Endolymphatic Radiotherapy in Malignant Lymphomas

139 Pages·1971·6.075 MB·English

by  Sergio Chiappa M.D., Renato Musumeci M.D., Carlo Uslenghi M.D. (auth.)

Recent Results in Cancer Research
Fortschritte der Krebsforschung
Progres dans les recherches sur le cancer
37
Edited by
v.
G. All/rey, New York . M. Allgöwer, Basel' K. H. Bauer, Heidelberg
I. Berenblum, Rehovoth . F. Bergel, Jersey . J. Bernard, Paris
W.Bernhard, Villejui/ • N. N. Blokhin, Moskva . H. E. Bock, Tübingen
P. Bucalossi, Milano . A. V. Chaklin, Moskva . M. Chorazy, Gliwice
G. J. Cunningham, Richmond . W: Dameshek t, Boston' M. Dargent, Lyon
G. Della Porta, Milano . P. Denoix, Villejui/ . R. Dulbecco, La Jolla
H. Eagle, New York . R. Eker, Oslo . P. Grabar, Paris' H. Hamperl, Bonn
R. J. c. Harris, Salisbury . E. Hecker, Heidelberg . R. Herbeuval, Nancy
J. Higginson, Lyon' W. C. Hueper, Fort Myers . H. Isliker, Lausanne
D. A. Karno/sky t, N ew Y ork . J. Kieler, Kobenhavn . G. Klein, Stockholm
H. Koprowski, Philadelphia' L. G. Koss, New York • G. Martz, Zürich
G. Mathe, Villejui/ • O. Mühlbock, Amsterdam . W. Nakahara, Tokyo
V. R. Potter, Madison' A. B. Sabin, Rehovoth . L. Sachs, Rehovoth
E. A. Saxen, Helsinki • C. G. Schmidt, Essen' S. Spiegelman, New York
W. Szybalski, Madison' H. Tagnon, Bruxelles . R. M. Taylor, Toronto
A. Tissieres, Geneve . E. Uehlinger, Zürich' R. W. Wissler, Chicago
T. Y oshida, Tokyo
Editor in chief
P. Rentchnick, Geneve
Springer-Verlag New York . Heidelberg . Berlin 1971
s.
Chiappa . R. Musumeci . C. U slenghi
Endolymphatic Radiotherapy
in Malignant Lymphomas
With Contributions by
u.
G. Bonadonna· B. Dama~ce1li· G. Fava· F. Pizzetti . Veronesi
With 83 Figures
Springer-Verlag New York . Heidelberg . Berlffi 1971
Sponsored by the Swiss League against Cancer
-----------------------------------------------.------
ISBN-13: 978-3-642-80604-9 e-ISBN-13: 978-3-642-80602-5
DOI: 10.1007/978-3-642-80602-5
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned,
specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying
mamine or similar means, and storage in data banks.
Under § 54 of the German Copyright Law where copies are made for otber tban private use, a fee is payable
to the publisher, the amount of the fee to be determined by agreement with tbe publisher.
© by Springer-Verlag Berlin . Heidelberg 1971. Library of Congress Catalog Card Number 78-148260.
Softcover repnnt ofthe hardcover I st edition 1971
The use of general descriptive names, trade names, trade marks, eee. in this publication, even if
the former are not especially identified, is not to be taken as a sign that such names, as understood by the
Trade Marks and Mennandise Marks Act, may accordingly be used freely by anY0!,e. Typesetting, printing and
binding: Konrad Triltsch, Graphischer Betrieb, 87 Würzburg, Germany.
Foreword
Clinical trials with Lipiodol l3ll were started in 1961 by my associate, S. CHIAPPA,
and a group of physicians at the Institute of Radiology and the National Cancer
Institute in Milan and development has been vigorously pursued during the past
years. Once the rationale of this method was established, various aspects of the prob
lem have been investigated, particularly the distribution of the radioactive dye into
the lymph nodes as weIl as its fate and dosimetry in the body tissues. This mono
graph describes the extensive clinical evaluation and the radiological results obtained
in a large group of patients with malignant lymphomas.
Endolymphatic radiotherapy as a therapeutic tool employing radiönuclides has
aroused interest at several meetings concerned with lymphology. In the re cent mono
graph "Lymphography in cancer" by W. A. FUCHS, J. W. DAVIDSON and H. W.
FISCHER, Dr. JANTET wrote a chapter on this specific subject. Many aspects are still
debated, i. e. the choice of radionuclide, the specific clinical indications and the proper
evaluation of the therapeutic effects.
It is hoped that further studies will come to more precise conclusions.
Whatever the future of endolymphatic radiotherapy in the field of clinical onco
logy, I want to call the attention of readers to the monograph of S. CHIAPPA and
his coworkers. Their intelligent, exhaustive and critical work definitely constitutes,
in my opinion, a useful contribution in this particular field. I wish also to acknowl
edge with thanks their remarkable contribution to the scientific activity of the Insti
tute of Radiology.
Prof. ARDUINO RATTI, M. D.
Director, Istituto di Radiologia
University of Milan, Italy
Preface
In the fall of 1961, when I first injected a radioactive contrast material (Lipiodol
Fluid 1311) into the lymph vesse1s of the dorsum of the foot, it was in the belief that
the isotope could be useful in following the distribution of the dye throughout the
retroperitoneal lymph nodes, rather than for therapeutic purposes. The experience
gained, first in animals and subsequently in man, suggested the possibility of using
the radiation emission of 1311 for therapeutic purposes, too. It thus became possible
for the first time to irradiate the lymphatic tissue and at the same time to check the
results t\:lrough periodical follow-up films.
Endolymphatic radiotherapy (ERTr'has been used extensive1y in the past few
years in several centers throughout the world. Both favorable results and criticism
have he1ped to define its indications mbre precise1y. After some nine years of ex
perience with its use in the therapy of several types of neoplastic diseases, and
especially of malignant lymphomas, I can state once more that endolymphatic radio
therapy is a therapeutic tool practically devoid of significant side effects. Since a
good filling of the nodes is possible, particularly when the lymphatic tissue is not
severe1y invaded by neoplastic cells, endolymphatic radiotherapy finds its principal
indication as a prophylactic treatment for radiologically normal or suspicious lymph
no des be10w the diaphragm. In stage IV malignant lymphomas, however, where
radiation therapy plays only a palliative role, endolymphatic radiotherapy can be
used succesfully in combination with chemotherapy.
I be1ieve that experiments and clinical trials with radioactive contrast materials
of any kind could represent an interesting approach for treatment of cancer. I wish to
thank all coauthors of this monograph, and in particular Dr. R. MUSUMECI and Dr.
C. USLENGHI, whose diligence and competent work has contributed substantially in
collecting the case material and in evaluating the results.
This book is dedicated to the memory of my father.
SERGIO CHIAPPA
Acknowledgment
The authors wish to acknowledge with thanks the critical review of the manuscript by
A. RATTI, M. D., Director of the Institute of Radiology, University of Milan,' and P. BUCA
LOSSI, M. D., Director of the National Cancer Institute, Milan.
Contents
Chapter 1 Present Position of Radieal and Palliative Treatment of Malignant
Lymphomas. G. BONADONNA. With 2 Figures. 1
Chapter 2 Lymphangiography and Endolymphatie Radiotherapy: General
Prineiples. S. CHIAPPA, R. MUSUMECI, and C. USLENGHI. With 3
Figures 23
Chapter 3 Technique of Lymphography and Endolymphatie Radiotherapy.
B. DAMAscELLI. With 7 Figur,es 31
Chapter 4 Physieal Properties of Lipiodol 131I and Dosimetrie Studies.
G. FAVA. With 23 Figures .' . 38
Chapter 5 Clinieal Results of Endolymphatie Radiotherapy. S. CHIAPPA,
R. MUSUMECI, and C. USLENGHI. With 21 Figures 71
Chapter 6 Side Effeets and Complieations. S. CHIAPPA, R. MUSUMECI, and
C. USLENGHI. With 11 Figures. 96
Chapter 7 Results of Endolymphatie Radiotherapy: Histologieal Aspeets.
F. PIZZETTI, and U. VERONESI. With 14 Figures . 107
Chapter 8 Endolymphatie Radiotherapy in Relation to Other Treatments
for Malignant Lymphomas. S. CHIAPPA, R. MUSUMECI, and C.
USLENGHI. With 2 Figures . 119
Chapter 9 Conclusions. S. CHIAPPA, R. MUSUMECI, and C. USLENGHI 124
Subjeet Index 126
List of Authors
GIANNI BONADONNA, M. D., Clinical Associate, Clinical Chemotherapy Unit,
National Cancer Institute, Milan
SERGIO CHIAPPA, M. D., Assistant Professor of Radiology, University of Milan; Chief,
Radiological Department, Fatebenefratelli Hospital, Milan
BRUNO DAMASCELLI, M. D., Assistant Professor of Radiology, University of Milan
GIANNINO FAVA, Ph. D., Head, Section of Physics, National Cancer Institute, Milan
RENATO MUSUMECI, M. D., Assistant Professor of Radiology, University of Milan
FEDERICO PIZZETTI, M. D., Chief, Division of Pathology, National Cancer Institute,
Milan
CARLO USLENGHI, M. D., Assistant Professor of Radiology, University of Milan;
Clinical Assistant, National Cancer Institute, Milan
UMBERTO VERONESI, M. D., Head, Division of Clinical Oncology, National Cancer
Institute, Milan
Chapter 1
Present Position of Radical
and Palliative Treatment
of Malignant Lymphomas
GIANNI BONADONNA
With 2 Figures
In the past deeade advanees in both diagnosis and treatment of malignant lym
phomas, and partieularly of Hodgkin's disease, have yielded a large amount of
new information about their natural history, histopathologie classifieation and
diagnostie evaluation, as weIl as new ideas eoneerning the basis for a rational thera
peutie approach [46, 88, 100 a, 115, 123-125]. From a praetieal point of view,
the most important result derived from all these studies is the fact that most
physieians today, when faeing the therapeutie problem, show greater optimism in
their prognosis. Medieal people are now aware that, eontrary to what has for years
been taught at universities and published, a malignant lymphoma need no longer be
eonsidered invariably fatal, but rather that adequate doses of radiation therapy in
the early stages produce a high long-term survival rate, statistieally eompatible with
eure [58,63,75,91,93,99,119].
The purpose of this introductory chapter is to outline briefly the modern eoneepts
on radieal and palliative therapy of malignant lymphomas. These new ideas are
prineipally based on their histologie expression, mode of spread, metieulous diagnostie
evaluation, both on admission and during the follow-up, and clinieal classifieation.
1. Histopathologie Classifieation
For many years the histologie gradation of change proposed by jACKSON and
PARKER in 1947, stressing the variation in malignant charaeteristies, has been widely
aeeepted in differentiation between Hodgkin's paragranuloma, granuloma and
sareoma. Reeently, the simplified LUKES classifieation [84,85] has gained aeeeptanee
all over the world in view of the fact that preferential loealizations and a distinet
prognostie evolution vary aeeording to the four fundamental histologie al expressions
CTable 1.1). In fact, a retrospeetive clinieal study according to histologieal type,
1 RRCR, VoJ. 37 Chiappa et al.
2 G.BoNADoNNA
Table 1.1. Terminology for the histologie expressions of Hodgkin's disease (proposed by the
Nomenclature Committee, Rye, New York, September 13-15, 1966) [106]
Histologie terms Deseription
Lymphoeytie predominanee A histoeytie component of variable degree is usually found
and represents a prominent eomponent in approximately half
of the eases. The proeess may be nodular or diffuse in histo
logie pattern. The group therefore includes not only the para
granuloma type of ]ACKSON and PARKER, where lymphoeytes
predominate, but also the lymphoeytie and/or histoeytie types,
both nodular and diffuse of LUKES and BUTLER.
Nodular sclerosis This histologie type is charaeterized by orderly bands of inter
eonneeting eollagenous eonneetive tissue that subdivides dis
tinetively abnormal lymphoid tissue, partially or entirely, into
isolated eellular nodules.
Mixed eellularity The histologie response in this group is intermediate between
lymphoeytie predominanee and lymphoeytie depletion and
includes a eomplete variety of histologie components as fol
lows': eosinophils, plasma eells, mature neutrophils, lympho
eytes, hystioeytes and Reed-Sternberg eells, as well as variable
not ,severe degrees of disorderly fibrosis without birefringent
collagen formation.
Lymphoeytie depletion This group is eomposed of several histologie expressions of
Hodgkin's disease that have in common lymphoeytie deple
tion. It includes the diffuse fibrosis and retieular types of
LUKES and BUTLER and the sarcoma type of ]ACKSON and
PARKER.
made by KELLER et al. [72J on 176 cases, showed that the two largest groups were
nodular selerosis and mixed cellularity, while lymphocytie predominanee and lym
phoeytie depletion oeeurred as much smaller entities. These results are very elose to
those published previously by HANSON [53 J, while in other series mixed eellularity
appears to be the largest histologie group [34, 43J. Nodular selerosis oceurs mainly
in patients with cervieal and mediastinal involvement [29, 43, 53, 72]. Lymphoeytie
predominanee oeeurs almost always in patients with stage land II, while lymphoeytie
depletion and mixed cellularity in stages III and IV and are often assoeiated with
systemie symptoms [34, 72]. Lymphoeytie predominance and nodular selerosis have
a favourable pro gnosis with prolonged median survival time in comparison to mixed
eellularity and lymphoeytie depletion [61 a, 72]. Finally, non-eontinuous dissemination
occurs more often in the mixed eellularity and lymphoeytic depletion types [72].
For lymphosareoma and retieulum eell sareoma, a less weH defined histologie
deseription is available at the present moment. Usually, lymphosareoma is morpho
logieally elassified as lymphocytie and lymphoblastie, and reticulum cell sareoma as
differentiated or undifferentiated. Lymphoblastie lymphosarcoma and undifferen
tiated retieulum eell sarcoma are assoeiated with a poorer prognosis. A partieular
type of lymphosareoma is the giant foHiele lymphosarcoma or Brill-Symmers'
disease whieh in eomparison to other types of malignant lYI+1phomas has a fairly
benign prognosis.