Table Of ContentGynecologic Oncology
Cancer Treatment and Research
WILLIAM L. MCGUIRE, series editor
1. R. B. Livingston, ed., Lung Cancer 1. 1981. ISBN 90-247-2394-9.
2. G. B. Humphrey, L. P. Dehner, G. B. Grindey and R. T. Acton, eds., Pediatric Oncology 1.
1981. ISBN 90-247-2408-2.
3. J.J. DeCosse and P. Sherlock, eds., Gastrointestinal Cancer 1. 1981. ISBN 90-247-2461-9.
4. J.M. Bennett, ed., Lymphomas 1, including Hodgkin's Disease. 1981. ISBN 90-247-2479-
1.
5. C.D. Bloomfield, ed., Adult Leukemias 1. 1982. ISBN 90-247-2478-3.
6. D. F. Paulson, Genitourinary Cancer 1. 1982. ISBN 90-247-2480-5.
7. F.M. Muggia, ed., Cancer Chemotherapy 1. 1982. ISBN 90-247-2713-8.
8. G. B. Humphrey and G. B. Grindey, eds., Pancreatic Tumours in Children. 1982. ISBN 90-
247-2702-2.
9. John J. Costanzi, ed., Malignant Melanoma 1. 1982. ISBN 90-247-2706-5.
Gynecologic Oncology
edited by
c. THOMAS GRIFFITHS, M.D.
Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA
ARLAN F. FULLER, Jr., M.D.
Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
1983 MARTINUS NIJHOFF PUBLISHERS
a member of the KLUWER ACADEMIC PUBLISHERS GROUP
BOSTON / THE HAGUE / DORDRECHT / LANCASTER
Distributors
for the United States and Canada: Kluwer Boston, Inc., 190 Old Derby Street,
Hingham, MA 02043, USA
for all other countries: Kluwer Academic Publishers Group, Distribution Center,
P.O.Box 322,3300 AH Dordrecht, The Netherlands
Library of Congress Cataloging in Publication Data
Main entry under title:
Gynecologic oncology.
(Cancer treatment and research ; v. 10)
1. Reproductive organs, Female--Cancer.
I. Griffiths, C. Thomas. II. Fuller, Arlan F.
III. Series. [DNLM: 1. Genital neoplasms,
Female. WI CA693 v. 10 / WP 145 G99651]
lU'\2lfO.C5G886 1983 616.99'465 82-14491
ISBN-13: 978-1-4613-3854-3 e-ISBN-13: 978-1-4613-3852-9
DOl: 10.1007/978-1-4613-3852-9
Copyright
© 1983 by Martinus Nijhoff Publishers, Boston.
Softcover reprint of the hardcover I st edition 1983
All rights reserved. No part of this publication may be reproduced, stored in a
retrieval system, or transmitted in any form or by any means, mechanical,
photocopying, recording, or otherwise, without the prior written permission of
the publishers,
Martinus Nijhoff Publishers, 190 Old Derby Street, Hingham, MA 02043, USA.
Contents
Foreword to the Series vii
Preface ix
List of Contributors xiii
1. Evidence for a Viral Etiology of Squamous Cell Carcinoma of the
Cervix ........................ .
LAURE AURELIAN
2. Tumor Markers in Gynecologic Malignancies 63
JOHN R. VAN NAGELL
3. Hormonal Receptors in Endometrial and Ovarian Neoplasia 81
GEORGE S. RICHARDSON and DAVID T. MACLAUGHLIN
4. Germ Cell Tumors of the Ovary: Pathology, Behavior and Treat-
ment ................ . 103
ROBERT J. KURMAN and EDMUND S. PETRILLI
5. Treatment of Advanced Trophoblastic Disease . . 155
RICHARD H. J. BEGENT and KENNETH D. BAGSHA WE
6. The Immunobiology of Ovarian Carcinoma . . 187
ROBERT C. BAST Jr. and ROBERT C. KNAPP
7. Lymph Node Metastases from Gynecologic Cancer - Biological
Concepts and Therapeutic Implications . . . . . . . . . . . 227
ARLAN F. FULLER Jr.
8. Radiation Therapy of Ovarian Carcinoma 263
ALON J. DEMBO and RAYMOND S. BUSH
vi
9. Heavy Particle Radiation Therapy in Gynecological Malignan-
cies . . . . . . . . . . . . . . . . . . . . . . . .. 299
ROBERT D. HILGERS, STEVEN E. BUSH and FRANCISCO AMPUERO
10. Growth of Gynecologic Neoplasms in Tissue Culture and as
Heterografts ...................... 313
CHARLES E. WELANDER and JOHN L. LEWIS Jr.
11. Clinical Trials in Gynecologic Oncology: Cooperative Group
Research . . . . . . . . . . . . . . . . . . . . . 343
GEORGE C. LEWIS Jr., JOHN BLESSING and JOHN R. KELLNER
Subject Index ... 385
Foreword to the Series
Where do you begin to look for a recent, authoritative article on the
diagnosis or management of a particular malignancy? The few general onco
logy textbooks are generally out of date. Single papers in specialized journals
are informative but seldom comprehensive; these are more often prelimi
nary reports on a very limited number of patients. Certain general journals
frequently publish good indepth reviews of cancer topics, and published
symposium lectures are often the best overviews available. Unfortunately,
these reviews and supplements appear sporadically, and the reader can
never be sure when a topic of special interest will be covered.
Cancer Treatment and Research is a series of authoritative volumes
which aim to meet this need. It is an attempt to establish a critical mass of
oncology literature covering virtually all oncology topics, revised frequently
to keep the coverage up to date, easily available on a single library shelf or
by a single personal subscription.
We have approached the problem in the following fashion. First, by divid
ing the oncology literature into specific subdivisions such as lung cancer,
genitourinary cancer, pediatric oncology, etc. Second, by asking eminent
authorities in each of these areas to edit a volume on the specific topic on an
annual or biannual basis. Each topic and tumor type is covered in a volume
appearing frequently and predictably, discussing current diagnosis, staging,
markers, all forms of treatment modalities, basic biology, and more.
In Cancer Treatment and Research, we have an outstanding group of
editors, each having made a major commitment to bring to this new series
the very best literature in his or her field. Martinus Nijhoff Publishers has
made an equally major commitment to the rapid publication of high quality
books, and world-wide distribution.
Where can you go to find quickly a recent authoritative article on any
major oncology problem? We hope that Cancer Treatment and Research
provides an answer.
WILLIAM L. MCGUIRE
Series Editor
Preface
At the turn of the century gynecology had achieved independence from
surgery in most medical schools; although gynecologists were surgeons, their
interests were turning toward nonsurgical aspects of their specialty. In 1900,
merely two years after the Curies' discovery, radium was first used as a
treatment for carcinoma of the cervix. In that day cervical cancer claimed
more women's lives than any other malignancy and was described by Wil
liam P. Graves, the second professor of gynecology at Harvard as follows:
'Cancer of the cervix may rightly be termed of all tumors one of the most
deadly and most ghastly. It kills by slow torture, causing in later stages
months of agonizing pain and producing a discharge of such a foul and
nauseating character as to repel proper medical assistance. Nurses declined
to care for these cases, while many public hospitals closed their wards to
them as patients.' In late twentieth century parlance the dramatic results of
radium therapy would indeed have been called a 'breakthrough'? and
radium techniques, later combined with external irradiation, were devel
oped by gynecologists, no longer just surgeons. Pathology was the basic
science of gynecology and gynecologists with a special interest in pathology
served as pathologist to the departments of gynecology. As late as 1970 six
months of the three-year residency program in obstetrics and gynecology at
Harvard were devoted to formal training in pathology. After the observa
tion in the early 1950s that nitrogen mustard could induce regression of
ovarian cancers, clinical trials with this agent and its congeners were carried
out by gynecologists. In 1961 Howard W. Jones, Jr. ofJohns Hopkins Medi
cal School admonished gynecologists to become further involved in cancer
chemotherapeutic research and then added a prophetic warning that 'a new
specialty might arise which would include gynecological cancer in its
ken.'
As we entered the last quarter of the twentieth century gynecologic onco
logy became formally recognized as a subspecialty of obstetrics and gyneco-
x
logy. At the same time, it became apparent that the era of multimodality
expertise had waned; a gynecologic oncologist would function primarily as a
surgeon but also as a consultant by virtue of erudition in the natural history
of a particular class of diseases. The establishment and rapid growth of the
specialties of radiation oncology and medical oncology had so expanded the
therapeutic potential in gynecologic cancer that no one person or specialty
could be qualified to undertake the broad range of complex therapies. In
addition, a small but active group of pathologists had attained special know
ledge through fellowship training in the field of gynecologic pathology.
Only 202 gynecologists in the United States have been certified for special
competence in gynecologic oncology. In order to maintain their identity,
much less their visibility, gynecologic oncologists cannot function merely as
surgical technicians. Expansion of their knowledge to include the latest
developments in all phases of cancer research and treatment which pertain
to the female genitalia has become even more important at a time when
keeping abreast has become all the more difficult.
With these thoughts in mind we designed this first volume in the series on
gynecologic malignancies for the gynecologic oncologist in particular. We
selected subjects for the chapters based upon our perception of need for
scholarly reviews of certain complex, rapidly moving areas. Our goal has
been to synthesize all currently available information in selected areas in a
manner that will enable the clinician to reconcile his clinical observations
with related scientific observations.
In a traditional sense we began with carcinoma of the cervix and some
exciting new information brilliantly espoused by Aurelian that increases the
probability of a viral etiology. We then turned to radiation therapy with
chapters on irradiation for ovarian cancer by Dembo and Bush and on
heavy particle therapy for gynecologic malignancy by Hilgers and associates.
The former authors, having induced the revival of interest in radiotherapy
for ovarian cancer whereas the latter authors introduce an altogether new
biophysical approach to the deliverance of lethal radiation to the cancer
cell.
Recent advances in pathological research and their clinical application are
demonstrated in the chapter on germ cell tumors of the ovary by Kurman
and Petrilli. Utilizing immunoperoxidase histochemical techniques Robert
Kurman in collaboration with Henry J. Norris at the Armed Forces Insti
tute of Pathology established embryonal carcinoma of the ovary as a dis
tinct entity and clearly defined the influence on prognosis of the histologic
counterparts of mixed germ cell tumors of the ovary. Some newer biologic
concepts of lymph node metastasis in gynecologic cancer, particularly as a
manifestation of systemic disease, are presented by one of us (AFF Jr.).
The victories of cancer chemotherapy are exemplified by accomplish-
xi
ments in the management of choriocarcinoma. Innovations in the treatment
of advanced trophoblastic disease and its complications have come from the
Charing Cross Hospital in London and Richard H.J. Begent and Kenneth D.
Bagshawe ofthat institution have presented their approach to these diseases.
Clinical trials by cooperative groups have become the means whereby the
efficacy of rational chemotherapeutic regimens are evaluated. The scientific
approach to group trials as well as the bureaucratic mechanisms involved in
their conduct are described best by those qualified, George C. Lewis, Jr. and
his associates at the Gynecologic Oncology Group headquarters.
We have selected three areas of basis preclinical research in which clinical
application has begun to emerge. The identification of estrogen and proges
terone receptor proteins in the cytosol of endometrial carcinomas has been
with us for some time and that of ovarian neoplasms only recently. Rele
vance of this knowledge to treatment has been slowed by the infrequency of
recurrent endometrial cancer wherein receptor status and endocrine respon
siveness can be correlated. George. S. Richardson and David T. MacLaugh
lin, have been active investigators in this field for more than a decade and
have contributed a succinct' state of the art' review. Cell cultures of gyne
cologic cancers have a long history dating from the successful passage of
HeLa cells into immortality by George Gey in the late 1940s. Although cell
cultures in soft agar for clonogenic assays of chemotherapeutic sensitivity
have dominated the scene in recent years, other in vivo and in vitro tech
niques need review. We have chosen two modem experts in gynecologic
cancer cell culture, Charles E. Welander and John L. Lewis Jr. of Sloan
Kettering Memorial Hospital to review this field. Finally, clinical applica
bility of long-term studies of the immunobiology of ovarian carcinoma has
now arrived. Clinical trials of immunodiagnostic techniques are underway
and immunotherapy is now moving from nonspecific to specific immunos
timulants. Robert C. Bast and Robert C. Knapp who have developed a
monoclonal antibody to a purified ovarian cancer antigen have contributed
a chapter on the immunobiology of ovarian carcinoma.
The usefulness of tumor markers in monitoring therapy is well brought
out in the chapters on germ cell tumors of the ovary, trophoblastic disease,
and immunobiology, but we felt that for completeness a summary on tumor
markers in gynecologic cancer in general was needed. John R. van N agell
has contributed more than any other to the application of a broad range of
oncofetal antigens and other biochemical markers to gynecologic cancer in
general. Van Nagell's summary of this subject overlaps somewhat with the
aforementioned chapters but we believe that the information presented is
more complementary than repetitive. Accordingly these areas are cross
referenced in the text.
The selection of authors for this volume was easy. We simply asked those
