Pediatric radiation oncology

72607_FM 7/19/10 12:14 PM Page i Pediatric Radiation Oncology 72607_FM 7/19/10 12:14 PM Page ii 72607_FM 7/19/10 12:14 PM Page iii F I F T H E D I T I O N Pediatric Radiation Oncology Edward C Halperin, M.D., M.A Louis S Constine, M.D Nancy J Tarbell, M.D Larry E Kun, M.D 72607_FM 7/19/10 12:14 PM Page iv Senior Executive Editor: Jonathan W Pine, Jr Senior Product Manager: Emilie Moyer Senior Manufacturing Manager: Benjamin Rivera Senior Marketing Manager: Angela Panetta Design Coordinator: Holly McLaughlin Production Service: MPS Limited, A Macmillan Company © 2011 by Lippincott Williams & Wilkins, a Wolters Kluwer business Two Commerce Square 2001 Market Street Philadelphia, PA 19103 USA LWW.com All rights reserved This book is protected by copyright No part of this book may be reproduced in any form by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Materials appearing in this book prepared by individuals as part of their official duties as U.S government employees are not covered by the above-mentioned copyright Printed in China Library of Congress Cataloging-in-Publication Data Pediatric radiation oncology / Edward C Halperin [et al.].—5th ed p ; cm Includes bibliographical references and index Summary: “Pediatric Radiation Oncology is the definitive text and reference on use of radiation therapy for childhood cancer The fifth edition reviews all significant recent clinical trials—including significant European clinical trials—and provides increased coverage of international and Third World issues The latest cancer staging guidelines are included New chapters cover psychosocial aspects of radiotherapy for the child and family and medical management of pain, nausea, nutritional problems, and blood count depression in the child with cancer”—Provided by publisher ISBN 978-1-60547-260-7 (alk paper) Tumors in children—Radiotherapy I Halperin, Edward C [DNLM: Neoplasms—radiotherapy Child QZ 275 P3713 2011] RC281.C4P447 2011 618.92’9920642—dc22 2010020276 Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication Application of the information in a particular situation remains the professional responsibility of the practitioner The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions This is particularly important when the recommended agent is a new or infrequently employed drug Some drugs and medical devices presented in the publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320 International customers should call (301) 223-2300 Visit Lippincott Williams & Wilkins on the Internet: at LWW.com Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to pm, EST 10 72607_FM 7/19/10 12:14 PM Page v Dedication For our children 72607_FM 7/19/10 12:14 PM Page vi Contents Contributors vii 14 Preface x Bow-Wen Chen, Stella Y Tsai, Skye H Cheng, Andrew T Huang Acknowledgments xii The Cancer Problem in Children 15 Edward C Halperin Leukemias in Children 12 Larry E Kun Tumors of the Posterior Fossa and the Spinal Canal 53 16 17 18 Hemangioma, Lymphangioma, and Skin Cancer 346 Edward C Halperin, L Claude, John P Kirkpatrick James Fontanesi, Jeffery Taub, John P Kirkpatrick, Edward C Halperin 19 Neuroblastoma 108 20 Late Effects of Cancer Treatment 353 Debra L Friedman, Louis S Constine Secondary Primary Cancers 397 Smita Bhatia, Louis S Constine 21 Hodgkin Lymphoma 137 Stephanie A Terezakis, Melissa M Hudson, Louis S Constine Anesthesia for External Beam Radiotherapy 414 Scott R Schulman, Heather J Frederick, Edward C Halperin 22 Langerhans Cell Histiocytosis 332 Edward C Halperin Retinoblastoma 85 Katherine K Matthay, Daphne Haas-Kogan, Louis S Constine Endocrine, Aerodigestive Tract, and Breast Tumors 311 Line Claude, C Nozières Larry E Kun, Shannon MacDonald, Nancy J Tarbell Germ and Stromal Cell Tumors of the Gonads and Extragonadal Germ Cell Tumors 303 Christian Carrie, Edward C Halperin Supratentorial Brain Tumors 26 Larry E Kun, Shannon MacDonald, Nancy J Tarbell Liver Tumors in Children 290 Non-Hodgkin Lymphoma 166 Stabilization and Immobilization Devices 425 Kim L Light, Edward C Halperin Mary S Huang, Nancy J Tarbell, Howard J Weinstein 23 Ewing Sarcoma 172 Cancer Pain Management in Children 429 Pesach Shvartzman Karen J Marcus, Torunn Yock, Nancy J Tarbell 24 10 Osteosarcoma, Chordoma, and Chondrosarcoma 184 Blood Count Depression in the Child With Cancer 434 Myriam Weyl Ben Arush Shiao Y Woo, Edward C Halperin 25 11 Rhabdomyosarcoma 204 Shannon M MacDonald, Alison M Friedman, Nancy J Tarbell, Louis S Constine 12 Soft Tissue Sarcomas Other Than Rhabdomyosarcoma; Desmoid Tumor 230 Kenneth B Roberts, Edward C Halperin 13 Jerry Stein 26 Psychosocial Aspects of Radiotherapy for the Child and Family with Cancer 447 Shulamith Kreitler, Myriam Weyl Ben Arush, Elena Krivoy, Hana Golan, Michal Kreitler, Amos Toren Wilms Tumor 257 John A Kalapurakal, Edward C Halperin vi Nutritional Problems in the Child with Cancer 439 Index 457 72607_FM 7/19/10 12:14 PM Page vii Contributors Myriam Weyl Ben-Arush, MD Pediatric Hematology Oncology Department Meyer Children’s Hospital Rambam Medical Center, Technion The Bruce Rappaport Faculty of Medicine Haifa, Israel Smita Bhatia, MD, MPH Professor and Chair Department of Population Science City of Hope Duarte, California Christian Carrie, MD Chief Department of Radiotherapy Centre Leon Berard Lyon, France Bow-Wen Chen, MD Senior Attending Physician Division of Pediatric Hematology and Oncology Koo Foundation Sun Yat-Sen Cancer Center Taipei, Taiwan Skye H Cheng, MD Clinical Professor Department of Radiation Medicine National Yang-Ming University Adjunct Associate Professor Department of Radiation Oncology Duke University Medical Center Durham, North Carolina Chief Department of Radiation Oncology Koo Foundation Sun Yat-Sen Cancer Center Taipei, Taiwan Line Claude Assistant Head of Department Department of Radiation Oncology Centre Léon Bérard Lyon, France Louis S Constine, MD, FASTRO Professor of Radiation Oncology and Pediatrics Section Chief, Pediatric Radiation Oncology Vice Chairman, Department of Radiation Oncology James P Wilmot Cancer Center University of Rochester Medical Center Rochester, New York James Fontanesi MD Professor Department of Radiation Oncology Oakland University School of Medicine Rochester, Michigan Director Department of Radiation Oncology Botsford General Hospital Farmington Hills, Michigan Heather J Frederick MD Assistant Professor Department of Anesthesiology Duke University Medical Center Durham, North Carolina Alison M Friedman, MD, MSC Assistant Professor Department of Pediatrics Harvard Medical School Cambridge, Massachusetts Assistant Pediatrician Department of Pediatrics Massachusetts General Hospital Boston, Massachusetts Debra L Friedman, MD Associate Professor of Pediatrics E Bronson Ingram Chair in Pediatric Oncology Department of Pediatrics Vanderbilt University School of Medicine Cancer Control and Prevention Program Director Division of Hematology-Oncology Vanderbilt-Ingram Cancer Center Nashville, Tennesee Hana Golan, MD Physician Department of Pediatric Hematology Oncology The Edmond and Lily Safra Children’s Hospital The Claim Sheba Medical Center Ramat Gan, Israel Daphne Haas-Kogan, MD Vice Chair and Program Director Department of Radiation Oncology University of California, San Francisco Professor Department of Radiation Oncology and Neurosurgery University of California, San Francisco San Francisco, California Edward C Halperin, MD, MA Dean of the School of Medicine Ford Foundation Professor of Medical Education Professor of Radiation Oncology, Pediatrics, and History University of Louisville Louisville, Kentucky vii 72607_FM 7/19/10 12:14 PM Page viii viii CONTRIBUTORS Andrew T Huang, MD Professor Department of Medicine Duke University Medical School Durham, North Carolina President and CEO Koo Foundation Sun Yat-Sen Cancer Center Taipei, Taiwan Mary S Huang, MD Instructor Department of Pediatrics Harvard Medical School Pediatric Hematology and Oncology Massachusetts General Hospital for Children Boston, Massachusetts Melissa M Hudson, MD Director, Cancer Survivorship Division Member, Department of Oncology Saint Jude Children’s Research Hospital Memphis, Tennessee John A Kalapurakal, MD Professor Department of Radiation Oncology Northwestern University Co-Director Department of Pediatric Radiation Oncology Northwestern Memorial Hospital Chicago, Illinois John P Kirkpatrick, MD, PhD Associate Professor Department of Radiation Oncology Duke University School of Medicine Director of Radiation Oncology Clinical Services Department of Radiation Oncology Duke University Medical Center Durham, North Carolina Michal Kreitler, MD Psychooncology Researcher Sheba Medical Center Tel Hashome, Israel Shulamith Kreitler, PhD Professor of Psychology Department of Psychology Tel-Aviv University Tel-Aviv, Israel Head of Psychooncology Research Center Sheba Medical Center Tel-Hashomer, Israel Elena Abigail Krivoy, MSc Chief Psychologist Department of Pediatric Hematology Oncology Meyer Children’s Hospital Rambam Health Care Campus Haifa, Israel Larry E Kun, MD Member and Chair, Department of Radiological Sciences St Jude Children’s Research Hospital Professor, Departments of Radiology and Pediatrics University of Tennessee College of Medicine Memphis, Tennessee Kim L Light, BS, CMD Chief Dosimetrist Department of Radiation Oncology Duke University Medical Center Durham, North Carolina Shannon MacDonald, MD Assistant Professor Department of Radiation Oncology Harvard Medical School Radiation Oncologist Department of Radiation Oncology Massachusetts General Hospital Boston, Massachusetts Karen J Marcus, MD Associate Professor Department of Radiation Oncology Division Chief Division of Radiation Oncology Department of Medicine Children’s Hospital of Boston Harvard Medical School Boston, Massachusetts Katherine K Matthay, MD Professor Department of Pediatrics University of California, San Francisco Chief, Pediatric Hematology/Oncology Department of Pediatrics University of California, San Francisco San Francisco, California C Nozières Assistant Doctor Department of Endocrinology Groupement Hospitalier Est Lyon, Bron, France Kenneth B Roberts, MD Associate Professor Department of Therapeutic Radiology Yale University School of Medicine Attending Physician Department of Radiation Oncology Yale-New Haven Hospital New Haven, Connecticut Scott R Schulman, MD, MHSc Associate Professor Department of Anesthesiology and Pediatrics Duke University Medical Center Durham, North Carolina 72607_FM 7/19/10 12:14 PM Page ix CONTRIBUTORS Pesach Shvartzman, MD Professor and Chairman Division of Pain, Palliative Care and Family Medicine Ben Gurion University of the Negev Soroka University Medical Center Beer Sheva, Israel Amos Toren MD, PhD Head of Hematology Division Division of Hematology Sackler School of Medicine Tel Aviv University Tel Aviv, Israel Jerry Stein, MD Director, BMT Unit Department of Pediatric Hematology Oncology Schneider Children’s Medical Center Petach Tikva, Israel Stella Y.C Tsai, MD Clinical Professor Department of Radiation Medicine National Yang-Ming University Deputy Chief Department of Radiation Oncology Koo Foundation Sun Yat-Sen Cancer Center Taipei, Taiwan Nancy J Tarbell, MD C C Wang Professor of Radiation Oncology Dean for Academic and Clinical Affairs Massachusetts General Hospital Harvard Medical School Boston, Massachusetts Jeffrey W Taub MD Professor Department of Pediatrics Wayne State University School of Medicine Hematologist/Oncologist Department of Pediatric Hematology/Oncology Children's Hospital of Michigan Detroit, Michigan Stephanie A Terezakis, MD Assistant Professor Department of Radiation Oncology and Molecular Radiation Sciences Johns Hopkins School of Medicine Assistant Professor Department of Radiation Oncology and Molecular Sciences Johns Hopkins Hospital Baltimore, Maryland Howard J Weinstein, MD Professor of Pediatrics Department of Pediatrics Harvard Medical School Chief Department of Pediatrics Hematology–Oncology Massachusetts General Hospital Boston, Massachusetts Shiao Y Woo, MD, FACR Professor and Chairman Department of Radiation Oncology University of Louisville Louisville, Kentucky Torunn I Yock, MD, MCH Assistant Professor Department of Radiation Oncology Harvard Medical School Massachusetts General Hospital Boston, Massachusetts ix 72607_Ch26 7/16/10 8:28 PM Page 453 CHAPTER 26 ■ PSYCHOSOCIAL ASPECTS OF RADIOTHERAPY FOR THE CHILD 453 and the first RT session and as weekly visits during the RT itself was accomplished, so that each patient was met on the average five times for the duration of to 7.5 hours The groups did not differ in age at RT, gender, diagnosis, localization of RT, and positioning during RT The major result was that following the intervention there was a reduction in the need for using anesthesia: in the experimental group, 9% of the children needed anesthesia as compared to 21% in the control group Further, the median age of cooperating patients without anesthesia decreased from 3.2 to 2.7 years In sum, the psychosocial intervention programs show the utility of preparations of this kind for reducing the distress and anxiety of the children, increasing their cooperation with the procedure and minimizing the need for applying anesthesia LeBaron and Zeltzer (58,59) have pioneered the use of guided imagery and hypnotherapy for reducing pain and anxiety in children with cancer Other means for overcoming the anxiety of children evoked by RT may be based on art therapy, play therapy, music therapy, role playing, drama, and production of stories These and other psychological procedures that could be applied for reducing the distress of undergoing RT are described by Kreitler, Oppenheim, and Segev-Shoham (60) Developing, applying, and evaluating such programs would render it possible to select in each case the best program inline with the needs of the child, the utility of the intervention, and the resources of the clinic or hospital A The Views of the Children and the Parents about RT B C Figure 26.2 A–C: Pediatric radiation oncology waiting room, Sheba Medical Center, Tel Aviv, Israel In order to get a more comprehensive view of the problems and difficulties involved in undergoing RT from the perspective of the patients, we conducted a preliminary survey with 20 children and 20 parents (not of the interviewed children) in two major medical centers in Israel The participants were selected randomly as a convenience sample The children were 7–17 years old, of varied diagnoses, all of whom were either in the last phase of RT or terminated the treatment 0–10 days previously It was expected that the survey conducted with the actual participants in the RT procedures would provide information about problem areas that have not been discerned in the research focused on psychosocial aspects of RT up to now The survey was based on conducting individual guided interviews in line with an ordered set of questions The questions were the same for parents and children, except for necessary but minor differences in wording The major questions were whether the child has undergone RT, for how long and to which part of the body; awareness of immediate or short-term side effects of RT; awareness of long-term effects of RT; any difficulties concerning RT that the children had; any particular behaviors of the children in regard to parents and friends or at school noted during RT; the difficulties the children had experienced during RT; comparing the difficulty of RT to chemotherapy and to what has been expected prior to RT; and suggestions for rendering RT easier Results Based on Interviewing Parents fractions The intervention included talks with the patient and the parents about practical aspects of the upcoming RT and an age-appropriate explanation of the RT treatment and procedure, implemented by picture books, playful inclusion of toys, and a reward system using beads as tokens for every completed RT session Attendance by one of two specially trained nurses at least for preparing the CT, RT simulation, The interviews of the parents indicated that 55% of the children got RT to the head, 15% to neck, 5% to the chest, 15% to the abdomen, and 10% to the limbs The child got RT 7–35 times Eighty percent claimed that RT had immediate or shortterm effects, which were mainly the following: nausea, diarrhea, reddening of the skin in the treatment area, loss of hair in the treatment area, tiredness, somnolence, headaches, and 72607_Ch26 7/16/10 8:28 PM Page 454 454 PEDIATRIC RADIATION ONCOLOGY impaired gustatory and olfactory sensations A higher number (85%) claimed they knew of possible long-term effects, which were mainly cognitive impairment (40%), fertility difficulties (30%), problems in regard to growing and overall development (40%), and the risk of a secondary cancer (20%) Concerning difficulties of the treatment, the parents mentioned the emotional difficulty (50%) and the technical difficulty they had to get to the hospital every day for RT (60%) Concerning the difficulties of the children, the parents mentioned in particular the difficulty of waiting for the treatment in a waiting room shared by children and adults, the unpleasantness of getting the treatment in the radiation unit that is not the regular ward with which the children are familiar, the fear evoked by the noise of the machine, staying alone in the treatment room, coming to the hospital every day, and tiredness As compared to chemotherapy, all parents (100%) noted that RT was easier, but as compared to the expectations beforehand, 20% claimed that RT was more difficult than they had expected, 45% claimed it was easier, and 35% claimed it was as they had expected beforehand The major suggestions of the parents for rendering RT easier referred to the following three issues: information, site of RT, and support treatment Concerning information, most of the parents (85%) emphasized the desirability of improving the provision of information about the treatment and its effects beforehand as well as in the course of the RT itself to the parents and to the children, using verbal materials implemented by films, videos, and modeling, especially for the children, in order to make it easier to understand the material and recall it Concerning the site of RT, the parents emphasized the desirability of using waiting rooms and treatment rooms designed specifically for the use of children alone rather than for the use of both adults and children, and prepare waiting rooms with toys, pictures, music, and other objects for distracting and relaxing the children prior to the treatment Concerning support, most of the parents emphasized the necessity of providing continuous psychosocial support to the parents (85%) and to the child (75%) prior to the treatment and in the course of it, at least to the termination of RT Results Based on Interviewing the Children The interviewed children got RT to varied organs or body parts, according to their self-reports: the head (35%), face (10%), neck (10%), abdomen (15%), chest (10%), back (5%), and limbs (15%) All children said that they got RT at least several times Almost all children (95%) distinguished between chemotherapy and RT, although some claimed that RT was a phase of chemotherapy Concerning side effects, the majority (70%) listed several short-term side effects, mainly feeling sick, loosing hair, feeling tired, difficulty to concentrate, pain, nausea, no appetite, feeling sad, and feeling lonely A higher percentage (90%) said that they knew about longterm effects The effects they mentioned were fertility problems (90%); body image deformities (90%; e.g., irregularities in the skin, brown dirty-looking skin, too short neck, remaining small and not growing up tall as other children, shorter limb, baldness for ever); various physical disorders (75%; malignancies, heart problems, endocrine disorders, remaining in general “weak” or vulnerable in regard to diseases); and various social and interpersonal issues (35%; e.g., being rejected by other kids, not finding friends or partners because of physical deformities or aesthetic appearance) Concerning difficulties of the treatment, children mentioned the difficulty of having to come everyday to the hospital for getting RT (80%) and the unpleasantness (i.e., anxiety, fear, tension, sense of being abandoned) associated with being alone in the RT room (85%) Especially frequent were descriptions of the experiences the children had in the RT room For example, one 8-year-old child said, “I feel as if all the world recedes far away and gets smaller and smaller, and I am the last dot in that increasing emptiness.” Another 12-year-old said, “When I get into the room I am afraid that when I get out there will be no one to meet me and I will be alone outside too.” Only a few children (30%) referred to the difficulty of the technical setup but mentioned in this context only the unpleasantness of getting the treatment in an unfamiliar ward, rather in the ward in which they had undergone chemotherapy and other treatments No one mentioned anything concerning the fact that in the radiation unit children were treated in the same location as adults When asked to compare RT with chemotherapy, 60% said RT was easier, whereas 40% said they are equally difficult although for different reasons As compared to the expectations they had beforehand, 60% claimed that RT was more difficult than they had expected, 20% claimed it was easier, and 20% claimed it was as they had expected beforehand Notably, those who said that RT was more difficult than they had expected complained about the misleading information they had received concerning RT As one child said, “I did not think about radiation and I even waited for it because everyone in the ward said that it is easy, that I go into a room and one hardly feels it; but then I saw that I had to be alone in the room with the noisy machine and I had to stay paralyzed … it is horrible” (Fig 26.3) The children were also asked about their suggestions for rendering the RT easier for children Most of the children provided suggestions The major suggestions referred to decreasing the feeling of loneliness in the RT room, for example, by enabling the child to hear the voice of the parents or nurse outside, by listening to music, or by seeing projected pictures Other suggestions referred to being able to discuss the experience with someone from the staff or the family everyday and getting the treatment in some place close to home so as to be able to avoid the traveling to the hospital everyday Figure 26.3 A 7-year-old with leukemia receiving cranial irradiation; immobilization thermoplastic mark and wrapped to avoid falling 72607_Ch26 7/16/10 8:28 PM Page 455 CHAPTER 26 ■ PSYCHOSOCIAL ASPECTS OF RADIOTHERAPY FOR THE CHILD Some Comments Concerning the Interviews Both sets of interviews indicate that the parents and the children identify RT as a distinct phase of the treatment the child gets and are, on the whole, aware of the common short-term and long-term effects of RT The emphasis of the parents on the need for more information coincides with the results of a recent study that shows that although the parents feel knowledgeable about neurocognitive late effects of RT, they continue to have a need for further information, and those who reported high emotional distress wanted the information earlier than the others (61) The interviews with the children highlighted both the emotional distress of the children in the RT room and their suffering through the procedure Notably, many children not share the commonly expressed attitude toward RT as easier than chemotherapy In addition, children brought to the fore a specific domain of long-term side effects that has not received sufficient attention in the psychosocial studies up to now These are the effects of RT on the body image Children noted specifically changes in limbs, skin, stature, body symmetry, scalp, and hair, that may affect the functioning of their body and change their physical appearance The functional and aesthetic problems associated with the damaged body image may affect the children’s functioning also in other domains The children themselves mentioned that an impaired physical appearance may affect the attitude of peers to them in the present and perhaps also in the future and thus alienate them at school and affect negatively their academic achievements The distress of the children that may be caused by the difficulties of coping with physical handicaps and impaired physical appearance deserve the awareness and attention of health professionals no less than the distress of children in the course of the RT itself SUMMARY The chapter deals with psychosocial effects of radiotherapy in pediatric cancer patients The presented materials are based on empirical published studies referring specifically to RT, amplified by a survey conducted by the authors with parents and children undergoing RT The major reviewed domains include cognitive effects, behavioral and social effects, and distress in the course of RT The major cognitive effects of CRT and RT are declines in general intelligence and specific 455 deficits in nonverbal and verbal cognitive functions, mainly memory and attention, that increase with time since RT and are especially notable in children who have received RT at a younger age Yet, there are indications that overall academic performance may be a function of factors additional to the cognitive deficits and sometimes overriding the deficits The major social and behavioral effects concern interpersonal relations and possible difficulties in social adjustment Children are conscious of short-term and long-term effects of RT, and emphasize in particular body image changes Various programs for alleviating the distress of children during the administration of RT are underway Yet, it appears that children still suffer unduly in the course of RT, mainly because of the need to be alone and without moving in the treatment room Psychosocial interventions designed to alleviate distress in the course of RT and also after termination of treatment are highly recommended for improving the children’s quality of life during the course of treatment and in later years SELECTED REFERENCES The full list of References for this chapter can be found online at the book’s website Listed here are References particularly recommended for further reading *9 Mulhern RK, Merchant TE, Gajjar A, et al Late neurocognitive sequelae in survivors of brain tumors in childhood Lancet Oncol 2004;5:399–408 *17 Bhatia S, Landler W Evaluating survivors of pediatric cancer Cancer J 2005;1:340–354 *29 Ribi K, Relly C, Landolt MA, et al Outcome of medulloblastoma in children: long-term complications and quality of life Neuropediatrics 2005;36:357–365 *39 Butler RW, Mulhern RK Neurocognitive interventions for children and adolescents surviving cancer J Pediatr Psychol 2005;30: 65–78 *43 Mulhern RK, Carpentieri S, Shema S, et al Factors associated with social and behavioral problems among children recently diagnosed with brain tumor J Pediatr Psychol 1993;18:339–350 *47 Maurice-Stam H, Grootenhuis MA, Caron HN, et al Course of life of survivors of childhood cancer is related to quality of life in young adulthood J Pychosoc Oncol 2007;25:43–58 *51 Klosky JL, Tyc VL, Tong X, et al Predicting pediatric distress during radiation therapy procedures: the role of medical, psychosocial, and demographic factors Pediatrics 2007;119:1159–1166 *57 Haeberli S, Grotzer MA, Niggli FK, et al A psychoeducational intervention reduces the need for anesthesia during radiotherapy for young childhood cancer patients Radiat Oncol 2008;3:17 72607_Ch26 7/16/10 8:28 PM Page 456 72607_index 7/16/10 8:30 PM Page 457 Index Page numbers followed by “f” designate figures; page numbers followed by “t” indicate tables Abdominal mass, Wilms tumor and, 263 Abdominal ultrasound, 293 Absolute neutrophil count (ANC), 436 ACC See Adenoid cystic carcinoma (ACC); Adrenocortical carcinoma (ACC) Acute lymphoblastic leukemia (ALL), 397, 408–409, 447 biologic findings, 12–13 B-precursor, 12 central nervous system chemotherapy for, 18 craniospinal irradiation for, 14, 16, 16f, 18 diagnostic criteria for, 14 established, treatment of, 17–19 incidence of, 17 preventive therapy for, 14–17 radiotherapeutic management, 17 relapse of, 17–18 retinal findings, 17 extramedullary disease, 20 genotypes in, 13f hematopoietic stem cell transplantation (HSCT) for, 21 outcome in, 12f SDS for, 361, 361f second cancers after childhood, 409t sites of, 13 staging of, 13–14 survival rates, 14 symptoms of, 13, 14f testicular involvement, 19 total body irradiation for, 12, 22–23, 22f T-precursor, 12 treatment of chemotherapy, 14 cranial irradiation, 14–17, 15t Acute myeloid leukemia (AML), 12 alkylating agent–associated, 401–402, 402t chemotherapy for, 20 classification of, 19 extramedullary disease in, 20 French–American–British (FAB) classification of, 19 hematopoietic stem cell transplantation (HSCT) for, 21 incidence of, 19 prevalence of, 19 radiation therapy for, 20 survival rates, 6t topoisomerase II inhibitor–associated, 402–403, 402t Acute nonlymphocytic leukemia (ANLL), 340 Adenoid cystic carcinoma (ACC), 326 Adolescents hematopoietic stem cell transplantation (HSCT) in, 21 neuroblastoma in, 127–128 Adrenocortical carcinoma (ACC), 311–313 biology of, 311 clinical aspects of, 311 epidemiology of, 311 follow up, 313 genetics of, 311 histology of, 311 imaging studies of, 312 molecular biology of, 311 prognostic factor of, 311–312 results, 313 treatment of, 312–313 chemotherapy, 312 radiotherapy, 312–313 surgical treatment of, 312 Adults neuroblastoma in, 127–128 with nonrhabdomyosarcoma soft tissue sarcoma large-scale studies of adjuvant chemotherapy, 245–246 Aerodigestive tract esthesioneuroblastoma, 323–326 juvenile nasopharyngeal angiofibroma, 317–320 nasopharyngeal carcinoma, 320–323 Age diagnosis and treatment of primary cancer, 398 radiation-induced SPCs and, 401 Age-specific cancer incidence rates, 2, 2f, 4f AIEOP-CNR-H.X*83, 340 AJC on Cancer Staging See American Joint Commission (AJC) on Cancer Staging Alkylating agents, 401 associated AML/MDS, 401–402, 402t ALL See Acute lymphoblastic leukemia (ALL) Alpha Cradle Mold Maker, 428 Alphafetoprotein (AFP), 290–291 See also Hepatoblastoma (HBL); Hepatocellular carcinoma (HCC) in pregnant women, 293–294 Alveolar rhabdomyosarcoma, 206, 207 Alveolar soft part sarcomas, 234 American Academy of Pediatrics Section on Anesthesiology, 420 American Joint Commission (AJC) on Cancer Staging, 237, 238t American Joint Committee on Cancer (AJCC) TNM staging system, 294 American Society of Anesthesiologists, 420 American Thyroid Association (ATA), 315 AML See Acute myeloid leukemia (AML) Anaplasia, 261 diffuse, 261, 262 focal, 261, 262 Anaplastic ependymomas, 67, 68 Anaplastic Wilms tumor, 261, 262f ANC See Absolute neutrophil count (ANC) Anemia, 290 anesthetic considerations, 424 aplastic, 21–22 erythropoietin treatment for, 437–438 Fanconi, 21 Anesthesia barbiturates for, 418 behavioral techniques to avoid, 414 benzodiazepines for, 418 frequency of, 414–415, 415t goals of, 415–416, 415t implications of underlying disease, 423–424 inhaled anesthetics, 416–418, 416f, 416t, 417f intravenous anesthetics, 418–420 monitoring of, 420–422, 421f, 422f narcotic analgesics for, 419 sedation vs., 420 ventilation monitoring of, 420, 421f ANLL See Acute nonlymphocytic leukemia (ANLL) Anticipatory nausea, 446 Antiemetics, 63 with lower therapeutic indices, 445t Antineoplastic drugs, 395t APC gene mutation, 54 Aplastic anemia, 21–22 Apoptosis, 405 Aquaplast, 426–428 Arrhythmias, 372 Askin tumor, 234 Astrocytoma(s) brainstem, 72, 74, 74f cerebellar, 75–78 chemotherapy for, 31–32 fibrillary, 29, 29f, 30 gemistocytic, 30 giant cell, 27, 30 holocord, 79 incidence of, 26t juvenile pilocytic, 29, 29f, 30f, 31, 72, 73f, 74 low-grade, 28–34 percent distribution of, 3t pilomyxoid, 29 pleomorphic, 30 protoplasmic, 30 radiation therapy for dosage of, 32 results of, 32–34 studies of, 31 techniques, 32, 33f, 34f volume, 32 spinal cord, 79, 79f, 82 surgical treatment of, 30–31 thalamic, 31 ATA See American Thyroid Association (ATA) Atrioventricular (AV) conduction abnormalities, 372 Avascular necrosis, 368–369 Barbiturates, 418 Barr, Yvonne M., 166f See also Epstein-Barr virus (EBV) Basal cell carcinomas, 349–350 Basal cell nevus syndrome (BCNS), 349 Base excision repair (BER) pathway, 404 BCNS See Basal cell nevus syndrome (BCNS) Beckwith-Wiedemann syndrome (BWS), 258 Benzodiazepines, 418 Benzydamine, 444 BER pathway See Base excision repair (BER) pathway Bevacizumab, 299 Bladder, rhabdomyosarcoma of, 217–218 Bleomycin, 424 457 72607_index 7/16/10 8:30 PM Page 458 458 INDEX Blood count depression colony-stimulating factors, 437–438 hematologic complications of cancer chemotherapy, 434–435 radiotherapy, 435–436 overview, 434 pediatric protocols guidelines, 436–437 BMI See Body mass index (BMI) BMT See Bone marrow transplantation (BMT) Body mass index (BMI), 439 Bone abnormalities, radiation-induced avascular necrosis, 368–369 evaluation of, 370t growth retardation, 366 kyphosis, 366, 368 pathological fracture, 370t pathophysiology of, 366 scoliosis, 366, 368 slipped femoral capital epiphysis, 368, 370t Bone marrow, radiation therapy effects on, 393–395, 395f Bone marrow transplantation (BMT), 12, 343 effects of, 361 Bone tumors, 409–410 B-precursor leukemia, 12 Brachytherapy, nonrhabdomyosarcoma soft tissue sarcoma treated with, 247–248, 249–251, 250f BrainLAB, 427 Brainstem astrocytomas, 72, 74, 74f Brainstem gliomas, 72–77, 73f, 74f chemotherapy for, 75–76 description of, 72 diffusely infiltrating, 72, 73f focal, 72, 77 magnetic resonance imaging of, 72 radiation therapy for, 75 surgical treatment of, 74–75 symptoms of, 72 Brain tumors See also specific tumor astrocytoma See Astrocytoma(s) classification of, 53 clinical presentation of, 28 craniopharyngiomas See Craniopharyngiomas craniospinal radiotherapy in, 436 embryonal classification of, 39–40 ependymoblastoma, 40 medulloblastomas, 26t, 39 See also Medulloblastomas medulloepithelioma, 40 pineoblastoma, 39, 39f, 40 radiation therapy for, 40 treatment of, 40 types of, 39–40 gangliogliomas, 37 germ cell tumors See Germ cell tumors (GCT) histopathologic classification of, 26t imaging of, 27 incidence of, 26t infratentorial, incidence of, 26t malignant gliomas, 37–38 neurocytomas, 37 neurofibromatosis and, 27 oligodendroglioma, 26t, 36–37 optic pathway, 35–36 sites of, 26–27, 27f as SPCs, 412 supratentorial, 26t See also specific tumors BRC-ABL fusion gene, 13 BRCA1 C-terminus (BRCT) domain, 404 BRCT domain See BRCA1 C-terminus (BRCT) domain Breast cancer, 330 in Hodgkin lymphoma survivors by age and latency, 411t as SPCs, 410–411 British Cancer Survivor Study, 287 Burkitt, Denis Parsons, 166f Burkitt lymphoma, 166 See also Non-Hodgkin lymphoma (NHL) chemotherapy, 169 clinical presentation, 167 percent distribution of, 3t prognostic factors, 169 radiotherapy, 170 staging, 168 Busulfan, 402 BWS See Beckwith-Wiedemann syndrome (BWS) CAD See Coronary artery disease (CAD) Cade technique, 188, 190t Calcifications, 293 Calvarial lesions, 335 Cancer See also specific cancer chemotherapy, hematologic complications of, 434–435 defense mechanisms, 10 evil and, 10–11 global incidence of, 2, incidence of description of, 2f, 4f global, 2, increases in, 5–6 mortality rates of description of, 1, 5t trends in, percent distribution of, 3t relative frequency of, 1–5 survivors, 7–8, 9t Cancer care center, 9t Cancer pain management medications for, 429–430 neuropathic pain, 430 diagnosis of, 430 medications for, 430t radiotherapy for, 432 treatment of, 430 opioids, 430–431 initiation of analgesia, 431–432 side effects of, 432 Cancer Therapy Evaluation Program, 402 Capnometry, 422 Carboplatin, 298 Carcinoid, 328 Cardiac abnormalities, radiation-induced arrhythmias, 372 coronary artery disease, 372–373, 374t description of, 369, 372 evaluation of, 374t myocardial infarction, 373 myocardiopathy, 371–372, 374t pericarditis, 371, 374t valvular disease, 372, 374t Cardiac effects, in Wilms tumor, 284t, 287 Cardiac function, long-term complications of, 284t Care, site of, Cassady system, for Wilms tumor, 264 Cataracts, 104, 387, 388, 389 CCSG–POG protocol, 300 CCSK See Clear cell sarcoma of the kidney (CCSK) CCSS See Childhood Cancer Survivor Study (CCSS) CED See Convection-enhanced delivery (CED) Cell-cycle activity, of chemotherapeutic agents, 435t Central nervous system (CNS), 418 leukemia of chemotherapy for, 18 craniospinal irradiation for, 14, 16, 16f, 18 diagnostic criteria for, 14 established, treatment of, 17–19 incidence of, 17 preventive therapy for, 14–17 radiotherapeutic management, 17 relapse of, 17–18 retinal findings, 17 radiation-induced necrosis of, 357 chronic progressive radiation myelitis, 359 evaluation of, 360t intellectual deficits, 357–359 mineralizing microangiopathy, 357 myelopathy, 359 necrosis of, 357 necrotizing leukoencephalopathy, 357 neuropsychologic deficits, 357–359 pathophysiology of, 356–357 psychological effects, 359, 361 somnolence syndrome, 359 tumors of See Brain tumors Cerebellar astrocytomas, 77–78 chemotherapy for, 78 radiation therapy for, 78 sites of, 77 surgical treatment of, 78 Cerebellopontine angle (CPA), 67 Cerebrospinal fluid (CSF), 207 cytology testing, for retinoblastoma (RB), 88 Cervical rhabdomyosarcoma, 220–221 Chang staging system, 54–55 for medulloblastoma, 55t Chemotherapeutic agents, risk of SPCs and, 401 Chemotherapy esthesioneuroblastoma, 325–326 for Ewing sarcoma, 176–178 hematopoietic stem cell transplantation conditioning regimen, 20 for Hodgkin lymphoma, 144, 150–151 indications acute lymphoblastic leukemia, 14 acute myelogenous leukemia, 20 astrocytomas, 31–32 brainstem gliomas, 75–76 central nervous system leukemia, 18 germ cell tumors, 48–49 malignant gliomas, 38 nonrhabdomyosarcoma soft tissue sarcoma, 243–246 optic pathway tumors, 36 rhabdomyosarcoma, 212, 213, 214, 222, 228 Wilms tumor, 282 JNA, 318 Langerhans cell histiocytosis, 340–342 late effects of, 354, 356t for neuroblastoma, 119, 121–123 for non-Hodgkin lymphoma, 169–170 for osteosarcoma, 195–197, 197f, 198f ovary effects, 376 for pheochromocytoma/paraganglioma, 314 pulmonary effects, 373–374, 375, 376t for retinoblastoma, 99–100 Chemotherapy-induced hematopoietic malignancies features of, 403t Chest computed tomography, 207 Childhood, ALL, second cancers after, 409t Childhood Cancer Survivor Study (CCSS), 349, 398, 410 72607_index 7/16/10 8:30 PM Page 459 INDEX Children’s Cancer Group (CCG), 296 Children’s Cancer Study Group (CCSG) trial, 292 Children’s Oncology Group (COG), 31, 412 chemotherapy regimens, 274t classifications of renal tumors, 260t Long-Term Follow-Up Guidelines, 412 protocols, 272t AREN0321, 272 AREN0532, 272, 274 AREN0533, 274 AREN0534, 274–275 AREN03B2, 272 ARST0332, 272 radiation therapy guidelines, 273t staging guidelines for Wilms tumor, 264, 265t studies, Wilms tumor, 271–275 Children’s Oncology Group Data and Safety Monitoring Committee, 299 Chlorambucil, 402 Chondroblasts, radiation therapy effects on, 366 Chondrocytes, radiation therapy effects on, 366 Chondrosarcoma, 202 mesenchymal, 203 percent distribution of, 3t treatment, 203 Chordoma, 202–203, 202f treatment, 202–203 Chromaffin cells, 313 Chromosomal translocations leukemia and, 13 Chronic myeloid leukemia See also Acute myeloid leukemia (AML) percent distribution of, 3t Chronic progressive radiation myelitis (CPRM), 359 Cisplatin-based chemotherapy, 296 Civco, 427 Clear cell ependymoma, 67 Clear cell sarcoma, 234 Clear cell sarcoma of the kidney (CCSK), 259, 262–263, 263f Clinical target volume (CTV), 57 Clinical tumor volume (CTV), 31, 217 CNS See Central nervous system (CNS) COG See Children's Oncology Group (COG) Color Doppler ultrasound, 293 Colorectal malignancies, 330 Combined-modality therapy, Complete Response (CR), 297 Computed tomography (CT), 218, 219 abdominal, 264f chest, 207 Hodgkin lymphoma (HL), 158 juvenile nasopharyngeal angiofibroma, 318 nasopharyngeal carcinoma, 321 nonrhabdomyosarcoma soft tissue sarcoma, 237 for osteosarcoma, 185, 185f of retinoblastoma (RB), 88 Wilms tumor, 263–264 Conjunctiva, 390t Contributions to the Microscopic Anatomy of the Pancreas, 332 Convection-enhanced delivery (CED), 76 Cooperative German–Austrian–Swiss Osteosarcoma Study Group (COSS), 185 Cooperative soft tissue sarcoma (CWS), 203 Cornea, 390t Cornelia de Lange syndrome, 327 Coronary artery disease (CAD), 372–373, 374t Corticosteroids, 441 COSS See Cooperative German–Austrian–Swiss Osteosarcoma Study Group (COSS) CPA See Cerebellopontine angle (CPA) CPRM See Chronic progressive radiation myelitis (CPRM) Cranial irradiation (CrI) for central nervous system leukemia, 14, 16, 16f, 18 dosage of, 19 indications for, 18t Cranial radiotherapy (CRT), 447 Craniopharyngiomas, 40–44, 41f, 42t, 44f characteristics of, 40 clinical presentation of, 40–41, 41f diagnosis of, 27 incidence of, 26t mortality rates, 41 outcomes of, 42t radiation therapy for, 43 dosage, 43 results, 43 technique, 43 volume, 43 treatment of, 41–43 Craniospinal irradiation (CSI), 438 See also Radiation therapy central nervous system leukemia treated with, 14, 19 medulloblastoma treated with, 56–63 patient positioning for, 59–61, 60f technique for, 59–63, 60f, 61f Craniospinal radiotherapy, in brain tumors, 436 Craniotomy, 56 “Crankcase oil,” 40 CrI See Cranial irradiation (CrI) CRT See Cranial radiotherapy (CRT) Cryotherapy, for retinoblastoma, 92 CSF See Cerebrospinal fluid (CSF) CSI See Craniospinal irradiation (CSI) CT See Computed tomography (CT) CTV See Clinical target volume (CTV); Clinical tumor volume (CTV) Cure, 6–7 defined, CWS See Cooperative soft tissue sarcoma (CWS) Cyclophosphamide, 401 CYP enzymes See Cytochrome P450 (CYP) enzymes Cyproheptadine hydrochloride, 442 Cytochrome P450 (CYP) enzymes, 398 Cytomegalovirus, 441 Cytopenia, degree of, 434 Dacarbazine, 402 DAL-HX83, 340 DAL-HX90, 340 Daunorubicin, 424 Death caused by cancer, for five leading cancer sites, 5t leading causes of in children, 1t Defense mechanisms, 10 Dendritic cells, 332 Desmoid tumors characteristics of, 252–253 in children, 252f right buttock, 253f treatment of, 253–255, 253t, 254t Desmoplastic blue cell tumor, 234 Dexmedetomidine, 419 Dexrazoxane (DZR), 371–372 Diazepam (Valium), 418 DIBSG See Diffusely infiltrating brainstem gliomas (DIBSG) 459 Die Mischgeschwulste der Niere, 257f Diffuse anaplasia, 261, 262 Diffuse fibrillary astrocytomas, 29, 29f, 30 Diffusely infiltrating brainstem gliomas (DIBSG), 72, 73f Diffuse plaque-like retinoblastoma, 90 Digestive tract, radiation therapy effects on, 384, 385t, 386–387 Disease-free survival (DFS), 296–297 DNA repair, SPC development and, 403–404 DNET See Dysembryoplastic neuroepithelial tumors (DNET) Dosage calculation abdominal disease, 283 nonrhabdomyosarcoma soft tissue sarcoma, 247 Dose volume histograms (DVH), 32 Doxorubicin, 424 Duloxetine, 432 DVH See Dose volume histograms (DVH) Dysembryoplastic neuroepithelial tumors (DNET), 37 DZR See Dexrazoxane (DZR) ECG See Electrocardiogram (ECG) Ectomesenchymomas, 234 E2F, 405 EFS See Event-free survival (EFS) Electrocardiogram (ECG), 421 Embryonal brain tumors classification of, 39–40 ependymoblastoma, 40 medulloblastomas See Medulloblastomas medulloepithelioma, 40 pineoblastoma, 39, 39f, 40 radiation therapy for, 40 treatment of, 40 types of, 39–40 Embryonal rhabdomyosarcoma, 206, 207, 292–293 Embryonal sarcoma of liver, 292–293 EN See Esthesioneuroblastoma (EN) Endophytic retinoblastoma, 89 Endoscopic third ventriculostomy (ETV), 46, 48f Enucleation, for retinoblastoma, 91 EOES See Extraskeletal Ewing sarcoma (EOES) EORTC See European Organization for the Research and Treatment of Cancer's (EORTC) Ependymoblastoma, 67 description of, 40 Ependymomas anaplastic, 67, 68 characteristics of, 40, 67 grade 1, 67 grade 2, 67 chemotherapy for, 69–70 classification of, 67 clear cell, 67 histologic findings, 67 magnetic resonance imaging of, 68 myxopapillary, 67 radiation therapy for, 68–72, 69t, 71f spinal cord, 79, 81 surgical treatment of, 68, 69t symptoms of, 68 Epipodophyllotoxins, 402 Epithelioid sarcoma, 234 EPO See Erythropoietin (EPO) EPO-R See Erythropoietin receptor (EPO-R) EPSSG See European Paediatric Soft Tissue Sarcoma Study Group (EPSSG) Epstein, Michael, 168f See also Epstein-Barr virus (EBV) 72607_index 7/16/10 8:30 PM Page 460 460 INDEX Epstein-Barr virus (EBV), 166 Erythropoietin (EPO), 437 Erythropoietin receptor (EPO-R), 438 Esophageal carcinoma, 327 Esthesioneuroblastoma (EN), 323–326 classification of, 324–325 clinical aspect of, 324 epidemiology of, 323 histology of, 323–324 imaging studies, 324 recurrence rates in, 326t results of, 326 treatment of, 325–326 chemotherapy for, 325–326 radiotherapy for, 325 surgery, 325 Etoposide, 298 ETV See Endoscopic third ventriculostomy (ETV) EUROCARE database, 351 Euro-Ewing protocol, 437 European Organization for the Research and Treatment of Cancer’s (EORTC), 245 European Paediatric Soft Tissue Sarcoma Study Group (EPSSG), 245 Event-free survival (EFS), 243, 313 Ewing, James, 172 See also Ewing sarcoma Ewing sarcoma, 261f, 437 cure rates, 182 diagnosis, 173–175, 173t, 174f, 175t metastatic, 181 overview, 172–173 pathology, 173 percent distribution of, 3t treatment chemotherapy, 176–178 local control, 175–176 radiation therapy, 178–181 See also Radiation therapy, for Ewing sarcoma side effects, 182 stem cell transplantation, 181 surgery, 176 TBI, 181, 182 Exenteration, for retinoblastoma, 91 Exophytic retinoblastoma (RB), 89, 90 External beam radiotherapy (EBRT) pheochromocytoma: paraganglioma, 314 for pheochromocytoma: paraganglioma, 314 for retinoblastoma cataracts secondary to, 104 description, 93 dosage, 97–99 lacrimal gland effects, 105–106 metastases treated with, 103 orbital development effects, 104–105 technique, 93–97 Extracorporeal irradiation, for osteosarcoma, 195 Extradural spinal cord neoplasms, 78 Extramedullary disease in acute myelogenous leukemia, 20 Extraskeletal Ewing sarcoma (EOES), 234 Eye abnormalities, radiation-induced cataract, 387, 388, 389 conjunctiva, 390t cornea, 390t eyelids, 380t, 389 iris, 391t lacrimal apparatus, 390t lens, 387, 388–389, 391t optic nerve, 389 orbit, 389 retina, 387, 391t sclera, 390t Eyelids, 380t, 389 FAB See French–American–British (FAB) classification Failure-free survival (FFS), 213 Familial adenomatous polyposis (FAP), 294 Fanconi anemia, 21, 403 Favorable histology (FH) Wilms tumor, 259t Fentanyl, 431 FFS See Failure-free survival (FFS) FH Wilms tumor See Favorable histology (FH) Wilms tumor Fibrillary astrocytomas, diffuse, 29, 29f, 30 Fibrolamellar (FL) histologic variant of HCC, 292 Fibromyxoid sarcoma, low-grade, 234 Fibrosarcoma, 233–234, 234f 5-Hydroxytryptamine blockers, 444 Flexner-Wintersteiner rosettes, 40 FNCLCC system See French Federation of Cancer Centres (FNCLCC) system Focal anaplasia, 261, 262 Focal brainstem tumors, 72 Focal nodular hyperplasia (FNH), 291 French-American-British (FAB) classification See Acute myeloid leukemia (AML) French–American–British (FAB) classification, 19 French Federation of Cancer Centres (FNCLCC) system of grading soft tissue sarcomas, 239, 240t tumor differentiation scores of sarcoma in, 239t Fuorodeoxyglucose (FDG)-PET for nasopharyngeal carcinoma, 321 Gairdner, Ebenezer, Dr., 257 Gangliogliomas, 37 Gastrointestinal malignancies, 327 Gastrointestinal stromal tumors, 230 G-CSF See Granulocyte colony-stimulating factor (G-CSF) Gemistocytic astrocytomas, 30 Genetic predisposition, in SPC development DNA repair, 403–404 drug-metabolizing enzyme, 403 Genitourinary system, radiation therapy effects on, 385t German Cooperative Ewing’s Sarcoma Study (CESS), 176 CESS-81 trial, 82t, 176, 177, 178, 182 CESS-86 trial, 82t, 176, 177, 182 German Cooperative Pediatric Liver Tumor Studies, 296–297 Germ cell tumors (GCT) bimodal age distribution, 303–304 classification, 303f diagnosis, 304 extragonadal, 307–310 intracranial, 44–50 characteristics of, 44–45 chemotherapy for, 48–49 pineal, 45, 45t radiation therapy for, 48–50, 50f suprasellar, 45 surgery for, 46, 48f treatment of, 46–50, 47t–48t mediastinal, 309 ovarian, 304–306, 304f, 305t overview, 303 radiotherapy, 309–310 sacrococcygeal, 307–309 staging, 304 teratomas, 303 testicular, 306–307, 306f, 307t GFR See Glomerular filtration rate (GFR) GH See Growth hormone (GH) GHRH See Growth hormone-releasing hormone (GHRH) Giant cell astrocytomas, 27, 30 Gliomas brainstem chemotherapy for, 75–76 description of, 72 diffusely infiltrating, 72, 73f focal, 72, 77 magnetic resonance imaging of, 72 radiation therapy for, 75 surgical treatment of, 74–75 symptoms of, 72 low-grade chemotherapy for, 31–32 description of, 27, 28 radiation therapy for, 31–34 surgery for, 30–31 malignant, 37–38 pontine, 72, 72f, 73f Gliomatosis cerebri, 28, 31, 32 Glomerular filtration rate (GFR), 287 Glutathione S transferase (GST), 403 Gorlin syndrome, 53 Graft-versus-host disease (GVHD), 21, 361 Granulocyte colony-stimulating factor (G-CSF), 437 Gross tumor volume (GTV), 31, 57, 217, 218 Growth abnormalities, Wilms tumor, 287–288, 287t Growth curves of different tissues, 355, 357f Growth hormone (GH) cranial irradiation effects on, 361 Growth hormone–releasing hormone (GHRH), 361 Growth retardation, bone, 366 GST See Glutathione S transferase (GST) GTV See Gross tumor volume (GTV) GVHD See Graft-versus-host disease (GVHD) HB-89, 296–297 HB-94, 296–297, 298 Head rhabdomyosarcoma of, 225–226 “Health Links,” 412 Hearing radiation therapy effects on, 389, 392, 393t Hemangiomas, 290 bone, 347 cavernous, 346 classification of, 346, 346t clinical presentation of, 346 diagnosis of, 346 natural history of, 346–347 orbital, 348 treatment of, 347 Hemangiopericytomas, 234 Hematologic complications of cancer chemotherapy, 434–435 of radiotherapy, 435–436 Hematologic toxicity, in Wilms tumor, 286 Hematopoietic stem cells, 435 Hematopoietic stem cell transplantation (HSCT), 365 acute lymphoblastic leukemia treated with, 21 acute myeloblastic leukemia treated with, 21 in adolescents, 21 in children, 21 description of, 20–21 hematologic diseases and, 21–22 principles of, 20–21 Hemochromatosis, 233 Hepatic adenomas, 291 72607_index 7/16/10 8:30 PM Page 461 INDEX Hepatic artery embolization, 290 Hepatobiliary rhabdomyosarcoma, 226–227, 227f Hepatoblastoma (HBL), 290 clinical presentation, 292–292, 295 diagnosis, 293–294 genetic abnormalities, 294 histologic classification, 291–292 staging of, 294, 294t treatment chemotherapy, 296–299 radiation therapy, 299–301 surgery, 294–296 Hepatocellular carcinoma (HCC), 290, 292 clinical presentation, 292, 293–294 hepatitis B immunization and, 292 histologic variant, 292 prevalence, 292 treatment chemotherapy, 296–299 radiation therapy, 299–301 surgery, 294–296 Hepatotoxicity, in Wilms tumor, 286–287 Herpes simplex virus, 441 High-risk, acute lymphoblastic leukemia, 13–14 Hodgkin disease pediatric protocols guidelines, 437 percent distribution of, 3t Hodgkin lymphoma (HL), 406–408, 440 advance, 152–153 biology, 137–138, 138f clinical presentation, 139 diagnosis, 141, 142–143 early-stage, 152 epidemiology, 138–139 overview, 137 pathologic classification, 139–140 pronosis factors, 143–144 radiation therapy complications, 162–164 conformal planning, 158–161 3D-CRT, 159, 160 description, 155 dosage, 161 energy used in, 161 IMRT, 159–161 INRT, 158 PET/CT, 158 recurrent disease treated with, 153–155 results, 161–162 sequence, 161 volume, 155–158 refractory, 153–155 relapse, 153–155 staging, 140–141 survival rates, 6t treatment chemotherapy, 144, 150–151 radiation therapy See Hodgkin lymphoma (HL), radiation therapy recommendations, 150t relapse after, 153–155 results, 145t–149t risk adapted therapy, 151–153 selection, 144 Holocord astrocytomas, 79 Homer–Wright rosettes, 40 Homologous repair (HR) pathway, 403 HP irradiation See Hypothalamic-pituitary (HP) irradiation HR pathway See Homologous repair (HR) pathway HSCT See Hematopoietic stem cell transplantation (HSCT) Hydromorphone, 431 Hyperthyroidism, 365–366 Hypopharynx, malignancies of, 326 Hypothalamic/chiasmatic gliomas, 34 Hypothalamic-pituitary (HP) irradiation clinical manifestations, 361–362 growth hormone, 361 non–growth hormone tropins, 362 Hypothryoidism, 365 IE See Ifosfamide and etoposide (IE) Ifosfamide, 402 Ifosfamide and etoposide (IE), 213 IGF-1 See Insulin-like growth factor (IGF-1) IKZF1, 13 Immobilization devices, 425–429 acquaplast for, 426–428 mechanical aids for, 425 polyurethane foams, 428 posicast for, 426–428 thermal plastic mask, 426–427, 427f vaccum bags, 428 IMRT See Intensity-modulated radiation therapy (IMRT) Infantile hemangioendothelioma, 290 Infantile subglottic hemangiomas, 327 Inhaled anesthetics, 416–418, 416f, 416t, 417f Insulin-like growth factor (IGF-1), 361 Intensity-modulated radiation therapy (IMRT), 32, 57, 247, 301, 400 Hodgkin lymphoma (HL), 159–161 Intergroup Rhabdomyosarcoma Study Group (IRSG), 204 Intergroup Rhabdomyosarcoma Study (IRS), 204, 212 design and results of, 212t–213t grouping system, 208, 208t radiation therapy and, 215 International Society of Pediatric Oncology Liver Tumor Study Group (SIOPEL), 294, 296 International Society of Pediatric Oncology (SIOP), 204, 216, 295 classifications of renal tumors, 260t nonrhabdomyosarcoma soft tissue sarcoma, 244–245 SIOP results of, 275t treatment protocol, Wilms Tumor, 275t SIOP 2, 275–276 results of, 276t treatment protocol, Wilms Tumor, 276t SIOP 5, 276 effect of preoperative treatment, 277t results of, 276t treatment protocol, Wilms Tumor, 276t SIOP 6, 277 results of, 278t treatment protocol, Wilms Tumor, 277t SIOP 9, 277–279 results of, 279t treatment protocol, Wilms Tumor, 278t SIOP 93-01, 279–280 results of, 280t treatment protocol, Wilms Tumor, 279t SIOP 2001, 280t–281t Wilms tumor, 264, 265, 275–280 staging system used in, 265t Intracranial germ cell tumors See Germ cell tumors (GCT), intracranial Intradural spinal cord neoplasms, 78 Intramedullary spinal cord neoplasms, 78–79, 79f Intraoperative electron beam therapy (IO-ERT), 251 461 Intraoperative high–dose rate brachytherapy (IO-HDRBT), 251 Intraoperative radiation therapy (IORT), 251 Intravenous anesthetics, 418–420 Intravenous pyelogram (IVP), 263 IO-ERT See Intraoperative electron beam therapy (IO-ERT) IO-HDRBT See Intraoperative high-dose rate brachytherapy (IO-HDRBT) IORT See Intraoperative radiation therapy (IORT) IQ level, effects of radiotherapy on, 448t Iris, 391t Irradiation See also Radiation therapy cranial for central nervous sytem leukemia, 14, 16, 16f, 18 dosage of, 19 craniospinal central nervous system leukemia treated with, 14, 19 medulloblastoma treated with, 56–63 patient positioning for, 59–61, 60f technique for, 59–63, 60f, 61f total body acute lymphoblastic leukemia treated with, 12, 22–23, 22f dosage of, 23 techniques for, 22–23, 22f testicular boost in, 23 IRS See Intergroup Rhabdomyosarcoma Study (IRS) IRSG See Intergroup Rhabdomyosarcoma Study Group (IRSG) Israeli Cancer Association, 429 Israeli Medical Association, 429 IVP See Intravenous pyelogram (IVP) Japanese Study Group for Pediatric Liver Tumor ( JPLT), 292 JLSG-96, 341 JNA See Juvenile nasopharyngeal angiofibroma ( JNA) JPA See Juvenile pilocytic astrocytomas ( JPA) JPLT Protocol-1, 297 Juvenile nasopharyngeal angiofibroma ( JNA), 317–320 clinical aspect of, 318 epidemiology of, 317 histology of, 317 imaging study of, 318 prognostic factor, 318 stages for, 319t treatment of chemotherapy, 318 endoscopic resection, 318–319 radical surgery, 318 radiotherapy, 319–320, 320t Juvenile pilocytic astrocytomas (JPA), 27, 29, 29f, 30f, 31, 72, 73f, 74 Kasabach–Merrit syndrome, 290 Kasabach-Merritt phenomenon (KMP), 346 Keratinocyte growth factor (KGF), 444 Ketamine, 419 KGF See Keratinocyte growth factor (KGF) Kidney radiation therapy effects on, 383–384 clinical manifestations, 383–384 pathophysiology of, 383 KMP See Kasabach-Merritt phenomenon (KMP) Kyphosis, 366, 368 72607_index 7/16/10 8:30 PM Page 462 462 INDEX Lacrimal apparatus, 390t Langerhans cell histiocytosis clinical presentation of, 334–336, 334t defined, 332–334 diabetes inspidus associated with, 332, 336t, 343f diagnostic evaluation for, 334–336 history of, 332 immunophenotype of, 333t incidence of, 334 long-term sequelae of, 344–345 organ system involvement in, 336t pathology of, 332–334, 333f radiotherapeutic management, 343–344 dosage for, 343 volume for, 344 results of, 345 sites of bone involvement in, 335t stages for, 334–336 treatment of bone marrow transplantation, 343 chemotherapy, 340–342 direct injection of steroids, 337, 337t liver transplantation, 343 radiation therapy, 337–340, 338t surgery, 336–337 Laparoscopic resection, for pheochromocytoma/paraganglioma, 314 Large congenital nevocytiv nevi (LCNN), 350 Laryngeal mask airway (LMA), 416 Larynx, malignancies of, 326 Laser hyperthermia, for retinoblastoma, 92 LCH2, 341 LCH3, 341 management strategy for, 342t LCH Trial 1, 341 LCNN See Large congenital nevocytiv nevi (LCNN) Left ventricular ejection fraction (LVEF), 371 Leiomyosarcoma, 233 Lens, 387, 388–389, 391t Leukemia acute lymphoblastic See Acute lymphoblastic leukemia acute myeloblastic, 12 acute myelogenous See Acute myeloid leukemia (AML) incidence of, 2f percent distribution of, 3t testicular, 19 Leukocytosis, 290 Leukoencephalopathy, necrotizing, 357 risks of, 358f Li–Fraumeni syndrome, 230, 403 Limb-sparing surgery, 240–241 Liposarcomas, 233 Liver diseases, radiation-induced, 386–387 Liver transplantation, 295–296, 343 LMA See Laryngeal mask airway (LMA) LOH See Loss of heterozygosity (LOH) Loss of heterozygosity (LOH), 259, 259t Low-grade astrocytoma, 28–34 Low-grade fibromyxoid sarcoma, 234 Low-grade gliomas chemotherapy for, 31–32 description of, 27, 28 radiation therapy for, 31–34 surgery for, 30–31 Low-LET radiation See Low-linear energy transfer (low-LET) radiation Low–linear energy transfer (low-LET) radiation, 399 Low risk, acute lymphoblastic leukemia, 13 Lung irradiation, for osteosarcoma, 193–195, 194t Lungs chemotherapy effects on, 373–374, 375, 376 radiation therapy effects on, 373–374, 375, 376t clinical manifestations, 373 pathophysiology of, 373 LVEF See Left ventricular ejection fraction (LVEF) Lymphangiomas, 348–349 Lymph node dissection, in nonrhabdomyosarcoma soft tissue sarcoma, 241 Lymph node metastasis, 211t Lymphoma incidence of, 2f percent distribution of, 3t Magnetic resonance imaging (MRI), 207 brainstem gliomas, 72 ependymomas, 68 juvenile nasopharyngeal angiofibroma, 318 medulloblastoma, 54f nasopharyngeal carcinoma, 321 nonrhabdomyosarcoma soft tissue sarcoma, 237 for osteosarcoma, 185, 185f spinal cord neoplasms, 79 Malignancies, chemotherapy-induced hematopoietic, 403t Malignant fibrous histiocytoma (MFH), 230–231, 234 histologic appearance of, 233f Malignant gliomas, 37–38 chemotherapy for, 38 radiation therapy for, 38–39 dosage, 39 results, 39 technique, 38 volume, 38 surgical treatment of, 38 Malignant melanoma, 350–352 classification of primary lesion in, 351 Malignant mesenchymoma, 234 Malignant peripheral nerve sheath tumor (MPNST), 233 Mallory Weiss tears, 441 Malnutrition, in children with cancer causes of, 439–440 treatment related, 440–441 diagnosis of, 439 Masimo Signal Extraction Technology, 421 Massachusetts General Hospital (MGH), 241 MEC See Mucoepidermoid carcinoma (MEC) Mechanical immobilization, 425, 426 Mechlorethamine, 402 Medullary thyroid carcinoma, 317 Medulloblastomas characteristics of, 26t, 39, 53 chemotherapy for, 56–57, 58t definition of, 53 genetic abnormalities associated with, 53–54 high-risk, 57 histologic findings, 53 magnetic resonance imaging of, 54f metastasis of, 54 radiation therapy for delivery of, 63` description, 56 dosage, 57, 59 technique, 59–63, 60f, 61f, 62f volume, 57 recurrence of, 57 sites of, 54, 54f staging of, 54–55, 55t standard of care for, 54, 57 surgery for, 55–56 Medulloepithelioma, 40 Melphalan, 402 Memorial Sloan–Kettering Cancer Center (MSKCC), 242, 250 Meningiomas, radiation-induced, 28 Mesenchymal chondrosarcoma, 203 Mesenchymal hamartomas, 290 Mesoblastic nephroma, 259–260 Metastases of medulloblastoma, 54 rhabdomyosarcoma, 228 Wilms tumor, 285–286 Metastatic Ewing sarcoma, 181 Methadone, 429, 431 Methotrexate (MTX), 357 for central nervous system leukemia, 14 MFH See Malignant fibrous histiocytoma (MFH) MGH See Massachusetts General Hospital (MGH) MI See Myocardial infarction (MI) Midazolam (Versed), 418 Midbrain tumors, 73, 74 Minimal residual disease (MRD), 13 Mismatch repair (MMR), 403 Mixed lineage leukemia (MLL), 13, 402 MLL See Mixed lineage leukemia (MLL) MLL-AF4 fusion gene, 13 MMR See Mismatch repair (MMR) Morphine, 429, 431 Mortality rates, cancer, MPNST See Malignant peripheral nerve sheath tumor (MPNST) MRD See Minimal residual disease (MRD) MRI See Magnetic resonance imaging (MRI) MRT See Intensity-modulated radiotherapy (IMRT) MSKCC See Memorial Sloan-Kettering Cancer Center (MSKCC) M stage, medulloblastoma, 55, 55t MTX See Methotrexate (MTX) Mucoepidermoid bronchial tumors, 328 Mucoepidermoid carcinoma (MEC), 326 Multiple midline germinomas, 45, 45f Musculoskeletal tumors, as SPC, 410 Mutagenicity, 402 Myelodysplasia, alkylating agent–associated, 401–402, 402t Myelopathy, 359 Myelosuppression, duration of, 434t Myocardial infarction (MI), 373 Myocardiopathy, 371–372, 374t Myxopapillary ependymoma, 67 Nadir, 436 NAD(P)H:quinone oxidoreductase-1 (NQO1), 403 Narcotic analgesics, 419 Nasopharyngeal carcinoma (NPC), 320–323 biology of, 321 classification of, 321 clinical aspects of, 320 epidemiolgy of, 320 genetic of, 320 histology of, 320 imaging study, 321 late effects, 323 metastasis involvement, 321 prognostic factor, 321 results, 323 staging system for, 322t survival in childhood, studies during 1990s and 2000s, 324t treatment of, 321–323 hyperfractionation for, 323 radiotherapy for, 322–323 National Cancer Institute (NCI), 1, 239, 241 National Wilms Tumor Studies (NWTS), 259 findings of, 266–271 NWTS-1 design of, 266f results of, 266t NWTS-2 72607_index 7/16/10 8:30 PM Page 463 INDEX design of, 267f results of, 267t NWTS-3, 267–268 design of, 268f relapse rates, 269t results of, 269t NWTS-4, 268–270 design of, 270f results of, 271t risk of local recurrence in, 271t National Wilms Tumor Study Group (NWTSG) protocols, 366 Nausea, 441, 444–446 first-line medications for, 445t NBCCS See Nevoid basal cell carcinoma syndrome (NBCCS) NCI See National Cancer Institute (NCI) Neck rhabdomyosarcoma of, 225–226 Necrosis, 239 avascular, 368–369 radiation-induced, 357, 360t Necrotizing leukoencephalopathy, 357 Nelson Textbook of Pediatrics, Neoplasms of appendix, 329 of pancreas, 329 in Wilms tumor, 287 Nephroblastoma See Wilms tumor Nephrogenic rests, 260 NER See Nucleotide excision repair (NER) Neuroblastoma (NB) in adolescents, 127–128 in adults, 127–128 biology, 110–111 clinical presentation, 113–115 CNS metastases, 127 epidemiology, 108–109 incidence of, 2f metastases, 127 molecular target agents, 134 MRD, 123 overview, 108 pathology, 111 pediatric protocols guidelines, 437 percent distribution of, 3t prognostic factors, 116–117 radiation therapy complications, 132–134 dosage, 129–130 hepatomegaly, 125 high-risk disease, 126–127 intermediate-risk disease, 125–126 intraoperative, 130–131 irradiation, 130–131 low-risk disease, 124–125 stage 4S, 125 techniques, 130–131 volume, 128 staging, 115–116 survival rates, 6t targeted radioisotope therapy, 134 treatment chemotherapy, 119, 121–123 MRD, 123 radiationb therapy See Neuroblastoma (NB), radiation therapy selection, 119 surgery, 123–124 Neurocytomas, 37 Neuroendocrine, radiation therapy effects on clinical manifestations, 361–362 evaluation of, 363t–364t growth hormone, 361 non–growth hormone tropins, 362 Neurofibromatosis, 27, 233 Neurofibromatosis type (NF1), 233 brain tumors and, 27 Neuropathic pain, 429 diagnosis of, 430 medications for, 430t radiotherapy for, 432 treatment of, 432 Neutron therapy nonrhabdomyosarcoma soft tissue sarcoma treated with, 251–252 for osteosarcoma, 198–199 Nevoid basal cell carcinoma syndrome (NBCCS), 53–54 NF1 See Neurofibromatosis, type I (NF1); Neurofibromatosis type (NF1) Nitrosoureas, 402 Nodular renal blastemas, 260 Non–growth hormone tropins, cranial irradiation effects on, 362 Non-Hodgkin lymphoma (NHL), 327, 410 classification, 168 epidemiology, 166 etiology, 166 evaluation, 167 overview, 166 percent distribution of, 3t staging, 167–169 survival rates, 6t treatment chemotherapy, 169–170 radiation therapy, 170–171 result, 171 Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) adults with large-scale studies of adjuvant chemotherapy, 245–246 cells of origin of, 233t clinical presentation of, 237 cytogenetic changes in, 231t defined, 230 grading systems for, 239 lymph node dissection in, 241 pathologic findings, 230–237 POG grading system for pediatric, 239t pulmonary metastases, 241, 243 radition therapy for brachytherapy, 247–248, 249–251, 250f description of, 241–243, 246 dosage, 247 intraoperative, 247, 251 results, 252 volume, 246–247 risk stratification of, 238f staging of, 237, 238t treatment of chemotherapy, 243–246 hyperthermia, 251 neutrons, 251–252 radition therapy See Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS), radition therapy for surgery, 240–241 types of, 232t workup for, 237 Nonsteroidal anti-inflammatories (NSAID), 429 NPC See Nasopharyngeal carcinoma (NPC) NQO1 See NAD(P)H:quinone oxidoreductase-1 (NQO1) NRSTS See Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) NSAID See Nonsteroidal anti-inflammatories (NSAID) Nucleotide excision repair (NER), 404 Nutritional interventions, for children with cancer, 442 caloric intake, 442–443 diarrhea, 443 463 mucositis, 443–444 nausea, 444–446 vomitting, 444–446 Nutritional problems, in child with cancer See also Malnutrition assessment of, 439 overview, 439 treatment tolerance, 441–442 NWTS See National Wilms Tumor Studies (NWTS) NWTSG See National Wilms Tumor Study Group (NWTSG) protocols Oligodendrocyte, 357 Oligodendrogliomas, 36–37 Opioids, 430–431 for children, 430t conversion of, 431t initiation of analgesia, 431–432 side effects of, 432, 432t OPT See Optic pathway tumors (OPT) Optic chiasm gliomas presenting for radiation therapy, 33f radiation dosimetry for, 34f Optic nerve, radiation therapy effects on, 389 Optic pathway tumors (OPT), 30f, 35–36 characteristics of, 35 chemotherapy for, 36 chiasmatic, 33f, 35 radiation therapy for, 35–36 dosage, 36 technique, 36 volume, 36 surgical treatment of, 35 Oral cavity, malignancies of, 326 Orbit, radiation therapy effects on, 389 Orbital rhabdomyosarcoma, 224, 225 proton treatment for, 225f Orchiectomy, 218 Oropharynx, malignancies of, 326 Orthopedic effects, in Wilms tumor, 287 OS See Overall survival (OS) Osler, William, 357 Osteonecrosis (ON) See Avascular necrosis Osteopenia, 369 Osteosarcoma bones in, 184–185, 185f Enneking staging, 185, 186t evaluation of, 185, 186 histology, 185, 186t histopathology of, 184f incidence, 184, 184f radiation therapy Cade technique, 188, 190t dosage, 197, 198 extracorporeal irradiation, 195 lung irradiation, 193–195, 194t photon, 188, 189, 190, 193 prebiopsy, 188 technique, 198 whole-lung irradiation (WLI), 193–195, 194t retinoblastoma (Rb) inactivation for, 184 signs and symptoms of, 184–185, 185f staging for, 185, 186t surgery localized disease, 186–187, 187t metastatic disease, 187–188, 188t treatment charged particle therapy, 199 chemotherapy, 195–197, 197f, 198f intraoperative therapy, 199, 200, 201 neutron therapy, 198–199 palliation, 201–202, 201f radiation therapy See Osteosarcoma, radiation therapy radioisotope, 201 72607_index 7/16/10 8:30 PM Page 464 464 INDEX Ovary, radiation therapy effects on, 376–377, 377t clinical manifestations, 376, 377 pathophysiology of, 376 Overall survival (OS), 313 Oxisensor, 421 Oxycodone, 431 P21, 405 Pain severity, evaluation of, 430 Pancreas, radiation therapy effects on, 386 Parameningeal (PM) rhabdomyosarcoma, 222–223 proton plan for treatment for, 224f Paratesticular rhabdomyosarcoma, 218, 219–220 Peak filling rate (PFR), 371 Pediatric cancer center, requirements for, 8, 9t Pediatric Intergroup Hepatoma Study INT-0098, 296 Pediatric Oncology Group (POG), 237, 292 grading system for pediatric nonrhabdomyosarcoma soft tissue sarcomas, 239t protocol 8653, 241, 241t, 243, 244f protocol 8654, 243 protocol 9553, 243 Pediatric protocols guidelines craniospinal radiotherapy in brain tumors, 436 Hodgkin disease, 437 neuroblastoma, 437 radiotherapy in sarcoma, 436–437 Wilms tumor, 437 Percent distribution of childhood cancer, 3t Pericarditis, 371, 374t Perineal rhabdomyosarcoma, 226, 227f Perioperative mortality in surgery for HBL, 295 Peripheral primitive neuroectodermal tumor (PNET), 234 PET See Positron emission tomography (PET) PET scan See Positron emission tomography (PET) scan PFR See Peak filling rate (PFR) PFS See Progression-free survival (PFS) P53 gene, 184, 405 Pheochromocytoma of the Adrenal Gland Scaled Score, 313 Pheochromocytoma/paraganglioma (PH/PGL) biology of, 314 clinical aspects of, 314 defined, 313 epidemiology of, 313 genetics of, 313 histology of, 313 imaging studies of, 314 results, 314 Philadelphia chromosome (Ph??, 13 Photocoagulation, for retinoblastoma, 91–92 Photon radiation therapy, for osteosarcoma, 188, 189, 190, 193 PH/PGL See Pheochromocytoma/paraganglioma (PH/PGL) Pilomyxoid tumors, 29 Pineal germ cell tumors, 45, 45t Pineoblastoma, 39, 39f, 40 Pineocytomas, 45 Pleomorphic xanthoastrocytomas, 30 Pleuropulmonary blastoma (PPB), 328 Plexopathy, 432 PM rhabdomyosarcoma See Parameningeal (PM) rhabdomyosarcoma PNET See Peripheral primitive neuroectodermal tumors (PNET) POG See Pediatric Oncology Group (POG) POG-8697, 297 POG-9345, 298–299 Polyurethane foams, 428 Pontine gliomas, 72, 72f, 73f description of, 72 radiation therapy for, 75–77 Posicast, 427–428 Positron emission tomography (PET), 207, 440 Hodgkin lymphoma (HL), 158 nasopharyngeal carcinoma, 321 nonrhabdomyosarcoma soft tissue sarcoma, 237, 237f Posterior fossa craniotomy, 56 Posterior fossa tumors brainstem gliomas See Brainstem gliomas medulloblastoma See Medulloblastoma Postgraduate training, 8, 10 Posttraumatic stress disorder (PTSD), 359 PPB See Pleuropulmonary blastoma (PPB) PRB See RB1 protein (pRB) Prealbumin, 439 Pregabalin, 432 Pregnant women AFP in, 293–294 Wilms tumor in, 284t, 287 Pretreatment Extent of Disease (PRETEXT), 294, 295f Primary cancer diagnosis and treatment of age at, 398 Primary malignant liver tumors (PMLT) See Hepatoblastoma (HBL); Hepatocellular carcinoma (HCC) Primary spinal cord neoplasms, 78–79, 79f Primitive neuroectodermal tumors (PNET), 53, 324 description of, 39 percent distribution of, 3t peripheral, 234 Programmed cell death See Apoptosis Progression-free survival (PFS), 56 Propofol, 419 Prostate gland, rhabdomyosarcoma of, 217–218 Proto-oncogenes, 206, 404 categories of, 404–405 Protoplasmic astrocytomas, 30 PTSD See Posttraumatic stress disorder (PTSD) Pulmonary neoplasm, 327–328 clinical presentation of, 328 diagnosis of, 328 epidemiology of, 327 genetics of, 328 pathology of, 327–328 results, 328 treatment of, 328 Pulse oximetry, 421, 422f RAD51, 403 Radiation-associated SPC, 399–401 characteristics, 399–401 dose–response relationship, 399, 400f frequency of, 399 Radiation hepatitis, 301 Radiation-induced liver disease (RILD), 301 Radiation-induced meningiomas, 28 “Radiation signature,” 399 Radiation therapy, 290, 447 See also Craniospinal irradiation; Total body irradiation acute toxicity from, 435–436 anesthesia barbiturates for, 418 behavioral techniques to avoid, 414 benzodiazepines for, 418 frequency of, 414–415, 415t goals of, 415–416, 415t implications of underlying disease, 423–424 inhaled anesthetics, 416–418, 416f, 416t, 417f intravenous anesthetics, 418–420 monitoring of, 420–422, 421f, 422f narcotic analgesics for, 419 sedation vs., 420 ventilation monitoring of, 420, 421f behavioral effects of, 450, 451t bone effects avascular necrosis, 368–369 evaluation of, 370t growth retardation, 366 kyphosis, 366, 368 pathological fracture, 370t pathophysiology of, 366 scoliosis, 366, 368 slipped femoral capital epiphysis, 368, 370t bone marrow effects, 393–394, 395 cardiac effects arrhythmias, 372 coronary artery disease, 372–373, 374t description of, 369, 371 evaluation of, 374t myocardial infarction, 373 myocardiopathy, 371–372, 374t pericarditis, 371, 374t valvular disease, 372, 374t central nervous system effects, 357 chronic progressive radiation myelitis, 359 evaluation of, 360t intellectual deficits, 357–359 mineralizing microangiopathy, 357 myelopathy, 359 necrosis of, 357 necrotizing leukoencephalopathy, 357 neuropsychologic deficits, 357–359 pathophysiology of, 356–357 psychological effects, 359, 361 somnolence syndrome, 359 children’s distress in, 451–452 chronic toxicity from, 436 cognitive effects of, 447–450, 448t–449t effects on intelligence, 447 specific functions, 447–450 digestive tract effects, 384, 385t, 386–387 effects of, on IQ level, 448t for Ewing sarcoma, 178–181 dosage, 178, 179 metastatic disease, 181 technique, 179, 180–181 volume, 178 eye abnormalities caused by cataract, 387, 388, 389 conjunctiva, 390t cornea, 390t eyelids, 380t, 389 lacrimal apparatus, 390t lens, 387, 388–389 optic nerve, 389 orbit, 389 retina, 387, 390t sclera, 390t field placement errors, 426 flank, 283f gastrointestinal system effects, 388t genitourinary system effects, 385t for HBL, 299–301 hearing effects, 389, 392, 393t hematological complications of, 435–436 for Hodgkin lymphoma (HL) complications, 162–164 conformal planning, 158–161 3D-CRT, 159, 160 description, 155 dosage, 161 energy used in, 161 72607_index 7/16/10 8:30 PM Page 465 INDEX IMRT, 159–161 INRT, 158 PET/CT, 158 recurrent disease treated with, 153–155 results, 161–162 sequence, 161 volume, 155–158 immobilization devices, 425–428 acquaplast for, 426–428 mechanical aids for, 425 polyurethane foams, 428 posicast for, 426–428 thermal plastic mask, 426–427, 427f vaccum bags, 428 indications for acute myelogenous leukemia, 20 astrocytomas, 31–34 brainstem gliomas, 75 cerebellar astrocytomas, 78 craniopharyngiomas, 43 desmoid tumors, 253–255, 254t embryonal brain tumors, 40 ependymomas, 68–72, 69t, 71f germ cell tumors, 48–50 low-grade gliomas, 31–34 malignant gliomas, 38–39 medulloblastoma, 56–63 nonrhabdomyosarcoma soft tissue sarcoma, 241–243, 246–251 optic pathway tumors (OPTs), 35–36 pontine gliomas, 75–77 rhabdomyosarcoma, 214–215, 216, 217 spinal cord neoplasms, 81–82 testicular leukemia, 19 Wilms tumor, 282–286 intervention procedures, for reducing distress during interviewing children, 454 interviewing parents, 453–454 overview, 452–453 views of children and parents, 453 juvenile nasopharyngeal angiofibroma, 319–320, 320t Langerhans cell histiocytosis, 337–340, 338t late effects of, 354 nadir, 436 nasopharyngeal carcinoma, 322–323 for neuroblastoma complications, 132–134 dosage, 129–130 hepatomegaly, 125 high-risk disease, 126–127 intermediate-risk disease, 125–126 intraoperative, 130–131 irradiation, 130–131 low-risk disease, 124–125 stage 4S, 125 techniques, 130–131 volume, 128 for non-Hodgkin lymphoma, 170–171 for osteosarcoma Cade technique, 188, 190t dosage, 197, 198 extracorporeal irradiation, 195 lung irradiation, 193–195, 194t photon, 188, 189, 190, 193 prebiopsy, 188 technique, 198 whole-lung irradiation (WLI), 193–195, 194t ovary effects, 376–377, 377t clinical manifestations, 376, 377 pathophysiology of, 376 psychological preparation, 425–426 pulmonary effects, 373–374, 375, 376t clinical manifestations, 373 pathophysiology of, 373 renal effects, 383–384 clinical manifestations, 383–384 pathophysiology of, 383 salivary glands affected by, 392, 393 in sarcoma, 436–437 social effects of, 450, 451t stabilization during devices for, 426 teeth effects, 392, 393, 394t testicular effects description of, 377–378 evaluation of, 382t infertility, 378–379, 380–381 pathophysiology of, 378 reproduction and offspring, 381, 382–383 spermatogenesis, 378–379, 379t, 380–381 for thyroid carcinoma, 315 thyroid gland effects description of, 362 evaluation of, 367t hyperthyroidism, 365–366 hypothryoidism, 365 management of, 366 pathophysiology of, 362, 365 whole-abdomen, 283f whole-lung, 283f Radical nephrectomy, 284 Radioactive plaque, for retinoblastoma, 92–93 Radioiodine ablation (RAI), for thyroid carcinoma, 315 Radioisotope therapy, for osteosarcoma, 201 Radiotherapy (RT) See Radiation therapy RAI See Radioiodine ablation (RAI) Rance, Thomas F., 257 RB1 protein (pRB), 405 REE See Resting energy expenditure (REE) Relative survival rate, 6, 6t, 8t Renal effects, in Wilms tumor, 283t, 287 Renal function, long-term complications of, 283t Renal tumors classifications of, 260t Children’s Oncology Group, 260t international society of pediatric oncology, 260t clear cell sarcoma of the kidney, 262–263, 263f mesoblastic nephroma, 259–260 nephrogenic rests, 260 nodular renal blastemas, 260 percent distribution of, 3t rhabdoid tumor, 262, 262f Wilms tumor, 260–262 Residency programs, 10 Resting energy expenditure (REE), 440 Retina, 387, 391t Retinoblastoma (RB), 406–410 acute leukemia, 408–409 biology, 85–87 bone tumors, 409–410 cerebrospinal fluid (CSF) cytology testing, 88 clinical trials, 106–107 computed tomography (CT) of, 88 diagnosis, 85, 88 differential diagnosis, 88 diffuse plaque-like, 90 endophytic, 89 exophytic, 89, 90 external beam radiotherapy cataracts secondary to, 104 description, 93 dosage, 97–99 lacrimal gland effects, 105–106 metastases treated with, 103 orbital development effects, 104–105 technique, 93–97 465 genetics, 85–87, 87f growth patterns, 89–90 growth repressive action of, 87 histology, 85, 85f, 89 Hodgkin lymphoma, 406–408 incidence, 85 inheritance pattern, 87, 88f late effects, 104 leukocoria, 88, 89, 89f metastases bony, 104 optic nerve involvement, 103 radiation therapy, 103, 104 risk factors, 90 non-Hodgkin lymphoma, 410 orbital extension, 103 in osteosarcoma, 184 overview, 85 percent distribution of, 3t prognostic factors, 88–89 recurrent ocular, 102 orbital, 103 secondary nonocular tumors, 104 treatment chemotherapy, 99–100 cryotherapy, 92 enucleation, 91 exenteration, 91 laser hyperthermia, 92 local therapies, 91 photocoagulation, 91–92 radioactive plaque, 92–93 selection, 91 trilateral, 100, 101–102 Wilms tumor, 409 workup for, 87–88 Retroperitoneal lymph node dissection (RPLND), 218 Retroperitoneal lymph nodes (RPLN), 218 Retroperitoneal rhabdomyosarcoma, 226 Rhabdoid tumor (RTK), of kidney, 259, 262, 262f Rhabdomyosarcoma (RMS), 437 alveolar, 206, 207 biologic findings, 205–206 bladder, 217–218 cervical, 220–221 classification of, 207, 207t clinical features of, 205f clinical presentation of, 206 cytogenetics of, 206 description of, 204 diagnostic evaluation of, 206–207 embryonal, 206, 207 epidemiology of, 204, 205 extremity, 221–222 head and neck, 225–226 hepatobiliary tree, 226–227, 227f metastatic, 228 myogenesis findings, 206 orbital, 224, 225 parameningeal, 222–223 paratesticular, 218, 219–220 perineal, 226, 227f prognostic features, 207–209 prostate gland, 217–218 proto-oncogenes, 206 recurrent, 228 retroperitoneal, 226 risk groups for, 209 site of, 208–209 staging of, 208, 208t treatment of chemotherapy, 212, 213, 214, 222, 228 lymph node dissection, 212 72607_index 7/16/10 8:30 PM Page 466 466 INDEX Rhabdomyosarcoma (RMS) (Continued) principles of, 209, 210 radiation therapy, 214–215, 216, 217 surgery, 210, 212 truncal sites, 226 tumor suppressor genes in, 206 uterus, 220, 221 vaginal, 220 vulvar, 220 Risk adapted therapy, for Hodgkin lymphoma, 151–153 RMS See Rhabdomyosarcoma (RMS) RPLN See Retroperitoneal lymph nodes (RPLN) RPLND See Retroperitoneal lymph node dissection (RPLND) RT See Radiation therapy RTK, of kidney See Rhabdoid tumor (RTK), of kidney Salivary glands, radiation therapy effects on, 392, 393 Salivary gland tumors clinical aspects of, 326 epidemiology of, 326 pathology of, 326 treatment of, 326 Salvage therapy, for LCH, 341 Samarium-153 ethylene diamine tetramethylene phosphonate, 201 “Sanctuary sites,” 12 Sarcomas chondrosarcoma percent distribution of, 3t radiotherapy in, 436–437 Scandinavian Sarcoma Group, 245 Sclera, 390t Scoliosis, 287, 366, 368 SCT See Solid-cystic tumor (SCT) SDS See Standard deviation score (SDS) Second malignant neoplasms (SMN), 286, 397 radiation-induced, 400 Second primary cancers (SPC), 397–413 brain tumors, 412 breast cancer, 410–411 classification of, 397 defined, 397 environmental and lifestyle factors, 405–406 genetic predisposition in, 403–405 DNA repair, 403–404 drug-metabolizing enzyme, 403 incidence of, 397, 397f musculoskeletal tumors, 410 pathogenesis of, 404–405 pathways, 404f prevention strategies, 412–413 relationship between, 398t retinoblastoma, 406–410 acute leukemia, 408–409 bone tumors, 409–410 Hodgkin lymphoma, 406–408 non-Hodgkin lymphoma, 410 Wilms tumor, 409 risk factors for, 397–403 host-related, 398 integral dose, 401t primary diagnosis, 398 therapy-related, 309–403 thyroid cancers, 411–412 type of, 397 SEER See Surveillance, epidemiology, and end results (SEER) program SEER database See Surveillance, epidemiology and end results (SEER) database SEER program See Surveillance, Epidemiology, and End Results (SEER) program Sensorineural hearing loss (SNHL), 389 Serum AFP test, 293–294 SIOP See International Society of Pediatric Oncology (SIOP) SIOPEL-1 trial, 297 Skin therapy, for LCH, 342 Slipped femoral capital epiphysis, 368, 370t 153 Sm, 201 Small bowel neoplasmas, 329 SMN See Second malignant neoplasms (SMN) SMR See Standardized mortality ratio (SMR) SNHL See Sensorineural hearing loss (SNHL) Soft tissue sarcomas, nonrhabdomyosarcoma See Nonrhabdomyosarcoma soft tissue sarcoma Solid-cystic tumor (SCT), 329 Somatomedin-C See Insulin-like growth factor (IGF-1) Somnolence syndrome, 359 Sorafenib, 299 Sorafenib versus Placebo in Advanced Hepatocellular Carcinoma (SHARP), 299 SPC See Second primary cancers (SPC) Spinal cord neoplasms, 78–82 astrocytomas, 79, 79f, 82 characteristics of, 78–79 chemotherapy for, 81 ependymomas, 79, 81 extradural, 78 intradural, 78 magnetic resonance imaging of, 79 primary (intramedullary), 78–79, 79f radiation therapy for, 81–82 dosage, 81–82 technique, 81 volume, 81 surgical treatment of, 80–81 Spinal irradiation, 62f SPNET See Supratentorial primitive neuroectodermal tumor (sPNET) Squamous cell carcinomas, 349–350 St Jude Children’s Research Hospital, 242, 242t Standard deviation score (SDS), for ALL, 361, 361f Standardized mortality ratio (SMR), 287 Standard risk, acute lymphoblastic leukemia, 13, 14 Stem cell transplantion, for Ewing sarcoma, 181 Sturge–Weber syndrome (SWS), 346 Subependymomas, 67 Supraclavicular fossa, right, superficial mass in, 235f Suprasellar germ cell tumors, 45 Supratentorial cranial compartment, 27f Supratentorial primitive neuroectodermal tumor (sPNET), 39 Surgery astrocytomas treated with, 30–31 brainstem gliomas treated with, 74–75 cerebellar astrocytoma treated with, 78 craniopharyngiomas treated with, 41–43 ependymomas treated with, 68, 69t esthesioneuroblastoma (EN) treated with, 325 Ewing sarcoma treated with, 176 germ cell tumors treated with, 46, 48f HBL treated with, 294–296 HCC treated with, 294–296 malignant gliomas treated with, 38 medulloblastoma treated with, 55–56 neuroblastoma treated with, 123–124 nonrhabdomyosarcoma soft tissue sarcoma treated with, 240–241 NRSTS treated with, 240–241 optic pathway tumors treated with, 35 osteosarcoma treated with localized disease, 186–187, 187t metastatic disease, 187–188, 188t rhabdomyosarcoma treated with, 210, 212 spinal cord neoplasms treated with, 80–81 thyroid carcinoma treated with, 315 Wilms tumor treated with, 280, 281–282 Surveillance, Epidemiology, and End Results (SEER) program, 1–5, 230, 290, 397 Survival rates cancer-free, description of, 6t relative, 6, 6t, 8t SWS See Sturge–Weber syndrome (SWS) Synovial sarcoma, 233 T3 See Triiodothyronine (T3) T4 See Thyroxine (T4) Tancytic ependymomas, 67 TBI See Total body irradiation (TBI) Technetium-90m sulfur colloid scan, 293 Tectal plate glioma, 74, 75f Teeth, radiation-induced damage to, 392, 393, 394t Tegmental tumors, 74 TEL-AML1 fusion gene, 13 Teratomas, 303 Testes leukemia of, 19 radiation therapy effects on description of, 377–378 evaluation of, 382t infertility, 378–379, 380–381 pathophysiology of, 378 reproduction and offspring, 381, 382–383 spermatogenesis, 378–379, 379t, 380–381 Testicular boost in total body irradiation, 23 Thalamic astrocytomas, 31 Thallium scintigraphy, for osteosarcoma, 185 Thermodynamic death, 442 Thrombocytopenia, 290 thrombopoietic agents for treatment of, 438 Thyreostimuline (TSH), 315 Thyroid cancers, as SPC, 411–412 Thyroid carcinoma, 314–315, 317 biology of, 315 in children from 11 pediatric series, 316t clinical aspect of, 314–315 epidemiology of, 314 follow-up, 315 histology of, 314 imaging studies, 315 prognostic factor, 315 radiation-associated with children, 317 cancer survivors, 317 Tchernobyl accident, 317 results, 315, 317 risk factors for, 314 treatment of radioiodine ablation, 315 radiotherapy, 315 surgery, 315 TSH suppression, 315 Thyroid gland radiation therapy effects on description of, 362 evaluation of, 367t hyperthyroidism, 365–366 hypothryoidism, 365 management of, 366 pathophysiology of, 362, 365 Thyroid-stimulating hormone (TSH), 365 Thyrotoxicosis, 365 Thyrotropin- releasing hormone (TRH), 365 72607_index 7/16/10 8:30 PM Page 467 INDEX Thyroxine (T4), 365 TNF See Tumor necrosis factor (TNF) TNI See Total nodal irradiation (TNI) TNM See Tumor node metastasis (TNM) TNM staging system See Tumor, node, and metastasis (TNM) staging system “Tolerance dosages,” 354, 355t Topoisomerase II inhibitors, 401 associated AML, 402–403, 402t Total body irradiation (TBI), 440 See also Radiation therapy acute lymphoblastic leukemia treated with, 12, 22–23, 22f dosage of, 23 Ewing sarcoma, 181, 182 techniques for, 22–23, 22f testicular boost in, 23 volume, 22–23 Total nodal irradiation (TNI), 437 Toxicities, Wilms tumor, 286–288 cardiac effects, 284t, 287 growth abnormalities, 287–288, 287t hematologic, 286 hepatotoxicity, 286–287 orthopedic effects, 287 in pregnancy, 284t, 287 renal effects, 283t, 287 treatment-induced neoplasms, 287 T-precursor leukemia, 12 Transarterial chemoembolization (TACE), 301 TRH See Thyrotropin- releasing hormone (TRH) Triiodothyronine (T3), 365 TSH See Thyreostimuline (TSH); Thyroidstimulating hormone (TSH) T stage, medulloblastoma, 55, 55t Tumor, node, and metastasis (TNM) staging system, 208 Tumor necrosis factor (TNF), 440 Tumor node metastasis (TNM), 315 Tumor suppressor genes, 405 in rhabdomyosarcoma, 206 in Wilms tumor, 259 Turcot syndrome, 54 Uber die Nerven der menschlichen Haut, 332 UKCCSG See United Kingdom Children's Cancer Study Group (UKCCSG) Ultrasonography (US) thyroid carcinoma, 315 Wilms tumor, 263 Undifferentiated sarcomas, 234 United Kingdom Children’s Cancer Study Group (UKCCSG), 265 US See Ultrasonography (US) Uterus, rhabdomyosarcoma of, 220, 221 VACA See Vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) Vaccum bags, 428 Vagina rhabdomyosarcoma, 220 brachytherapy plan for, 221f VAI See Vincristine, actinomycin D, and ifosfamide (VAI) Valvular disease, 372, 374t Van Eys stresses, 442 Vascular endothelial growth factor (VEGF), 299, 318 Vascular tumors, 290 VEGF See Vascular endothelial growth factor (VEGF) Ventriculoperitoneal shunts, 56 VI cycles See Vincristine and irinotecan (VI) cycles VIE See Vincristine, ifosfamide, and etoposide (VIE) Vincristine, actinomycin D, and ifosfamide (VAI), 212 Vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA), 243 Vincristine, ifosfamide, and etoposide (VIE), 212 Vincristine and irinotecan (VI) cycles, 213 Vincristine and melphalan (VM), 213 VM See Vincristine and melphalan (VM) Vomitting, 441, 444–446 first-line medications for, 445t Von Recklinghausen, Friedrich Daniel, 233 Von Recklinghausen disease, 233 Vulva rhabdomyosarcoma, 220 WBC See White blood cell (WBC) White blood cell (WBC), 436 WHO See World Health Organization (WHO) Whole-lung irradiation (WLI), 267 for osteosarcoma, 193–195, 194t Will Rogers effect, Wilms, Max, 357 Wilms tumor, 260–262, 409 abdominal, 283 467 anaplastic, 261, 262f bilateral, 283–285 Children’s Oncology Group studies, 271–275 clinical presentation for, 263–264 congenital anomalies associated with, 258 in eastern Nigeria, frequency of, 5t epidemiology of, 258 favorable histology, results for, 259t history of, 257–258, 257f incidence rate of, infant age-specific, 2f International Society of Pediatric Oncology studies, 265, 275–280 metastatic, 285–286 molecular biology findings of, 258–259 National Wilms Tumor Studies findings, 266–271 pathology of, 259–263 pediatric protocols guidelines, 437 percent distribution of, 3t recurrent, 286 signs and symptoms of, 263 staging system for, 264, 265t survival rates, 6t toxicities, 286–288 cardiac effects, 284t, 287 growth abnormalities, 287–288, 287t hematologic, 286 hepatotoxicity, 286–287 orthopedic effects, 287 in pregnancy, 284t, 287 renal effects, 283t, 287 treatment-induced neoplasms, 287 treatment of chemotherapy, 282 radition therapy, 282–286 surgery, 280, 281–282 tumor suppressor genes in, 259 workup for, 263–264 WLI See Whole-lung irradiation (WLI) Wnt/beta-catenin signaling pathway, 294 World Health Organization (WHO), 320, 429 Xeroderma pigmentosa (XP), 349 Xerostomia, 393 XP See Xeroderma pigmentosa (XP) XRCC1 protein role of, 404 Z-score measures, 439 ... Department of Radiation Oncology Centre Léon Bérard Lyon, France Louis S Constine, MD, FASTRO Professor of Radiation Oncology and Pediatrics Section Chief, Pediatric Radiation Oncology Vice Chairman,... impossible Some have proposed eliminating pediatric radiation oncology training from general radiation oncology training By this line of argument, pediatric radiation oncology would become a subspecialty,... 7/19/10 12:14 PM Page i Pediatric Radiation Oncology 72607_FM 7/19/10 12:14 PM Page ii 72607_FM 7/19/10 12:14 PM Page iii F I F T H E D I T I O N Pediatric Radiation Oncology Edward C Halperin,