The effects of combination therapy, radiation and two local administrations of OK-432, a biological response modifier, were studied using a radioresistant and weakly immunogenic murine fibrosarcoma that originated spontaneously in a C3H female mouse. The inhibition of tumor growth by OK-432 depended on both dose and timing of administration, and was most prominent when a total of 2 or more KE (Klinische Einheit) with one week interval was used in combination with a single 40 Gy irradiation. Fifty percent tumor control doses were 83.5 (79.6-87.4) Gy in animals given radiation alone and 60.7 (55.9-65.4) Gy in animals given a total of 6 KE of OK-432. Thus, OK-432 enhanced the radiation dose effectiveness by a factor of 83.5/60.8, i. e. 1.38. Examination of subsets of lymphocytes infiltrating into the tumor tissue using monoclonal antibodies showed that Lyt-1, Lyt-2 and L3T4 positive lymphocytes increased significantly more in the group given two administration of OK-432 than in the group given radiation alone. The administration of antiasialoGM 1 antibody before intraperitoneal tumor injection enhanced the tumor growth, but it did not enhance the tumor growth in tumor-bearing mice in the groups given radiation with or without OK-432.

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PURPOSE: In the treatment of prostatic cancer using daily intermittent multiportal therapy (DIMT), which we propose as a novel conformational therapy, acute reactions, change in tumor marker levels, and complications after more than 6 months of treatment were evaluated. MATERIAL AND METHODS: From June 1989 to September 1990, 26 patients with prostatic cancer (stage A2, 3 patients; B, 9 patients; C, 2 patients; D, 10 patients; recurrence, 2 patients) were treated. The mean follow up period 11.6 months and 15 patients have been followed up for more than 1 year. The treatment schedule is 52.5 Gy 16 fractions of 52.5 Gy each in 4 weeks for radical treatment, and 8 fractions of 30.0 Gy each in 2 weeks for palliative treatment. The 360 degree rotation about the patient was devided into 16 fractons, and 2 opposing fractions were used in one day as parallel opposed portals to treat the target volume. The fractions were serially treated one per days, so that 8 treatment days produced a total dose distribution similar to that for conventional conformational therapy. The size of the irradiation field varied from 6×6 cm to 9×9 cm. No hormonal therapy was performed for stage A2 or B. RESULTS: Acute effect was minimal including skin erythema 2/26 (7%), pollakisuria 1/26 (4%), mild symptoms due to acute proctitis 9/26 (35%). Abnormally high PSA and/or PAP levels returned to the normal range after the treatment in 7 of 10 patients. Local recurrence was detected in 1 patient with stage D, 15 months after completion of therapy, but 21 other patients continued for more than 6 months with no clinical evidence of local recurrence. No residual disease was detected by biopsy undertaken in 10 patients after more than 6 months. No severe complication was detected after more than 6 months except in 1 patient who needed colostomy for the relief of rectal bleeding. CONCLUSION: DIMT can have the total dose distribution similar to that of conventional conformational therapy without specific devices. Initial results on prostatic cancer treatment were encouraging.

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From 1967 through 1982, 274 cases with T1 glottic carcinoma were treated with telecobalt therapy at the Department of Radiology, Osaka University Hospital. Of these, 209 were treated with daily doses of 2 Gy and 57 were treated with 2.5 Gy. The tumor clearance rate of cases treated with 2.5 Gy per day was significantly lower than that of cases treated with 2 Gy per day at the same value of TDF. Tumor clearance of the 2.5 Gy Group occurred later than expected, based on the clearance data of the 2 Gy Group. The five-year local control rate of cases treated with 2 Gy was 80% and of those treated with 2.5 Gy per day the rate was 87%. The ultimate local control rate with salvage surgery of cases treated with 2 Gy and 2.5 Gy per day were both 93%. There was no statistically significant difference between the local control rates of tumors treated with 2 Gy and 2.5 Gy per day.

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Clinical studies of different fractionation regimens have been evaluated for 56 cases with non-small cell lung cancer irradiated over 60 Gy from July, 1985 to December, 1989. Eleven to 19 patients were treated annually by one of four treatment regimens:(1) Conventional fractionation [C-f: 2 Gy/Fr, 5 Frs/W; 11 cases], (2) Boost therapy [B-t: 40-50Gy/4-5wks→4-5Gy/Fr, 2-3Frs/w;19 cases], (3) Hyperfractionation [H-f: 1.1-1.2Gy×2Frs/Day, 5 Days/W; 11 cases], (4) Dose increment [D-i: 1.8Gy→2.2 (2.4) Gy→2.6 (3.0) Gy/Fr, at intervals of 1 to 2 weeks, 5 Frs/W;15 cases].Theeffectiveness of these four regimens against primary tumors was analyzed for initial response, clinical course after radiotherapy, autopsy findings, radiation injuries and prognosis. The following results were obtained. 1) Complete response rate by D-i·EB-t·EC-f·EH-f relative to tumor size; and the regimens were 0%·E100%·E50% effective in 9 cases with tumors 3 cm or less in diameter, 29%·E20%·E12.5%·E0% in 27 cases with tumors 3.1 to 6 cm in diameter and 29%·E12.5%·E 0%·E0% in 20 cases with tumors 6.1 cm or larger. 2) Cases with tumors 3 cm or less in diameter treated by B-t or D-i showed no tumor regrowth during observation for 8 to 54 months. Moreover in cases with tumors 3.1 cm or larger, both regimens were superior to others in the periods required for regrowth (P<0.05-0.001). 3) One of 24 autopsy cases was free of cancerous cells in the primary site (Ef. 3). Five cases showed moderate radiation effects (Ef. 2). These 6 cases, including 4 with tumors over 3.1 cm in diameter, had been irradiated with B-t or D-i except for 1 with C-f. 4) Radiation injuries were within acceptable limits although augmentation of radiation pneumonitis had been incessantly taken by a feeling of unrest in cases irradiated with B-t and D-i. 5) Cumulative survival rate showed C-f·EB-t·ED-i > H-f (P<0.05). However, 9 cases that survived more than 1 year without local recurrence had been irradiated with B-t or D-i. The above results indicate that fractionation regimens with B-t or D-i are hopeful for control of primary tumors; resulting in improved prognosis in non-small cell lung cancer. We are thus going to start study of dose-increment radiotherapy combined with boost therapy.

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This study analyzes the results of 129 patients of stage I and II non-Hodgkin's lymphomas of the head and neck treated at the National Cancer Center Hospital from 1969 to 1987. The 5 year survival rates of primary Waldeyer's ring lymphoma according to stage were 72.7% of stage I and 58.9% of stage II. Survival rates in patients treated with combined radiation and chemotherapy were superior to the rates of those treated with radiation alone (67.2% vs 50.4%). After adriamycin (ADM) was introduced, disease free survival rate was improved (ADM+, 59.2%; ADM-, 46.2%). The main histologic subtype and phenotypes were B-cell, and diffuse large cell type. The 5 year Survival rates of sinonasal lymphomas were 15.7% of primary nasal lymphoma and 17.1% of paranasal sinuses. Several clinicopathologic differences were observed between nasal and paranasal lymphomas: 1) Local recurrence occurred more often in nasal lymphoma, 2) The main histologic subtypes and phenotypes of nasal lymphoma were T-cell, diffuse medium sized cell type contrary to B-cell, and diffuse large cell type in paranasal lymphoma. The 5 years survival rates primary lymphomas of cervical lymph nodes were better for stage II patients (77.8%) than those for stage I patients (54.5%). This may have been due to poor outcome of stage I patients treated with radiation alone. In histologic subtypes, survival rate was not significantly dfferent for diffuse and follicular types.

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The combined effect of radiation and etoposide on the survival of cultured Chinese hamster V 79 cells was investigated. Cells in exponential growth phase were treated with various combinations of radiation and etoposide. The surviving fraction was assessed by colony formation.
Etoposide significantly reduced so-called shoulder width, as expressed in Dq (quasithreshold dose), of radiation survival curves. The reduction depended on the increase of etoposide concentrations, although steepening of slopes of exponentially regressing portions of the radiation survival curves was slight. Split dose experiments showed that cells did not recover from sublethal radiation damage in the presence of low concentration of etoposide, although they did recover from sublethal radiation damage under a drug free condition. The results show the suppressive effect of etoposide on recovery from sublethal radiation damage. The effect of a sequential combination of radiation and etoposide was also investigated. The effect was more marked when the interval between radiation and etoposide was shorter regardless of the sequence.

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The immunological activity of host mice following local hyperthermia combined with radiation was examined and compared with results obtained by determining the specific anti-tumor cell-mediated immunity in host mice induced and/or enhanced by local irradiation of transplanted tumor. MM 46 tumor cells were inoculated into the left thigh of C3H/He mice (2×10⁶ cells each) and then treated with a single dose of X-ray irradiation and/or local hyperthermia 7 days after inoculation. Suppression of tumor growth in the group of mice treated with local hyperthermia combined with radiation was greater than that in the group of mice treated with irradiation alone. Spleen cells from these treated mice inhibited the growth of tumor cells in vitro when assessed by ³H-TdR incorporation by tumor cells (cytostatic activity). The suppressive activity of spleen cells from mice treated by local hyperthermia with irradiation were clearly reduced. These results suggest that local hyperthermia combined with irradiation induce the and-tumor immunity more effectively than irradiation alone.

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This was a phase I-II nonrandomized study that explored the toxicity and response of fractionated half-body irradiation (F-HBI) in patients with multiple symptomatic osseous metastases. The patients had no premedication and received 10 Gy in 5 fractions with a dose rate of 15 cGy/min. At the Cancer Institute Hospital, 9 patients were treated by this technique (1 upper and lower F-HBI, 6 upper F-HBI, 2 lower F-HBI). All patients were female and had adenocarcinomas (8 breast and 1 lung). Adverse effects were myelosuppression, vomiting and partial alopecia. But hematologic toxicity was treated with blood transfusion or G-CSF. All toxicity was transient, and no pneumonitis nor radiationrelated deaths occurred. When given as palliation, F-HBI was found to relieve pain in 80% of the patients. In 10% of the patients the pain relief was complete. The mean time to achieve pain relief in responders after F-HBI was 9 days. The pain relief was long-lasting and continued without need of reirradiation for 40% of the remaining patient's life. This treatment modality appears to be well tolerated and effective in patients with multiple symptomatic osseous metastases. The optimal indications, dose and fractionation for F-HBI should be further explored in randomized trials.

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