ELSEVIER

Int. J. Radiation Oncology Biol. Phys., Vol. 36, No. 5, pp. 1263-1265, 1996 Copyright 0 1996 Elsevier Science Inc.

Printed in the USA. All rights reserved 0360-3016/96 $15.00 + .OO

PII: SO360-3016(96)00405-l

l Radiation Oncology Centennial Series

HISTORY AND DEVELOPMENT OF RADIATION ONCOLOGY IN JAPAN

TAKASHI YAMASHITA, M.D.* AND MITSUYUKI ABE, M.D.+

*Cancer Institute Hospital, 1-37-1 Kamiikebukuro, Toshima, Tokyo 170, Japan; and +National Kyoto Hospital, l-l Mukaihata-cho Fukakusa, Fushimi-ku, Kyoto 612, Japan

INTRODUCTION

The Japan Radiological Society (JRS) was founded in 1923 by physicians and scientists active in the field of radiology. This society now covers three fields: diagnostic radiology, therapeutic radiology, and nuclear medicine, with a membership of approximately 6,400 as of August 1995. The Japanese Society of Nuclear Medicine was or- ganized in 1964, followed by the Japanese Society for Medical Imaging in 1986. These organizations are sepa- rate from the JRS, but most of their members are also members of the JRS.

The Japanese Society for Therapeutic Radiology and Oncology (JASTRO) was created with a constitution and bylaws in 1988 to form an association to promote research on all aspects of radiation oncology in Japan. The membership was initially 614 but reached 1293 in 1995, with 978 physicians, 37 physicists, 39 radiobi- ologists, 54 medical engineers, and 184 technicians. Of the physicians, 567 are full-time radiation oncologists and the others are engaged in both the fields of diag- nostic and therapeutic radiology. Again, most of the JASTRO members are also members of the JRS. The International Congress of Radiation Oncology was held in Kyoto in 1993 under the leadership of JASTRO. It was the first independent and successful world scientific assembly in radiation oncology.

In Japan, there are 629 institutions in which a total of 685 megavoltage machines, including telecobalt, linacs, and betatrons, are installed. However, there are only 567 full-time radiation oncologists, which demonstrates an ur- gent need to increase the number of radiation oncologists. Such a shortage of not only radiation oncologists but also diagnostic radiologists resulted mainly from the tragedy of the atomic bombing of Hiroshima and Nagasaki. There is a strong aversion to radiation in Japan, which makes people afraid of receiving radiation therapy. This is clearly demonstrated by the fact that radiation therapy is used only on about 20% of all cancer patients (4).

The Japanese Board of Radiology was authorized by the JRS to certify radiologists and has offered certification in general radiology since 1966. The certification exami- nation is composed of oral and written examinations on diagnostic radiology, therapeutic radiology, and nuclear medicine. Candidates, desiring certification must have 5 years of training at board-certified training centers for ra- diologists. Those who succeed in the examination in all three fields are certified as board-certified radiologists. Be- cause of the rapid strides in both therapeutic radiology and diagnostic radiology, more specialized radiologists were required. Therefore, separate certification in therapeutic radiology and diagnostic radiology, which includes nu- clear medicine, was started in 1989. Currently, 2934 ra- diologists hold certificates from the Japanese Board of Radiology.

The Society for Radiation Physics in Medicine was founded in 1961 and the board examination for Radiation Physics in Medicine was started in 1987.

Several areas of remarkable development are described below in tracing the rise of radiation oncology in Japan.

DEVELOPMENT OF RADIOTHERAPY EQUIPMENT

From KV to MeV equipment Kilovolt x-ray radiotherapy equipment from Shimadzu

Corporation was first installed in Japan in 1922 at Kyushu University and was used for the treatment of tuberculosis. In 1937, S. Nakaidzumi developed convergent therapy us- ing a convergent collimator to treat deep-seated tumors and published a paper on rotational x-ray therapy under fluoroscopic control (2). During World War II there was no improvement. Japanese 6oCo teletherapy machines have been distributed by Toshiba Corporation since 1953, and in the following year, the first Japanese betatron was made by Shimadzu Corporation. These two companies have been competitively developing radiotherapy equip- ment in Japan ever since.

Reprint requests to: Takashi Yamashita, M.D., 1-37-1 Ka- miikebukuro, Toshima, Tokyo 170, Japan.

Accepted for publication 8 August 1996.

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1264 I. J. Radiation Oncology l Biology 0 Physics Volume 36, Number 5, 1996

Particle beam therapy Neutron therapy. Using Van de Graaff, a clinical study

of fast neutron therapy was started at the National Institute of Radiological Science (NIRS) in Chiba in 1970. In 1975, NIRS was equipped with a cyclotron for fast neutron ther- apy, and since then, it has been used to treat about 2000 patients. In 1976, Tokyo University started neutron treat- ment using a cyclotron (11). From the clinical results ob- tained, H. Tsunemoto demonstrated that osteosarcoma, soft tissue sarcoma, and salivary gland tumors are indi- cations for neutron therapy.

Neutron capture therapy. Boron Neutron capture ther- apy (BNCT) was started in Japan in 1968 on 147 patients with brain tumors (mostly glioblastoma) and 12 patients with malignant melanoma who were being treated at Kyoto University and Musashi Engineering University. The 5-year survival rate of all patients with malignant gliomas was about 20%. However, when BNCT was se- lectively applied to those with shallow-seated tumors, the survival rate was about 60%, which is significantly better than that obtained by photon radiotherapy.

Proton therapy. The first proton treatment was started at NIRS for melanoma of the eye in 1978. In 1983, high energy proton therapy was introduced for deep-seated tu- mors at the National Laboratory for High Energy Physics in Tsukuba University. The results of proton therapy by T. Kitagawa and H. Tsujii showed good complete re- sponse rates for esophageal cancer, bladder cancer, and prostatic cancer (10).

Heavy ion therapy. To obtain not only the superiority of dose distribution but also the gain of biological effec- tiveness, treatment by heavy ions was programmed in the 1980s in our country. A medically dedicated heavy ion therapy facility was constructed in NIRS in 1994. The accelerator is capable of accelerating helium and argon to a maximum energy of 880 MeV/atomic mass unit. The facility is called the Heavy Ion Medical Accelerator in Chiba (HIMAC), and its first patient was treated with car- bon ions in June 1994.

Brachytherapy Low dose rate brachytherapy. In 1929, 5 g of radium

sources were imported for medical use and held at the Cancer Institute Hospital (CIH) in Tokyo. With this ra- dium source, radon gas was collected to make radon seeds for medical use from 1935 through 1975. The Radioiso- tope Association was founded in 1951 to supply radio- isotopes. An afterloading system called a Tazaki- Arai-Oryu (TAO) applicator for cervical cancer was stan- dardized in 1968 (8). The Japanese Atomic Institute started to produce Rn seeds for medical use beginning in 1975.

High dose rate brachytherapy. In 1966, H. Wakaba- yashi of Hokkaido University developed the first remote afterloading machine (RALSTRON) using 6oCo for cer- vical cancer (13). In the past 30 years, 170 of these RAL- STRONs have been distributed throughout Japan. In 1989,

the first high dose rate 19’Ir remote afterloading machine was imported and 34 institutions now use this machine.

“ICf pilot study A pilot study with 252Cf brachytherapy was conducted

with 252Cf sources made available on loan to the Cancer Institute Hospital and Keio University in 1977- 1989 (14). Radioresistant tumors such as cervical adenocarcinoma, advanced head and neck tumors, and melanoma were treated.

Treatment planning A rotational tomography machine for planning of ra-

diotherapy was developed by Toshiba Corporation in 1962, which later developed into the computed tomogra- phy scanner (CT). In 1963, the first simulator using an x- ray video system was produced by Shimadzu Corporation. A real-time, CT-linked, 3D treatment-planning system called a CT simulator was developed by M. Abe in 1987 (3). It consists of a CT scanner, multiimage display com- ponent, and a treatment-planning device that includes a laser beam projector to outline the designed portals on the patient. Significant advantages include implementation of conformal radiotherapy, particle radiotherapy, and gamma knife or radiosurgery, which requires a precise determi- nation of the target volume. About 30 CT simulators are now installed in major radiotherapy centers throughout Japan.

DEVELOPMENT OF RADIOTHERAPY TECHNIQUE

Hitachi Roentgen Corporation developed an arc con- vergent therapy apparatus with Y. Umegaki in 1956. In 1957, Umegaki patented the variously shaped collimator rotation therapy, which was developed into conformal ra- diotherapy by S. Takahashi in 1960 and was computerized by T. Matsuda in 1980 (7, 12). In Japan, 53 institutions currently perform conformal radiotherapy.

Intraoperative radiotherapy (IORT) Intraoperative radiotherapy (IORT) was started inde-

pendently in 1964 by M. Abe of Kyoto University and by the National Cancer Center, and is performed in about 60 institutions in Japan (1). This IORT technique has spread to the US and several countries in Europe, China, and Korea.

Radiotherapy based on radiobiology Hyperbaric oxygen therapy and radiosensitizer. In

1963, T. Terashima reported on the age-response function of cells to radiation (9). Hyperbaric oxygen therapy was started in the 1970s but as in many other countries, no clinical benefit was obtained. In the field of radiation sen- sitization, the fundamental research was started in the late 197Os, and since then, numerous compounds have been synthesized and screened. Among them, KU-2285 (fluor-

inated 2-nitroimidazole), AK-2123 (3-nitrotriazole), and RP-3.50 (Znitroimidazole nucleoside) have now entered clinical trials (5, 6).

Hyperthermia Clinical hyperthermia studies were started in 1978. In

1984, the Japanese Society of Hyperthermic Oncology was founded, and its membership had grown to approxi- mately 1300 in 1995. Various types of heating equipment have been developed, and radiotherapy combined with hy- perthermia has gained the continuous approval of health insurance since 1990. Hyperthermia is performed in about 180 institutions. The Thermotron RF-8 and the Thermox 1000 are two major radiofrequency wave capacitive heat- ing machines that were developed in Japan. The devel- opment of noninvasive thermometry is underway, but it is still far from satisfactory.

Quality assurance in radiotherapy To assure the quality of dosimetry, the JRS in collab-

oration with the Japanese Association of Radiological

Physicists has founded 14 regional centers to measure standard doses in medicine. Dose calibration in radiation therapy institutions is performed at the nearest regional centers.

DISCUSSION

The Department of Radiology in most universities or hos- pitals includes three fields: diagnostic radiology, therapeutic radiology, and nuclear medicine and is managed by one or two professors. There are only a few universities where com- plete separation of the three fields has been obtained by as- signing a total of three professors. There are still many more megavoltage machines than full-time radiation oncologists to operate them. Part-time radiologists, who are engaged in both the fields of diagnostic and therapeutic radiology, make up for the shortage. For these reasons, the JASTRO is man- aged at present under close cooperation with the JRS through a liaison committee of the two societies.

History and development of radiation oncology in Japan 0 T. YAMASHITA AND M. ABE 1265

REFERENCES

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7. Takahashi, S. Conformation radiotherapy. Acta Radiol. Suppl.:l-142; 1965.

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14. Yamashita, T.; Kaneta, K.; Tsuya, A.; Hasumi, K.; Fukuda, K. Update on intracavitary radiotherapy with Cf-252 for uterine cervical carcinomas at the Japan Cancer Institute Hospital. Nuclear Sci. Appl. 4:193-196; 1991.