissue in the neck, chest, abdomen, or pelvis, but usually originates in the abdomen in the tissues of the adrenal gland. By the time it is diagnosed, the cancer usually has spread (metastasized), most commonly to the lymph nodes, liver, lungs, bones, and bone marrow. Neuroblastoma is predominantly a tumor of early childhood; two thirds of children with neuroblastoma are diagnosed when they are younger than 5 years of age. It is often present at birth but usually is not detected until later; in rare cases, neuroblastoma can be detected before birth by fetal ultrasound. The most common symptoms of neuroblastoma are the result of pressure by the tumor or bone pain from cancer that has spread to the bone. Protruding eyes and dark circles around the eyes are common and are caused by cancer that has spread to the area behind the eye. Neuroblastomas may compress the spinal cord, causing paralysis. Fever, anemia, and high blood pressure are found occasionally. Rarely, children may have severe watery diarrhea, uncoordinated or jerky muscle movements, or uncontrollable eye movement.

The following guidelines appeared on the NCI website on Aug. 26, 2002. The text was last modified in August 2002. The text has been adapted for this sourcebook. 7

12 Neuroblastoma

If your child has symptoms that may be caused by neuroblastoma, his or her doctor will conduct a careful examination and order laboratory tests and special x-rays. A computed tomographic (CT) scan, a diagnostic test that uses computers and x-rays to create pictures of the body, may be performed. A magnetic resonance imaging (MRI) scan, a diagnostic test similar to a CT scan, but which uses magnetic waves instead of x-rays, may also be performed. Often, removal of tissue from the tumor and/or bone marrow is required to determine whether neuroblastoma exists. A small sample of the tissue may be surgically removed and examined under a microscope. This is called a biopsy. Sometimes a biopsy is done by making a small hole and using a needle to extract a sample of the tissue. Your child’s chance of recovery (prognosis) and choice of treatment depend on the stage of your child’s cancer (how far the cancer has spread), your child’s age at diagnosis, the location of the tumor, and evaluation of the tumor cells under a microscope.

Stage Information Once neuroblastoma is found, more tests will be done to find out if the cancer has spread from where it started to surrounding tissues or other parts of the body. This is called staging. Your child’s doctor needs to know the stage of the disease to plan treatment. Although there are several staging systems currently available for neuroblastoma, for the purposes of treatment the disease is categorized as follows: Localized Resectable The cancer is confined to the site of origin, there is no evidence of spread, and the cancer can be surgically removed. Localized Unresectable The cancer is confined to the site of origin, but the cancer cannot be completely removed surgically.

Guidelines 13

Regional The cancer has extended beyond the site of origin to regional lymph nodes and/or surrounding organs or tissues, but has not spread to distant parts of the body.

Disseminated The cancer has spread from the site of origin to distant lymph nodes, bone, liver, skin, bone marrow, and/or other organs (except as defined for stage 4S). Stage 4S Stage 4S neuroblastoma is also called “special” neuroblastoma because it is treated differently. The cancer is localized, with dissemination (spread) limited to liver, skin, and/or, to a very limited extent, bone marrow. Recurrent Recurrent neuroblastoma means that the cancer has come back (recurred) or continued to spread (progressed) after it has been treated. It may come back in the original site or in another part of the body.

Treatment Option Overview There are treatments for all children with neuroblastoma. Treatment options are related to age at diagnosis, tumor location, stage of disease, regional lymph node involvement, and tumor biology. Four types of treatment are used: ·

Surgery (removing the tumor in an operation)

·

Radiation therapy (using high-dose x-rays or other high-energy rays to kill cancer cells and shrink tumors)

·

Chemotherapy (using drugs to kill cancer cells and shrink tumors)

·

Bone marrow transplantation (replacing the patient’s bone marrow with healthy bone marrow)

14 Neuroblastoma

More than one method of treatment may be used, depending on the needs of the patient.

Surgery Surgery is used when possible to remove as much of the cancer as possible. If the cancer cannot be removed, surgery may be limited to a biopsy of the cancer.

Radiation Therapy Radiation therapy uses high-energy rays (radiation) to damage or kill cancer cells and shrink tumors. Radiation usually comes from a machine outside the body (external beam radiation therapy). Chemotherapy Chemotherapy is the use of drugs to kill cancer cells and shrink tumors. Chemotherapy drugs may be taken by mouth or injected into a vein (intravenous) or a muscle. Chemotherapy is called a systemic treatment because the drug enters the bloodstream, travels through the body, and can kill cancer cells throughout the body. Chemotherapy may be given after the tumor has been surgically removed to kill any remaining cancer cells; this is called adjuvant chemotherapy. Chemotherapy can also be given before surgery to shrink the cancer so that it can be removed during surgery; this is called neoadjuvant chemotherapy. Bone Marrow Transplantation Bone marrow transplantation is a procedure in which healthy bone marrow is given to replace bone marrow destroyed by treatment with high doses of anticancer drugs or radiation. Transplantation may be autologous (the patient’s own marrow saved earlier and possibly treated with drugs to kill any cancer cells), allogeneic (marrow from a healthy “matched” donor, usually a brother or sister), or syngeneic (marrow from an identical twin).

Guidelines 15

Treatment by Stage For the purposes of treatment presented here, neuroblastoma is categorized as localized resected, localized unresected, regional, disseminated, and special. Your child may receive treatment that is considered standard based on its effectiveness in a number of people in past studies, or you may choose to enter your child in a clinical trial. Not all patients are cured with standard therapy and some standard treatments may have more side effects than are desired. For these reasons, clinical trials are designed to test new treatments and to find better ways to treat people with cancer. Clinical trials are ongoing in most parts of the country for most stages of neuroblastoma. If you want more information, call the Cancer Information Service at 1-800-4CANCER (1-800-422-6237); TTY at 1-800-332-8615.

Localized Resectable Neuroblastoma Your child’s treatment may be one of the following: ·

Surgery to remove the cancer.

·

Surgery plus adjuvant chemotherapy.

·

Surgery plus radiation therapy.

Localized Unresectable Neuroblastoma Initial treatment generally consists of surgical removal of as much of the cancer as possible followed by chemotherapy. A second surgery may be performed to remove any cancer that remains, and radiation therapy may then be given.

Regional Neuroblastoma Treatment depends on your child’s age. If your child is younger than 1 year of age, treatment may include the following: ·


·

Chemotherapy.

16 Neuroblastoma

If your child is older than 1 year of age, treatment may be one of the following: ·


·

Surgery followed by chemotherapy.

·

Chemotherapy with or without radiation therapy to reduce the tumor, followed by surgery.

·

Multi-drug chemotherapy.

·

Radiation therapy.

·

A clinical trial of new methods of treatment. Listings of current clinical trials are available on PDQ or by calling the National Cancer Institute’s Cancer Information Service at 1-800-4-CANCER.

Disseminated Neuroblastoma Your child’s treatment may be one of the following: ·

Multi-drug chemotherapy with or without surgery and/or radiation therapy.

·

Chemotherapy followed by peripheral stem cell transplantation and 13cis retinoic acid.

·

A clinical trial of new methods of treatment. Listings of current clinical trials are available on PDQ or by calling the National Cancer Institute’s Cancer Information Service at 1-800-4-CANCER.

Stage 4S Neuroblastoma Children with this special type of neuroblastoma may not require therapy. You may want to have your child take part in a clinical trial of new methods of treatment. Listings of current clinical trials are available on PDQ or by calling the National Cancer Institute’s Cancer Information Service at 1-800-4CANCER.

Recurrent Neuroblastoma The selection of treatment of recurrent or progressive neuroblastoma depends on the location and extent of the recurrence or progression and on the previous therapy as well as individual patient considerations. A clinical

Guidelines 17

trial may be appropriate. Listings of current clinical trials are available on PDQ or by calling the National Cancer Institute’s Cancer Information Service at 1-800-4-CANCER.

To Learn More Call For more information, U.S. residents may call the National Cancer Institute’s (NCI’s) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-4226237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-ofhearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.

Web Sites and Organizations The NCI’s Cancer.gov Web site (http://cancer.gov) provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. There are also many other places where people can get materials and information about cancer treatment and services. Local hospitals may have information on local and regional agencies that offer information about finances, getting to and from treatment, receiving care at home, and dealing with problems associated with cancer treatment.

Publications The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator (https://cissecure.nci.nih.gov/ncipubs). These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-8004-CANCER (1-800-422-6237), TTY at 1-800-332-8615.

18 Neuroblastoma

LiveHelp The NCI’s LiveHelp service, a program available on several of the Institute’s Web sites, provides Internet users with the ability to chat online with an Information Specialist. The service is available from Monday - Friday 9:00 AM - 10:00 PM Eastern Time. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer. Write For more information from the NCI, please write to this address: National Cancer Institute Office of Communications 31 Center Drive, MSC 2580 Bethesda, MD 20892-2580

About PDQ PDQ Is a Comprehensive Cancer Database Available on Cancer.gov PDQ is the National Cancer Institute’s (NCI’s) comprehensive cancer information database. Most of the information contained in PDQ is available online at Cancer.gov, the NCI’s Web site. PDQ is provided as a service of the NCI. The NCI is part of the National Institutes of Health, the federal government’s focal point for biomedical research. PDQ Contains Cancer Information Summaries The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries are available in two versions. The health professional versions provide detailed information written in technical language. The patient versions are written in easy-tounderstand, non-technical language. Both versions provide current and accurate cancer information. The PDQ cancer information summaries are developed by cancer experts and reviewed regularly. Editorial Boards made up of experts in oncology and related specialties are responsible for writing and maintaining the cancer

Guidelines 19

information summaries. The summaries are reviewed regularly and changes are made as new information becomes available. The date on each summary (“Date Last Modified”) indicates the time of the most recent change.

PDQ Contains Information on Clinical Trials In the United States, about two-thirds of children with cancer are treated in a clinical trial at some point in their illness. A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about new treatments, the risks involved, and how well they do or do not work. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become “standard.” Listings of clinical trials are included in PDQ and are available online at Cancer.gov. Descriptions of the trials are available in health professional and patient versions. For additional help in locating a childhood cancer clinical trial, call the Cancer Information Service at 1-800-4-CANCER (1-800-4226237), TTY at 1-800-332-8615. The PDQ Database Contains Listings of Groups Specializing in Clinical Trials The Children’s Oncology Group (COG) is the major group that organizes clinical trials for childhood cancers in the United States. Information about contacting COG is available on Cancer.gov or from the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615.

The PDQ Database Contains Listings of Cancer Professionals and Hospitals with Cancer Programs

Health

Because cancer in children and adolescents is rare, the majority of children with cancer are treated by health professionals specializing in childhood cancers, at hospitals or cancer centers with special facilities to treat them. The PDQ database contains listings of health professionals who specialize in childhood cancer and listings of hospitals with cancer programs. For help locating childhood cancer health professionals or a hospital with cancer

20 Neuroblastoma

programs, call the Cancer Information Service at 1-800-4-CANCER (1-800422-6237), TTY at 1-800-332-8615.

More Guideline Sources The previous guideline on neuroblastoma is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to neuroblastoma. Many of the guidelines listed below address topics that may be of particular relevance to your child’s specific situation, while certain guidelines will apply to only some children with neuroblastoma. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.

Topic Pages: MEDLINEplus For parents wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and parentoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following as being relevant to neuroblastoma: ·

Guides On Neuroblastoma Neuroblastoma http://www.nlm.nih.gov/medlineplus/neuroblastoma.html Neuroblastoma http://www.nlm.nih.gov/medlineplus/ency/article/001408.htm

·

Guides on Human Anatomy and Systems Cancers Topics http://www.nlm.nih.gov/medlineplus/cancers.html

Guidelines 21

·

Other Guides Ganglioneuroblastoma http://www.nlm.nih.gov/medlineplus/ency/article/001436.htm

Within the health topic page dedicated to neuroblastoma, the following was recently recommended to parents: ·

General/Overviews What Is Neuroblastoma? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_1X_What_is_neuroblastoma_31?sitearea=&level=

·

Diagnosis/Symptoms Can Neuroblastoma Be Found Early? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_3X_Can_neuroblastoma_be_found_early_31?sitearea=&level= Gene Chips Accurately Diagnose Four Complex Childhood Cancers Source: National Human Genome Research Institute http://www.nih.gov/news/pr/may2001/nhgri-30.htm How Is Neuroblastoma Diagnosed? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_3X_How_is_neuroblastoma_diagnosed_31?sitearea=&level= How Is Neuroblastoma Staged? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_3X_How_is_neuroblastoma_staged_31?sitearea=&level=

·

Treatment Neuroblastoma (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancer_information/doc_pdq.aspx?version= patient&viewid=eb787dfc-d074-4716-9284-be3281d0018c

22 Neuroblastoma

·

Nutrition Nutrition for Children with Cancer Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/PED/PED_3_1_nutrit ion_for_children_with_cancer?

·

Specific Conditions/Aspects Do We Know What Causes Neuroblastoma? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_2X_Do_we_know_what_causes_neuroblastoma_31?sitearea=PED What are the Differences Between Cancers in Adults and in Children? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_1X_What_are_the_differences_between_cancers_in_adults_and_in_ children_31?sitearea=&level= What Should You Ask Your Child's Doctor About Neuroblastoma? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_5X_What_should_you_ask_your_physician_about_neuroblastoma_ 31?sitearea=CRI Young People with Cancer: A Handbook for Parents Source: National Cancer Institute http://www.cancer.gov/templates/page_print.aspx?viewid=2944f6e 7-996c-47b0-ad4e-23d8fbe9e033

·

From the National Institutes of Health Neuroblastoma Source: National Cancer Institute http://www.cancer.gov/cancer_information/cancer_type/neuroblas toma/

·

Organizations American Cancer Society http://www.cancer.org/ National Cancer Institute http://www.cancer.gov/

Guidelines 23

·

Prevention/Screening Neuroblastoma (PDQ): Screening Source: National Cancer Institute http://www.nci.nih.gov/cancerinfo/pdq/screening/neuroblastoma /patient/ What Are the Risk Factors For Neuroblastoma? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_2X_What_are_the_risk_factors_for_neuroblastoma_31?sitearea=PE D

·

Research What's New in Neuroblastoma Research and Treatment? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_6X_Whats_new_in_neuroblastoma_research_and_treatment_31?site area=CRI

·

Statistics What Are the Key Statistics About Neuroblastoma? Source: American Cancer Society http://www.cancer.org/eprise/main/docroot/CRI/content/CRI_2_ 4_1X_What_are_the_key_statistics_for_neuroblastoma_31?sitearea=&l evel=

If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly parent-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.

24 Neuroblastoma

The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “neuroblastoma” or synonyms.

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to neuroblastoma. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and parents. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than parents, you can view the current list of conditions covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

·

drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

·

Family Village: http://www.familyvillage.wisc.edu/specific.htm

Guidelines 25

·

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

·

Med Help International: http://www.medhelp.org/HealthTopics/A.html

·

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

·

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

·

WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Abdomen: The part of the body that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Anemia: A condition in which the number of red blood cells is below normal. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Biopsy: The removal of cells or tissues for examination under a microscope. When only a sample of tissue is removed, the procedure is called an incisional biopsy or core biopsy. When an entire tumor or lesion is removed, the procedure is called an excisional biopsy. When a sample of tissue or fluid is removed with a needle, the procedure is called a needle biopsy or fineneedle aspiration. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH]

26 Neuroblastoma

Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72. [NIH] Ganglioneuroblastoma: A moderately malignant neoplasm composed of primitive neuroectodermal cells dispersed in myxomatous or fibrous stroma intermixed with mature ganglion cells. It may undergo transformation into a neuroblastoma. It arises from the sympathetic trunk or less frequently from the adrenal medulla, cerebral cortex, and other locations. Cervical ganglioneuroblastomas may be associated with HORNER SYNDROME and the tumor may occasionally secrete vasoactive intestinal peptide, resulting in chronic diarrhea. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Intravenous: IV. Into a vein. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] MRI: Magnetic resonance imaging (mag-NET-ik REZ-o- nans IM-a-jing). A procedure in which a magnet linked to a computer is used to create detailed pictures of areas inside the body. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Oncology: The study of cancer. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH]

Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recurrence: The return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH]

Guidelines 27

Resected: Surgical removal of part of an organ. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH] Systemic: Affecting the entire body. [NIH] Transplantation: person. [NIH]

The replacement of an organ with one from another

Unresectable: Unable to be surgically removed. [NIH]

Seeking Guidance 29

CHAPTER 2. SEEKING GUIDANCE Overview Some parents are comforted by the knowledge that a number of organizations dedicate their resources to helping people with neuroblastoma. These associations can become invaluable sources of information and advice. Many associations offer parent support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.8 In addition to support groups, your child’s physician can be a valuable source of guidance and support. In this chapter, we direct you to resources that can help you find parent organizations and medical specialists. We begin by describing how to find associations and parent groups that can help you better understand and cope with your child’s condition. The chapter ends with a discussion on how to find a doctor that is right for your child.

Associations and Neuroblastoma In addition to associations or groups that your child’s doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your child’s insurance provider to find out if the cost will be covered):

Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 8

30 Neuroblastoma

·

Children's Blood Foundation Address: Children's Blood Foundation 333 East 38th Street, Room 830, New York, NY 10016-2745 Telephone: (212) 297-4336 Toll-free: (800) 458-6223 Fax: (212) 297-4340 Email: [email protected] Background: The Children's Blood Foundation (CBF) is a nonprofit organization dedicated to promoting and/or supporting research, medical training of physicians, and care of children with leukemia, thalassemia, hemophilia, anemia, cancer, immune disorders, and AIDS. Established in 1952, the CBF has the largest hemophilia center in the New York area and the largest thalassemia center in North America, receiving more than 5,000 patient visits every year. All affected children are served, regardless of the family's ability to pay. Educational materials include a self-titled brochure, a regular newsletter entitled 'The Key to Life for a Child,' and a booklet entitled 'What's It Called Again? - Answers to the Most Commonly Asked Questions About Idiopathic Thrombocytopenic Purpura (ITP) In Children.' CBF has support groups, offers networking services, and engages in educational activities. Relevant area(s) of interest: Neuroblastoma, Retinoblastoma

·

National Childhood Cancer Foundation Address: National Childhood Cancer Foundation 440 East Huntington Drive, Suite 300, Arcadia, CA 91066-6012 Telephone: (626) 447-1674 Toll-free: (800) 458-6223 Fax: (626) 447-6359 Email: nccf- [email protected] Web Site: http://www.nccf.org/nccf/ Background: The National Childhood Cancer Foundation (NCCF) is a charitable foundation that supports pediatric cancer treatment and research projects at over 115 pediatric medical institutions in the United States, Canada, and Australia. This network of pediatric medical institutions and over 2,800 pediatric cancer specialists is known as the Children's Cancer Group (CCG), a national cooperative research organization that was founded in 1955 to promote the development of new treatments and cures for cancers affecting children and young adults. The National Childhood Cancer Foundation, which was established in 1990 as the sponsor of the CCG, seeks grants, gifts, and bequests from individuals, foundations, corporations, and other

Seeking Guidance 31

organizations to support research, education, and advocacy for the needs of children with cancer. The NCCF's mission is to reduce and eventually eliminate the impacts of cancer that affect children and young adults. The Foundation works to accomplish its mission by supporting cooperative laboratory and clinical research that is designed to improve the treatment, survival, and cure of cancer; to discover new agents for treatment; and to obtain and apply new scientific information on the biology, causes, and possible prevention of cancers of infants, children, adolescents, and young adults. The NCCF is also committed to improving access to state-of-the-art interdisciplinary team care of children and young adults with cancer and advocating for the needs of patients and the institutions providing such care. The National Childhood Cancer Foundation also has a web site that enables visitors to locate CCG institutions and CCG clinical trial protocols. The site also provides facts about childhood cancer, press releases, and links to other information sources. Relevant area(s) of interest: Neuroblastoma ·

Neuroblastoma Children's Cancer Society Address: Neuroblastoma Children's Cancer Society P.O. Box 957672, Hoffman Estates, IL 60195 Telephone: (847) 490-4240 Toll-free: (800) 532-5162 Fax: (847) 490-0705 Email: None. Web Site: http://www.granitewebworks.com/nccs.htm Background: The Neuroblastoma Children's Cancer Society is a not-forprofit voluntary organization dedicated to significantly accelerating potential cures for neuroblastoma and its related children's cancers and to improve the quality of life of affected individuals and their families. The organization is an advocate for children and their families and is dedicated to providing support in the following ways: promoting research by highly trained medical professionals; providing research grant awards to medical specialists locally and nationwide; educating health care professionals on early detection and the latest advances in treatments and diagnosis; maintaining updated information on current treatment and diagnosis; maintains updated information on current treatments; providing moral, practical, and emotional support for affected individuals and their families through newsletters, Internet interaction, toll-free telephone support, etc.; and providing a resource booklet that lists nonprofit organizations and other resources that offer support for affected families. Consisting of 500 members, the Society

32 Neuroblastoma

produces educational materials including a resource handbook and a newsletter entitled 'HOPE for Families and Friends of Children With Neuroblastoma.'. Relevant area(s) of interest: Neuroblastoma ·

OncoLink: The University of Pennsylvania Cancer Center Resource Address: The University of Pennsylvania Cancer Center Resource Web Site on the Internet, Telephone: (212) 297-4336 Toll-free: (800) 458-6223 Email: [email protected] Web Site: http://www.oncolin.upenn.edu Background: OncoLink is a multimedia oncology information resource on the World Wide Web on the Internet. OncoLink's mission 'is consistent with that of the University of Pennsylvania Medical Center and the University of Pennsylvania Cancer Center, which have sanctioned the site's use and development. OncoLink is accessible worldwide to anyone with Internet access, and there is no charge for its use. Oncolink has been established with the following objectives: (1) dissemination of information relevant to the field of oncology; (2) education of health care personnel; (3) education of affected individuals, families, and other interested parties; and (4) rapid collection of information pertinent to the specialty. OncoLink's home page includes the following headings: Disease Oriented Headings (i.e., specific types of cancer); Medical Specialty Oriented Menus (i.e., medical specialities that deal with cancer, chemotherapy information, etc.); Psychosocial Support and Personal Experiences; Cancer Causes, Screening, and Prevention; Clinical Trials; Global Resources for Cancer Information; Cancer FAQs (frequently asked questions); Medical Supportive Care for the Cancer Patient; Conferences and Meetings; and Financial Issues for Cancer Patients. Relevant area(s) of interest: Neuroblastoma, Retinoblastoma

Seeking Guidance 33

Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for parent associations.

The National Cancer Institute (NCI) The National Cancer Institute (NCI) has complied a list of national organizations that offer services to people with cancer and their families. To view the list, see the NCI fact sheet online at the following Web address: http://cis.nci.nih.gov/fact/8_1.htm. The name of each organization is accompanied by its contact information and a brief explanation of its services. Information on a number of organizations specializing in children’s issues is also available.

The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about neuroblastoma. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov. Simply type in “neuroblastoma” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

34 Neuroblastoma

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “neuroblastoma”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “neuroblastoma” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with neuroblastoma. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific medical conditions. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “neuroblastoma” (or a synonym) in the search box.

Cancer Support Groups9 People diagnosed with cancer and their families face many challenges that may leave them feeling overwhelmed, afraid, and alone. It can be difficult to cope with these challenges or to talk to even the most supportive family members and friends. Often, support groups can help people affected by cancer feel less alone and can improve their ability to deal with the uncertainties and challenges that cancer brings. Support groups give people who are affected by similar diseases an opportunity to meet and discuss ways to cope with the illness.

9

This section has been adapted from the NCI: http://cis.nci.nih.gov/fact/8_8.htm.

Seeking Guidance 35

How Can Support Groups Help? People who have been diagnosed with cancer sometimes find they need assistance coping with the emotional as well as the practical aspects of their disease. In fact, attention to the emotional burden of cancer is sometimes part of a patient’s treatment plan. Cancer support groups are designed to provide a confidential atmosphere where cancer patients or cancer survivors can discuss the challenges that accompany the illness with others who may have experienced the same challenges. For example, people gather to discuss the emotional needs created by cancer, to exchange information about their disease—including practical problems such as managing side effects or returning to work after treatment—and to share their feelings. Support groups have helped thousands of people cope with these and similar situations. Can Family Members and Friends Participate in Support Groups? Family and friends are affected when cancer touches someone they love, and they may need help in dealing with stresses such as family disruptions, financial worries, and changing roles within relationships. To help meet these needs, some support groups are designed just for family members of people diagnosed with cancer; other groups encourage families and friends to participate along with the cancer patient or cancer survivor. How Can People Find Support Groups? Many organizations offer support groups for people diagnosed with cancer and their family members or friends. The NCI fact sheet National Organizations That Offer Services to People With Cancer and Their Families lists many cancer-concerned organizations that can provide information about support groups. This fact sheet is available at http://cis.nci.nih.gov/fact/8_1.htm on the Internet, or can be ordered from the Cancer Information Service at 1–800–4–CANCER (1–800–422–6237). Some of these organizations provide information on their Web sites about contacting support groups. Doctors, nurses, or hospital social workers who work with cancer patients may also have information about support groups, such as their location, size, type, and how often they meet. Most hospitals have social services departments that provide information about cancer support programs.

36 Neuroblastoma

Additionally, many newspapers carry a special health supplement containing information about where to find support groups.

What Types of Support Groups Are Available? Several kinds of support groups are available to meet the individual needs of people at all stages of cancer treatment, from diagnosis through follow-up care. Some groups are general cancer support groups, while more specialized groups may be for teens or young adults, for family members, or for people affected by a particular disease. Support groups may be led by a professional, such as a psychiatrist, psychologist, or social worker, or by cancer patients or survivors. In addition, support groups can vary in approach, size, and how often they meet. Many groups are free, but some require a fee (people can contact their health insurance company to find out whether their plan will cover the cost). It is important for people to find an atmosphere that is comfortable and meets their individual needs. Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms to discuss different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your child’s doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective.

The Cancer Information Service10 The Cancer Information Service (CIS) is a program of the National Cancer Institute (NCI), the Nation’s lead agency for cancer research. As a resource for information and education about cancer, the CIS is a leader in helping people become active participants in their own health care by providing the latest information on cancer in understandable language. Through its network of regional offices, the CIS serves the United States, Puerto Rico, the U.S. Virgin Islands, and the Pacific Islands. 10


Seeking Guidance 37

For 25 years, the Cancer Information Service has provided the latest and most accurate cancer information to patients and families, the public, and health professionals by: ·

Interacting with people one-on-one through its Information Service,

·

Working with organizations through its Partnership Program,

·

Participating in research efforts to find the best ways to help people adopt healthier behaviors,

·

Providing access to NCI information over the Internet. How Does the CIS Assist the Public?

Through the CIS toll-free telephone service (1–800–4–CANCER), callers speak with knowledgeable, caring staff who are experienced at explaining medical information in easy-to-understand terms. CIS information specialists answer calls in English and Spanish. They also provide cancer information to deaf and hard of hearing callers through the toll-free TTY number (1–800– 332–8615). CIS staff have access to comprehensive, accurate information from the NCI on a range of cancer topics, including the most recent advances in cancer treatment. They take as much time as each caller needs, provide thorough and personalized attention, and keep all calls confidential. The CIS also provides live, online assistance to users of NCI Web sites through LiveHelp, an instant messaging service that is available from 9:00 a.m. to 7:30 p.m. Eastern time, Monday through Friday. Through LiveHelp, information specialists provide answers to questions about cancer and help in navigating Cancer.gov, the NCI’s Web site. Through the telephone numbers or LiveHelp service, CIS users receive: ·

Answers to their questions about cancer, including ways to prevent cancer, symptoms and risks, diagnosis, current treatments, and research studies;

·

Written materials from the NCI;

·

Referrals to clinical trials and cancer-related services, such as treatment centers, mammography facilities, or other cancer organizations;

·

Assistance in quitting smoking from information specialists trained in smoking cessation counseling.

38 Neuroblastoma

What Kind of Assistance Does the CIS Partnership Program Offer? Through its Partnership Program, the CIS collaborates with established national, state, and regional organizations to reach minority and medically underserved audiences with cancer information. Partnership Program staff provide assistance to organizations developing programs that focus on breast and cervical cancer, clinical trials, tobacco control, and cancer awareness for special populations. To reach those in need, the CIS: ·

Helps bring cancer information to people who do not traditionally seek health information or who may have difficulties doing so because of educational, financial, cultural, or language barriers;

·

Provides expertise to organizations to help strengthen their ability to inform people they serve about cancer; and

·

Links organizations with similar goals and helps them plan and evaluate programs, develop coalitions, conduct training on cancer-related topics, and use NCI resources. How Do CIS Research Efforts Assist the Public?

The CIS plays an important role in research by studying the most effective ways to communicate with people about healthy lifestyles; health risks; and options for preventing, diagnosing, and treating cancer. The ability to conduct health communications research is a unique aspect of the CIS. Results from these research studies can be applied to improving the way the CIS communicates about cancer and can help other programs communicate more effectively. How Do People Reach the Cancer Information Service? ·

To speak with a CIS information specialist call 1–800–4–CANCER (1–800– 422–6237), 9:00 a.m. to 4:30 p.m. local time, Monday through Friday. Deaf or hard of hearing callers with TTY equipment may call 1–800–332–8615.

·

To obtain online assistance visit the NCI’s Cancer Information Web site at http://cancer.gov/cancer_information and click on the LiveHelp link between 9:00 a.m. and 7:30 p.m. Eastern time, Monday through Friday.

·

For information 24 hours a day, 7 days a week call 1–800–4–CANCER and select option 4 to hear recorded information at any time.

·

Visit NCI’s Web site at http://cancer.gov on the Internet.

·

Visit the CIS Web site at http://cancer.gov/cis on the Internet.

Seeking Guidance 39

Finding Cancer Resources in Your Community11 When your child has cancer or is undergoing cancer treatment, there are places in your community to turn to for help. There are many local organizations throughout the country that offer a variety of practical and support services to children with cancer and their families. However, parents often don’t know about these services or are unable to find them. National cancer organizations can assist you in finding these resources, and there are a number of things you can do for yourself. Whether you are looking for a support group, counseling, advice, financial assistance, transportation for your child to and from treatment, or information about cancer, most neighborhood organizations, local health care providers, or area hospitals are a good place to start. Often, the hardest part of looking for help is knowing the right questions to ask. What Kind of Help Can I Get? Until now, you probably never thought about the many issues and difficulties that arise with a diagnosis of cancer. There are support services to help you deal with almost any type of problem that might occur. The first step in finding the help you need is knowing what types of services are available. The following pages describe some of these services and how to find them. ·

Information on Cancer. Most national cancer organizations provide a range of information services, including materials on different types of cancer, treatments, and treatment-related issues.

·

Counseling. While some parents are reluctant to seek counseling, studies show that having someone to talk to reduces stress. Counseling can also provide emotional support to children with cancer and help them better understand their illness. Different types of counseling include individual, group, family, self-help (sometimes called peer counseling), bereavement, patient-to-patient, and sexuality.

·

Medical Treatment Decisions. Often, parents need to make complicated medical decisions. Many organizations provide hospital and physician referrals for second opinions and information on clinical trials, which may expand treatment options.

11

Adapted from the NCI: http://cis.nci.nih.gov/fact/8_9.htm.

40 Neuroblastoma

·

Home Health Care. Home health care assists patients who no longer need to stay in a hospital, but still require professional medical help. Skilled nursing care, physical therapy, social work services, and nutrition counseling are all available at home.

·

Hospice Care. Hospice is care focused on the special needs of terminally ill cancer patients. Sometimes called palliative care, it centers around providing comfort, controlling physical symptoms, and giving emotional support to patients who can no longer benefit from curative treatment. Hospice programs provide services in various settings, including the patient’s home, hospice centers, hospitals, or skilled nursing facilities. Your child’s doctor or social worker can provide a referral for these services.

·

Rehabilitation. Rehabilitation services help people adjust to the effects of cancer and its treatment. Physical rehabilitation focuses on recovery from the physical effects of surgery or the side effects associated with chemotherapy.

·

Advocacy. Advocacy is a general term that refers to promoting or protecting the rights and interests of a certain group, such as cancer patients. Advocacy groups may offer services to assist with legal, ethical, medical, employment, legislative, or insurance issues, among others. For instance, if you feel your insurance company has not handled your child’s claim fairly, you may want to advocate for a review of its decision.

·

Financial. Treating cancer can be a tremendous financial burden. There are programs sponsored by the government and nonprofit organizations to help parents of cancer patients with problems related to medical billing, insurance coverage, and reimbursement issues. There are also sources for financial assistance.

·

Housing/Lodging. Some organizations provide lodging for the family of a patient undergoing treatment, especially if it is a child who is ill and the parents are required to accompany the child to treatment.

·

Children’s Services. A number of organizations provide services for children with cancer, including summer camps, make-a-wish programs, and help for parents seeking child care. How to Find These Services

Often, the services that people with cancer are looking for are right in their own neighborhood or city. The following is a list of places where you can begin your search for help.

Seeking Guidance 41

·

Your child’s hospital, clinic, or medical center should be able to give you information. The doctor or nurse may be able to tell you about your child’s specific medical condition, pain management, rehabilitation services, home nursing, or hospice care.

·

Most hospitals also have a social work, home care, or discharge planning department. This department may be able to help you find a support group or a nonprofit agency that helps people who have cancer and their families. While your child is undergoing treatment, be sure to ask the hospital about transportation, practical assistance, or even temporary child care. Talk to a hospital financial counselor in the business office about developing a monthly payment plan if you need help with hospital expenses.

·

The public library is an excellent source of information, as are patient libraries at many cancer centers. A librarian can help you find books and articles through a literature search.

·

A local church, synagogue, YMCA or YWCA, or fraternal order may provide financial assistance, or may have volunteers who can help with transportation and home care. Catholic Charities, the United Way, or the American Red Cross may also operate local offices. Some of these organizations may provide home care, and the United Way’s information and referral service can refer you to an agency that provides financial help. To find the United Way serving your community, visit their online directory at http://www.unitedway.org on the Internet or look in the White Pages of your local telephone book.

·

Local or county government agencies may offer low-cost transportation (sometimes called para-transit) to individuals unable to use public transportation. The Federal government runs the Hill-Burton program (1–800–638–0742), which funds certain medical facilities and hospitals to provide children with cancer with free or low-cost care if their families are in financial need. Getting the Most From a Service: What To Ask

No matter what type of help you are looking for, the only way to find resources to fit your needs is to ask the right questions. When you are calling an organization for information, it is important to think about what questions you are going to ask before you call. Many people find it helpful to write out their questions in advance, and to take notes during the call. Another good tip is to ask the name of the person with whom you are speaking in case you have follow-up questions. Below are some of the

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questions you may want to consider if you are calling or visiting a new agency and want to learn about how they can help: ·

How do I apply [for this service]?

·

Are there eligibility requirements? What are they?

·

Is there an application process? How long will it take? What information will I need to complete the application process? Will I need anything else to get the service?

·

Do you have any other suggestions or ideas about where I can find help?

The most important thing to remember is that you will rarely receive help unless you ask for it. In fact, asking can be the hardest part of getting help. Don’t be afraid or ashamed to ask for assistance. Cancer is a very difficult disease, but there are people and services that can ease your burdens and help you focus on your child’s treatment and recovery.

Finding Doctors Who Specialize in Cancer Care12 A common way to find a doctor who specializes in cancer care is to ask for a referral from your child’s primary care physician. Sometimes, you may know a specialist yourself, or through the experience of a family member, coworker, or friend. The following resources may also be able to provide you with names of doctors who specialize in treating specific diseases or conditions. However, these resources may not have information about the quality of care that the doctors provide. ·

Your local hospital or its patient referral service may be able to provide you with a list of specialists who practice at that hospital.

·

Your nearest National Cancer Institute (NCI)-designated cancer center can provide information about doctors who practice at that center. The NCI fact sheet The National Cancer Institute Cancer Centers Program describes and gives contact information, including Web sites, for NCIdesignated cancer treatment centers around the country. Many of the cancer centers’ Web sites have searchable directories of physicians who practice at each facility. The NCI’s fact sheet is available at http://cis.nci.nih.gov/fact/1_2.htm on the Internet, or by calling the Cancer Information Service (CIS) at 1–800–4–CANCER (1–800–422–6237).

12

Adapted from the NCI: http://cis.nci.nih.gov/fact/7_47.htm.

Seeking Guidance 43

·

The American Board of Medical Specialties (ABMS) publishes a list of board-certified physicians. The Official ABMS Directory of Board Certified Medical Specialists lists doctors’ names along with their specialty and their educational background. This resource is available in most public libraries. The ABMS also has a Web site that can be used to verify whether a specific physician is board-certified. This free service is located at http://www.abms.org/newsearch.asp on the Internet. Verification of a physician’s board certification can also be obtained by calling the ABMS at 1–866–275–2267 (1–866–ASK–ABMS).

·

The American Medical Association (AMA) provides an online service called AMA Physician Select that offers basic professional information on virtually every licensed physician in the United States and its possessions. The database can be searched by doctor’s name or by medical specialty. The AMA Physician Select service is located at http://www.ama-assn.org/aps/amahg.htm on the Internet.

·

The American Society of Clinical Oncologists (ASCO) provides an online list of doctors who are members of ASCO. The member database has the names and affiliations of over 15,000 oncologists worldwide. It can be searched by doctor’s name, institution’s name, location, and/or type of board certification. This service is located at http://www.asco.org/people/db/html/m_db.htm on the Internet.

·

The American College of Surgeons (ACOS) Fellowship Database is an online list of surgeons who are Fellows of the ACOS. The list can be searched by doctor’s name, geographic location, or medical specialty. This service is located at http://web.facs.org/acsdir/default.htm on the Internet. The ACOS can be contacted at 633 North Saint Clair Street, Chicago, IL 60611–3211; or by telephone at 312–202–5000.

·

Local medical societies may maintain lists of doctors in each specialty.

·

Public and medical libraries may have print directories of doctors’ names, listed geographically by specialty.

·

Your local Yellow Pages may have doctors listed by specialty under “Physicians.”

The Agency for Healthcare Research and Quality (AHRQ) offers Your Guide to Choosing Quality Health Care, which has information for consumers on choosing a health plan, a doctor, a hospital, or a long-term care provider. The Guide includes suggestions and checklists that you can use to determine which doctor or hospital is best for you. This resource is available at http://www.ahrq.gov/consumer/qntool.htm on the Internet. You can also

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order the Guide by calling the AHRQ Publications Clearinghouse at 1–800– 358–9295. If you are a member of a health insurance plan, your choice may be limited to doctors who participate in your plan. Your insurance company can provide you with a list of participating primary care doctors and specialists. It is important to ask your insurance company if the doctor you choose is accepting new patients through your health plan. You also have the option of seeing a doctor outside your health plan and paying the costs yourself. If you have a choice of health insurance plans, you may first wish to consider which doctor or doctors you would like to use, then choose a plan that includes your chosen physician(s). The National Comprehensive Cancer Network (NCCN) Physician Directory lists specialists who practice in the NCCN’s 19 member institutions across the U.S. To access the directory, go to http://www.nccn.org/ and click on “Physician Directory“. To use this service, you will be required to scroll to the bottom of the page and select “I agree.” Enter your search criteria and select “Find” at the bottom of the page. To obtain more information on a physician or institution, contact the institution’s Physician Referral Department or the NCCN Patient Information and Referral Service at 1-888909-NCCN or [email protected]. If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Selecting Your Child’s Doctor13 There are many factors to consider when choosing a doctor. To make the most informed decision, you may wish to speak with several doctors before choosing one. When you meet with each doctor, you might want to consider the following: ·

Does the doctor have the education and training to meet my child’s needs?

·

Does the doctor use the hospital that I have chosen?

13 This

section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

Seeking Guidance 45

·

Does the doctor explain things clearly and encourage me to ask questions?

·

What are the doctor’s office hours?

·

Who covers for the doctor when he or she is unavailable? Will that person have access to my medical records?

·

How long does it take to get an appointment with the doctor?

If you are choosing a surgeon, you may wish to ask additional questions about the surgeon’s background and experience with specific procedures. These questions may include: ·

Is the surgeon board-certified?14

·

Has the surgeon been evaluated by a national professional association of surgeons, such as the American College of Surgeons (ACOS)?

·

At which treatment facility or facilities does the surgeon practice?

·

How often does the surgeon perform the type of surgery that my child needs?

·

How many of these procedures has the surgeon performed? What was the success rate?

It is important for you and your child to feel comfortable with the specialist that you choose, because you will be working closely with that person to make decisions about your child’s cancer treatment. Trust your own observations and feelings when deciding on a doctor for your child’s medical care. Other health professionals and support services may also be important during cancer treatment. The National Cancer Institute fact sheet Your Health Care Team: Your Doctor Is Only the Beginning has information about these providers and services, and how to locate them. This fact sheet is located at http://cis.nci.nih.gov/fact/8_10.htm on the Internet, or can be obtained by calling the CIS at 1–800–4–CANCER (1–800–422–6237).

While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified. 14

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Working with Your Child’s Doctor15 Research has shown that parents who have good relationships with their children’s doctors tend to be more satisfied with their children’s care. Here are some tips to help you and your child’s doctor become partners: ·

You know important things about your child’s symptoms and health history. Tell the doctor what you think he or she needs to know.

·

Always bring any medications your child is currently taking with you to the appointment, or you can bring a list of your child’s medications including dosage and frequency information. Talk about any allergies or reactions your child has had to medications.

·

Tell your doctor about any natural or alternative medicines your child is taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don’t, the doctor will assume that you understood everything that was said.

·

Write down your questions before the doctor’s visit. List the most important ones first to make sure that they are addressed.

·

Ask the doctor to draw pictures if you think that this will help you and your child understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Take information home. Ask for written instructions. Your child’s doctor may also have brochures and audio and videotapes on neuroblastoma.

By following these steps, you will enhance the relationship you and your child have with the physician.

Getting a Second Opinion16 Once you have chosen a doctor and discussed a diagnosis and treatment plan, but before treatment has started, you may want to get a second opinion - that is, you may want to ask a different doctor to review the diagnosis and This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 16 This section was adapted from the NCI: http://www.cancer.gov/CancerInformation/youngpeople. 15

Seeking Guidance 47

plan. Some insurance companies require a second opinion; some may pay for it if you ask. A second opinion may also be obtained during the course of treatment if it is not working as hoped. Most doctors support a parent’s decision to get a second opinion and many even suggest you do so. To find specialists to get a second opinion, you might: ·

Ask your child’s doctor to suggest a specialist for a second opinion.

·

Get the names of doctors who specialize in treating childhood cancer from the local medical society, a nearby hospital, or a medical school. You can find the telephone numbers for these organizations in your telephone directory or the Yellow Pages.

·

Contact an NCI Comprehensive Cancer Center for a second opinion and possible treatment. Considered “Centers of Excellence,” these cancer centers’ programs have been reviewed and selected by NCI. They offer the most up-todate diagnosis and treatment of cancer and are devoted to both basic and clinical research. To obtain information about the location of the different cancer centers, call the CIS at 1-800-4-CANCER (1-800422-6237) or TTY at 1-800-332-8615.

·

Contact the Pediatric Oncology Branch, NCI, located in Bethesda, Maryland, to ask for a second opinion appointment. They can be reached at 1-877-624-4878.

Finding a Cancer Treatment Facility17 Choosing a treatment facility is another important consideration for getting the best medical care possible. Although you may not be able to choose which hospital treats your child in an emergency, you can choose a facility for scheduled and ongoing care. If you have already found a doctor for your child’s cancer treatment, you may need to choose a facility based on where the doctor practices. The doctor may be able to recommend a facility that provides quality care. You may wish to ask the following questions when considering a treatment facility: ·

Has the facility had experience and success in treating my child’s condition?

·

Has the facility been rated by state, consumer, or other groups for its quality of care?

·

How does the facility check and work to improve its quality of care?

Adapted from the NCI: http://cis.nci.nih.gov/fact/7_47.htm. At this Web site, information on how to find treatment facilities is also available for patients living outside the U.S. 17

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·

Has the facility been approved by a nationally recognized accrediting body, such as the American College of Surgeons (ACOS) and/or the Joint Commission on Accredited Healthcare Organizations (JCAHO)?

·

Does the facility explain patients’ rights and responsibilities? Are copies of this information available to patients?

·

Does the treatment facility offer support services, such as social workers and resources to help me find financial assistance if I need it?

·

Is the facility conveniently located?

If you are a member of a health insurance plan, your choice of treatment facilities may be limited to those that participate in your plan. Your insurance company can provide you with a list of approved facilities. Although the costs of cancer treatment can be very high, you have the option of paying out-of-pocket if you want to use a treatment facility that is not covered by your insurance plan. If you are considering paying for treatment yourself, you may wish to discuss the potential costs with your child’s doctor beforehand. You may also want to speak with the person who does the billing for the treatment facility. In some instances, nurses and social workers can provide you with more information about coverage, eligibility, and insurance issues. The following resources may help you find a treatment facility for your child’s care: ·

The NCI fact sheet The National Cancer Institute Cancer Centers Program describes and gives contact information for NCI-designated cancer treatment centers around the country.

·

The ACOS accredits cancer programs at hospitals and other treatment facilities. More than 1,400 programs in the United States have been designated by the ACOS as Approved Cancer Programs. The ACOS Web site offers a searchable database of these programs at http://web.facs.org/cpm/default.htm on the Internet. The ACOS can be contacted at 633 North Saint Clair Street, Chicago, IL 60611–3211; or by telephone at 312–202–5000.

·

The JCAHO is an independent, not-for-profit organization that evaluates and accredits health care organizations and programs in the United States. It also offers information for the general public about choosing a treatment facility. The JCAHO Web site is located at http://www.jcaho.org on the Internet. The JCAHO is located at One Renaissance Boulevard, Oakbrook Terrace, IL 60181–4294. The telephone number is 630–792–5800.

Seeking Guidance 49

·

The JCAHO offers an online Quality Check service that parents can use to determine whether a specific facility has been accredited by the JCAHO and view the organization’s performance reports. This service is located at http://www.jcaho.org/qualitycheck/directry/directry.asp on the Internet.

·

The AHRQ publication Your Guide To Choosing Quality Health Care has suggestions and checklists for choosing the treatment facility that is right for you.

Questions and Answers about Children’s Cancer Centers 18 Survival rates for childhood cancer have risen sharply over the past 20 years. In the United States, more than 75 percent of children with cancer are now alive 5 years after diagnosis, compared with about 60 percent in the mid1970s. Much of this dramatic improvement is due to the development of improved therapies at children’s cancer centers, where the majority of children with cancer have their treatment. What Are Children’s Cancer Centers? Children’s cancer centers are hospitals or units in hospitals that specialize in the diagnosis and treatment of cancer in children and adolescents. Most children’s, or pediatric, cancer centers treat patients up to the age of 20. Are There Standards for Children’s Cancer Centers? The following groups have established standards for children’s cancer centers or programs: ·

The National Cancer Institute (NCI)-sponsored Children’s Oncology Group (COG), formerly known as the Children’s Cancer Group (CCG) and the Pediatric Oncology Group (POG), is a network of children’s cancer centers that meet strict quality assurance standards.

·

The American Academy of Pediatrics (AAP) published Guidelines for the Pediatric Cancer Center and Role of such Centers in Diagnosis and Treatment in 1986 and 1997.

18


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·

The American Society of Pediatric Hematology/Oncology (ASPH/O) established standard requirements for programs treating children with cancer and blood disorders.

These groups agree that a childhood cancer center should be staffed by trained pediatric oncologists (doctors who specialize in childhood cancer) and other specialists who work as a team. Other members of the health professional team usually include pediatric surgeons, specialist surgeons (for instance neurosurgeons and urologic surgeons), radiation oncologists, pathologists, nurses, consulting pediatric specialists, psychiatrists, oncology social workers, nutritionists, and home health care professionals—all with expertise in treating children and adolescents with cancer. Together, these professionals offer comprehensive care.

What Are the Advantages of a Specialized Children’s Cancer Center? Because childhood cancer is relatively rare, it is important to seek treatment in centers that specialize in the treatment of children with cancer. Specialized cancer programs at comprehensive, multidisciplinary cancer centers follow established protocols (step-by-step guidelines for treatment). These protocols are carried out using a team approach. The team of health professionals is involved in designing the appropriate treatment and support program for the child and the child’s family. In addition, these centers participate in specially designed and monitored research studies that help develop more effective treatments and address issues of long-term childhood cancer survival.

Can Children with Cancer Be Treated at the National Cancer Institute? The Pediatric Oncology Branch (POB) of the National Cancer Institute conducts clinical trials for a wide variety of childhood cancers at the Warren Grant Magnuson Clinical Center, which is located at the National Institutes of Health in Bethesda, Maryland. There is no charge to patients for services provided at the Clinical Center. Children, teenagers, and young adults with newly diagnosed or recurrent cancer (cancer that has come back) may be referred to the POB. To refer a patient with cancer, the patient’s doctor should call the POB’s toll-free number at 1–877–624–4878 between the hours of 8:30 a.m. and 5:00 p.m. and

Seeking Guidance 51

ask for the attending physician. The attending physician will discuss the case with the patient’s doctor, determine whether the patient is eligibile for treatment at NCI, and help arrange the referral. The POB can also be reached at http://www-dcs.nci.nih.gov/branches/pedonc/index.html on the Internet. POB attending physicians also are available to provide a second opinion about a patient. The patient, family, or physician can contact the POB to arrange for a second opinion. POB staff can offer assistance in cases where a diagnosis is difficult and also can aid in developing an appropriate treatment plan. Finding a Children’s Cancer Center A family’s pediatrician or family doctor often can provide a referral to a comprehensive children’s cancer center. Families and health professionals also can call the NCI’s Cancer Information Service (CIS) at 1–800–4– CANCER to learn about children’s cancer centers that belong to the Children’s Cancer Study Group and the Pediatric Oncology Group. All of the cancer centers that participate in these Groups have met strict standards of excellence for childhood cancer care.

Additional Cancer Support Information In addition to the references above, the NCI has set up guidance Web sites that offers information on issues relating to cancer. These include: ·

Facing Forward - A Guide for Cancer Survivors: http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=cc93a 843-6fc0-409e-8798-5c65afc172fe

·

Taking Time: Support for People With Cancer and the People Who Care About Them: http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=21a4 6445-a5c8-4fee-95a3-d9d0d665077a

·

When Cancer Recurs: Meeting the Challenge: http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=9e13 d0d2-b7de-4bd6-87da-5750300a0dab

·

Your Health Care Team: Your Doctor Is Only the Beginning: http://cis.nci.nih.gov/fact/8_10.htm

·

When Someone in Your Family Has Cancer: http://www.cancer.gov/CancerInformation/whensomeoneinyourfamily

52 Neuroblastoma

Vocabulary Builder Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Mammography: The use of x-rays to create a picture of the breast. [NIH] Neurosurgeon: A doctor who specializes in surgery on the brain, spine, and other parts of the nervous system. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Palliative: 1. affording relief, but not cure. 2. an alleviating medicine. [EU] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH]

Clinical Trials 53

CHAPTER 3. CLINICAL TRIALS AND NEUROBLASTOMA Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your child’s physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning neuroblastoma.

What Is a Clinical Trial?19 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for neuroblastoma is to try it on patients in a clinical trial.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

19

54 Neuroblastoma

What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on neuroblastoma.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for neuroblastoma compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment. How Is a Clinical Trial Conducted?

Various organizations support clinical trials at medical centers, hospitals, universities, and doctors’ offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your child’s visits. All doctors and researchers who take part in the study on neuroblastoma carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat your child in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on neuroblastoma. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.”

Clinical Trials 55

This treatment, like a placebo, has no effect on neuroblastoma and will not harm your child. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to have your child participate in a clinical trial, you will not know which group he or she will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request that your child receive the new treatment instead of the placebo or “sham” treatment. Often, you will not know until the study is over whether your child has been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the participants or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how neuroblastoma develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for neuroblastoma. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a medical condition develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a medical condition usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Your Child in a Clinical Trial? Not everyone can take part in a clinical trial for a specific medical condition. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of the condition, as well as, the age and previous treatment history of the patient. You or your child’s doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you would like your child to participate in a clinical trial, your child’s doctor must contact one of the trial’s investigators and provide details about his or her diagnosis and medical history.

56 Neuroblastoma

When participating in a clinical trial, your child may be required to have a number of medical tests. Your child may also need to take medications and/or undergo surgery. Depending upon the treatment and the examination procedure, your child may be required to receive inpatient hospital care. He or she may have to return to the medical facility for followup examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Neuroblastoma The National Institutes of Health and other organizations sponsor trials on various medical conditions. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every medical condition at all times. The following lists recent trials dedicated to neuroblastoma.20 If the trial listed by the NIH is still recruiting, your child may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your child’s physician who can help you determine if your child might benefit from participation. ·

Antineoplaston Therapy in Treating Recurrent, or Refractory Neuroblastoma

Patients With Metastatic,

Condition(s): recurrent neuroblastoma; disseminated neuroblastoma; localized unresectable neuroblastoma; stage 4S neuroblastoma; regional neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients who have metastatic, recurrent, or refractory neuroblastoma. Phase(s): Phase II 20

These are listed at www.ClinicalTrials.gov.

Clinical Trials 57

Study Type: Treatment Contact(s): Texas; Burzynski Research Institute, Houston, Texas, 77055, United States; Recruiting; Stanislaw R. Burzynski 713-335-5697. Study chairs or principal investigators: Stanislaw R. Burzynski, Study Chair; Burzynski Research Institute Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003513;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors Condition(s): childhood soft tissue sarcoma; childhood liver cancer; bone cancer; brain tumor; eye cancer; kidney tumor Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of arsenic trioxide in treating children who have advanced neuroblastoma or other solid tumors. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Brian H. Kushner 212639-6793. Study chairs or principal investigators: Brian H. Kushner, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00024258;jsessionid=FB8550 A371C882045C8F9C93E43BC900

·

beta-Glucan and Monoclonal Antibody in Treating Patients With Metastatic Neuroblastoma Condition(s): disseminated neuroblastoma; recurrent neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center

58 Neuroblastoma

Purpose - Excerpt: RATIONALE: Biological therapies such as beta-glucan use different ways to stimulate the immune system and stop cancer cells from growing. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining beta-glucan and monoclonal antibody may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining beta-glucan and monoclonal antibody in treating patients who have metastatic neuroblastoma. Phase(s): Phase I Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Nai-Kong V. Cheung 212-639-8401. Study chairs or principal investigators: Nai-Kong V. Cheung, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00037011;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors Condition(s): recurrent childhood soft tissue sarcoma; recurrent osteosarcoma; unspecified childhood solid tumor, protocol specific; metastatic osteosarcoma; recurrent neuroblastoma; recurrent melanoma; metastatic childhood soft tissue sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Children's Oncology Group Purpose - Excerpt: RATIONALE: Biological therapies such as hu14.18interleukin-2 fusion protein use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I trial to study the effectiveness of hu14.18-interleukin-2 fusion protein in treating children who have refractory or recurrent neuroblastoma or other tumors. Phase(s): Phase I Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003750;jsessionid=FB8550 A371C882045C8F9C93E43BC900

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·

Chemotherapy and Radiation Therapy in Treating Infants With Tumors of the Brain Condition(s): childhood choroid plexus tumor; childhood supratentorial ependymoma; childhood central nervous system germ cell tumor; childhood infratentorial ependymoma; regional neuroblastoma; localized resectable neuroblastoma; localized unresectable neuroblastoma; untreated childhood supratentorial primitive neuroectodermal tumors; untreated childhood medulloblastoma; newly diagnosed childhood ependymoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Pediatric Brain Tumor Consortium Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy and radiation therapy in treating infants who have tumors of the brain. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005063;jsessionid=FB8550 A371C882045C8F9C93E43BC900

·

Chemotherapy and Surgery Followed by Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Neuroblastoma Condition(s): stage 4S neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): United Kingdom Children's Cancer Study Group; Societe Francaise Oncologie Pediatrique Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs to kill more tumor cells. Chemotherapy, given before and after surgery, followed by peripheral stem cell transplantation may be an effective treatment for metastatic neuroblastoma. PURPOSE: Phase II trial to study the effectiveness of

60 Neuroblastoma

chemotherapy, given before and after surgery, followed by peripheral stem cell transplantation in treating patients who have metastatic neuroblastoma. Phase(s): Phase II; MEDLINEplus consumer health information Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00024193;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Brain Tumor Condition(s): extraocular retinoblastoma; childhood choroid plexus tumor; disseminated neuroblastoma; childhood supratentorial ependymoma; previously untreated childhood rhabdomyosarcoma; localized unresectable neuroblastoma; untreated childhood supratentorial primitive neuroectodermal tumors; stage 4S neuroblastoma; untreated childhood medulloblastoma; childhood infratentorial ependymoma; regional neuroblastoma; localized resectable neuroblastoma; newly diagnosed childhood ependymoma Study Status: This study is currently recruiting patients. Sponsor(s): Kaplan Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of different regimens of combination chemotherapy followed by peripheral stem cell transplantation in treating children who have newly diagnosed brain tumor. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003273;jsessionid=FB8550 A371C882045C8F9C93E43BC900

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·

Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Central Nervous System Cancer Condition(s): adult central nervous system germ cell tumor; adult medulloblastoma; adult oligodendroglioma; recurrent adult brain tumor; adult anaplastic astrocytoma; recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity; primary central nervous system lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Comprehensive Cancer Center

Institute

(NCI);

Herbert

Irving

Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy combined with peripheral stem cell transplantation in treating patients who have central nervous system cancer. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Herbert Irving Comprehensive Cancer Center, New York, New York, 10032, United States; Recruiting; Charles S. Hesdorffer 212-305-4907. Study chairs or principal investigators: Charles S. Hesdorffer, Study Chair; Herbert Irving Comprehensive Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00007982;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Chemotherapy, Radiation Therapy, and Monoclonal Antibody Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Neuroblastoma Condition(s): disseminated neuroblastoma; regional neuroblastoma; localized resectable neuroblastoma; recurrent neuroblastoma; peripheral blood stem cell transplantation; localized unresectable neuroblastoma; stage 4S neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Gesellschaft fur Padiatrische Onkologie und Hamatologie Germany Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or

62 Neuroblastoma

die. Radiation therapy uses high-energy x-rays to damage tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Combining these therapies may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy, radiation therapy, and monoclonal antibody therapy with or without peripheral stem cell transplantation in treating patients who have neuroblastoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00017225;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

CHP677: I-Metaiodobenzylguanidine (I-MIBG) therapy for refractory neuroblastoma: a Phase II study Condition(s): Neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: 131I-metaiodobenzylguanidine (131I-MIBG) is a norepinephrine analog that concentrates in adrenergic tissue and therefore holds promise for cell-specific treatment of neuroblastoma. This is a dual institution, Phase II study of 131I-MIBG administered at the previously defined maximum practical dose of 18 mCi/kg to children with relapsed or refractory neuroblastoma. Phase(s): Phase II Study Type: Interventional Contact(s): Pennsylvania; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, United States; Recruiting; John M. Maris, M.D. 215-590-5242 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00013806;jsessionid=FB8550 A371C882045C8F9C93E43BC900

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·

Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Neuroblastoma Condition(s): disseminated neuroblastoma; regional neuroblastoma; localized resectable neuroblastoma; recurrent neuroblastoma; localized unresectable neuroblastoma; stage 4S neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Pediatric Oncology Group; Children's Cancer Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of peripheral stem cell transplantation using either treated or untreated peripheral stem cells following combination chemotherapy in treating patients who have neuroblastoma. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004188;jsessionid=FB8550 A371C882045C8F9C93E43BC900

·

Combination Chemotherapy Before Surgery in Treating Children With Localized Neuroblastoma Condition(s): localized unresectable neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Societe Internationale d'Oncologie Pediatrique; United Kingdom Children's Cancer Study Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy drugs before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase III trial to determine the effectiveness of combination chemotherapy given before surgery in treating children who have localized neuroblastoma. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below

64 Neuroblastoma

Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00025428;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Combination Chemotherapy Followed by Surgery and Peripheral Stem Cell or Bone Marrow Transplantation in Treating Infants With Newly Diagnosed Neuroblastoma Condition(s): disseminated neuroblastoma; regional neuroblastoma; localized resectable neuroblastoma; localized unresectable neuroblastoma; stage 4S neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): European Infant Neuroblastoma Study 1999 Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy given before surgery followed by peripheral stem cell or bone marrow transplantation in treating infants who have newly diagnosed neuroblastoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00025649;jsessionid=FB8550 A371C882045C8F9C93E43BC900

·

Combination Chemotherapy Followed by Surgery in Treating Infants With Newly Diagnosed Neuroblastoma Condition(s): disseminated neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): European Infant Neuroblastoma Study 1999 Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them before surgery, may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by surgery in treating infants who have newly diagnosed neuroblastoma.

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Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00025623;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Combination Chemotherapy Followed by Surgery in Treating Infants With Newly Diagnosed Neuroblastoma. Condition(s): localized unresectable neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): European Infant Neuroblastoma Study 1999 Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by surgery in treating infants who have newly diagnosed neuroblastoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00025597;jsessionid=FB8550 A371C882045C8F9C93E43BC900

·

Combination Chemotherapy in Treating Children With Neuroblastoma Condition(s): disseminated neuroblastoma; localized unresectable neuroblastoma; stage 4S neuroblastoma; regional neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Pediatric Oncology Group; Children's Cancer Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Combination chemotherapy plus surgery may be an effective treatment for neuroblastoma. PURPOSE: Phase III trial to determine the effectiveness of combination chemotherapy consisting of carboplatin,

66 Neuroblastoma

etoposide, cyclophosphamide, and doxorubicin, followed by surgery to remove the tumor, in treating young patients with neuroblastoma. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003093;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Combination Chemotherapy Diagnosed Neuroblastoma

in

Treating

Infants

With

Newly

Condition(s): disseminated neuroblastoma; stage 4S neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): European Infant Neuroblastoma Study 1999 Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of different combination chemotherapy regimens in treating infants who have newly diagnosed neuroblastoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00025610;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Combination Chemotherapy With or Without Filgrastim Before Surgery, High-Dose Chemotherapy, and Radiation Therapy Followed by Isotretinoin With or Without Monoclonal Antibody in Treating Patients With Neuroblastoma Condition(s): disseminated neuroblastoma; regional neuroblastoma; localized unresectable neuroblastoma; stage 4S neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Societe Internationale d'Oncologie Pediatrique Purpose - Excerpt: RATIONALE: Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system

Clinical Trials 67

recover from the side effects of chemotherapy. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining isotretinoin and monoclonal antibodies may kill any remaining tumor cells following surgery. It is not yet known which treatment regimen is more effective in treating neuroblastoma. PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy with or without filgrastim before surgery, high-dose chemotherapy, and radiation therapy followed by isotretinoin with or without monoclonal antibody in treating patients who have neuroblastoma. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00030719;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Isotretinoin With or Without Monoclonal Antibody, Interleukin 2, and Sargramostim Following Stem Cell Transplantation in Treating Patients With Neuroblastoma Condition(s): disseminated neuroblastoma; regional neuroblastoma; localized unresectable neuroblastoma; stage 4S neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Children's Oncology Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Interleukin-2 and sargramostim may stimulate a person's white blood cells to kill cancer cells. It is not yet known if chemotherapy is more effective with or without monoclonal antibody therapy, interleukin 2, and sargramostim following stem cell transplantation in treating neuroblastoma. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without monoclonal antibody, interleukin-2, and sargramostim following stem cell transplantation in treating patients who have neuroblastoma. Phase(s): Phase III

68 Neuroblastoma

Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00026312;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Melphalan and Buthionine Sulfoximine Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Children With Recurrent or Refractory Neuroblastoma Condition(s): disseminated neuroblastoma; regional neuroblastoma; recurrent neuroblastoma; localized unresectable neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Children's Hospital Los Angeles Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of melphalan and buthionine sulfoximine followed by bone marrow or peripheral stem cell transplantation in treating children who have recurrent or refractory neuroblastoma. Phase(s): Phase I Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005835;jsessionid=FB8550 A371C882045C8F9C93E43BC900

·

Monoclonal Antibody Therapy Plus Etoposide in Treating Patients With Neuroblastoma Condition(s): disseminated neuroblastoma; regional neuroblastoma; recurrent neuroblastoma; localized unresectable neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor killing substances to them

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without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody therapy plus etoposide in treating patients who have neuroblastoma. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Nai-Kong V. Cheung 212-639-8401. Study chairs or principal investigators: Nai-Kong V. Cheung, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004110;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Monoclonal Antibody Therapy Plus Sargramostin in Treating Patients With Advanced Neuroblastoma Condition(s): recurrent neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining colony-stimulating factors, such as sargramostim, with monoclonal antibodies may be an effective treatment for advanced neuroblastoma. PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody 3F8 plus sargramostim in treating patients who have advanced neuroblastoma. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Brian H. Kushner 212639-6793. Study chairs or principal investigators: Brian H. Kushner, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002560;jsessionid=FB8550 A371C882045C8F9C93E43BC900

70 Neuroblastoma

·

Multiple Therapies Neuroblastoma

in

Treating

Patients

With

Advanced

Condition(s): disseminated neuroblastoma; regional neuroblastoma; recurrent neuroblastoma; localized unresectable neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Biological therapies use different ways to stimulate the immune system and stop cancer cell from growing. Combining different types of therapies may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy, monoclonal antibody therapy, surgery, peripheral stem cell transplantation, radiation therapy, and biological therapy in treating patients who have advanced neuroblastoma. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Nai-Kong V. Cheung 212-639-8401. Study chairs or principal investigators: Nai-Kong V. Cheung, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00040872;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Neuroblastoma Vaccine for Treatment of High-Risk Neuroblastoma After Chemotherapy Condition(s): Neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Baylor College of Medicine; Texas Children's Hospital Purpose - Excerpt: PRIMARY OBJECTIVE To determine the percentage of patients with high risk neuroblastoma in first or subsequent partial response or better, or with microscopic residual bone marrow disease,

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who demonstrate an immunological anti-tumor response at any time during, and for up to 12 months from initiation of, treatment with subcutaneous injections of autologous neuroblastoma cells, genetically modified by adenoviral vectors to secrete interleukin-2 (IL-2) (autologous neuroblastoma vaccine) SECONDARY OBJECTIVES 1. To determine the toxicity of the autologous neuroblastoma vaccine given according to this schedule 2. To obtain preliminary data on the effect of vaccine administration on progression-free survival from high-risk neuroblastoma Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): Heidi V Russell, MD 832-822-4885 [email protected]; Texas; Texas Children's Hospital, Houston, Texas, 77030, United States; Recruiting; Heidi V Russell, MD 832-822-4885 [email protected]. Study chairs or principal investigators: Heidi V Russell, MD, Principal Investigator; Baylor College of Medicine Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00048386;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors Condition(s): Brain Rhabdomyosarcoma

Tumor;

Ewing's

Sarcoma;

Neuroblastoma;

Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will examine the safety and side effects of tariquidar in children and adolescents with cancer and test whether it can improve current anticancer drug treatments. Tumor resistance to chemotherapy is a major problem in cancer treatment. Studies have found that a protein (P-glycoprotein) on some cancer cells pumps anticancer drugs out of the cells, reducing treatment effectiveness. In laboratory tests, an experimental drug called tariquidar has blocked pumping by this protein. It is being used in this study to try to increase amounts of the anticancer drugs vinorelbine (Navelbinea), doxorubicin (Adriamycin) or docetaxel (Taxotere) in cancer cells. Patients between 2 and 18 years of age with solid tumors-including rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, liver tumors, germ cell

72 Neuroblastoma

tumors, and primary brain tumors-who have relapsed or who do not respond to frontline therapy and have no other treatment options may be eligible for this study. Candidates will be screened with a medical history, physical and neurological examinations, blood and urine tests, electrocardiogram, MUGA (nuclear medicine scan of the heart) and radiologic studies to evaluate the extent of disease. Participants will receive tariquidar plus either doxorubicin, vinorelbine or docetaxel, depending on the type of cancer, previous treatments, and side effects of prior treatment. Patients taking doxorubicin will also receive GCSF, a drug that helps boost the immune system, and dexrazoxane, a medicine to lessen the harmful effects of doxorubicin on the heart. Patients taking docetaxel will also receive GCSF, plus medicines to prevent an allergic reaction to the docetaxel. Treatment will be given in 21-day cycles for no more than eight cycles. The first treatment cycle for each regimen begins with a baseline Sestamibi scan-an imaging procedure that uses the radioactive drug Tc-99m Sestamibi. This drug accumulates in tumor cells and is eliminated from them in much the same way that some cancer drugs are eliminated from cells. The drug is injected into a vein and a series of pictures taken with a camera that detects radioactivity shows where the radioactive Sestamibi distributes in the body, including in the cancer, liver and heart. This procedure can monitor for effects of tariquidar on resistance to therapy. The day after the Sestamibi scan, tariquidar is given intravenously (through a vein), followed by another Sestamibi scan. On the third day, tariquidar is given, followed by the treatment drug (doxorubicin, vinorelbine or docetaxel). Patients taking vinorelbine will repeat the tariquidar and vinorelbine doses 1 week after the first. Sestamibi scans are done during the first treatment cycle only for each drug regimen. In addition, for the first treatment cycle only, 17 blood samples of less than one-half teaspoon each are drawn to study the pharmacology of tariquidar (i.e., how the drug works in the body), and another 17 samples are taken to study the pharmacology of the chemotherapy drug. A device, such as a heparin lock, is put in place to avoid having multiple needlesticks for these blood draws. Routine blood tests are done twice a week and various tests, such as X-rays, CT and MRI scans are done periodically to follow the progress of the cancer throughout the treatment period. Patients taking doxorubicin will also have an echocardiogram or MUGA to evaluate heart function. Patients are examined by a doctor at least once a week. Phase(s): Phase I Study Type: Interventional

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Contact(s): Maryland; National Cancer Institute (NCI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Elizabeth Fox, M.D. 3014026641 [email protected] Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00011414;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Phase I Trial of ABT-751 in Children with Solid Tumors Condition(s): Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will determine the side effects and maximum tolerated dose of the experimental drug ABT-751 that can be safely given to children and young adults with solid tumors. ABT-751 belongs to a new class of anticancer drugs that hamper the replication of cancer cells. It works by binding to a protein called tubulin. Other drugs that work this way include vincristine, vinblastine, vinorelbine, paclitaxel, and docetaxel. In laboratory studies, ABT-751 kills cancer cells that are resistant to vincristine and paclitaxel. Patients up to 18 years of age with solid tumors (rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, liver tumors germ cell tumors, primary brain tumors, and other solid tumors) whose disease has relapsed, or whose tumor no longer responds to standard treatment, may be eligible for this study. Candidates will be screened with a history and physical, and neurological examinations, blood and urine tests, echocardiogram (heart ultrasound), and imaging studies to evaluate the extent of disease. Participants will take one ABT-751 capsule a day for 7 days each treatment cycle. A treatment cycle will be 21 to 28 days, depending on how long it takes the patient to recover from the drug side effects. The drug dose will be increased gradually in successive groups of patients if side effects of the previous dose were acceptable. Patients may continue treatment unless their disease worsens with ABT-751 or irreversible side effects occur. They will undergo the following evaluations during this study: - Physical examinations-weekly - Routine blood tests-twice a week - CT or MRI scans to evaluate the size of the tumor-after the first treatment cycle and then after every other cycle - Echocardiogram to evaluate heart structure and function - before starting treatment and then before every even-numbered cycle (cycle 2, 4, 6, and so on) - Blood tests to study how the body handles ABT-751-during the first treatment cycle. For this test, 8 blood samples of one teaspoon or less each will be drawn

74 Neuroblastoma

on the first day of ABT-751 therapy and one blood sample will be drawn on days 2, 5, and 7 before taking the drug. If possible, blood will be collected through a small plastic catheter placed in a vein (heparin lock or Hickman line or port-a-cath) to avoid multiple needle sticks. - Blood test to study the effects of ABT-751 on normal blood cells. For this test, blood samples of 2 teaspoons or less each will be drawn before the first dose of ABT-751, and 6 and 24 hours after the first dose-first treatment cycle only. - 24-hour urine collection-after the first dose of ABT-751 - Magnetic resonance imaging (MRI) with gadolinium contrast to analyze the effect of ABT-751 on blood flow to the tumor. This test will be done only in some patients. It will be done before starting the first treatment cycle and repeated 2 to 3 days after starting treatment. MRI uses a magnetic field and radio waves to show structural and chemical changes in tissues. For the procedure, the patient lies still on a stretcher that is moved into the MRI scanner (a narrow cylinder containing the magnet). Earplugs are worn to muffle loud noises caused by electrical switching of radio frequency circuits used in the scanning process. A gadolinium contrast material is injected to brighten the images. Phase(s): Phase I Study Type: Interventional Contact(s): Maryland; National Cancer Institute (NCI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Wendy Goodspeed, R.N. 3015944762 [email protected] Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00032266;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Radiolabeled Monoclonal Antibody Therapy After Radiation Therapy in Treating Patients With Primary Brain Tumors Condition(s): adult glioblastoma multiforme; adult central nervous system germ cell tumor; adult malignant meningioma; adult pineal parenchymal tumor; adult medulloblastoma; adult noninfiltrating astrocytoma; adult oligodendroglioma; adult anaplastic astrocytoma; mixed gliomas; adult well-differentiated mildly and moderately anaplastic astrocytoma; localized resectable neuroblastoma; adult craniopharyngioma; recurrent adult brain tumor; adult meningioma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Duke Comprehensive Cancer Center

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Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and deliver tumor-killing substances, such as radioactive iodine, to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody after radiation therapy in treating patients with newly diagnosed primary brain tumors that can be surgically resected. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): North Carolina; Duke Comprehensive Cancer Center, Durham, North Carolina, 27710, United States; Recruiting; David Allen Reardon 919-684-5301. Study chairs or principal investigators: Darell D. Bigner, Study Chair; Duke Comprehensive Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003484;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Primary or Metastatic Brain Tumors Condition(s): brain metastases; recurrent neuroblastoma; adult glioblastoma multiforme; adult central nervous system germ cell tumor; adult malignant meningioma; adult pineal parenchymal tumor; adult medulloblastoma; adult noninfiltrating astrocytoma; adult oligodendroglioma; adult anaplastic astrocytoma; mixed gliomas; adult well-differentiated mildly and moderately anaplastic astrocytoma; localized resectable neuroblastoma; adult craniopharyngioma; recurrent adult brain tumor; adult meningioma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Duke Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. This may be effective treatment for primary or metastatic brain tumors. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy in treating patients with primary or metastatic brain tumors. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): North Carolina; Duke Comprehensive Cancer Center, Durham, North Carolina, 27710, United States; Recruiting; David Allen

76 Neuroblastoma

Reardon 919-684-5301. Study chairs or principal investigators: Darell D. Bigner, Study Chair; Duke Comprehensive Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003461;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Rebeccamycin Analog in Treating Children With Relapsed or Refractory Neuroblastoma Condition(s): recurrent neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of rebeccamycin analog in treating children with relapsed or refractory neuroblastoma. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Tanya Trippett 212639-8267. Study chairs or principal investigators: Tanya Trippett, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003737;jsessionid=FB8550 A371C882045C8F9C93E43BC900

·

Surgery in Treating Children With Neuroblastoma Condition(s): recurrent neuroblastoma; disseminated neuroblastoma; stage 4S neuroblastoma; localized resectable neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Children's Cancer Group; Pediatric Oncology Group Purpose - Excerpt: RATIONALE: Surgery alone may be effective in treating children with neuroblastoma. PURPOSE: Phase III trial to study the effectiveness of surgery alone in treating children who have neuroblastoma. Phase(s): Phase III Study Type: Treatment

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003119;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

Surgery in Treating Patients With Neuroblastoma Condition(s): localized unresectable neuroblastoma; localized resectable neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): Societe Internationale d'Oncologie Pediatrique Purpose - Excerpt: RATIONALE: Surgery may be an effective treatment for neuroblastoma. PURPOSE: Phase II trial to study the effectiveness of surgery in treating patients who have neuroblastoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003122;jsessionid=FB8550 A371C882045C8F9C93E43BC900

·

Corticotropin With or Without Immunoglobulin in Treating Abnormal Muscle Movement in Patients With Neuroblastoma Condition(s): disseminated neuroblastoma; regional neuroblastoma; localized resectable neuroblastoma; localized unresectable neuroblastoma; stage 4S neuroblastoma Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Cancer Institute (NCI); Children's Oncology Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Steroid therapy decreases inflammation. Combining chemotherapy and steroid therapy with immunoglobulin may be effective in treating abnormal muscle movement associated with neuroblastoma. PURPOSE: Randomized phase II trial to compare the effectiveness of combining corticotropin with or without immunoglobulin in treating patients who have abnormal trunk muscle movements associated with neuroblastoma. Phase(s): Phase II Study Type: Treatment

78 Neuroblastoma

Contact(s): Gregory H. Reaman 202-884-2147. Study chairs or principal investigators: Gregory H. Reaman, Study Chair; Children's Oncology Group Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00033293;jsessionid=FB8550 A371C882045C8F9C93E43BC900 ·

New Therapeutic Strategies for Patients with Ewing's Sarcoma Family of Tumors, High Risk Rhabdomyosarcoma, and Neuroblastoma Condition(s): Ewing's Sarcoma; Neuroblastoma; Rhabdomyosarcoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: The prognosis for patients with metastatic Ewing's sarcoma family of tumors (ESF), rhabdomyosarcoma (RMS), and neuroblastoma (NBL) remains dismal, with less than 25% long-term disease-free survival. Though less grave, the prognosis for cure for other high-risk patients is approximately 50%. New treatment strategies, including the identification of highly active new agents, maximizing the dose intensity of the most active standard drugs, and the development of improved methods of consolidation to eradicate microscopic residual disease, are clearly needed to improve the outcome of these patients. This protocol will address these issues by commencing with a Phase II window, for the highest risk patients, to evaluate a series of promising drugs with novel mechanisms of action. All patients will then receive 5 cycles of dose-intensive "best standard therapy" with doxorubicin (adriamycin), vincristine, and cyclophosphamide (VAdriaC). Patients at high risk of relapse will continue onto a phase I consolidation regimen consisting of three cycles of dose-escalated Melphalan, Ifosfamide, Mesna, and Etoposide (MIME). Peripheral blood stem cell transfusions (PBSCT) and recombinant human G-CSF will be used as supportive care measures to allow maximal dose-escalation of this combination regimen. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Cancer Institute (NCI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001335;jsessionid=FB8550 A371C882045C8F9C93E43BC900

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·

Phase I Trial and Pharmacokinetic Study of TLC D-99 in Pediatric Patients with Refractory Solid Tumors Condition(s): Glioma; Neoplasm; Nephroblastoma; Neuroblastoma; Rhabdomyosarcoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Doxorubicin is one of the most effective and most widely used chemotherapeutic agents in the treatment of childhood cancers. Its broad spectrum of activity includes both hematological malignancies and solid tumors. However, its clinical usefulness is limited by the development of doxorubicin-induced cardiotoxicity, which is related to the cumulative dose of the drug, and children are at higher risk for this cardiotoxicity than are adults. Encapsulation of doxorubicin within liposomes reduces its acute and chronic toxicities, including cardiotoxicity. TLC D-99 is a liposomal formulation of doxorubicin in egg phosphatidylcholine/cholesterol liposomes. Fifteen phase I and phase II clinical trials of TLC D-99 have been conducted in over 400 adults, and 3 randomized phase III trials in women with breast cancer are ongoing (overall more than 700 adults have been treated with TLC D-99). Acute toxicity was less than would have been expected, even at higher than standard doses. A phase I trial and pharmacokinetic study of this liposome encapsulated formulation of doxorubicin will be conducted in children, to assess the drug's spectrum of toxicity at standard doses of doxorubicin and at doses of TLC D-99 that were tolerable in adults. Phase(s): Phase I Study Type: Interventional Contact(s): Maryland; National Cancer Institute (NCI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001798;jsessionid=FB8550 A371C882045C8F9C93E43BC900

80 Neuroblastoma

Benefits and Risks21 What Are the Benefits of Participating in a Clinical Trial? If you are considering a clinical trial, it is important to realize that your child’s participation can bring many benefits: ·

A new treatment could be more effective than the current treatment for neuroblastoma. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

·

If the treatment is effective, then it may improve your child’s health.

·

Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

·

People who take part in trials contribute to scientific discoveries that may help others with neuroblastoma. In cases where certain medical conditions run in families, your child’s participation may lead to better care or prevention for you and other family members. The Informed Consent

Once you agree to have your child take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial’s risks and benefits, the researcher’s expectations of you and your child, and your child’s rights as a patient.

What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment your child receives may cause side effects that are serious enough to require medical attention. This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f291. 21

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How Is Your Child’s Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect your child can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital’s Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect your child’s safety. During a clinical trial, doctors will closely watch your child to see if the treatment is working and if he or she is experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. Your child will only be asked to participate in a clinical trial as a volunteer with your informed consent. What Are Your Child’s Rights in a Clinical Trial? If your child is eligible for a clinical trial, you will be given information to help you decide whether or not you want him or her to participate. You and your child have the right to: ·

Information on all known risks and benefits of the treatments in the study.

·

Know how the researchers plan to carry out the study, for how long, and where.

·

Know what is expected of your child.

·

Know any costs involved for you or your child’s insurance provider.

·

Know before any of your child’s medical or personal information is shared with other researchers involved in the clinical trial.

·

Talk openly with doctors and ask any questions.

After your child joins a clinical trial, you and your child have the right to: ·

Leave the study at any time. Participation is strictly voluntary.

·

Receive any new information about the new treatment.

·

Continue to ask questions and get answers.

·

Maintain your child’s privacy. Your child’s name will not appear in any reports based on the study.

·

Know whether your child participated in the treatment group or the control group (once the study has been completed).

82 Neuroblastoma

What Questions Should You Ask before Your Child Participates in a Clinical Trial? Questions you should ask when deciding whether or not to enroll your child in a clinical trial include the following: ·

What is the purpose of the clinical trial?

·

What are the standard treatments for neuroblastoma? Why do researchers think the new treatment may be better? What is likely to happen to my child with or without the new treatment?

·

What tests and treatments will my child need? Will my child need surgery? Medication? Hospitalization?

·

How long will the treatment last? How often will my child have to come back for follow-up exams?

·

What are the treatment’s possible benefits to my child’s condition? What are the short- and long-term risks? What are the possible side effects?

·

Will the treatment be uncomfortable? Will it make my child sick? If so, for how long?

·

How will my child’s health be monitored?

·

Where will my child need to go for the clinical trial?

·

How much will it cost to participate in the study? What costs are covered by the study? How much will my child’s health insurance cover?

·

Who will be in charge of my child’s care?

·

Will taking part in the study affect my child’s daily life?

·

How does my child feel about taking part in a clinical trial? Will other family members benefit from my child’s contributions to new medical knowledge?

Clinical Trials and Insurance Coverage22 As you consider enrolling your child in a clinical trial, you will face the critical issue of how to cover the costs of care. Even if you have health insurance, your coverage may not include some or all of the patient care costs associated with a clinical trial. This is because some health plans define clinical trials as “experimental” or “investigational” procedures. Adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=1d92be79-8748-4bda-80052a56d332463b.

22

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Because lack of coverage for these costs can keep prospective participants from enrolling in trials, the National Cancer Institute is working with major health plans and managed care groups to find solutions. In the meantime, there are strategies that may help you deal with cost and coverage barriers. This section answers frequently asked questions about insurance coverage for clinical trial participation and directs you to additional information resources. The material here is mainly concerned with treatment clinical trials, since other types of trials (prevention, screening, etc.) are newer and generally not covered by health insurance at all. However, this guide may become more relevant for prevention and other types of trials as these trials grow more common. If you do not have any health insurance, you may find this section helpful for understanding some of the costs that trials involve.

What Costs Do Trials Involve? Who Is Usually Responsible for Paying Them? There are two types of costs associated with a trial: patient care costs and research costs. Patient care costs fall into two categories: ·

Usual care costs, such as doctor visits, hospital stays, clinical laboratory tests, x-rays, etc., which occur whether you are participating in a trial or receiving standard treatment. These costs have usually been covered by a third-party health plan, such as Medicare or private insurance.

·

Extra care costs associated with clinical trial participation, such as the additional tests that may or may not be fully covered by the clinical trial sponsor and/or research institution.

The sponsor and the participant’s health plan need to resolve coverage of these costs for particular trials. Research costs are those associated with conducting the trial, such as data collection and management, research physician and nurse time, analysis of results, and tests purely performed for research purposes. Such costs are usually covered by the sponsoring organization, such as NCI or a pharmaceutical company.

84 Neuroblastoma

Criteria Used by Health Plans to Make Reimbursement Decisions about Trials Health insurance companies and managed care companies decide which health care services they will pay for by developing coverage policy regarding the specific services. In general, the most important factor determining whether something is covered is a health plan’s judgment as to whether the service is established or investigational. Health plans usually designate a service as established if there is a certain amount of scientific data to show that it is safe and effective. If the health plan does not think that such data exist in sufficient quantity, the plan may label the service as investigational. Health care services delivered within the setting of a clinical trial are very often categorized as investigational and not covered. This is because the health plan thinks that the major reason to perform the clinical trial is that there is not enough data to establish the safety and effectiveness of the service being studied. Thus, for some health plans, any mention of the fact that your child is involved in a clinical trial results in a denial of payment. Your health plan may define specific criteria that a trial must meet before extending coverage, such as the following:

Sponsorship Some plans may only cover costs of trials sponsored by organizations whose review and oversight of the trial is careful and scientifically rigorous, according to standards set by the health plan.

Trial Phase and Type Some plans may cover patient care costs only for the clinical trials they judge to be “medically necessary” on a case-by-case basis. Trial phase may also affect coverage; for example, while a plan may be willing to cover costs associated with Phase III trials, which include treatments that have already been successful with a certain number of people, the plan may require some documentation of effectiveness before covering a Phase I or II trial. While health plans are interested in efforts to improve prevention and screening, they currently seem less likely to have a review process in place

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for these trials. Therefore, it may be more difficult to get coverage for the care costs associated with them. Some plans, especially smaller ones, will not cover any costs associated with a clinical trial. Policies vary widely, but in most cases your best bet is to have your child’s doctor initiate discussions with the health plan. Cost “Neutrality” Some health plans may limit coverage to trials they consider cost-neutral (i.e., not significantly more expensive than the treatments considered standard). Lack of Standard Therapy Some plans limit coverage of trials to situations in which no standard therapy is available. Facility and Personnel Qualifications A health plan may require that the facility and medical staff meet specific qualifications to conduct a trial involving unique services, especially intensive therapy such as a bone marrow transplant (high-dose chemotherapy with bone marrow/ stem cell rescue).

Increasing the Likelihood of Insurance Coverage for Trials23 There are several steps you can follow to deal with coverage issues up front when deciding to enroll your child in a clinical trial. Along the way, enlist the help of family members and your child’s doctor or other health professionals. You may find the following checklist useful:

This section has been adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=1d92be79-8748-4bda-80052a56d332463b&docid=0df4397a-eccb-465f-bd33-a89e7a708c46.

23

86 Neuroblastoma

Understand the Costs Associated with the Trial Ask your child’s doctor or the trial’s contact person about the costs that must be covered by you or your health plan. Are these costs significantly higher than those associated with standard care? Also, inquire about the experience of other patients in the trial. Have their plans paid for their care? Have there been any persistent problems with coverage? How often have the trial’s administrators been successful in getting plans to cover patient care costs?

Understand Your Health Plan Be sure you know what’s in your policy; request and carefully review the actual contract language. If there’s a specific exclusion for “experimental treatment,” look closely at the policy to see how the plan defines such treatment and under what conditions it might be covered. If it is not clearly defined, call the plan’s customer service line, consult their Web site, and/or write to them. Ask for specific information about clinical trials coverage.

Work Closely with Your Child’s Doctor Talk with the doctor about the paperwork he or she submits to your health plan. If there have been problems with coverage in the past, you might ask the doctor or the hospital to send an information package to the plan that includes studies supporting the procedure’s safety, benefits, and medical appropriateness. This package might include: ·

Publications from peer-reviewed literature about the proposed therapy that demonstrate patient benefits;

·

A letter that uses the insurance contract’s own language to explain why the treatment, screening method, or preventive measure should be covered;

·

Letters from researchers that explain the clinical trial;

·

Support letters from patient advocacy groups.

Be sure to keep your own copy of any materials that the doctor sends to your health plan for future reference.

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Work Closely with Your Company’s Benefits Manager This person may be helpful in enlisting the support of your employer to request coverage for your child by the health plan.

Give Your Health Plan a Deadline Ask the hospital or cancer center to set a target date for the therapy. This will help to ensure that coverage decisions are made promptly. Know Your Child’s Rights24 A number of state governments are addressing the question of whether insurance companies ought to cover the costs associated with patients’ participation in clinical trials. Lack of such coverage is a significant barrier to many patients who might otherwise benefit from enrolling in a trial. Lack of coverage also makes it harder for researchers to successfully conduct trials that could improve prevention and treatment options. Information on State initiatives and legislation concerning cancer-related clinical trials is available at http://www.cancer.gov/ClinicalTrials/insurancelaws. By conducting your own research and learning about your child’s rights, you may increase the likelihood that your insurance company will cover the costs of a trial.

If Your Insurance Claim Is Denied after the Trial Has Begun If a claim is denied, read your policy to find out what steps you can follow to make an appeal. In “What Cancer Survivors Need to Know about Health Insurance”, the National Coalition for Cancer Survivorship suggests that you and your doctor demonstrate to the health plan that: ·

The therapy in the trial is not just a research study, but also a valid procedure that benefits patients;

·

Your child’s situation is similar to that of other patients who are participating in clinical trials as part of a covered benefit;

·

Possible complications have been anticipated and can be handled effectively.

24

Adapted from Cancer.gov: http://www.cancer.gov/ClinicalTrials/insurancelaws.

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You also may wish to contact your state insurance counseling hotline or insurance department for more help, or write your state insurance commissioner describing the problem. Where Else Can I Turn for Assistance? It’s never easy to deal with financial issues when a loved one faces cancer. Unfortunately, costs can present a significant barrier to clinical trials participation. The range of insurance issues and health plan contracts makes it impossible to deal with all of them here. You may wish to consult this partial list of publications, organizations, and Web sites for more information: Publications What Cancer Survivors Need to Know about Health Insurance National Coalition of Cancer Survivorship 1010 Wayne Avenue, 5th floor Silver Spring, MD 20910 (301) 650-8868 http://www.cansearch.org/ Cancer Treatments Your Insurance Should Cover The Association of Community Cancer Centers 11600 Nebel Street, Suite 201 Rockville, MD 20852 (301) 984-9496 http://www.accc-cancer.org/main2001.shtml The Managed Care Answer Guide Patient Advocate Foundation 739 Thimble Shoals Boulevard, Suite 704 Newport News, VA 23606 (757) 873-6668 E-mail: [email protected]

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1998 Guide to Health Insurance for People with Medicare, The Medicare Handbook Medicare Helpline: 1-800-444-4606 Health Care Financing Administration: http://www.hcfa.gov/ New Medicare site: http://www.medicare.gov/ Assistance Programs Candlelighters Childhood Cancer Foundation Ombudsman Program 910 Woodmont Avenue, #4607 Bethesda, MD 20814 (301) 657-8401; 1-800-366-2223 (toll-free) E-mail: [email protected] http://www.candlelighters.org The Ombudsman Program helps families of children with cancer and survivors of childhood cancer resolve a range of problems, including insurance coverage difficulties. Local groups appoint a Parent Advocate who works with the treatment center on behalf of families. Medical Care Management Corporation 5272 River Road, Suite 650 Bethesda, MD 20816-1405 (301) 652-1818 email: [email protected] http://www.mcman.com/ Working for a range of clients, including health plans, employers, and patients, MCMC conducts independent, objective reviews of hightechnology medical care cases to assist in decision-making. While it does charge for its services, MCMC also offers a volunteer program for those who cannot afford to pay. More Information Resources OncoLink A service of the University of Pennsylvania Cancer Center. http://www.oncolink.com/ In addition to general cancer information, this web site features a section on financial information for patients. Among the topics: viatical settlements, life insurance, a glossary of financial and medical terms, and news about billing and insurance.

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American Association of Health Plans 1129 20th Street, NW, Suite 600 Washington, DC 20036-3421 (202) 778-3200 http://www.aahp.org/ The Web site section “For Consumers” includes a fact sheet on clinical research that describes various health plans’ efforts to support research initiatives and collaborate with academic health centers and universities. Health Insurance Association of America 555 13th Street, NW Washington, DC 20004 (202) 824-1600 ·

Home page: http://www.hiaa.org/

·

Consumer Information: http://www.hiaa.org/consumer/

·

Insurance Counseling Hotlines by State: http://www.hiaa.org/consumer/insurance_counsel.cfm

·

State Insurance Departments: http://www.hiaa.org/consumer/state_insurance.cfm

Government Initiatives to Expand Insurance Coverage for Trials25 The good news is that there has been a recent effort in the U.S. to assure clinical trials coverage, with NCI involved in several new initiatives as described below: NCI-Department of Defense Agreement An innovative 1996 agreement between NCI and the Department of Defense (DoD) has given thousands of DoD cancer patients more options for care and greater access to state-of-the-art treatments. Patients who are beneficiaries of TRICARE/CHAMPUS, the DoD’s health program, are covered for NCIsponsored Phase II and Phase III clinical treatment trials. NCI and DoD are refining a system that allows physicians and patients to determine quickly what current trials meet their needs and where they are taking place. Adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=1d92be79-8748-4bda-80052a56d332463b&docid=d8092601-daf9-4794-8536-3be2712eb6b9.

25

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NCI-Department of Veterans Affairs Agreement A 1997 agreement with the Department of Veterans Affairs provides coverage for eligible veterans of the armed services to participate in NCIsponsored prevention, diagnosis, and treatment studies nationwide. For additional information, see the VA/DoD Beneficiaries Digest Page at http://www.va.gov/cancer.htm.

Midwest Health Plans Agreement Some NCI Cooperative Groups have reached agreements with several insurers in Wisconsin and Minnesota to provide more than 200,000 people with coverage. The coverage is designated for patient care costs if they participate in a cooperative group-sponsored trial.

Pediatric Cancer Care Network This network, a cooperative agreement among the Children’s Cancer Group, the Pediatric Oncology Group, and the Blue Cross Blue Shield System Association (BCBS) nationwide, will ensure that children of BCBS subscribers receive care at designated centers of cancer care excellence and may promote the enrollment of children in Cooperative Group clinical trials.

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide the public and physicians with current information about clinical research across the broadest number of medical conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “neuroblastoma” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is

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updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

·

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

·

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment: Today’s Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

·

A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

·

The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

·

The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

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·

Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

·

Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

·

Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antineoplastons: Substances isolated from normal human blood and urine being tested as a type of treatment for some tumors and AIDS. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, starshaped cells called astrocytes. [NIH] Carboplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Cardiotoxicity: Toxicity that affects the heart. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH]

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Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Craniopharyngioma: A benign brain tumor that may be considered malignant because it can damage the hypothalamus, the area of the brain that controls body temperature, hunger, and thirst. [NIH] Cyclophosphamide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Dexrazoxane: A drug used to protect the heart from the toxic effects of anthracycline drugs such as doxorubicin. It belongs to the family of drugs called chemoprotective agents. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH] Doxorubicin: An anticancer drug that belongs to the family of drugs called antitumor antibiotics. It is an anthracycline. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH] Etoposide: An anticancer drug that is a podophyllotoxin derivative and belongs to the family of drugs called mitotic inhibitors. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Gadolinium: Gadolinium. An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Glioblastoma: A general term that refers to malignant astrocytoma, a type of brain tumor. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Heparin: A drug that helps prevent blood clots from forming. It belongs to the family of drugs called anticoagulants (blood thinners). [NIH] Ifosfamide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Inflammation: A response of redness, swelling, pain, and a feeling of heat in

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certain areas which is meant to protect tissues affected by injury or disease. [NIH]

Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Isotretinoin: A drug that belongs to the family of drugs called retinoids. It is used in the treatment of acne and psoriasis and is being studied in cancer prevention. Also called 13-cis retinoic acid. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Lymphoma: Cancer that arises in cells of the lymphatic system. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melphalan: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Mesna: A drug that helps protect the kidneys and bladder from the toxic effects of anticancer drugs such as ifosfamide and cyclophosphamide. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Mime: Facial expression. (NOT: mimicry = adaptation for survival in which an organism takes on the semblance another organism or a non-living object.) [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephroblastoma: A malignant kidney tumor made up of three cell types: blastemal, stromal, and epithelial, but not all present in every case. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic

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sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Oligodendroglioma: A rare, slow-growing tumor that begins in brain cells called oligodendrocytes, which provide support and nourishment for cells that transmit nerve impulses. Also called oligodendroglial tumor. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Paclitaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Rebeccamycin: An anticancer drug that belongs to the family of drugs called antineoplastic antibiotics. [NIH] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Sarcoma: A cancer of the bone, cartilage, fat, muscle, blood vessels or other connective or supportive tissue. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial

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s.) or the complete range of manifestations of a disease. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Subcutaneous: Beneath the skin. [NIH] Supratentorial: Located in the upper part of the brain. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH]

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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on neuroblastoma. All too often, parents who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on neuroblastoma. In Part II, as in Part I, our objective is not to interpret the latest advances on neuroblastoma or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with neuroblastoma is suggested.

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CHAPTER 4. STUDIES ON NEUROBLASTOMA Overview Every year, academic studies are published on neuroblastoma or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on neuroblastoma. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on neuroblastoma and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and neuroblastoma, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the

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format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “neuroblastoma” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·

Report on a Workshop of the UICC Project on Evaluation of Screening for Cancer Source: International Journal of Cancer. 46(5):761-769, November 15, 1990. Summary: The fifth report of the International Union Against Cancer (UICC) Project on the Evaluation of Screening for Cancer summarizes information presented at a workshop at which researchers evaluated screening for individual cancer sites or groups of sites. Information focuses on breast cancer screening, cervical cancer screening, ovarian cancer screening, colorectal cancer screening, and stomach cancer screening. Researchers looked for the first time at melanoma, neuroblastoma, nasopharyngeal carcinoma, and prostate cancer sites. For each site, the report describes work done internationally, draws conclusions, and makes recommendations for research. The report also examines issues relevant to the evaluation of screening: (1) Privacy laws, (2) screening test sensitivity and proportionate incidence, (3) the need for intermediate end-points that can be used for evaluation before mortality or incidence data become available, (4) models to enhance the understanding of the natural history of screen detected lesions and the process of screening, and (5) the application of different considerations to case control studies of screening when mortality is the endpoint than when incidence of disease is the endpoint. 8 references.

·

Radiotherapy for Metastases to the Mandible in Children Source: Journal of Oral and Maxillofacial Surgery. 60(3): 269-271. March 2002. Contact: Available from W.B. Saunders Company. Periodicals Department, P.O. Box 629239, Orlando, FL 32862-8239. (800) 654-2452. Website: www.harcourthealth.com. Summary: This article presents a retrospective review of all children treated since 1979 at the authors' institution with radiation therapy for

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symptomatic metastases (spread of cancer) that involved the mandible (lower jaw). Nine children were treated with 1 or more courses of radiotherapy for symptomatic metastases that involve the mandible. Six children had a neuroblastoma, 1 had angiosarcoma of the liver, 1 had adenocarcinoma of the rectum, and 1 had peripheral primitive neuroectodermal tumor (Ewing's sarcoma) of the spine. In 3 children, the mandible was the first bone involved by metastases. Seven children were treated with short intensive courses of radiotherapy consisting of 1 to 3 fractions to a total dose of 400 to 1,200 cGy. One child received 2,400 cGy in 6 fractions, and another child received 3,000 cGy in 10 fractions. Three children were treated with second courses of radiotherapy at 1, 2, and 5 months, respectively, from the initial course of radiotherapy. All children had received chemotherapy. All children died of disseminated disease at 5 to 59 months from their initial diagnosis, 5 to 29 months from the detection of metastases to bone, and only 6 days to 17 months (median, 20 months) from the first treatment of metastases to the mandible. The authors conclude that the outlook for children with metastases that involve the mandible is very poor, and the authors recommend short intensive courses of radiotherapy consisting of 1 to 3 treatments to total doses of 400 to 1,200 cGy for palliation of pain. 1 table. 7 references. ·

Prenatal Epidemiology of Pediatric Tumors Source: Current Oncology Reports. 2(3):234-241, May 2000. Summary: The authors present an overview of epidemiologic studies of childhood cancer. The review focuses on studies investigating the prenatal period, specifically those examining ecologic hypotheses related to prenatal exposure. The studies are categorized as descriptive studies that examine trends in childhood cancer incidence worldwide and in the United States, ecologic studies, and analytical studies. Nearly 12,000 children under the age of 19 years are diagnosed with cancer each year. The most frequently diagnosed childhood malignancies include (1) acute lymphoblastic (ALL) and acute myeloid leukemia (AML), (2) central nervous system tumors, (3) neuroblastoma, (4) Hodgkin's disease, (5) non-Hodgkin's lymphoma, (6) Wilms' tumor, (7) retinoblastoma, (8) soft tissue sarcoma, and (9) germ cell tumors. Recent analytic studies have focused on the following prenatal exposures and their association with childhood cancers: (1) Personal habits and physical characteristics; (2) occupation and occupational exposures; (3) environmental exposures, such as to electromagnetic fields; and (4) medical exposures, such as medications. With the exception of a small percentage of cases attributable to genetic syndromes such as familial retinoblastoma or Down's syndrome that predispose to childhood malignancies, the

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etiology of most childhood cancers is unknown. Four recent studies that investigated parental smoking and childhood malignancies produced inconsistent results. One study found a positive association between paternal smoking and elevated risks of childhood acute leukemia, lymphoma, and brain tumors. The second study found a significant positive association between paternal smoking and lymphoma and neuroblastoma and between maternal smoking and childhood ALL. The third study found no association with maternal smoking but a slightly increased risk between paternal smoking and infant ALL. The fourth study that examined paternal smoking and childhood AML and ALL found no association with either paternal or maternal smoking. 1 figure, 2 tables, 37 references. ·

From In Utero and Childhood Exposure to Parental Smoking to Childhood Cancer: A Possible Link and the Need for Action Source: Human and Experimental Toxicology. 18(4):192-201, 1999. Summary: Researchers critically summarize published studies in an effort to reassess the current state of knowledge regarding the potential association between prenatal exposure to environmental tobacco smoke (ETS), as well as maternal active smoking during pregnancy and postnatal exposure to ETS and enhanced incidence of childhood cancer. Elements to be considered include (1) the substantial reporting of pregnant women who remain smokers; (2) the widespread nature of exposure to environmental tobacco smoke during pregnancy as well as during childhood; (3) the known toxicology of tobacco smoke, and in particular, sidestream smoke, which is characterized by a rich carcinogen content; (4) the specific metabolism of fetuses and newborns; and (5) the amoun t of epidemiologic data already available. A thorough review of the literature identified studies that either exclusively dealt with the effect of passive smoking on the occurrence of childhood cancers, or more general etiologic studies of cancer. The researchers identified close to 50 publications presenting pertinent results from epidemiological investigations, and approximately 50 more on (1) mechanisms and metabolism, (2) smoking in pregnancy, and (3) exposure to environmental tobacco smoke, as well as selected reviews and commentaries. The vast majority were case-control studies dealing with (1) all cancers, (2) leukemia and lymphomas, (3) central nervous system tumors, (4) Wilms' tumor, (5) retinoblastoma, (6) neuroblastoma, (7) hepatoblastoma, (8) rhabdomyosarcoma, (9) bone and soft tissues tumors, (10) germ cell tumors, and (11) specific histological types of leukemias, lymphomas or central nervous system tumors. No strong association between maternal smoking in pregnancy and/or exposure to

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environmental tobacco smoke and childhood cancer was found. However, several studies found slightly increased relative risks, generally smaller than 1.5. Tumors most often found associated with maternal smoking in pregnancy or environmental tobacco exposure are childhood brain tumors and leukemia-lymphoma, with risks up to two or greater in selected studies. In a few studies, risks associated with paternal smoking are higher than the maternal ones. This evidence from human studies, coupled with the demonstration of genotoxic effects on the fetus of exposure to metabolites of tobacco smoke and demonstrable presence of adducts, should lead to strong recommendations that aim to fully protect fetuses, newborns, and infants from tobacco smoke. 115 references.

Federally-Funded Research on Neuroblastoma The U.S. Government supports a variety of research studies relating to neuroblastoma and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.26 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally-funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to neuroblastoma and related conditions. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally-funded studies use animals or simulated models to explore neuroblastoma and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for neuroblastoma:

26 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Project Title: Cellular Immunotherapy for Neuroblastoma with CTL Clones Principal Investigator & Institution: Jensen, Michael C.; Dr.; City of Hope National Medical Center Medical Center Duarte, Ca 91010 Timing: Fiscal Year 2001; Project Start 7-SEP-2001; Project End 1-AUG2003 Summary: (Provided by applicant): Disease relapse is the leading cause of mortality for children diagnosed with disseminated neuroblastoma despite the use of highly intensive front-line therapy. Studies conducted in our laboratory have focused on developing strategies to target neuroblastoma with adoptively transferred T lymphocytes genetically modified to express a chimeric immunoreceptor, designated CE7R, for redirected recognition of a neuroblastoma-specific epitope on the L1-CAM adhesion molecule. The engineering of CE7R was accomplished by assembling a cDNA construct encoding a single-chain antibody extracellular domain derived from the murine CE7 hybridoma fused to the cytoplasmic tail of the T cell receptor CD3 complex zeta chain (scFvFc:zeta). In vitro culture systems have been developed for genetically modifying human T cells with naked plasmid DNA by electroporation and expanding modified clones to numbers in excess of 10e10. Ex vivo expanded CE7R scFvFc:zeta-expressing cytotoxic T lymphocyte (CTL) clones specifically recognize human neuroblastoma tumor cells and are activated for tumor cell cytolysis and cytokine secretion. These pre-clinical studies have provided the rationale to explore the therapeutic utility of cellular immunotherapy with autologous CTL clones engineered to express the CE7R chimeric immunoreceptor and the selection/suicide fusion protein HyTK in children with recurrent/refractory disseminated neuroblastoma. The in vivo persistence, anti-tumor activity, and immunogenicity of infused clones will be assessed following adoptive transfer in order to delineate how the in vivo biology of ex vivo expanded CE7R+ CTL might be further optimized. The specific aims of this project are: 1.) To evaluate the safety and toxicity of adoptively transferred CE7R+/HyTK+ CD8+ CTL clones in children with recurrent/refractory neuroblastoma. 2.) To quantitate the anti-tumor activity of infused clones in patients with measurable disease. 3.) To study the persistence of transferred clones in research participants by Q-PCR and the impact of administering exogenous IL-2 on the duration and magnitude of in vivo persistence. 4.) To assess in this patient population the development of antibody and cellular immune responses against the scFvFc:zeta and HyTK chimeric proteins. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

Studies 107

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Project Title: Genetics Neuroblastoma

of

a

Transgenic

Mouse

Model

for

Principal Investigator & Institution: Weiss, William A.; Neurology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2000; Project Start 0-SEP-2000; Project End 1-AUG2005 Summary: (Adapted from the Applicant's Abstract): Neuroblastoma, a tumor of peripheral neural crest origin, is the third most common tumor of childhood. The broad, longterm objective of this project is to find genes that contribute to tumorigenesis in a multi-step transgenic mouse model for neuroblastoma. The transgenic mouse model to be used in this study is tumor prone. as a result of over-expression of the human MYCN gene in the peripheral neural crest. Since tumorigenesis in the mouse is initiated using a gene relevant to human neuroblastoma, it is likely that the additional genetic lesions which contribute to neuroblastoma formation in the mouse will be in genes relevant to neuroblastoma in children. Using PCR analysis of microsatellite markers, we have identified 6 chromosomal or subchromosomal regions that show consistent abnormalities in mouse tumors. Four of these were syntenic with corresponding regions of abnormality in human neuroblastoma. A region on the proximal part of chromosome 10 was affected in 30% of tumors and has been localized to an interval of less than 16 cM. Over the five years of this award, our goal is to identify the genetic region most amenable to further study, and to find the gene corresponding to that subchromosomal region. In specific aim 1, we will refine our primary screen to further localize the six regions that contributes to neuroblastoma in the mouse. We will also analyze tumors for differentiation, angiogenesis, apoptosis, proliferation, and invasion, to seek biological correlates for specific regions of LOH. We will focus subsequent positional cloning efforts on chromosome 10 unless our refined screens identify a more compelling region. In specific aim 11, we will further characterize a single genetic region which cooperates with MYCN to cause neuroblastoma in the mouse. We will analyze additional tumors and additional microsatellite markers to localize this interval to 12 cM a size appropriate for positional cloning. We will then construct a physical map and contig of this region to identify the corresponding genes. Candidate genes will be tested for expression and mutation in mouse tumors. Health Relatedness: Genes identified as important for the malignant progression of neuroblastoma in the mouse can be tested directly for their role in neuroblastoma in humans. Given the poor outcome associated with childhood neuroblastoma, this work has the

108 Neuroblastoma

potential to increase our understanding of the pathogenesis of neuroblastoma, and may result in improved therapies for children with this disorder. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Immunosuppressive Neuroblastoma Tumor Gangliosides Principal Investigator & Institution: Ladisch, Stephan K.; Professor and Scientific Director; Children's Research Institute 111 Michigan Ave Nw Washington, Dc 20010 Timing: Fiscal Year 2000; Project Start 1-MAY-1986; Project End 1-MAR2003 Summary: The goal of this renewal proposal is to characterize inhibition of antitumor immune responses by tumor gangliosides in vivo. The general hypothesis underlying this work is that gangliosides are shed by tumor cells, act as intercellular signaling molecules, block the cellular immune response, and protect tumor cells from host immune destruction. Findings of significant shedding and of potent immunosuppressive activity of human neuroblastoma gangliosides, and new preliminary data showing inhibition of murine cellular immune response to syngeneic tumor cells by these molecules, lay the foundation to directly test the hypothesis that tumor gangliosides downregulate host cellular immune responses to syngeneic tumor cell both in vitro and in vivo. Two approaches will be used to obtain neuroblastoma tumor gangliosides, homogeneous in both carbohydrate and ceramide structure, in large quantities: isolation from human neuroblastoma tumors (natural) and chemical synthesis (synthetic). All gangliosides will be further purified by HPLC to remove potential traces of contaminants prior to biological study. Molecular structures of the gangliosides will be confirmed by mass spectrometry and chemical methods. The delineation of inhibitory effects of tumor gangliosides upon both the afferent (priming) and efferent (effector function) phases of the cellular immune response in murine tumor models in vivo will be complemented by determination of the effects of these same gangliosides on the human cellular immune response in vitro. The in vivo studies will be performed in two murine syngeneic tumor models, FBL erythroleukemia and B78H1 melanoma. The proposed studies will conclusively demonstrate downregulation of syngeneic antitumor immune response by neuroblastoma tumor gangliosides in vivo. They will provide the foundation for future investigations (longer term aims) to elucidate the molecular mechanism(s) of inhibition by tumor gangliosides and to develop strategies to eliminate these immunosuppressive molecules (such as removal of gangliosides from the circulation or modulation of

Studies 109

ganglioside biosynthesis and shedding by pharmacologic agents), with the ultimate goal of achieving improved therapeutic approaches to neuroblastoma and other neuroectodermal tumors such as melanoma. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Neuroblastoma-Specific MRI Contrast Agents Principal Investigator & Institution: Voss, Stephan D.; Children's Hospital (Boston) 300 Longwood Ave Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 7-SEP-2002; Project End 1-AUG2007 Summary: (provided by applicant): Neuroblastoma is the most common pediatric malignancy diagnosed in the first year of life. More than onehalf of these children have disseminated disease at the time of diagnosis. Magnetic resonance imaging (MRI) is crucial in the diagnostic imaging evaluation of neuroblastoma, however, no neuroblastoma-specific MRI contrast agents currently exist. We propose to create neuroblastomaspecific MRI contrast agents by conjugating low-molecular weight peptide ligands (or=365d-21y |Amp |Fav ||Low | | >or=365d-21y |Amp |Unfav ||High |________|_______________|_____________|_______________|_________|____________ |3*** | or=365d-21y |Non-Amp |Unfav ||High | | >or=365d-21y |Amp |Any ||High |________|_______________|_____________|_______________|_________|____________ |4*** |

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