Heavy Particle Radiotherapy

506 Pages·1980·5.675 MB·English

by  M. Raju (Auth.)

HEAVY PARTICLE
RADIOTHERAPY
M. R. Raju
Life Sciences Division
Los Alamos Scientific Laboratory
University of California
Los Alamos, New Mexico
ACADEMIC PRESS 1980
A Subsidiary of Harcourt Brace Jovanovich, Publishers
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COPYRIGHT © 1980, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED.
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ACADEMIC PRESS, INC.
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United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
24/28 Oval Road, London NW1 7DX
Library of Congress Cataloging in Publication Data
Raju, M. R.
Heavy particle radiotherapy.
Includes index.
1. Heavy particles (Nuclear physics)—Physiological
effect. 2. Radiobiology. 3. Heavy particles (Nuclear
physics)—Therapeutic use. I. Title.
QP82.2.H45R34 615.8'42 79-27459
ISBN 0-12-576250-X
PRINTED IN THE UNITED STATES OF AMERICA
80 81 82 83 9 8 7 6 5 4 3 2 1
/ dedicate this book to my dear wife Subhadra Devi Raju, who has provided
an ideal home atmosphere all these years and especially during this writing.
FOREWORD
Dr. Raju is well known as a nuclear physicist turned radiobiologist. In the 1960s,
he made early contributions to the measurement and dosimetry of negative pion
beams. He became interested in the biological effects of this type of densely ioniz­
ing radiation and introduced biological systems into beams of pions and accelerated
helium nuclei. His results to date provide the most comprehensive set of biological
data available for assessing the potential value of pions in the treatment of human
cancer. He has extended this biological work into fundamental investigations of the
effects of lightly and densely ionizing radiation on mammalian cells. He is at pres­
ent working in the same field of radiobiology at the Los Alamos Scientific Labora­
tory! in Los Alamos, New Mexico.
I have read this book with unusually great pleasure, largely because of the clarity
of the writing. Dr. Raju has reviewed an enormous amount of work, including his
own major contributions to the field, but has described each aspect lucidly and with
remarkable balance. One is never in doubt about the details of experimental work
described, yet the details do not obtrude. That is why the book is so satisfying and,
more, it is enjoyable to read.
Most of the contents should be quite understandable to any scientist interested in
medicine, biology, physics, and associated subjects. It is an achievement to write
such a broadly interesting book without leaving gaps or making false impressions
through brevity. This book should become a standard text for heavy particle treat­
ment of cancer for many years.
My pleasure in this book is also enhanced because the author, like me, is a
physicist turned biologist. We have both obtained great interest and pleasure in
attempting to bring the quantitative approach of physics to bear on the field of
radiation biology applied to radiotherapy, with all its conditional probabilities.
Up to the present time, each advance in physical dose distribution has led to
improvements in the treatment of cancer at certain sites in the body. It would be
foolish to deny historical extrapolation. Thus, the particle beams that provide
superb dose patterns are very likely to give better results: protons, helium particles,
negative pi mesons, and heavier particles. At the same time, other advantages of
densely ionizing beams are beginning to be realized: a reduction of the problem of
radioresistant hypoxic cells in tumours; possibly differential repair in cells; possibly
differences in cell age radiosensitivity. Thus, neutron beams might give advantages
over present-day supervoltage therapy, but we shall not know for certain for several
years. If they do, then pions, helium nuclei, and heavier accelerated particles would
share these advantages.
Hence, protons represent the purely physical advantages, whereas neutrons rep­
resent the purely radiation-quality advantages. It is satisfactory that clinical work
has already begun using both modalities so that, if improved results are obtained
with beams of pions and heavy nuclear particles, we may learn which component
contributes most. Perhaps they both will.
ix
X Foreword
This field of work is a particularly good one for international collaboration. There
has always been excellent collaboration and sharing of information across the fron­
tiers of geography as well as of physics, biology, and medicine. Dr. Raju's book
will help this collaboration to continue,
Jack F. Fowler, D.Sc, Ph.D., F.Inst.P.
Director
Gray Laboratory of the Cancer Research Campaign
Mount Vernon Hospital
Northwood, Middlesex
England
ACKNOWLEDGMENTS
I am very grateful to the late Professor Swami Jnanananda for his spiritual and
nuclear physics guidance during my D.Sc. program in Nuclear Physics at Andhra
University, Waltair, India. I am indebted also to Drs. G. L. Brownell and J. H.
Lawrence for providing the opportunity for me to pursue research in the United
States in the field of heavy particle dosimetry and radiobiology. I acknowledge the
research support from the following agencies: the United States Department of
Energy (formerly the Atomic Energy Commission and the Energy Research and
Development Administration), the National Cancer Institute, the American Cancer
Society, and the Office of Naval Research. I am grateful also to the Los Alamos
Scientific Laboratory for its support, encouragement, and permission to write this
book and to use pertinent figures. I thank Mr. Charles I. Mitchell for technical
editing. I am deeply indebted to Mrs. Elizabeth M. Sullivan for her very careful and
meticulous work in editing and typing this manuscript. I am very grateful to Profes­
sor J. F. Fowler for writing the foreword and for his encouragement and many
suggestions for improvement of the manuscript. I am also grateful to Drs. D. K.
Bewley, G. W. Barendsen, E. Epp, J. P. Geraci, E. J. Hall, T. S. Johnson, H. S.
Kaplan, J. T. Lyman, G. F. Whitmore, N. Tokita, and R. A. Walters for their
general comments on improving the book; and to Drs. E. A. Blakely, J. Castro, A.
Chatterjee, S. B. Curtis, J. D. Chapman, J. F. Dicello, M. Goitein, L. S. Gold­
stein, S. Graffman, J. Howard, D. H. Hussey, A. M. Koehler, B. Larsson, J. A.
Linfoot, L. J. Peters, J. M. Quivey, L. D. Skarsgard, J. R. Stewart, C. A. Tobias,
P. W. Todd, and W. R. Withers for their comments on different sections of the
book. While the author takes the complete responsibility for the material in the
book, its present form is due largely to the helpful comments from the above men­
tioned people who have made major contributions to this field.
I would like to thank my many colleagues who generously and willingly gave
permission for diagrams and illustrations from their published work to be repro­
duced in this book. I also appreciate receiving permission to use copyright material
from the following publishers: Academic Press, Inc.; American Cancer Society;
American Medical Association; British Journal of Radiology; Lawrence Berkeley
Laboratory; H. K. Lewis and Co., Ltd.; Los Alamos Scientific Laboratory;
McMillian Journals; National Academy of Sciences; North-Holland Publishing
Company; Pergamon Press; Radiological Society of North America, Inc.; Rocke­
feller University Press; Societa Italiana di Physica; Taylor and Francis, Ltd.; The
Institute of Physics; The Institute of Physics and Physical Society; The Royal Soci­
ety of Medicine; and The Williams and Wilkins Co.
xi
INTRODUCTION
Extreme remedies are very appropriate for extreme
diseases.
--Hippocrates
Life is short and the art long.
--Hippocrates
In advanced countries, one person in four contracts
cancer, but only about one in six dies of it, so that long-
term control achieved for about one-third of all cancer
patients results in normal life expectancy.* Cases detected
earlier have a higher chance of control in most types of
cancer. About half of all cancer patients receive radiation
therapy and half surgery, where either group may receive
chemotherapy as well. Radiation therapy is an empirical
science and, as many people describe it, is even perhaps an
art. As Fowler (1966) pointed out, "If therapists had waited
for a fully scientific basis before treating the first
patient, radiotherapy would not have started yet." If we
knew scientifically how conventional radiations are bringing
about cancer control in some cases and are failing to do so
in other cases, it would be easier for us to predict the
complementary role of high-LETt radiations in improving the
results of radiation therapy.
The early source of radiation in therapy was low-energy
(< 100 kVP) X rays. Although these low-energy X rays
provided poor penetration, a large number of cancer patients
were treated. The relative worth of radiation, when compared
American Cancer Society Facts and Figures, New York
(1978).
LET (linear energy transfer) was introduced by Zirkle
(1954). It is the energy transferred per unit length of the
track and is usually expressed in keV/fjm of unit density
material.
1
2 Heavy Particle Radiotherapy
with surgery, had become a subject of debate as early as
1907. It was recognized early that radium emits energetic
gamma rays that have better penetration than the most
energetic early therapeutic X rays. By 1920, about six
radium units were built using many grams of radium at an
approximate cost of $50,000 per gram (Schulz, 1975). The
clinical results obtained using radium units for deep-seated
tumors gave impetus to the search for other high-energy,
reasonably low-cost X rays. By 1940, accelerators had been
built to produce high-energy X ra y6s.0 By 1950, with the
development of nuclear reactors, Co sources were produced.
Radioactive cobalt emits gamma radiation equivalent to 2.5 MV
X rays in penetration, and cobalt units replaced the expen­
sive radium units for teletherapy. Cobalt-60 has now become
a standard source for therapeutic application all over the
world. In advanced countries, even more penetrating radia­
tions such as 4- to 42-MV X rays have become common with the
development of linear electron accelerators and betatrons.
Thus, the historical trend of radiation therapy develop­
ment has been toward obtaining more penetrating radiations.
This trend has allowed more uniform irradiation of tumors,
irrespective of their location in the body, thereby resulting
in higher tumor doses with minimal damage to the intervening
normal tissues. In attempts to reduce further the damage to
normal tissues, significant progress has been made in radia­
tion therapy over the past 25 yr. This progress was made
possible by a better understanding of normal tissue tolerance,
together with the use of megavoltage radiation therapy sources
(Buschke, 1965).
Normal tissues exposed in radiotherapy treatment may be
divided into three compartments (Kramer, 1972). This is
illustrated inM Fig. 1. The first compartment is "transit
normal tissue--tissue that is unavoidably exposed to radia­
tion before it reaches the tumor. Damage sustained by
transit normal tissue, particularly the skin, was a limiting
factor in the early days of radiation therapy when low-
voltage, low-penetration X rays were used. Hence, in the
early days of radiation therapy, the successful results were
in cases where the tumors were situated relatively close to
the surface. With the advent of megavoltage sources of
radiation, transit normal tissue became less of a limiting
factor with the possible exception of the gut, kidney, and
spinal cord. In principle, the introduction of protons,
heavy ions, and negative pions in radiotherapy should further
reduce the damage to "transit normal tissue."
The second normal tissue compartment is the "safety zone
normal tissue." This normal tissue is included in the radia­
tion field because of our present inability to define the
exact local extension of the disease. Our inability to
Introduction 3
| ^ ^| Transit normal tissue
Fig. 1. Schematic representation of three normal tissue
compartments implicated in radiation therapy. The arrows
indicate the direction of radiation delivery, and matrix
normal tissue is denoted by the white space within the tumor
(adapted from Kramer, 1972).
define the limits of these extensions is one of the major
weaknesses in current radiation therapy. This "safety zone
normal tissue" is quite often of an appreciably greater
volume than tumor tissue and is the limiting factor in
present-day radiation therapy. Use of better methods such as
computerized tomography (CT) for determining the tumor loca­
tion and extension will help in minimizing the "safety zone
normal tissue" in the radiation field.
The third normal tissue compartment is the "matrix
normal tissue" or the normal tissue within the tumor itself.
It is very important in many sites that this normal tissue
survive irradiation and maintain a satisfactory anatomical
and functional condition. The ability of this matrix normal
4 Heavy Particle Radiotherapy
tissue to tolerate radiotherapy makes irradiation preferable
to surgery for certain anatomical sites. High-LET radiations
such as fast neutrons, negative pions, and heavy ions in
radiotherapy may produce an enhanced effect on tumor cells
for a given effect on matrix normal tissue, compared to X
rays, because of the X-ray resistance of hypoxic and late
S-phase tumor cells.
Despite significant developments in conventional radio­
therapy, local failures are still common. Suit (1969)
estimated that approximately 60,000 annual deaths out of
175,000 cases in the United States could be attributed to
failure to control the primary tumor by radiotherapy. Recent
estimates also indicate that approximately 100,000 deaths
occur annually due to failure to control local and regional
cancer by all means of therapy (Stewart and Powers, 1979).
Local control of the disease becomes even more important with
the improved ability of chemotherapy to control metastases.
The local or regional failure by radiotherapy is con­
sidered due to our inability to deliver tumor control doses
without unacceptable effects on normal tissues within the
treatment volume.* This is illustrated in Fig. 2, where it
is seen that tumor control, as well as incidence of normal
tissue complications, increases with dose. Normal tissue
complications can be reduced by minimizing the volume of
normal tissues in the radiation field; this, in turn, could
make it possible to increase the dose to the tumor without
exceeding normal tissue tolerance.
The implications of a steep response of tumors and late
complications with dose are discussed by Fletcher (1973). It
should be emphasized that massive increases in the delivered
or biologically effective dose may not be required for large
increases in local tumor control (Shukovsky and Fletcher,
1973).
Many tumors appear to have an inadequate blood supply
and hence may contain a proportion of hypoxic cells. For
Because of limitations introduced by the inherent
characteristics of radiations and techniques used in radio­
therapy, it is not always possible to administer the
prescribed dose to the target volume (tumor and suspected
tumor volume). In practice, the treatment volume is larger
than the target volume and of a simpler shape. The treatment
volume ideally should coincide with the target volume, and
this is almost achieved when heavy charged particles are used
in radiotherapy.