ADVANCES IN RADIATION THERAPY

Cancer Treatment and Research

Steven T. Rosen, M.D., Series Editor Robert H. Lurie Cancer Center, Northwestern University Medical School

Surwit, E.A., Alberts, D.S. (eds.): Endometrial Cancer. 1989. ISBN 0-7923-0286-9.

Champlin, R. (ed.): Bone Marrow Transplantation. 1990. ISBN 0-7923-0612-0.

Goldenberg, D. (ed.): Cancer Imaging with Radiolabeled Antibodies. 1990. ISBN 0-7923-0631-7.

Jacobs, C (ed.): Carcinomas of the Head and Neck. 1990. ISBN 0-7923-0668-6.

Lippman, M.E., Dickson, R. (eds.): Regulatory Mechanisms in Breast Cancer: Advances in Cellular and Molecular Biology of Breast Cancer. 1990. ISBN 0-7923-0868-9.

Nathanson, L. (ed.): Malignant Melanoma: Genetics, Growth Factors, Metastases, and Antigens. 1991. ISBN 0-7923-0895-6.

Sugarbaker, P.H. (ed.): Management of Gastric Cancer. 1991. ISBN 0-7923-1102-7.

Pinedo, H.M., Verweij,)., Suit, H.D. (eds.): Soft Tissue Sarcomas: New Developments in the Multidisciplinary Approach to Treatment. 1991. ISBN 0-7923-1139-6.

Ozols, R.F. (ed.): Molecular and Clinical Advances in Anticancer Drug Resistance. 1991. ISBN 0-7923-1212-0.

Muggia, F.M. (ed): New Drugs, Concepts and Results in Cancer Chemotherapy 1991. ISBN 0-7923-1253-8. Dickson, R.B., Lippman, M.E. (eds.): Genes, Oncogenes and Hormones: Advances in Cellular and Molecular Biology of Breast Cancer. 1992. ISBN 0-7923-1748-3.

Humphrey, G, Bennett, Schraffordt Koops, H., Molenaar, W.M., Postma, A. (eds.): Osteosarcoma in Adolescents and Young Adults: New Developments and Controversies. 1993. ISBN 0-7923-1905-2. Benz, CC, Liu, E.T. (eds.): Oncogenes and Tumor Suppressor Genes in Human Malignancies. 1993. ISBN 0-7923-1960-5. Freireich, E.)., Kantarjian, H. (eds.): Leukemia: Advances in Research and Treatment. 1993. ISBN 0-7923-1967-2.

Dana, B.W. (ed.): Malignant Lymphomas, Including Hodgkin's Disease: Diagnosis, Management, and Special Problems. 1993. ISBN 0-7923-2171-5.

Nathanson, L. (ed.): Current Research and Clinical Management of Melanoma. 1993. ISBN 0-7923-2152-9.

Verweij,)., Pinedo, H.M., Suit, H.D. (eds.): Multidisciplinary Treatment of Soft Tissue Sarcomas. 1993. ISBN 0-7923-2183-9. Rosen, S.T., Kuzel, T.M. (eds.): Immunoconjugate Therapy of Hematologic Malignancies. 1993. ISBN 0-7923-2270-3.

Sugarbaker, P.H. (ed.): Hepatobiliary Cancer. 1994. ISBN 0-7923-2501-X.

Rothenberg, M.L. (ed.): Gynecologic Oncology: Controversies and New Developments. 1994. ISBN 0-7923-2634-2.

Dickson, R.B., Lippman, M.E. (eds.): Mammary Tumorigenesis and Malignant Progression. 1994. ISBN 0-7923-2647-4.

Hansen, H.H. (ed.): Lung Cancer. Advances in Basic and Clinical Research. 1994. ISBN 0-7923-2835-3.

Goldstein, L.J., Ozols, R.F. (eds.): Anticancer Drug Resistance. Advances in Molecular and Clinical Research. 1994. ISBN 0-7923-2836-1.

Hong, W.K., Weber, R.S. (eds.): Head and Neck Cancer. Basic and Clinical Aspects. 1994. ISBN 0-7923-3015-3.

Thall, P.F. (ed.): Recent Advances in Clinical Trial Design and Analysis. 1995. ISBN 0-7923-3235-0.

Buckner, CD. (ed.): Technical and Biological Components of Marrow Transplantation. 1995. ISBN 0-7923-3394-2.

Winter, ).N. (ed.): Blood Stem Cell Transplantation. 1997. ISBN 0-7923-4260-7.

Muggia, F.M. (ed.): Concepts, Mechanisms, and New Targets for Chemotherapy. 1995. ISBN 0-7923-3525-2.

Klastersky,). (ed.): Infectious Complications of Cancer. 1995. ISBN 0-7923-3598-8.

Kurzrock, R., Talpaz, M. (eds.): Cytokines: Interleukins and Their Receptors. 1995. ISBN 0-7923-3636-4.

Sugarbaker, P. (ed.): Peritoneal Carcinomatosis: Drugs and Diseases. 1995. ISBN 0-7923-3726-3.

Sugarbaker, P. (ed.): Peritoneal Carcinomatosis: Principles of Management. 1995. ISBN 0-7923-3727-1.

Dickson, R.B., Lippman, M.E. (eds.): Mammary Tumor Cell Cycle, Differentiation and Metastasis. 1995. ISBN 0-7923-3905-3.

Freireich, E.)., Kantarjian, H. (eds.): Molecular Genetics and Therapy of Leukemia. 1995. ISBN 0-7923-3912-6.

Cabanillas, F., Rodriguez, M.A. (eds.): Advances in Lymphoma Research. 1996. ISBN 0-7923-3929-0.

Miller, A.B. (ed.): Advances in Cancer Screening. 1996. ISBN 0-7923-4019-1.

Hait, W.N. (ed.): Drug Resistance. 1996. ISBN 0-7923-4022-1.

Pienta, K.). (ed.): Diagnosis and Treatment of Genitourinary Malignancies. 1996. ISBN 0-7923-4164-3.

Arnold, A.). (ed.): Endocrine Neoplasms. 1997. ISBN 0-7923-4354-9.

Pollock, R.E. (ed.): Surgical Oncology. 1997. ISBN 0-7923-9900-5.

Verweij,)., Pinedo, H.M., Suit, H.D. (eds.): Soft Tissue Sarcomas: Present Achievements and Furure Prospects. 1997. ISBN 0-7923-9913-7.

ADVANCES IN RADIATION THERAPY

Edited by

Bharat B. MittaI, M.D. ROBERT H. LURIE CANCER CENTER

NORTHWESTERN UNIVERSITY MEDICAL SCHOOL NORTHWESTERN MEMORIAL HOSPITAL

CHICAGO, ILLINOIS

James A. Purdy, Ph.D. MALINCKRODT INSTITUTE OF RADIOLOGY

WASHINGTON UNIVERSITY MEDICAL CENTER ST. LOUIS, MISSOURI

K.K. Ang, M.D. UNIVERSITY OF TEXAS

M. D. ANDERSON CANCER CENTER HOUSTON, TEXAS

Springer Science+Business Media, LLC

Library of Congress Caealoging-in-Publication Data

Advances in radiation therapy / edited by Bharat B. Mittal, James A. Purdy, K.K. Ang. p. cm. - (Cancer ueatment and research; 93) Includes bibliographical references and index.

ISBN 978-1-4613-7644-6 ISBN 978-1-4615-5769-2 (eBook) DOI 10.1007/978-1-4615-5769-2

1. Cancer - Radiotherapy. 1. Mitral, Bharat B. II. Purdy, James A. III. Ang, K.K. (K. Kian) IV. Series.

[DNLM: 1. Radiotherapy. W1 CA693 v.93 1988/ WN 250 R128 1988} RC271.R3R3319 1998

616.99'40642-dc21 DNLMIDLC

for Library of Congress 97-24461 CIP

Copyright © 1998 Springer Science+Business Media New York Originally published by Kluwcr Academic Publishers in 1998 Softcover reprint of the hardcover 1 st edition 1998

AII rights reserved. No part of this publicat ion may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, photocopying, record­

ing, or otherwise, without the prior written permission of the publisher, Springer Science+Business Media, LLC.

Printed on acid-free pa per.

CONTENTS

List of Contributors Vll

Preface

1. Three-Dimensional Treatment Planning and Conformal Dose Delivery -A Physicist's Perspective 1 James A. Purdy

2. Radiation Therapy Beam Modulation Techniques 35 Arthur L. Boyer

3. Computer-Controlled Delivery of 3D Conformal Radiation Treatments 49 Radhe Mohan, Gikas Mageras, and Qiuwen Wu

4. Implementation and Clinical Use of Portal Imaging 69 Cynthia L. Thomason

5. Altered Fractionation: Radiobiological Principles, Clinical Results, and Potential for Dose Escalation 101 Howard D. Thames and K. Kian Ang

6. Pharmacologic Modification of Radiation­Induced Late Normal Tissue Injury 129

John E. Moulder, Michael E.C. Robbins, Eric P. Cohen, John W. Hopewell, and William F. Ward

7. Role of Gene Therapy in Radiation Oncology 153 Dennis E. Hallahan and Ralph Weichselbaum

Xl

8. Potential Applications of Cell Cycle Manipulation to Clinical Response 169 Eleanor E.R. Harris, Gary D. Kao, Ruth]. Muschel, and W. Gillies McKenna

9. Advances in Brachytherapy Ravinder Nath and Lynn D. Wilson

191

10. Recent Advances in External Electromag-netic Hyperthermia 213 V. Sathiaseelan, Bharat B. Mittal, Alan]. Fenn, and Allen Taflove

11. Implementation of Newer Radiotherapeutic Technology in the Management of Prostate Cancer 247 Mack Roach III, Barby Pickett, Pamela F. Akazawa, and Michael Weil

12. Conformal Radiation Therapy - A Physician's Perspective 269 Srinivasan Vijayakumar, Leon Myrianthopoulos, Russell Hamilton, and George Chen

13. Clinical Applications of Stereotactic Radiosurgery 283 John C. Flickinger, Douglas Kondziolka, and L. Dade Lunsford

Index 299

v

LIST OF CONTRIBUTORS

AKAZAWA, Pamela F., Department of Radiation Oncology, University of California at San Francisco, Mt. Zion Cancer Center, 2356 Sutter Street, San Francisco, CA 94115

ANG, K.K., University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030

BOYER, Arthur 1., Division of Radiation Physics, Department of Radiation Oncology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305

CHEN, George, Michael ReeselUniversity of Chicago Center for Radiation Therapy, Michael Reese Hospital and Medical Center, 2929 South Ellis Avenue, Chicago, IL 60616

COHEN, Eric P., Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226

FENN, Alan J., Lincoln Laboratoty, Massachusetts Institute of Technology, Lexington, MA 02173-9108

FLICKINGER, John c., Departments of Radiation Oncology and Neurological Surgery, Center for Image-Guided Neurosurgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213

HALLAHAN, Dennis E., Department of Radiation and Cellular Oncology, Division of the Biological Sciences and The Pritzker School of Medicine, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637

HAMILTON, Russell, Michael Reese/ University of Chicago Center for Radiation Therapy, Michael Reese Hospital and Medical Center, 2929 South Ellis Avenue, Chicago, IL 60616

HARRIS, Eleanor E.R., Department of Radiation Oncology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104-4283

HOPEWELL, John W., Normal Tissue Radiobiology Group, Research Institute, University of Oxford, Oxford, England, United Kingdom

KAO, Gary D., Department of Radiation Oncology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104-4283

KONDZIOLKA, Douglas, Departments of Radiation Oncology and Neurological Surgery, Center for Image-Guided Neurosurgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213

LUNSFORD, 1. Dade, Departments of Radiation Oncology and Neurological Surgery, Center for Image-Guided Neurosurgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213

MAGERAS, Gikas, Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021

McKENNA, W. Gillies, Department of Radiation Oncology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104-4283

vii

V111 LIST OF CONTRIBUTORS

MITTAL, Bharat B., Department of Radiology, Section of Radiation Oncology, Robert H. Lurie Cancer Center, Northwestern University Medical School and Northwestern Memorial Hospital, 250 East Superior Street, Chicago, IL 60611

MOHAN, Radhe, Department of Radiation Oncology, Radiation Physics Section, Medical College of Virginia, Virginia Commonwealth University, 401 College Street, P.O. Box 980058, Richmond, VA 23298-0058

MOULDER, John E., Department of Radiation Oncology, Section of Radiation Biology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226

MUSCHEL, Ruth]., Department of Radiation Oncology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104-4283

MYRIANTHOPOULOS, Leon, Michael Reese/ University of Chicago Center for Radiation Therapy, Michael Reese Hospital and Medical Center, 2929 South Ellis Avenue, Chicago, IL 60616

NATH, Ravinder, Department of Therapeutic Radiology, Division of Radiobiological Physics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510

PICKETT, Barby, Department of Radiation Oncology, University of California at San Francisco, Mt. Zion Cancer Center, 505 Parnassus Avenue, San Francisco, CA 94143-0226

PURDY, James A., Radiation Oncology Center, Malinckrodt Institute of Radiology, Washington University Medical Center, 510 South Kingshighway Boulevard, St. Louis, MO 63110

ROACH III, Mack, Department of Radiation Oncology, University of California at San Francisco, Mt. Zion Cancer Center, 505 Parnassus Avenue, San Francisco, CA 94143-0226

ROBBINS, Michael E.C., Radiation Research Laboratory, University of Iowa, Iowa City, LA 52242-1009

SATHIASEELAN, V., Department of Radiology, Section of Radiation Oncology, Northwestern University Medical School and Northwestern Memorial Hospital, 250 East Superior Street, Chicago, IL 60611

T AFLOVE, Allen, Department of Electrical Engineering and Computer Science, Northwestern University, Evanston, IL 60208

THAMES, Howard D., Departments of Biomathematics and Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030

THOMASON, Cynthia 1., Department of Radiology, Section of Radiation Oncology, Northwestern University Medical School and Northwestern Memorial Hospital, 250 East Superior Street, Chicago, IL 60611

VIJAYAKUMAR, Srinivasan, Michael Reese/ University of Chicago Center for Radiation Therapy, Michael Reese Hospital and Medical Center, 2929 South Ellis Avenue, Chicago, IL 60616

WARD, William F., Department of Radiology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611

WElL, Michael, Department of Radiology, Division of Radiation Oncology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80202

LIST OF CONTRIBUTORS

WEICHSELBAUM, Ralph, Department of Radiation and Cellular Oncology, Division of the Biological Sciences and The Pritzker School of Medicine, University of Chicago Medical Center, 5841 Maryland Avenue, Chicago, IL 60637

WILSON, Lynn D., Department of Therapeutic Radiology, Division of Radiobiological Physics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510

WU, Qiuwen, Department of Radiation Oncology, Radiation Physics Section, Medical College of Virginia, Virginia Commonwealth University, 401 College Street, P.O. Box 980058, Richmond, VA 23298-0058

IX

PREFACE

Radiation oncology has progress«!. dramatically sinc~ the discovery by Wihelm Conrad Roentgen of"uber" eine neue art von strahlen" on the night

of November 8,1895. Recent advances in radia­

tion oncology have depended on and are inter­twined with subsequent scientific discoveries and the development of new techniques in the fie lds of radiation and molecular biology, phys­

ics, electrical enginttcing, surgery, and medical oncology.

It is a privilege for us to have been invited to edit Advanas in Radiation Therapy . Taken to­

gerher, the chapters in this volume show dra­marically how some of the recent discoveries in the radiological sciences have influenced the way we practice radiation oncology. In a book of this nature it is impossible to discuss all aspectS of the many advances in our field. Therefore, we have chosen to concentrate on selected topics in clinical radiotherapy, radiation physics, and bi­ology, and technical innovations that have had a major impact on radiation oncology in the past 20 years.

The first fou r chapters of this book are devoted to the ways in which developments in electronic microcircuitry and computer technology have increased our ability to deliver rad iation much more efficiently to achieve superior dose distri­bution. Likewise, the development of computed tomography and magnetic resonance imaging has g iven us access to increasing ly sophisticated volumetric images. We are now able to perform three-dimensional (3D) treatment planning us­ing beam's-eye view (BEV) and Room-view 3D displays, making it possible for US to conform radiation to the target volume and to decrease doses to critical normal StruCtures. Facilitating these techniques are three-dimensional con­formal radiotherapy (3D CRn and Clinac­conrrolled computers, which drive the multileaf

collimator dynamically and modulate beam in­tensity. National Cancer Institute research con­tracts have supported these developments, and the prototypes of automated machines to deliver 3D CRT are being used in selected institutions in the United States. With the advent of sophis­t icated techniques of 3D localization and confor­mal radiotherapy, it has become clear that there is a need fo r improved verification technology, including an electtonic portal imagi ng device (EPID) and advanced record-and-verification systems to minimi ze random and systematic setup errors.

Radiation induces cellular damage, leading to cell death and a variety of tissular responses. In particular, late radiation injury involves complex and dynamic interactions among parenchymal and vascular cells, and it is important to quantify repairable and nonrepairable target-<ell damage. The use of the linear quadratic (LQ) model pro­vides a simple estimate of repair capacity. Chap­ters 5-8 describe the various strategies born out of basic radiobiology and molecular biology; these have given us the following important new techniques: (1) the potential to increase the therapeutic ratio through the use of altered frac­tionation schemes, (2) ~tradiation pharmaco­log ical intervention that can modulate steps in the cascade of events leading to decreased normal tissue injury without compromising tumor con­trol, (3) gene therapy through radiosensitization in rumor and radioprotection in normal tissues. and (4) the manipulation of key components of cell-<ycle regulation, including pRb, pH. and various oncogenes, such as myc and raJ, as the potential target sites. Examples of successful pharmacological intervent ion in experimental systems include the use of the angiotensin­convening enzyme (ACE) inhibitor captopril, angiotensin II- receptor antagonists, polyunsatu-

..

xu PREFACE

rated fa t ty acids such as gamma-linoleic acid , and others now being tested.

Chapters 9-13 discuss clinical challenges fac­ing contemporary radiation oncology, including the obstacles to implement ing newer tech­nologies and the results of clinical trials once these newer technologies have been imple­mented in treating selected tumors. The chapter on brachytherapy discusses the use of low and hig h dose-rate afterloading techniques and the results of this technique in treating various tu­mors. During brachytherapy, because of rhe continuous nature of irradiation, cell death and proliferation and repair kinetics modify the ra­diation response of tumor and normal tissues; in addition, because of the influence of the inverse square law, the therapeutic index is affected. Future applications of some of the newer radio-

'·d . ' d· 16'}... 14)5 d "'Am nuc I es, Inc u 109 . IO, m, an , are

discussed. The chapter on hyperthermia explores the

progress being made in the technical and clinical methodology of external electromagnetic hyper­thermia. Also d iscussed are the uses of 3D t reatment planning, numerical modeling of electromagnetic power deposition, real-time adaptive nulling, the simultaneous use of hyper­thermia and radiation, and the resultS of phase 1II European clinical trials.

The use of 3D CRT and srereotactic radio­surgery has become a standard of care in the treatment of variety of tumors. We hope that an im proved therapeutic ratio and patients survival will be the result of future innovations in tech­nology. Progress will also occur through a better understandi ng of dose-volume responses of tu­mor and normal tissues as a result of the analysis of research data and the refinement of radiation delivery techniques, as well as advancements in combined-modality treatments.

By grouping various topics in this way, we hope to give readers an opportunity to evaluate the future research potent ial and clinical utility of these advances. An array of these advances is currently being used to understand the basic mechanisms of radiation-induced damage, and ways of modulating radiation damage and improving the delivery of radiation therapy to patients. Ultimately, it is hoped that these techniques will increase tumor cont rol and prolong patient survival and, at the same t ime, decrease radiation-induced side effects and complications.

Bharat B. Mittal, MD jarlUJ A. Pllrdy, PhD

K. K. Ang, AID, PhD