The techniques of radiotherapy have been improved by development of particle accelerators, radionuclides and computers. This paper presents a historical review of the physical and technical aspects of radiotherapy in Japan. Changes in the kinds of radiation, such as X-rays, gamma rays, electrons, neutrons and protons used for external radiotherapy, and the equipment involved are described chronologically, and historical changes in the quality of radiotherapy apparatus are outlined. Patient data aquisition equipment, such as X-ray simulator and X-ray CT, beam modifying devices, patient setup devices, and devices to verify treatment fields and patient doses are reviewed historically. Radiation sources for brachytherapy and internal radiotherapy, and remotely controlled afterloading systems are reviewed chronologically. Historical changes in methods to evaluate absorbed doses, dose monitor systems and beam data aquisition systems are outlined. Changes in methods of calculating dose distributions for external X-ray and electron therapy, brachytherapy and internal radiotherapy by unsealded radionuclides are described and calculation techniques for treatment planning system are reviewed. Annual figures in the numbers of radiotherapy equipment, such as telecobalt and telecesium units, linear accelerators, betatrons, microtrons, stereotactic gamma units, conformation radiotherapy units, remotely contorolled afterloading systems, and associated equipment such as X-ray simulators and treatment planning systems are provided, as are changes in the numbers of accelerators by maximum X-ray energy and maximum electron energy, and in the numbers of licensed hospitals and clinics using small sealed sources. Changes in techniques of external radiotherapy and brachytherapy are described briefly from the point of view of dose distributions.

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To determine the field factor and dose distribution for narrow beams of megavoltage X-rays used for stereotactic radiosurgery, an X-ray film (Fuji, MI-NC) was used. Dependence of the film sensitivity on X-ray energy was determined at a depth of 3cm in a MixDp phantom for 6 MV and 10 MV X-rays. Result showed that energy dependence of the film was negligibly small. In field sizes of 10×10-4×4cm, the fild factor measured by an ionization chamber agreed well with the field factor measured by film dosimetry, so the field factor of a narrow beam can be measured by film dosimetry. The dose profile of narrow beams measured by film dosimetry also agreed well with the dose profile measured by an ionization chamber (0.0092ml), It was concluded that X-ray film can be used to measure dose distribution of narrow beams in stereotactic radiosurgery.

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The concept of Nominal Standard Dose (NSD) determined from the time dosefractionation relation between acute reaction of skin and normal connective tissue to radiation, was suggested by F. Ellis. Using Ellis' formula, C. G. Orton proposed the time, dose, and fractionation (TDF) factor. The TDF value is generally used to evaluate tolerance of normal connective tissue. However, the TDF is not applicable to other organs such as the spinal cord and lungs.
Cohen, using data from radiation complications, has determined exponents of the Ellis' formula for some organs. From those formulae, we have calculated organ-specific TDFs, based on treatment schedule and dose distribution.
In the case of esophageal cancer, organ-specific TDF distributions of the irradiation technique were compared and evaluated.

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From 1976 through 1989, 94 patients with epidermoid carcinoma of the lung without mediastinal nodal involvement were treated with definitive radiation therapy (RT) at Gunma University hospital. All patients were treated with 10 MV X-rays and the mediastinum was treated in 86% of the patients. The total dose ranged from 60 Gy to 80 Gy with once-daily conventional fractionation. The actuarial two and five-year survival rates of the entire group were 44% and 22%, respectively with a median survival time (MST) of 17 months. Patients with a performance status of 0-1 lived longer than those with a status of 2 or more (MST 22.5 versus 12 months; p<0.05). The survival of 60 patients with Stage T2 tumors was better than that of 24 patients with T3 tumors (MST 19 versus 13.5 months; p<0.1). Forty-seven patients with tumors less than 5 cm in diameter had a two-year progression rate of 25%, in comparison with 39% for 47 patients with tumors greater than 5 cm. The survival difference between these two groups was statistically significant (p<0.01). Patients given a total dose of 80 Gy or over had only 20% local progression at the time of the last follow-up, but they had a lower long-term survival rate than those given a total dose of 60-74 Gy because of the development of pulmonary insufficiency after high-dose irradiation. There was no relapse in the field given 40 Gy or more to the mediastinum for prophylaxis in the patients with no evidence of primary progression. The actuarial five-year survival rates for the patients given 40 Gy or more to the mediastinum, and for the patients given less than 40 Gy were 32% and 9%, respectively. There was a statistically significant difference between these two survival curves, (p<0.05). Differences in survival did not depend on age, sex, or location of the primary tumor. These results should provide support for definitive RT to manage patients with medically inoperable or unresectable epidermoid carcinoma of the lung without mediastinal nodal involvement.

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Changes of vascular density and drug distribution after 25 Gy single local irradiation were studied in two different mouse tumor systems. Histologically, squamous cell carcinoma (SCC) and fibrosarcoma (Fib) were used. Squamous cell carcinoma was much more radiosensitive than fibrosarcoma. In SCC, the vascular density and the distribution were remarkably decreased from 3 to 7 days after irradiation. These changes were observed earlier than tumor regression. Fourteen days after irradiation when tumor regrowth was evident, vascular density and drug distribution had recovered significantly. In Fib, in which no regression was observed after irradiation, the vascular density and drug distribution decreased as the tumor grew. The vascular density 3 days after irradiation could not be evaluated in Fib due to homogeneous stain of the whole tumor.

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Depth dose distribution of a proton beam with the best quality has been calculated for a small field. The normal tissue dose around a target irradiated by a proton beam was estimated based on irradiation conditions for a few typical cases of small lung cancer treated by multi-portal irradiation. The surface dose at each port was estimated to be below 10% of the maximum dose when 6 portal irradiations doses were applied to a target smaller than 3 cm in diameter. However the relative dose averaged for a “dose increasing region” was calculated to exceed 10%. Rusults indicate the need for a precise rotational irradiation system when designing a dedicated proton radiotherapy facility.

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A new protocol for the treatment of nasopharyngeal cancer was designed and has been employed since 1984 at Hyogo Medical Center for Adults. Thirty-three previously untreated patients who were assigned to this protocol from 1984 to 1991 were analyzed in this study. Eighty-six nasopharyngeal cancer patients who were treated at our institution from 1972 to 1983 were chosen as an historical control group. All patients were followed up for a minimum of 2 years. The essence of the treatment philosophy of our protocolwas; 1) Combination chemo-radiotherapy using CDDP (but excluding patients 70 years old or older). 2) Boost irradiation of 10-20 Gy for patients with tumors persisting evenat 40 Gy or T4 cases. 3) Prophylactic neck irradiation. The protocol yielded a better 5-year survival rate (56.6% vs 47.6%, p<0.05) and less frequent locoregional failure rate (18.2%vs 48.8%, p<0.01) than those of patients in the control group. Among the patients with T1-3 and NO-2 disease, the difference between survival rates with and without protocol was statistically significant but not for the patients with T4 and N3 disease. The protocol was well tolerated by most of the patients.

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Characteristics of hypoxic cells subjected to radiation were investigated and compared with those of microcirculation for two murine fibrosarcomas growing in C3H mice. Small NFSa tumors, growing in air-breathing mice, developed a radioresistant tail on the survival curve. The tail was indistinguishably parallel to a survival curve for an artificially hypoxic tumor. As the NFSa tumors increased in size, the hypoxic tail moved upward with no change of Do, resulting in increase of hypoxic traction from 3.9% to 40%. The R1137 tumors had no radioresistant tail nor hypoxic fraction regardless of tumor size. However, large-sized R1137 tumors developed a significant number of radioresistant, hypoxic cells with an intermediate Do, and were effectively sensitized by administrating misonidazole before irradiation. Thus, the NFSa tumors were fractionally hypoxic, and the large R1137 tumors had intermediate hypoxia. Measurement of tumor microcirculation by gadolinium-enhanced nuclear magnetic resonance indicated that both blood flow and blood volume decreased significantly when the NFSa tumor grew large. Similar reduction in these microcirculation parameters was also observed for the R1137 tumor. The small-sized NFSa tumor had relatively larger blood volume and faster blood flow than the small-sized R1137 tumor. When large-sized tumors were compared to each other, the NFSa again had better blood flow than the R1137. However, the blood volume in the large-sized tumors was significantly (P<0.05) smaller for the NFSa tumor than for the R1137 tumor. It was concluded that blood flow could not be a single determinant for tumor hypoxia, and the difference between fractional hypoxia and intermediate hypoxia would be reflected in the ratio of blood flow to blood volume.

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This overview summarized the most important clinical fundamentals to implement combined hyperthermia (HT) and radiotherapy (RT) in clinical trials and reviews clinical HT-RT data obtained in superficial and medium depth tumors treated with external heating devices.
In the first part we discuss the following clinical fundamentals: selection of appropriate clinical sites for HT-RT studies, selection of suitable HT-devices, priniciple design of clinical HT-RT studies, requirements for treatment prescription, relevant treatment endpoints, definition and assessment of a thermal enhancement ratio (TER) and therapeutic gain factor (TGF), impact of prognostic parameters on treatment stratification and statistical evaluation.
In the second part we review and discuss clinical results of thermoradiotherapy (HT-RT) for advanced breast carcinoma, recurrent breast cancer, advanced head and neck tumors, cervical neck node metastases, malignant melanomas and residual microscopic disease. In addition, clinical results of pilot studies are reviewed, which have applied a triple modality approach of thermo-radiochemotherapy (HRC) for various tumors. Finally, possible future perspectives of clinical HT-RT research are outlined.

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