Table Of ContentRADIATION 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
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