R. C. S. Pointon (Ed.) The Radiotherapy of Malignant Disease Second Edition With 325 Figures Springer-Verlag London Berlin Heidelberg New York Paris Tokyo Hong Kong R.C.S. Pointon, MA, FRCP, FRCR Former Director of Radiotherapy, Christie Hospital and Holt Radium Institute, Manchester, UK ISBN-13:978-1-4471-3170-0 e-ISBN-13:978-1-4471-3168-7 DOl: 10.1007/978-1-4471-3168-7 British Library Cataloguing in Publication Data Pointon, R.C.S. (Robert Charles Snow), 1923- The radiotherapy of malignant disease. - 2nd ed. 1. Medicine. Radiotherapy I. Title 615.842 ISBN-13:978-1-4471-3170-0 C.I.P. Data available Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers. © Springer-Verlag London Limited 1991 Softcoverreprintof the hardcover 2nd edition 1991 First published 1985 Second edition 1991 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 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. Typeset by Wilmaset, Birkenhead, Wirral 212813830-543210 Printed on acid-free paper Preface to the Second Edition The preface to the first edition continues to provide the rubric for this volume. The essential new elements relate to brachytherapy, viz.: (a) The endorsement of the recommendations of the British Committee on Radiation Units and Measurements (BCRU84) that brachytherapy source strength should be specified in terms of air kerma rate at 1 metre and that the unit used should be the microgray per hour. This recommendation provides a consistent and simple scheme for the use of the Manchester System with any gamma-ray emitting radionuclide. (b) The replacement of radium by caesium-137 at the Christie Hospital and Holt Radium Institute. Some refinements of technique have evolved which are described in the relevant chapters. The essence remains to present techniques and treatments which are practical and tried. To quote Ralston Paterson from his introduction to the first edition of The Treatment of Malignant Disease by Radiotherapy (Edward Arnold, 1948): "The dogmatic presentation should be taken as definiteness of statement not fixity of opinion." Manchester R. C. S. Pointon October 1990 Preface to the First Edition Radiotherapy or radiation therapeutics, as the name suggests, is a branch of general therapeutics. In this case the therapeutic agent is ionising radiation which induces specific and predictable biological changes. Radiotherapy is sometimes described as therapeutic radiology because historically the earliest X-ray machines were used both for diagnostic and therapeutic purposes. Diagnostic radiology has since become a very complex and time-consuming speciality requiring the undivided care and attention of the diagnostic radiologist. Similarly, radiotherapy now embraces both X-ray beams and the radiations from radium and various artifical radium substitutes. This too requires the full-time attention of the radiotherapist. In recent years radiotherapy has sometimes been described as radiotherapeutic oncology, to indicate the involvement of the radiotherapist in oncological management and indeed in all aspects of oncology from prevention and early detection to the treatment, after-care, and (for those who need it) terminal care of the patient. The radiotherapist, by total commitment to the cancer problem, is in truth the epitome of the oncologist. In the same way as the medical physician or internist requires a proper understanding of the pharmacology of the therapeutic agents he or she employs-the nature, metabolic biochemistry, and biological effects of any administered drug-so also the radiotherapist needs to understand the nature, biological effects, and therapeutic potentialities of ionising radiations. The radiotherapist's "pharmacology" involves an understanding of the relevant physics and radiobiology. The first two chapters of this book therefore deal respectively with the physics and the radiobiology of specific relevance to radiotherapy and the radiotherapist's field of work. It might be added that the internist, whilst requiring a thorough understanding of pharmacology, is not expected to be a professional pharmacologist. Similarly a radiotherapist need not be a professional physicist or radiobiologist. An adequate understanding of the scientific basis of radiotherapy is, however, essential. Since radiation therapy is a branch of therapeutics we are concerned not only with the fundamental "mode of action" of ionising radiations but, as with digitalis, morphine, or penicillin, we are concerned with dosage. Dosage of ionising radiations is measured in precise physical terms, and sensitive physical instruments are employed to measure radiation dosage. However, the connotations of the word "dose" are much wider than the simple quantitative measurement of a centigray (the radio therapist's equivalent of a milligram). Time is involved in all dosage systems whatever the nature of the therapeutic agent, but while the correct time internval between individual doses is vital, for example, in the case of insulin for the diabetic patient, it is clearly less vital when giving iron tablets for iron-deficient anaemia. The spacing or "fractionation" of radiation dosage is of considerable importance to the radiotherapist, and so also is the overall time in which a prescribed dose of radiation is given. The possible physical combinations and permutations of dosage (again, as with any drug) are infinite and thus viii Preface we come to employ "courses" of treatment whose biological effects, at a clinical level, have become well-established and predictable. Whereas physics and radiobiology are to the radiotherapist what pharmacology is to the physician, radiotherapeutic technique is the counterpart of the surgeon's operative surgery. The radiotherapist must ensure that the correct dose of radiation reaches the target tissue-usually a malignant tumour. The techniques for achieving this objective can be complex and always require a high degree of geometric precision. Different clinical situations present their own special technical problems, and the radiotherapist must be competent to overcome these problems, since to fail with a malignant lesion usually means the death of the patient. However, just as the surgeon may be compelled to accept that a lesion is technically inoperable, the radiotherapist may at times find a tumour equally beyond effective irradiation. As with all clinical medicine, such decisions are based on experience and clinical judgment. In this respect also the radiotherapist must be in every way as competent a clinician as the physician and the surgeon. Each must have wide general clinical experience as well as a profound knowledge and experience in his specialised field. Since so much of the radiotherapist's work (though not all of it) is concerned with cancer, he cannot know too much about its protean characteristics, its natural history and pathogenesis, its epidemiology, causation, prevention, detection, clinical care and treatment, after-care and rehabilitation, and finally, when necessary, the terminal care of cancer patients. Medicine continues to become increasingly specialised, and this has led to the concept of multi-disciplinary teams concerned with the management and care of patients. However sensible this may seem, we feel it essential that once a decision is made about an appropriate line of treatment, the clinician concerned should then be solely responsible for that phase of the patient's management. So far as the radiotherapist is concerned, once the decision has been taken that irradiation is the appropriate method of treatment, the clinical care of the patient must remain firmly in the hands of the radiotherapist. It may be that surgery or chemotherapy has to precede or follow the irradiation and the patient may at that time pass into the care of a surgeon or a chemotherapist. It is important, therefore, that the radiotherapist must be not only competent but confident and self-reliant. This book is aimed at the radiotherapist in training, but should be of value even to the more experienced radiotherapist by providing practical details of the technical approaches to specific clinical problems. Chapters 1 and 2 are concerned with the "pharmacology" or scientific basis of radiation therapy-physics and radiobiology respectively. It would clearly be out of place to attempt here an exhaustive account of these two subjects, and many complete textbooks are already available for the reader who requires them. Only the most clinically relevant and important aspects of physics and radiobiology are presented here, providing a background to what follows. Chapter 3 likewise provides a general outline of chemotherapy for malignant disease, concerned with principles rather than practice, though the latter is introduced where and when necessary in the subsequent chapters on practical radiotherapy. Many radiotherapists around the world are inescapably involved in adjuvant hormone treatment and chemo therapy, and an understanding of the scope and limitations of the agents involved is therefore essential. This, of course, is a rapidly changing field of medicine, characterised also by many extravagant claims of high success which further experience fails to confirm. We have, therefore, confined ourselves throughout this book to general commentaries and recommendations based on acceptable chemotherapeutic practice for the 19808. In chapter 4 an account is given of the functions of a mould room, one of the nerve centres of a radiotherapy department. The technical staff of the mould room work in close collaboration with the radiotherapists in preparing a variety of precision-made applicators essential for the accurate treatment of many kinds of cancer. But the preparation of a surface mould or a beam-direction shell cannot be learned from the written word alone, Preface ix however detailed and lucid the description. This is a practical task requiring much experience and meticulous care. Before embarking on the main part of the text (chapters 6-18), some general principles of radiation therapy are discussed in chapter 5, to draw attention to what we regard as the fundamental clinical considerations in this field, some of which represent indeed the very essence of the Manchester school of thought. The previous two textbooks from this hospital (Ralston Paterson, 1947 and 1963) were deliberately designed to discuss in detail how to treat, by X-rays and radium, malignant tumours in various anatomical sites. This third textbook has the same principal objective and we have endeavoured to provide practical guidance on how the radiotherapist can plan and execute a satisfactory technique for irradiating those lesions for which this kind of treatment is considered clinically appropriate. We have deliberately confined ourselves to describing "how it is done" at this hospital, and in a didactic fashion. We are, of course, conscious of widely differing practices around the world, and even surprisingly divergent opinions on basic principles. No one textbook could adequately present all these views, even in general terms, and ours is therefore unashamedly a Manchester book. We do, however, have statistical grounds for believing that our survival and cure rates are at least encouraging, at best excellent, and this book tries to show how these results can be achieved. Some readers may be surprised that we do not discuss the treatment of some tumours which they are themselves called upon to treat. Examples of this are cancer of the stomach or of the pancreas. It has been our experience over five decades that these tumours (and others) do not lend themselves to curative irradiation, and palliative radiotherapy is in our view likely to create more problems than it solves. This does not mean that were some new, as yet unforeseen development to present itself we would not eagerly re-examine our established attitudes. At the moment, however, the contributions presented in chapters 6-18 must remain our testament of faith. The editors would like first to acknowledge their profound indebtedness to Mrs. Elsa Hughes and Miss Joan Moores for their labours, over many months, to prepare the typescripts for this book. They are also indebted to Mr. Richard Schofield and the staff of the Department of Medical Illustration for their painstaking work to provide the many illustrations, graphs, and photographs. They are grateful, too, to those colleagues who, in spite of heavy clinical committments, were willing to bum the midnight oil in order to contribute their chapters to this work. Finally, the editors are acutely aware of the vital collaborative involvement of many colleagues in other disciplines, all contributing in their special ways to the dynamic life of the hospital. They are too numerous to mention by name but to all of them we owe a deep debt of gratitude. Manchester, 1984 Eric C. Easson R. C. S. Pointon Contents List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii 1 Physics P. C. Williams, J. M. Wilkinson and H. NottIey .................................... 1 2 Applied Radiobiology M. L. Sutton and J. H. Hendry.......................................................... 33 3 Principles of Chemotherapy P. M. Wilkinson ............................................................................. 57 4 Mould Room Practice R. C. S. Pointon and D. Studd ... ............ ........ ..... ............. ................. 81 5 General Principles of Radiotherapy E. C. Easson..... ... ......... ...... ............. .......... .............. ...................... 111 6 Skin E. Allan ........................................................................................ 131 7 Head and Neck M. B. Duthie, N. K. Gupta and R. C. S. Pointon .................................. 145 8 Adult Central Nervous System M. L. Sutton .................................................................................. 207 9 Lung, Oesophagus and Thymus R. Stout ........................................................................................ 235 10 Breast G. G. Ribeiro ................................................................................ 255 11 Female Genital Tract R. D. Hunter ........... ................ ......... ......... ...... ...... .......... .............. 279 12 Genitourinary Tract R. C. S. Pointon ............................................................................. 309 13 Testis G. Read ........................................................................................ 329 14 Malignant Lymphomas (including Myeloproliferative Disorders) I. D. H. Todd and A. L. Stewart ....................................................... 349 Total Body Irradiation as a Preparation for Bone Marrow Transplantation D. P. Deakin ................................................................................ .380 xii Contents 15 Soft Tissues and Bone D. P. Deakin ................................................................................. 385 16 Paediatric Radiotherapy G. Rao Gattamaneni and D. Pearson .................................................. 403 17 Gastrointestinal Tract R. D. James ............ ............ .......... ....... ....... ....... ..... ....... ...... ....... ... 435 18 Clinical Trial Methods M. K. Palmer and R. Swindell ........................................................... 443 Appendix 1 Physical Data ....................................................................... 461 Appendix 2 Clinical Staging .................................................................... 465 Subject Index ......................................................................................... 473 Contributors . All the contributors are current or former members of the Christie Hospital and Holt Radium Institute staff. E. Allan, FRCS, FRCR D. Pearson, MB, ChB, FRCR D.P.Dewon,MB,ChB,FRCR R. C. S. Pointon, MA, FRCP, FRCR M. B. Duthie, BSc, MB, ChB, FRCR G. Read, MA, MRCP, FRCR E. C. Easson, CBE, MSc, MD, FRCP, G. G. Ribeiro, MB, BCh, FRCR FRCR A. L. Stewart, MD, FRCR G. Rao Gattamaneni,MD, FRCR R. Stout, MRCP, FRCR N. K. Gupta, MB, BS, FRCR D. Studd, FBIST J. H. Hendry, BSc, MSc, PhD M. L. Sutton, MA, MRCP, FRCR R. D. Hunter, MB, ChB, MRCP, FRCR R. Swindell, MSc, FSS R. D. James, MA, MB, BCh, MRCP, I. D. H. Todd, FRCP, FRCR FRCR J. M. Wilkinson, MSc H. Nottley, MSc P. M. Wilkinson, MSc, MB, ChB, FRCP M. K. Palmer, BSc, PhD, FSS P. C. Williams, PhD