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Radiation Oncology: Radiobiological and Physiological Perspectives: The boundary-zone between clinical radiotherapy and fundamental radiobiology and physiology PDF

676 Pages·1990·25.902 MB·English
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RADIATION ONCOLOGY: RADIOBIOLOGICAL AND PHYSIOLOGICAL PERSPECTIVES Developments in Oncology Volume 60 Radiation Oncology: Radiobiological and Physiological Perspectives The boundary-zone between clinical radiotherapy and fundamental radiobiology and physiology by Hassan K. Awwad National Cancer Institute. University of Cairo. Cairo. Egypt SPRINGER-SCIENCE+BUSINESS MEDIA, B.V. Library of Congress Calaloging in Publication Data Awwad. Hassan K. Radli!ltlon oncology ri.'ldlob101og1cal and phYS10logical perspectlvliIS the baundary-zone bet,.-een cllnlcal radlotherapy and fundallental radloblo1ogy and pl'lyslology I by Hassan K. Awwad. p. CII. -- <DBvelopaents In oncology ; 60) ISBN 978-94-015-7867-7 ISBN 978-94-015-7865-3 (eBook) DOI 10.1007/978-94-015-7865-3 1. Cancer--RldlothlrIPY. 1. Tlt1e. II. Ser les, [DNLM: 1. Dose-Response Re hit lonsh IP. Radlatlon. 2. Neoplasms- -radlDtheraphy. 3. Radlatlan Effects. 4. Radlatlan InJurles. Wl DE998N v. 60 I az 269 A967r J RC271 ,R3A98 1990 616,99' 40642--dc20 DNLM I DLC for L Ibrary of Congress 90-4471 ISBN 978-94-015-7867-7 Primed on acid-free paper Ali Rights Reserved C 1990 by Springer Science+Business Media Oordrecht Originally published by Kluwer Academic Publishers in 1990 Sofu:over reprint oft he hardcover 1s t edition 1990 No pari of the material protected by this copyright nolice may be reproduced or utilized in any form Of by any means, electronic or mechanical, including photocopying, reconling Of by any information storage and retrieval system, without written permission from the copyright owner, CONTENTS Foreword by G. W. Barendsen vii Foreword by H. Suit ix Preface xi Acknowledgements xiii Part I. Development of Radiation Damage from the Initial Physical Events to the Expression of the Clinical Response Chapter 1.1 The Overall Radiobiological Effect: the Evolution of Radiation Damage 3 Part II. Measurement of Reproductive Cell Death Modification of the Radiation-response by some Intrinsic and Extrinsic Factors Chapter II. I Dose Survival Relationships: Methodology, Forms, and Interpretations 19 Chapter II.2 Some Modifiers of Dose-response Relationships 53 Chapter 11.3 Interaction of Radiation and Chemotherapeutic Agents 85 Part III. Radiation-induced Normal Tissue Damage: General Principles and Specific Examples Chapter III. 1 Radiation Effects on Normal Tissues: General Principles 109 Chapter III.2 Dose-time-volume Relationships in Normal Tissue Response to Irradiation 129 Chapter I1I.3 Early Reacting Tissues: Skin 189 Chapter IlIA Early Reacting Tissues: the Haematopoietic Tissue 223 Chapter I1I.5 Early Reacting Tissues: the Lymphoid Tissue and the Immune Systems 247 Chapter 111.6 Early Reacting Tissues: the Digestive Tract 291 Chapter III.7 Early Reacting Tissues: the Testes 323 Chapter III. 8 Radiation Effects on the Ovary: a Nonrenewal System 345 Chapter I1I.9 Late Reacting Tissues: Radiation-induced Lung Damage 357 Chapter III. I 0 Late Reacting Tissues: the Urinary Tract 395 Chapter III. 1 1 Late Reacting Normal Tissues: Radiation-induced Liver Damage 421 vi CONTENTS Chapter m.12 Late Reacting Tissues: Radiation-induced Damage to the Central Nervous System 429 Chapter m.13 Late Reacting Tissues: Radiation-induced Heart Disease 449 Part IV. Radiation Response of Tumours Chapter IV. 1 Tumour Growth: Organization of Tumour Proliferative Activity 459 Chapter IV.2 Tumour Growth: Patterns, Parameters and Measurement 473 Chapter IV.3 Analysis of the Growth Parameters of Human Tumours: Oinicallmplications 493 Chapter IV.4 Tumour Radiation Response: A. Response to a Single Dose 529 Chapter IV.5 Tumour Radiation Response: B. Response to Multifraction and Protracted Low Dose Rate Irradiation 541 Chapter IV.6 Hypoxia in Solid Tumours and Normal Tissues: Clinical Implications 593 Chapter IV.7 Estimates of the Outcome of Radiotherapy. Accuracy requirements 647 Index 667 FOREWORD During the past four decades knowledge about biological effects of ionizing radiations on mammalian cells, normal tissues and tumours has increased enormously and has enabled radiotherapists to obtain a better insight into the advantages and disadvantages of cancer treatments with modified regimens of irradiations and combinations with chemotherapeutic agents. Even for the older scientists and clinicians who have wit nessed all these developments and have contributed to the vast amount of information, it is difficult to integrate this knowledge and to apply it in their daily work. For younger workers it is often difficult to select the important main concepts and results from the overwhelming number of publications. It is evident that a book which provides an integrated view of basic and applied radiation oncology can be of great value to students, scientists and, most importantly, to clinicians who can devote only part of their time to the task of understanding the radiobiological background of their application of radiation in cancer treatment. This book "Radiation Oncology" is written by a radiotherapist who has for a long time participated in the integration of basic knowledge and clinical experience. He has selected radiobiological information which is considered important to radiotherapy and in the description and interpretation of normal tissue tolerance and tumour eradication probability, he illustrates how basic knowledge can be applied clinically. To achieve this aim the development of radiation damage to the proliferative capacity of cells is described as the underlying basis of the pathogenesis in most normal tissues. It is shown that this applies to early as well as late reacting normal tissues. The radiobiologist will find in these chapters a wealth of information on clinically based observations, which will allow him to judge whether his hypotheses, always involving simplifications based on experimental systems, are adequate to explain the complex responses to irradation of primary tumours and different tissue. In addition to effects of dose, dose fractionation, dose rate and tissue conditions, the topic of volume effects, including cellular migration and spatial tissue organisation are among the important subjects discussed. Examples are the description of pathogenesis of damage to bowel, kidney etc. For the radiotherapist sufficient information on cellular dose response curves and mechanisms is given to enable the assessment of the influence of various radiobiologi cal factors on clinical responses. An important part is the discussion of radiotherapy in combination with chemotherapy. Also of great interest is the discussion of the influence of uncertainties in various parameters on the clinically observed responses. As noted earlier, important progress has been made in the understanding of the significance of differences in intrinsic sensitivity of cells from tumours as well as from normal tissues, and of modifying factors in the final outcome of cancer treatments. Important further developments will undoubtedly be pursued in the coming years, but a first important task of the present generation of radiotherapists and radiobiologists is to vii viii FOREWORD integrate and dissiminate the infOimation obtained up till the present time. This book will contribute to this aim and thus enhance the optimal application of ionizing radiation in the treatment of patients. G. W. BARENDSEN Amsterdam May, 1990 FOREWORD This represents the most comprehensive single author book on the subject of radiation biology to have appeared. That the book provides useful and appropriately detailed discussion over such a broad field by one individual gives to the work a unity and clarity that is usually absent in the standard multi-author books. Although there is some inevitable variation in the depth of coverage of the various subjects as a consequence of a single author, the total result is quite impressive. The text does read easily. The coverage extends from the biophysical events of the interactions of the radiation particles with the atoms and molecules of the target through to a discussion of the requirements for accuracy in the actual administration of the radiation. The organiza tional structure is attractive in providing a brief summary of the principal points to be rnade at the beginning of the chapter. This text should be of interest and value to the young physicians in education programs and to practicing clinicians. Dr. Awwad is a highly respected physician/scientist on the international scene. He regularly contributes to and participates in congresses and symposia. He is a very busy clinician and directs the well regarded radiation therapy program at the University of Cairo. HERMAN SUIT Boston May, 1990 ix PREFACE An optimum complication-free tumour control is a cardinal principle in modem radiotherapy. With this principle as a broad background, this book is meant to cover two main domains: the radiobiological processes underlying the current radiotherapy practice and the potential exploitation of radiobiological principles for better cancer treatment. For this we need to identify and scrutinize the "boundary-zone" between fundamental radiobiology and radiotherapeutic oncology. This book is addressed to readers from a number of disciplines involved in cancer treatment and related research. For the practicing radiotherapist the main focus would be the basic mechanisms related to the genesis and progression of the clinical syndromes resulting from normal tissue damage, the radiobiological and physiological bases of the tests used for the diagnosis and measurement of such damage as well as the radiobiological aspects of radiocurability of human cancer. The practicing radiotherapist is directly involved in such practical problems as the possibility of expressing isoeffec tive doses in terms of clinically relevant models together with the limitations of such models. He would also be concerned with the fundamental processes underlying such complex clinical issues as the volume effect, re-irradiation of recurrent tumours and the combined use of chemotherapy and radiotherapy. For the radiotherapist engaged in clinical research and trials, the radiobiological processes implicated in unconventional fractionation, the oxygen effect and measurement of tumour growth and its clinical relevance assume special importance. The fundamental processes associated with the dose-rate effect and their implications for brachytherapy, the basic mechanisms in the radiotherapy-chemotherapy interaction and the immunological perturbations induced by irradiation are receiving increasing attention in clinical research. This book is addressed also to the radiobiologist with interest in cancer treatment research. For him the emphasis would be on the development of experimental models for clinical problems and the validation of theoretical models using clinical observations and measurements. Diagnostic imaging techniques are increasingly used for the diagnosis and measure ment of radiation-related normal tissue damage. The radiobiological and physiological interpretation of the information acquired through imaging procedures should be of value in diagnostic radiology and nuclear medicine. The biological consequences of the physical dose distribution in brachytherapy and the impact of uncertainties in the physical dose delivery on the outcome of external beam radiotherapy should be of concern to the radiotherapy physicist particularly in relation to quality assurance programmes. Some comments have to be made as to the general format of the book. First: an extended summary is given at the beginning of each chapter as a guide to the material covered. Second: for the sake of uninterrupted reading and within practical limitations, each chapter is set as an independent treatise with as little cross-reference as is practical xi

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