Table Of ContentJiro Suzuki (Ed.)
Treatment of
Glioma
With 137 Figures
Springer-Verlag
Tokyo Berlin Heidelberg New York London Paris
Prof. JIRO SUZUKI, MD
Division of Neurosurgery
Institute of Brain Diseases
Tohoku University
School of Medicine
Sendai, 980 Japan
ISBN-13: 978-4-431-68455-8 e-ISBN-13: 978-4-431-68453-4
001: 10.1007/978-4-431-68453-4
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© Springer-Verlag Tokyo 1988
Softcover reprint ofthe hardcover 1st edition 1988
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vidual case the respective user must check its accuracy by consulting other
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Typesetting: Asco Trade Typesetting, Hong Kong/Fujicom, Tokyo
Preface
The world's first successful diagnosis and treatment of a glioma was
done on a 24-year-old man on 25 November 1884. This historic
achievement was made possible by the collaboration of a diagnostician,
Bennett, who diagnosed the disease on the basis of local neurological
signs, and a London neurosurgeon, Godlee, who performed a
craniotomy and excision of the glioma located in the right premotor
cortex. Unfortunately, the patient died of meningitis 4 weeks post
operatively and Godlee's name is not to be found in the history of
neurosurgery. Thereafter, White and others argued that gliomas
were not suitable for surgical excision and treated glioma patients for
syphilis, which was believed to be the source of the brain disorder.
In 1892, Keen maintained that gliomas should be removed using the
fingers, but Cushing in 1908 rejected this as being too invasive a
procedure. Conversely, Dandy argued that there were many cases in
which such treatment was effective and, moreover, that a portion of
the surrounding normal tissue should also be excised. Dandy also
reported a case of complete hemispherectomy.
Clearly, the early history of surgical treatment of gliomas is charac
terized by uncertainty, but by 1926 Bailey and Cushing had provided
a histological classification of gliomas which has since been recognized
as a major contribution to the initial research and treatment of these
tumors. It is also noteworthy that Ewing first discussed the possibility
of radiation treatment in 1921, and Olivecrona, T6nnis, and others
maintained that even when the effectiveness of radiation therapy could
not be completely assured, it should nonetheless be implemented.
Following the Second World War, the clinical application of anti
cancer drugs began and, more recently, immunopotentiators have
been employed. Research into combined radiation and drug therapy
has advanced considerably, particularly with respect to the timing,
dosage, and administrative methods.
Since 1977, the Sendai Group of Neurosurgeons (originally under
the leadership of Dr. Teruaki Mori) has used the so-called RAFP
therapy for the treatment of glioma. This therapy involves the admini
stration of radiation treatment and three chemical compounds:
VI Preface
ACNU (a nitrosourea agent), Futraful (a masked compound of
5-FU), and PSK (an immunopotentiator). Following Dr. Mori's
academic promotion to Associate Professor at Oita University, the
responsibility for basic research and clinical applications of RAFP
therapy fell on the shoulders of Dr. Ryuichi Katakura and his team.
They have produced remarkable results, both with regard to elucida
tion of the theoretical foundations of the timing of these drugs and to
their clinical use.
With the cooperation of the neurosurgeons of northern Japan,
extensive statistics on gliomas have been collected for this region's
population of 10 million. The statistics include the incidence of
gliomas, symptoms, diagnosis, effectiveness of RAFP therapy, and
histological, CT, and angiographic findings in such cases. These
statistics and data from follow-up studies have been collected and
recorded in a computer database and constitute an important source
of basic information on gliomas.
The effectiveness of RAFP therapy has been found to vary in the
different histological subcategories of gliomas: It is particularly effec
tive for medulloblastoma and anaplastic astrocytoma, but glioblastoma
multiforme has thus far proven resistant to all forms of therapy. Even
if dissolution of a glioblastoma has been confirmed in CT scans,
recurrence is frequent and RAFP therapy can be expected to prolong
life by only a few months. Therapy for this form of glioma has thus
progressed little since the days of Cushing and Dandy. As a conse
quence, glioblastoma multiforme is a reminder to neurosurgeons of the
limitations of current therapies. It is the duty, therefore, of researchers
in this field, to meet the challenge of glioblastoma multiforme and to
find a cure for this disease.
The present volume deals with many aspects of gliomas, including
factors related to the incidence and epidemiology, and surveys the
history of glioma therapies. Experimental studies carried out by the
Sendai Group of Neurosurgeons are reported, together with the
results of many clinical studies and clinical experience. A recent
technique for evaluating the effectiveness of therapy based upon the
MRI diagnostic method is introduced.
I hope that this book will make an important contribution to the
continuing development of therapies for glioma. Through such efforts,
I fully expect that glioblastoma multiforme will, before long, be
included among the human cancers which are capable of being cured.
I wish to express my heartfelt thanks to Drs. Teruaki Mori, Ryuichi
Katakura, and Masakazu Kitahara, whose efforts have been central
both to the research described herein and the completion of the book
itself. I also wish to thank the team of researchers whose dedicated
efforts have made this book possible and Mr. Norman D. Cook, who
has translated this work into such fine English.
Sendai, Japan, January 1988 JIRO SUZUKI
Table of Contents
Part I. Statistical Analysis
1. Epidemiology and Statistical Analysis of Gliomas.
R. KATAKURA, T. YOSHIMOTO. ..................................... 3
2. Statistical Considerations of Therapeutic Results in
Glioblastoma. K. MINEURA.
With 3 Figures ......................................................... 17
Part ll. Basic Studies
3. Combined Effects of Radiation, ACNU, and 5-FU on
Gliomas: An Experimental Combination Therapy.
S. MASHIYAMA, S. SUGIYAMA, K. KUWAHARA,
M. KITAHARA, K. TAKAHASHI, T. SASAKI.
With 71 Figures ........................................................ 37
4. The Pharmacokinetics of ACNU in Patients with
Malignant Brain Tumor. T. MORI.
With 3 Figures ......................................................... 109
5. The Effects of Induced Hypertension on the Uptake of
ACNU in Experimental Brain Tumor. Y. TSURUMI.
With 5 Figures .......................................................... 117
6. A Study of Intratumoral Oxygen Pressure in Brain
Tumors. T. KAYAMA.
With 6 Figures ......................................................... 125
Part m. Clinical Studies
7. An Outline of RAFP Therapy. T. MORI.
With 5 Figures ......................................................... 137
8. Results of RAFP Therapy on CT Scan.
J. SHINGAI. .............................................................. 149
VIII Table of Contents
9. Clinical Analysis of Glioma: Anaplastic Astrocytoma and
Glioblastoma. J. SHINGAI, M. KANNO.
With 10 Figures ........................................................ 153
10. Clinical Analysis of Glioma: Low-Grade Astrocytoma.
M. KITAHARA.
With 9 Figures ......................................................... 173
11. Clinical Analysis of Glioma: Oligodendroglioma.
M. KITAHARA.
With 5 Figures ......................................................... 187
12. Clinical Analysis of Glioma: Ependymoma.
M. KITAHARA.
With 6 Figures ................................... : ..................... 197
13. Clinical Analysis of Glioma: Medulloblastoma.
Y. TAKAHASHI.
With 3 Figures ......................................................... 209
14. Side Effects of RAFP Therapy. M. KITAHARA.
With 2 Figures ......................................................... 221
15. Clinical Study Using MRI in Patients Treated with
RAFP Therapy. S. FUJIWARA.
With 9 Figures ......................................................... 231
Subject Index ................................................................ 241
List of Contributors
FUJIWARA, SATORU Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
KANNO, MITsUNoBu Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
KATAKuRA, RYUICHI Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
KAYAMA, TAKAMASA Department of Neurosurgery, National
Hospital, Sendai, 980 Japan
KITAHARA, MAsAKAzu Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
KUWAHARA, KENJI Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
MASHIYAMA, SHOJI Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
MINEuRA, KATSUYOSHI Neurosurgical Service, Akita University
Hospital, Akita, 010 Japan
MORI, TERUAKI Department of Neurosurgery, Medical
College of Ohita, Ohita, 870 Japan
SASAKI, TAKEHITO Department of Radiation Research,
Tohoku University School of Medicine,
Sendai, 980 Japan
SHINGAI, JUNJI Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
X List of Contributors
SUGIYAMA, SATORU Department of Neurosurgery, Medical
College of Ohita, Ohita, 870 Japan
TAKAHASHI, Ko Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
TAKAHASHI, Y ASUHIRO Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
TSURUMI, Yun Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
YOSHIMOTO, T AKASHI Division of Neurosurgery, Institute of Brain
Diseases, Tohoku University School of
Medicine, Sendai, 980 Japan
Part I
Statistical Analysis
