Clinical trials on proton radiotherapy began in November, 1979 at NIRS-Chiba. Proton beams have a highly defined dose distribution, resulting in no radiation exposure beyond the beam range and very little side scatter. Since a 70MeV proton beam penetrates about 38mm through aqueous environments, only superficial tumors and ocular neoplasms are indicated for treatment with this radiotherapy. To optimize the dose distribution, the most important factors to consider are correct positioning, reproducibility of the clinical set up, and immobilization during irradiation. For treatment, fixed horizontal or vertical beams are used. Over the past 9 years, a total of 59 patients have been treated, and some preliminary clinical results have been obtained:(1) Thirty-nine patients were treated for skin cancer, soft tissue sarcoma, malignant melanoma, etc. Local control was achieved in 67.5% using radiotherapy alone, and in 30% with salvage surgery. Skin reactions after proton irradiation were generally mild to moderate.(2) Twenty ocular neoplasms (17 malignant melanomas and 3 retinoblastomas) were treated. For melanoma, average radiation dose was TDF 137, and the result was 1 complete regression, 7 partial regressions, and 2 enucleations due to glaucoma. For retionblastoma, average dose was TDF 77, and the result was 2 complete regressions and 1 partial regression. There were no severe radiation-related complications.

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Between 1969 and 1985, a total of 298 patients with cervical cancer were treated by radiation therapy at the Department of Radiology, Gunma University Hospital. Another 111 patients were treated with irradiation as a follow up to surgery; 69 for prophylactic reasons and 42 to treat residual tumors. Patients treated with irradiation alone were given a combination of external irradiation to the pelvis and low dose rate intracavitary irradiation. Patients treated post-operatively were given intracavitary electron beam irradiation of the resected end of the vagina, and external irradiation of the entire pel vis. The following results were obtained: In patients treated by r adiation therapy alone, the rel ative 5-year survival rates according to clinical stage were: 108% for patients with stage I c ancer, 90% for stage II, 62% for stage III, and 31% for stage IV. Stage IV patients with no evidence of hematogenous metastasis could be candidates for radical therapy. Local recu rrence was observed in 13% of stage II and III patients, attributed to inadequate intracavitary treatment and the histological diagnosis of adenocarcinoma. Severe complica-tions occurr ed in only 12 (4%) of the 298 patients treated with irradiation alone.The relative 5-year survival rates for patients treated with post-operative irradiation were 91% for patients treated prophylactically and 49% for patients treated forresidual tumor. Patients treated with post-operative irradiation for residual tumor at the resected end of the vagina showed a high cumulative survival rate of 77%. Since urinary sequelae developed in only 4 patients, it would seem that electron beam irradiation of the resected end of the vagina is a safe and effective method of therapy.

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N-methylformamide (NMF) is a known maturation agent, capable of inducing in vitro neuroblastoma differentiation. In this paper, the radiosensitizin effectsof NMF on an in vitro murine neuroblastoma were investigated. A/J mice bearing i.m. C-1300 tumors were treated i.p. with NMF daily for 6 days. NMF administered at a dosage of 300mg/kg significantly inhibited tumor growth. NMF treatment alone inhibited growth of a 300cu. mm tumor for 12.5days, comparable to the effects of 22.5Gy gamma irradiation. When irradiation and NMF treatment were combined, the effect was more than additive, particularly at higher irradiation doses. These results suggest that NMF may be useful as an irradiation modifier for the clinical treatment of neuroblastoma.

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Between May 1978 and March 1988, 31 patients with nasopharyngeal carcinomas were treated by radical radiation therapy at Hamamatsu University Hospital. Of these, 33% were diagnosed with T4 primaries and 42% with N3 lymph nodes. The overall 2 and 5 year survival rates were 65% and 30%, respectively. Irradiation dose had no effect on survival rate. Seventeen patients (55%) had recurrences, 12 at the primary site and 8 at distant sites. Patients with advanced N-classifications showed a high incidence of distant metastasis, while those with T-classifications showed a high incidence of local recurrence. Ten of 12 patients with local recurrences received 65-70Gy at the primary site. Nine of these 12 patients received re-irradiation using the conformation technique (mean dose=40Gy). Symptoms were alleviated in 8 of the 9 retreated patients; these patients exhibited a median survival period of 12 months. Eight patients were treated with induction chemotherapy (involving administration of cisplantin). Despite the high initial response rate (89%) to chemotherapy, combination therapy resulted in no significant improvement to survival rate compared to radiation therapy alone. These data suggest that induction chemotherapy has little beneficial role in the treatment of nasopharyngeal carcinomas.

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A planning system has been developed to automatically calcul ate and display the optimum source arrangement, irradiation conditions and dose distributions for patients treated for carcinoma of the uterine cervix by high dose-rate intracavitary therapy using a remote afterloading system. In our system:(1) the optimum dose distributions are defined as those obtained using source arrangements like the Manchester system, (2) to determine the optimum source arrangement and irradiation conditions similar to the Manchester system for the size and geometry of applicators in a patient, the shape of the isodose curve passing through points A in a series of isodose distributions is calculated, (3) the optimum irradiation condition is calculated to have a dose value on the isodose curve equal to the predefined dose value using quadratic programming, and (4) the optimized dose distributions for an optimum irradiation condition are automatically calculated and displayed. This opti mization can be calculated in about 2.5 minutes, and overall therapy can be conducted in about 25 minutes. Our system has proven very useful for routine clinical work.

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