Hiroshi Tsunemoto

Intraoperative radiotherapy for advanced carcinoma of the biliary system

Since November 1973, intraoperative radiotherapy has been performed on five patients with unresectable, advanced carcinoma of the bile duct at the hepatic hilus and six patients with unresectable carcinoma of the gallbladder. A treatment cone with a diameter ranging from 4–10 cm was directly applied at the lesion. A single dose of 2500–3000 rad with 11 to 20 meV electrons was delivered. In all patients, recanalization of the obstructed bile duct was observed by the postoperative cholangiography. The local efficacy was confirmed histopathologically in eight autopsied materials and a specimen resected 105 days after radiotherapy. Mean survival time of patients with unresectable tumors was 10.9 ± 5.6 (SD) months after this radiotherapy. Intraoperative radiotherapy increased the effectiveness and length of palliation for the unresectable lesion.

Proton Therapy in Japan

There are two facilities for clinical trials with protons in Japan: the National Institute of Radiological Sciences (NIRS), Chiba, and the Particle Radiation Medical Science Center (PARMS), University of Tsukuba. At the National Institute of Radiological Sciences, patient treatment with the 70 MeV proton beam began in November 1979, and 29 patients were treated through December 1984. Of 11 patients who received protons only, 9 have had local control of the tumor. Two of the 9 patients, suffering from recurrent tumor after radical photon beam irradiation, developed complications after proton treatment. In the patients treated with photons or neutrons followed by proton boost, tumors were controlled in 12 of 18 patients (66.6%), and no complications were observed in this series. Malignant melanoma could not be controlled with the proton beam. A spot-beam-scanning system for protons has been effectively used in the clinical trials to minimize the dose to the normal tissues and to concentrate the dose in the target volume. At the Particle Radiation Medical Science Center, University of Tsukuba, treatment with a vertical 250 MeV proton beam was begun in April 1983, and 22 patients were treated through February 1984. Local control of the tumor was observed in 14 of 22 patients (63.6%), whereas there was no local control in the treatment of glioblastoma multiforme. There have been no severe complications in patients treated at PARMS. The results suggest that local control of tumors will be better with proton beams than with photon beams, whereas additional modalities are required to manage radioresistant tumors.

Indications of particle radiation therapy in the treatment of carcinoma of the esophagus

Studies were made to evaluate the role of radiations in the treatment of carcinoma of the esophagus to confirm indications for charged particles. Results of the studies showed that prognosis of the patients treated with radiations depend strongly on length of tumor as well as on invasion of tumor cells into the adventitia of the esophagus. It was concluded that patients suffering from carcinoma of the esophagus less than 8 cm length are indicated for particle radiations.

Repopulation of Tumour Cells Following Irradiation with X-rays or Low Energy Neutrons

The repopulation of C3H mouse mammary carcinoma cells following X-ray or fast neutron irradiation was investigated in vivo using TCD50 as an endpoint. Tumours in the C3H mouse leg were irradiated in air with an X-ray dose of 9.6, 28.8 or 48.0 Gy, or a neutron dose of 2.6 or 5.2 Gy, and, various times thereafter, graded X-ray doses were given under hypoxic conditions to determine TCD50. Substantial recovery from sublethal and potentially lethal radiation damages was observed within 48 h following X-ray irradiation, and less recovery was found after neutrons. The effective number of tumourigenic cells was calculated at the time of the second irradiation using the TCD50 equation based on the multitarget model. The effective cell doubling time following X-rays depended on radiation dose. Repopulation appeared to be faster after small and intermediate X-ray doses (9.6 and 28.8 Gy) than after the largest dose, but substantial division delay was observed after the largest X-ray dose. A significant finding was that the tumour cells treated with a neutron dose, either 2.6 or 5.2 Gy, appeared to repopulate slightly more rapidly than those irradiated with X-rays, and the doubling times following two different neutron doses were not significantly different. These results suggest the use of a short overall treatment time for the high LET radiotherapy, and that caution must be exercised if the high LET radiation is given before photon doses.

Clinical experience of fast neutron therapy for carcinoma of the uterine cervix

Fast neutron therapy for locally advanced or radioresistant malignant tumors was started in November 1975 at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. To evaluate the effectiveness of fast neutron therapy, mixed neutron-photon fractionated irradiation, on squamous cell carcinoma of the uterine cervix, 98 patients with Stage IIIb disease were examined to study the correlation between local control rate and histological types. The local control rate after neutron-mixed beam therapy was 73%, which decreased to 66% with photon irradiation. The five year survival rate was 49% for patients receiving neutron therapy and 49% for those receiving photon therapy. There was no statistical significance between neutron and photon therapy; we then attempted to analyze histological types to check for any gain using neutron therapy. This study was a nonrandomized trial. The preliminary results however, gave us useful information for the next of neutron therapy.

Combination therapy of local administration of OK-432 and radiation for esophageal cancer

Local administration of OK-432, a biological response modifier, was combined with radiation in 30 patients with esophageal cancer as a pilot study. Complete response was obtained in 22 of 30 patients (73.3%); and partial response was obtained in the remaining eight cases (26.7%). Complete response was obtained in all eight patients with a tumor less than 5 cm in length. In the group with tumors 5-10 cm in length, complete response was obtained in 11 of 14 cases (78.6%); and partial response was obtained in 3 of 14 cases. In the group with a tumor length of more than 10 cm, complete response was obtained in 3 of 8 cases (37.5%); and partial response was obtained in 5 of 8 cases. One-year, 2-year, and 3-year survival rates of the 30 patients, including four patients who died of other diseases, were 67.9%, 40.8% and 29.0%, respectively. This new combination therapy may contribute not only to local control, but also to survival.

Japanese experience with clinical trials of fast neutrons

Abstract Between November, 1975 and November, 1981, 825 patients were treated with 30 MeV (d-Be) neutrons at the National Institute of Radiological Sciences, Chiba. At the Insitute of Medical Science, Tokyo, 302 patients were referred to the Radiation Therapy department and were treated with 16 MeV (d-Be) neutrons. The emphasis of these clinical trials with fast neutrons was placed on the estimation of the effect of fast neutrons for locally advanced cancers or radioresistant cancers, and on evaluation of the rate of complication of normal tissues following irradiation with fast neutrons. Results were evaluated for patients with previously untreated cancer; local control of the tumor was observed in 59.1%. Complications requiring medical care developed in only 32 patients. Patients who had received pre- or postoperative irradiation were excluded from this evaluation. Late reaction of soft tissue seemed to be more severe than that observed with photon beams. The results also suggest that for carcinoma of the larynx, esophagus, uterine cervix, Pancoasts tumor of the lung and osteosarcoma, fast neutrons were considered to be effectively applied in this randomized clinical trial. For carcinoma of the larynx, a fast neutron boost was effectively delivered, although an interstitial implant was necessarily combined with fast neutrons for carcinoma of the tongue. The cumulative survival rate of the patients with carcinoma of the esophagus treated with fast neutrons was 26% compared to the survival rate of 10.5% obtained using photons. This was supported by evidence from the pathological studies that showed that the tumor cells which had deeply invaded into the esophagus were effectively destroyed when fast neutrons were applied. Local recurrence of carcinoma of uterine cervix was 29% and 42% for patients who had received fast neutron therapy and photon beam therapy, respectively. The results also indicate that local control and relief of the symptom related to Pancoasts tumor of the lung seemed to be better with neutrons than with photons. For patients suffering from osteosarcoma, the surgical procedures preserving the function of the leg and arm were studied according to the better local control rate of the tumor following fast neutron beam therapy.

Results of clinical applications of fast neutrons in Japan

Clinical trials with fast neutrons were carried out to estimate the indications and schedules for high-LET radiation therapy. Local control rate and incidence of moist desquamation of the patients surviving more than 6 months after completion of therapy was 39.8% and 11% respectively. Radioresistant tumors, such as malignant melanoma, soft-tissue sarcoma or osteosarcoma, and locally advanced tumors have responded well to fast neutrons, whereas late reactions of the normal tissues were slightly more severe after fast neutron therapy than those after low-LET irradiations. It is suggested that improvement of the dose distributions will be indispensable to make the best use of high-LET radiation therapy.

The Effect of Acute Total-Head X Irradiation on C3H/He Mice

A total of 505 mice were divided into 15 groups and exposed to different X-ray doses in the range of 475 to 38,000 rad at 200 kVp, 20 mA, 1.15 mm Cu HVL (0.5 mm Cu + 0.5 mm Al), with a single dose to the total head. Mean life spans ( LD50 time) of mice were: 1900 rad, 11.04 days after irradiation; 2850 rad, 10.67 days; 3800 rad, 10.32 days;...; 8550 rad, 8.87 days; 9,500 rad, 8.67 days; 19,000 rad, 4.33 days; and 28,500 rad, 0.87 days. The LD50 (5 days) was 18,715 rad. A high incidence of gastrointestinal bleeding, intracranial bleeding, and brain edema was found after head exposure to 1900 and 19,000 rad, respectively. No mice exposed to 475 and 950 rad died within 300 days. Platelet count increased on the fifth day and the white cell count was decreased on the fourth day after exposure to 19,000 rad. Fifty-six mice were exposed to 1900 or 19,000 rad by the same method; all the mice were sacrificed at the same postirradiation periods, and pathological examination was done. The degree of the brain tissue ...

Analysis of bone scintigram data using a speech recognition reporting system.

A total of 649 bone scintigram reports were stored using a voice pattern recognition system in a general-purpose medium-sized computer ACOS-650, and bone scintigraphy carried out in this institute was examined by analysing these data. The results showed that the introduction of the system made it possible to analyse all the data quickly, whereas previously the amount of information that could be analysed was restricted because of the complexity of the data. The results also showed that the system would be useful for understanding the examinations carried out in the whole hospital as well as for analysing metastatic tumours and the numbers of patients receiving examinations. Furthermore, it would be helpful in the logical analysis of reports prepared by doctors.