Clinical trials of heavy particle radiotherapy using a HIMAC (Heavy-Ion Medical Accelerator in Chiba) synchrotron will start in 1994. A group of physicists and Biologists from the National Institute of Radiological Sciences along with other institutions have organized collaborative research and investigated the biological effectiveness of heavy paticle beams which were provided with a RIKEN Ring Cyclotron. A Bragg peak of 135Mev/u carbon-12 (C-12) was spead out by a lucite range modulator which was biologically designed by Dr.Kanai. The Spread-Out-Bragg-Peak (SOBP), with 3-cm width, showed homogeneous lethal effects not only to chinese hamster V79 cells, which were used to design the range modulator, but also to human salivary gland tumor HSG cells and mouse intestinal crypt cells. RBE of C-12 distal SOBP-12, as measured by the growth delay of murine NFSa fibrosarcoma, showed a prominent dose dependence while the proximal SOBP and unmodulated plateau with a relatively low LET showed less dose dependence.
Increase of therapeutic gain was anticipated by franctionated irradiation; normal tissue which recieves low LET at the entrance position would repair radiation damage more prominently than a tumor being irradiated by high LET of SOBP. Repair of potentially lethal and sublethal damage was less for SOBP than entrance. Also introduced here were subjects including particle dependence of RBE-LET relationship, potentiation effects of fractionated irradiation, volume effects of normal tissue damage.

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Local control rates for T3 and T4 laryngeal carcinoma treated with radiation alone have been reported as 42 to 63% and 18 to 56%, respectively. We investigated the factors which affect survival and local control rates for T3 and T4 laryngeal carcinoma. From 1967 through 1985, 43 advanced laryngeal carcinoma (T3: 14, T4: 29) cases were treated with radical radiotherapy and 35 (T3: 14, T4: 21) with preoperative radiotherapy at the Department of Radiology, Osaka University Hospital. The 5-year cause-specific survival rates for T3 and T4 cases treated with radical radiotherapy were 48% and 52%, and for those treated with preoperative radiation 71% and 43%, respectively. No statistically significant differences were found between cause-specific survival rates for cases treated with radical radiotherapy and preoperative groups. The 5-and 10-year cause-specific survival rates for NO cases treated with radical radiation were 67% and 67% and those for N+ cases 42% and 25%, respectively. Causespecific survival rates for NO cases were significantly higher than for N+ cases (p<0.05). The 5-year local control rates for T3 and T4 cases treated with radical radiation were 48% and 24%, respectively. Ultimate local control rates for tumors with invasion of the base of the tongue (13%) were significantly lower than that for those with invasion of other sites (67%)(p=0.034). Nodal metastasis proved to be an important prognostic factor for T3-4 laryngeal carcinoma treated with radical radiation, and base of the tongue invasion for T4 supraglottic carcinoma.

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Ninety-one fresh autopsied esophageal carcinomas treated with a radiation dose of more than 40 Gy were analyzed, because no primary tumor with under 40 Gy was controlled. There were no residual tumors in 6.6% of the patients. Radiation controlled 28.6%of the loco regional tumors. The local control rate was higher in patients with a tumor length under 5cm. Metastasis was detected in 76.9% of all the patients. Twenty patients (22.0%) hadno primary tumor but metastases. The most common sites of metastasis were the lymph node, lung and liver.
Multivariate analysis indicated that the primary tumor control correlated directly with the survival period. Some patients with a primary tumor which was easy to control developed lung metastasis more often. Liver metastasis was found more frequently in patients where the primary tumor was located in the lower portion of the esophagus. Patients with a tumor length of more than 10 cm had neck or mediastinal lymph node involvement more often; neck or mediastinal lymph node metastases were not always fatal immediately.
Perforations into other organs were observed in 41.8% of the patients. Younger patients, patients with the tumor located in the upper portion of the esophagus, and patients with T4 tumor have a significantly higher risk of perforation. In such a patient, the total radiation dose should be reduced to less than 70 Gy. Nine patients (9.9%) had double cancers.

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In endoluminal brachytherapy for the tracheobronchial tree, esophagus, and bile duct, a reference point for dose calculation has been often settled at 1cm outside from the middle of source travel path. In the current study, a change in the ratio of the reference point dose on the convex to concave side (Dq/Dp) was calculated, provided the source travel path bends as is the case in most endoluminal brachytherapies. Point source was presumed to move stepwise at 1cm interval from 4 to 13 locations. Retention time at each location was calculated by personal computer so as to deliver equal dose at 1 cm from the linear travel path. With the retention time remaining constant, the change of Dq/Dp was assessed by bending the source travel path. Results indicated that the length of the source travel path and radius of its curve influenced the pattern of change in Dq/Dp. Therefore, it was concluded that the difference in reference dose on the convex and concave side of the curved path is not negligible under certain conditions in endoluminal brachytherapy. In order to maintain the ratio more than 0.9, relatively greater radius was required when the source travel path was decreased.

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In our department, 17 patients with stage I histologically confirmed squamous cell carcinoma of the vocal cord were treated with ⁶⁰Co γ-rays, 25 with 10MV γ-rays, and 52 with 4MV γ-rays. The 5-year recurrence-free survival rates were 88%, 60% and 91%, respectively. The results might indicate that ⁶⁰Co y-rays and 4MV γ-rays are suitable for treating for early laryngeal carcinoma, and high photon energy beams such as 10MV γ-rays are not.

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In prophylactic whole cranial irradiation (PCRT) without compensation for the shape of head and neck, hot spots will occur in the anterior, posterior and parietal portions of the brain and also in the upper cervical cord. A system for making three-dimensional compensating filters (3DCFs) conforming to CT images of the head and neck has been developed in our department. Using 3DCFs, uniform dose distribution without hot spots can be achieved in PCRT.

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A multi-institutional prospective randomized trial was conducted to determine the optimal timing for use of Romurtide, in treatment of leukopenia caused by radiotherapy. Of the 94 patients with malgnant tumors who were enrolled in this study in the period from April to October 1992, 78 are reviewed here. Romurtide was given to 41 of the 78 patients in their first and second weeks of radiotherapy (Group A), and to 37 patients in their third and fourth weeks (Group B). Radiation therapy was carried out in all cases without interruption because there were no remarkable decreases in WBC counts. WBC counts in Group A remained higher than those in Group B throughout the treatment period. It was concluded that Romurtide is an effective supportive drug in treatment of leukopenia caused by radiotherapy, and that administration of Romurtide should be early in the treatment period.

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Thermal enhancement effects of Vindesine Sulfate (VDS) with or without Tumor Necrosis Factor (TNF) was tested by determining the delay in growth of mouse transplantable tumor (FSa-II). The growth curve after an administration of VDS (100 mg/kg) alone showed no difference from the control group while at a dose of 200 mg/kg of VDS a slight growth delay was observed. TNF (1000 units) did not sensitize the effects of VDS (100 mg/kg), a dose of 200mg/kg of VDS tumor growth delay was observed.
The tumor growth curve after heat alone (43°C 20 min. x2) showed no difference from the control group. Combined use of VDS (200 mg/kg) and heat (45°C, 20 min. x2) caused a marked delay in tumor growth but not at 43°C. Though combined use of VDS and TNF had no effect on tumor growth time, an addition of 1000 unit of TNF to the combination of VDS (200 mg/kg) and heat (45°C, 20 min. x2), eradicated all tumors. This implies that trimodality treatment of TNF, VDS and hyperthermia would be promissing.

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