Cancer in Children: Clinical Management PDF
Preview Cancer in Children: Clinical Management
International Union Against Cancer Treatment and Rehabilitation Programme Chairman: Ismail Elsebai Project on Current Treatment of Cancer Ismail Elsebai, Chairman H. Julian G. Bloom· Ian Burn· Folke Edsmyrt . Roberto A. Estevez Joseph Fortner· Barth Hoogstraten Coordinating Editor of this volume: H. Julian G. Bloom The series Current Treatment of Cancer consists of the following 10 volumes: Cancer in Children, 2nd edition (1986) Hematologic Malignancies (1986) Breast Cancer and Gynecological Tumours Urogenital Tumours' Cancer of the Digestive Tract Lung Tumours Skin, Soft Tissue and Bone Tumours Head and Neck Tumours Brain and Endocrine Tumours General Principles of Oncology Cancer in Children Clinical Management Second Revised and Enlarged Edition Edited by P. A. Voute A. Barrett H. J. G. Bloom J. Lemerle M. K. Neidhardt With 118 Figures Springer-Verlag Berlin Heidelberg New York Tokyo DICC, Rue du Conseil-General 3, CH-1205 Geneva Editors: Jean Lemerle Service de Pediatrie Institut Gustave Roussy Rue Camille Desmoulins F-94805 Villejuif Cedex Ann Barrett France Department of Radiotherapy Glasgow Institute of Malte K. Neidhardt Radiotherapeutics and Oncology Krankenhauszweckverband Augsburg Western Infirmary I. Kinderklinik GB-Glasgow GIl 6NT StenglinstraBe England D-8900 Augsburg FRG H. Julian G. Bloom Paul A. Vm Ite The Royal Marsden Hospital Department of Radiotherapy Department of Paediatric Oncology and Oncology Emma Kinderziekenhuis Downs Road Spinozastraat 51 GB-Sutton, Surrey SM2 5PT NL-I018 HJ Amsterdam England The Netherlands TSBN-13: 978-3-540-15342-9 Springer-Verlag Berlin Heidelberg New York Tokyo ISBN-13: 978-3-540-15342-9 Springer-Verlag New York Heidelberg Berlin Tokyo ISBN-13: 978-3-540-15342-9 e-ISBN-13: 978-3-642-96889-1 DOl: 10.1007/978-3-642-96889-1 Library of Congress Cataloging in Publication Data Cancer in children. "International Union against Cancer" - P. facing t. p. Includes bibliographies and index. 1. Tumors in children. I. Voute, P. A. (Paul Antoine), 1906- . II. International Union against Cancer. [DNLM: Neoplasms - in infancy & childhood. QZ 200 C21519] RC281.C4C37 1986 618.92'994 86-3991 [SBN-13: 978-3-540-[5342-9 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law where copies are made for other than private use a fee is payable to ,.Verwertungsgesell schaft Wort", Munich. ~! Springer-Verlag Berlin Heidelberg 1975 and 1986 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Typesetting and printing: Oscar Brandstetter GmbH & Co. KG, Wiesbaden Bookbinding: J. Schaffer OHG, Grilnstadt 2121/3140-543210 Members of the Project Current Treatment of Cancer H. Julian G. Bloom Ismail Elsebai The Royal Marsden Hospital National Cancer Institute Cairo Department of Radiotherapy Kasr El-Aini Street and Oncology Cairo, Egypt Downs Road GB-Sutton, Surrey SM2 5PT Roberto A. Estevez England Facultad de Medicina del Salvador Catedra de Oncologia Clinica Ian Burn Avenida Santa Fe 5089 9-20 British Association 1425 Buenos Aires, Argentina of Surgical Oncology Charing Cross Hospital Joseph Fortner Fulham Palace Road Memorial Sloan-Kettering GB-London W6 8RF Cancer Center England York Avenue 1275 Folke Edsmyrt New York, NY 10021, USA Department of Urological Oncology Barth Hoogstraten Karolinska Sjukhuset Radiumhemmet Cancer Treatment Center P.O. Box 60500 Bethesda Hospital S-10401 Stockholm Oak Street 629, Suite 409 Sweden Cincinnati, OH 45206, USA v Foreword Cancer in Children is the first volume in this new series, sponsored by the DICC, on the treatment of cancer. The editors and authors feel strongly that more standardization is needed on a worldwide basis in cancer therapy. This, of course, is only possible if experts from all countries subscribe to a joint policy of making their treatment designs available to practising oncologists all over the world. Current Treatment of Cancer will discuss all the equipment and methods now in use in cancer therapy. It will cover all types of cancer, thus providing the reader with comprehensive information on cancer manage ment. The appearance of a book on paediatric oncology as the first in the series is intentional: in recent decades there has been a tremendous improvement in the treatment of cancer in children, and there is hope for even further success in this fight. We are convinced that this book and the series it is introducing will help us to make a concerted response to the challenge of cancer. DICC Treatment and Rehabilitation Programme Ismail Elsebai Chairman VII Preface Since the publication of the first edition ten years ago extraordinary progress has been made in paediatric oncology. The 1975 edition reflected the clinical and laboratory research that had gone on over the previous 30 years. In the Preface the editors pleaded for the mUltidisciplinary approach to the management of childhood cancer and for referral to centres where teams of specialists experienced in the management of children with cancer were to be found. Those recommendations were based on the improved survival rates recorded by such centres for Wilms' tumour, brain tumours, rhabdomyosarcoma, Ewing's sarcoma, retino blastoma, lymphoma and "even" leukaemia. The chapter on leukaemia discussed prolongation of complete remission as a result of total therapy in acute lymphoblastic leukaemia, but did not use the word "cure". The really staggering advances in the 10 years between the first and the present editions are manifested, in many ways. Clinical management is marked by the growth of specialized centres for children with cancer, multidisciplinary care, and collaborative clinical studies. All of these have now become the current norm for paediatric oncology. In the United States 70%-75% of children with cancer are treated according to a na tional study protocol. Understanding of childhood cancer has improved materially. It is now well recognized that diseases originally consid ered to be single entities, such as acute lymphocytic leukaemia (ALL) and neuroblastoma, encompass spectra of conditions with different prognoses requiring differing treatment strategies. Thus, it is known that children with localized neuroblastoma and other favourable prognostic factors need no further treatment following surgery. A high proportion of children with low white count L1lymphocytic leukaemia can be expected to be cured with what would have been considered minimal treatment when the first edition was published. At the other end of the treatment spectrum, even very aggressive therapies, such as the Berlin, Frankfurt, Muenster (BFM) regimen for ALL with unfavourable prognosis and bone marrow transplantation (BMT) for stage IV neuroblastoma, are in sufficient to cure the majority of high-risk patients, and entirely new therapies are being evolved to cope with these problems. The prognostic factors used in defining outcome include histological appearance, as exemplified by the favourable and unfavourable types of Wilms'. tumour, biological parameters, such as serum ferritin and neurone-specific enolase levels in patients with neuroblastoma, and the cell morphology of lymphoblasts in lymphocytic leukaemia. Thus, children can be grouped according to the expected outcome, and treatment can be modulated according to the risk. The objectives of these IX studies are to determine how little treatment is needed to cure the patient at low risk and how much more can be given without prohibitive toxicity to those patients whose expectation of survival is very low. Modulation of treatment depends on an accurate definition of prognosis, and this depends among other things on precision in establishing the extent of disease. Here, too, astounding advances have been made through modern imaging methods. Ultrasonography has achieved a precision hitherto unknown. Computer-assisted tomography, a rarity if not a curiosity 10 years ago, is now widely available. Magnetic resonance imaging (MRI) is just entering the diagnostic armamentarium, with images that are astonishing in their detail and precision. Normal and abnormal anatomy is displayed without any radiation exposure or the need for invasive procedures. Moreover, MRI techniques can be used to provide evidence ofin vivo biochemistry. 31 P-NMR has been used to assay the metabolic activity of neuroblastoma, with changes in signal amplitude correlating with progression or regression, whether spontaneous or after therapy. This new type of image is especially intriguing, and will surely be developed to the point that changes in therapy will be based on the results of such studies. Another factor of increasing importance as cure rates ciimb is the late adverse consequences of treatment. In the 1990s one in a thousand young adults aged 20 will have been cured of childhood cancer, an incidence which is higher than that for paralytic polio in the 1950s. Not only do paediatric oncologists have the responsibility of curing patients; it is also their duty to ensure that patients survive as healthy young adults. If the advances in the clinic in the past 10 years have been outstanding, those in the laboratory have been no less extraordinary. As in the clinical sphere, the malignant diseases of childhood have provided the basis for many advances in molecular biology and biological response modifiers. For years people spoke loosely about the "immune response" in patients with cancer, but it was not clear that anything of the kind actually occurred, or if it did, what the nature of this response might be. With the aid of cell sorters and hybridoma technology, it is now possible to study the functions of the various subpopulations of lymphocytes as they apply to the problems of the malignant disease of childhood. Knowledge in this area may help us to understand the basic mechanisms of lymphocyte proliferative disorders and provide clues as to how the immune response might be manipulated for the patient's benefit. Interferon, tumor necrosis factor and monoclonal antibodies are being used alone or in conjunction with more traditional therapies to increase the therapeutic effect. Physical agents such as neutron beams and hyperthermia are being explored in early human trials. Standard radionuclides such as 1251, 1311 and 206Bi are being used in novel ways to "target" the irradiation; for example, by attachment to monoclonal antJ.bodies or chemicals such as metaiodobenzyl guanidine (MIBG) to limit the radioactive dose to the tumour cell population alone. MIBG is a compound metabolized by tumours of the sympathetic nervous system, and its attachment to a radio nuclide allows it to be used for both diagnostic scans and therapy. x Most important of all are the strides that have been taken in the genetics of childhood cancer. These include the results of research ranging from epidemiological studies to chromosomal morphology and micromolecu lar genetics. Our understanding of the pathogenesis of Wilms' tumour, rhabdomyosarcoma, retinoblastoma, neuroblastoma and leukaemia has been advanced through these investigations. The future of research in this field holds great promise. One can say with confidence that the nature of the malignant transformation process will shortly be clarified for some of the cancers of childhood. In addition, the presence of oncogenes in the cells, either normal or cancerous, will serve to identify high-risk patients. The progress made in morphological and molecular genetics is especially promising and can be exemplified by the neuroblastoma. The homoge nously staining regions seen in the chromosomes of children with the aggressive forms of neuroblastoma are now known to be associated with the expansion ofN-myc, a human cellular DNA sequence related to the C myc proto-oncogenes. Its expression can thus be related to prognosis at diagnosis and after primary management, since its amount increases in relapse. The first clinical applications of molecular genetics to the management of human cancer will probably come in paediatric tumours. Retinoic acid is effective in regulating N-myc expression and can cause maturation of neuroblastoma cells in culture. The maturation of neuro blastoma is seen clinically, though rarely; the discovery of therapeutic agents to bring this about could be a great advance. What of the future? It is of interest to speculate on the contents of the preface to the third edition. Where will the next few years carry the field of paediatric oncology? I would like to think that many cancers of childhood will have their appropriate targeted therapy for maximum therapeutic effect and minimum side effects, that our understanding of the cause or causes of malignant transformation through molecular genetics will be much clearer, and that clues from the laboratory will suggest ways in which the disease might be prevented in susceptible populations or made to mature if not disappear in children who develop cancer. Audrey E. Evans Division of Oncology The Children's Hospital of Philadelphia 34th & Civic Center Blvd. Philadelphia, PA 19104 XI Contents General Chapters 1. Aetiology and Epidemiology R. W. Miller . . . . . . . 3 2. Oncogenes and Chromosomal Aberrations A. Hagemeijer and D. Bootsma . . 9 3. Pharmacology of Cytostatic Drugs J. G. McVie and J. de Kraker . 17 4. Chemotherapy D. Olive and M. Peeters . . 21 5. Radiation Therapy R. Sandland and A. Barrett . 36 6. Surgical Oncology in Children J. Plaschkes 46 7. Supportive Care P.J.Moe .... 54 8. Infections in Children with Malignant Disease W. T. Hughes. . . . . . . . . . 60 9. Delayed Consequences of Therapy A. T. Meadows and J. Silber . . . 70 10. Clinical Trials and Cooperative Studies J. Michaelis. . . . . . . . . 82 11. Paediatric Imaging S. T. Meller and J. E. Husband 89 Special Chapters 12. Acute Lymphoblastic Leukaemia H. Riehm, H.-J. Feickert, and F. Lampert 101 13. Acute Non-Lymphoblastic Leukaemia M. L. N. Willoughby. . . . . . . . 119 14. Chronic Leukaemia G. Schaison and H. Castro-Malaspina 131 15. Malignant B Cell Lymphoma of Childhood J. Lemerle, A. Bernard, C. Patte, and J. K. Plo 137 16. Malignant T Cell and Other Non-Hodgkin's Lymphoma M. D. Amylon, M. P. Link, and S. B. Murphy 152 17. Hodgkin's Disease S. S. Donaldson. . . . . . . . . . . . . . 164 XIII
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