Oxygen deficient hypoxic cells, which are resistant to sparsely ionizing radiation, have been identified in most animal and some human solid tumors. This hypoxia (H.) can be divided into 2 type of hypoxia, namely chronic H. arising from an oxygen diffusion limitation and acute H., resulting from transient stoppages in microregional blood flow. Although clinical trial have attempted to overcome, these defirencies, results have been far from satisfactory. Recent studies have shown that nicotinamide could improve tumor blood perfusion in tumors.
In many solid tumors, the pH of the extracellular fluid is acidic, low oxygen tension and decreased blood flow. During hyperthermia at the temperature usually applied clinically (above 43°C), the heat induced reduction in blood flow is often greater in tumors than in normal tissues and then, their temperature rises higher.
However, recent studies revealed that modest temperature hyperthermia (MTH) may be an efficient and useful means to improve the oxygenation of human tumors.
Recent studies showed that hypoxia induces apoptosis in transformed cells and that further genetic alterations, such as p53 mutation and bcl-2 overexpression, substantially suppress apoptosis induced by radiation and chemotherapy. These results explain the resistance of tumors to cancer therapy.
Recently, hypoxia plays an important role for to increase VPF (vascular permeability factor) expression in tumor angiogenesis.
These useful developments in tumor angiogenesis inhibitors are quite important for cancer therapy.

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The tumor control effects of total body irradiation (TBI) for tumor bearing mice and human tumor were investigated fundamentally and clinically. TBI is usually used in tissue transplantation experiment in order to prevent rejective response for transplanted tissues by immunological reaction. This kind of suppressive effect of immunological response by TBI is considered as to be caused even if very small dose of TBI. However, there are only a few data concerning the effect of low dose of TBI, and TBI of low dose level is concluded to bring about the same effect as in high dose level by back extrapolation from the data of high dose level.
In present paper, firstly the effects of TBI for tumor control in murine squamous carcinoma are reported, and secondly the results of clinical trial in malignant lymphoma are demonstrated.
In fundamental studies, TBI of low doses (10-15 cGy) suggests potentiating effect in cell killing in combination of TBI of 10 cGy and local irradiation given at 12 hours after TBI, though TBI of 10 cGy is not able to detect any cell killing effect. TBI of 10 cGy or 15 cGy also stands for suppressive effect of distant metastasis (lung metastasis).
In clinical studies, malignant lymphoma (non-Hodgikin's lymphoma) is selected as the first disease of clinical trial, and the results is seemed to be prospective method to overcome cancers with radiotherapy, though the trial is not phase III clinical trial.

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OBJECTIVE: To evaluate the effect of radiotherapy (RT) on hepatocellular carcinoma (HCC) that appears as a solitary nodule on radiologic studies.
MATERIALS AND METHODS: We irradiated 17 patients with solitary HCC lesions (25-150 mm in diameter) with approximately 60 Gy (range 50-70 Gy). Patients underwent dynamic CT and/or ultrasound imaging at 3-month intervals after treatment. Patients were classified based on lesion size, degree of cirrhosis (Child A, 6; Child B, 6; Child C, 5), and whether they had received other therapy such as transarterial chemoembolization (TACE). The responses were classified as complete, partial, no change, or progression.
RESULTS: The median survival was 12.8 months for all 17 patients, with 1-, 2-, and 3-yea cumulative survival rates of 59%, 35%, 24%, respectively. Patients classified as Child A showed significantly longer survival than those classified as either Child B (p<0.04) or C (p<0.01). Four of the five Child C patients died of liver failure within 6 months after RT despite the absence of tumor recurrence. The initial tumor diameter, concurrent treatment with TACE, and radiation dose showed no significant effect on survival.
CONCLUSION: Survival in patients with solitary HCC lesions appears to be affected mainly by the degree of liver dysfunction, and not the initial tumor diameter, radiation dose, or concurrent use of TACE.

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This is a retrospective analysis of 50 patients with squamous cell carcinoma of the oral tongue who were treated with interstitial iridium-192 brachytherapy alone between 1984 and 1995. Local control and incidence of late complications were analyzed with respect to dose and dose rate. We analyzed tumors of up to 30 mm in long diameter, which were treated with single plane implants. Local control was 46/50. Local control rates were comparable with age, sex, tumor size, macroscopic size and dose rate. Local control was relatively poor (13/15) in dose<63 Gy. Ulcer incidence was 11/50. Ulcers occurred in 3/28 at a dose of less than 60 cGy/hr compared with 8/22 at a dose of 60 cGy/hr or greater (P=0.0490 by Log-rank test). The significant factor of mucosal ulcer formation was dose rate by multivariate analysis. Ulcers occurred in 7/18 in case of 65 Gy or greater and 60 cGy/hr or greater. To maximize local control and minimaize ulcers, we recommend a dose of 63-70 Gy at a dose rate of less than 70 cGy/hr.

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Purpose: To examine the influence of various prognostic factors on local control of medulloblastoma. Materials and methods: Sixty-five patients who had been treated between 1980 and 1990 at our six hospitals were retrospectively studied. Factors included in the Cox's multivariate analysis were sex, age (log [y.o. + 1]), performance status, pretreatment T-stage (judged from the findings of CT and/or MRI; T 1: 3 patients, T2: 17, T3 [with hydrocephalus]: 44, T4: 1), extent of surgical resection (total: 30 patients, less than total: 35), total dose (21-87 Gy, median: 55) and overall treatment time (19-163 days, median: 54) of local irradiation, and use of adjuvant chemotherapy or immunotherapy. Results: Recurrence occurred in one T2 patient and in 17 T3 patients. The multivariate analysis showed that local tumor control decreased with advance in T-stage (p=0.04) and with prolonged overall treatment times (p=0.003), and that it increased with higher total doses (p=0.01). When analysis was limited to T3 patients, usefulness of the chemotherapy was also suggested (p=0.03). However, the influence of the extent of resection on local tumor control was not statistically significant, because resectability depended on T-stage. Conclusion: This analysis showed that local control of medulloblastoma was influenced by pretreatment T-stage, total dose and overall irradiation treatment time, and probably by the adjuvant chemotherapy used. Some of the observed losses by prolongations in radiotherapy may reflect proliferation of tumor cells during radiotherapy.

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To evaluate the effectiveness of combination chemotherapy with radiation therapy for esophageal carcinoma, treatment results of 355 esophageal cancer patients who received radiation therapy with and without chemotherapy were analyzed retrospectively. Two hundred and twenty four patients received radiation therapy alone (Group A), while 97 patients received single agent chemotherapy or multi-agent chemotherapy without CDDP (Group B) and 34 patients received multi-agent chemotherapy including CDDP (Group C). There was no significant difference in the incidence of distant metastasis at one year between each group. The local control rates at one year in Group A, B and C were 27.2%, 37.8% and 46.7%, respectively (p<0.01). The median survival time in group A, group B and group C were 8 months, 9 month and 16 months, respectively. The five year survival rates in group A, group B and group C were 9.8%, 6.7% and 23.2%, respectively. Improved survival due to chemotherapy was observed in stage II, III and IV patients. There was no significant difference in the incidence of life threatening complication between each group. The treatment results of multi-drug combination chemotherapy including CDDP seemed to be superior to that of radiation therapy alone.

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It is important for radiotherapy in breast conservative treatment to equalize dose distribution for a conserved breast, as well as to reduce radiation dose for the ipsilateral lung and contralateral breast. To obtain the optimal method of radiotherapy, I carried out an experimental study using an original hand-made phantom which was made from Mix-Dp and cork. In these experiments, I evaluated relative dose using the film dosimetry method and absolute dose using TLD, with three methods as a function of wedge filter angle; opposed pair method, non-opposed pair method, and half-field block method. As a result, we concluded that a non-opposed pair method with a 15-degree wedge filter seems to be optimal for the 4MV-Xray Liniac in our institute.

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To evaluate the role of combined hyperthermia and radiotherapy in the management of cervical lymphnode metastasis, a multi-institutional retrospective analysis was undertaken by the JASTRO Hyperthermia Study Group. Clinical records of cervical lymph nodes metastasis treated with thermoradiotherapy in nine Japanese institutions were reviewed. In total, 132 tumors were enrolled in this study. Among primary sites of thsese patients, 79 tumors were metastasis from head and neck cancer and 53 tumors were from other than head and neck cancers. Eighty-four tumors were squamous cell carcinomas and 29 adenocarcinomas. Hyperthermia was given within 30 minutes after radiation for most tumors. Average total radiation dose was 50±15 Gy and average heat sessions was 7±3.9 times. Response rates 1 month after combined treatment CR were 38 tumors (29%), PR, 57 tumors (42%) and NR, 37 timors (28%). No correlation between radiation dose and local response was observed. Correlation between minimum temperature and tumor response was noted. Higher minimum temperature showed higher response rates. These phenomena indicate that temperature measurement of tumor the periphery is important for clinical hyperthermia.

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A survey on radiotherapy resources in Japan was conducted at the end of 1995 as a regular activity of the JASTRO Database Committee. The census was carried out by mailing a questionnaire to 682 radiotherapy facilities. Five hundred and fourty nine (549) questionnaires were returned (80.5%), and 504 responses were suitable for analysis.

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