Masaji Takahashi

Intraoperative radiotherapy: The japanese experience☆

Abstract Clinical results of intraoperative radiotherapy ([OR) which have been obtained since 1964 in Japan were reviewed. In this radiotherapy a cancerocidal dose can be delivered safely to the lesions, since critical organs are shifted from the field so that the lesions may be exposed directly to radiation. Intraoperative radiotherapy has spread in Japan and the number of institutions in which this radiotherapy is performed has continued to increase to a total of 26 in 1979. The total number of patients treated was 717. It has been demonstrated that intraoperative radiotherapy has definite effects on locally advanced abdominal neoplasms and unresectable radioresistant tumors.

Multi-institutional studies on hyperthermia using an 8-MHz radiofrequency capacitive heating device (Thermotron RF-8) in combination with radiation for cancer therapy

A joint clinical trial of hyperthermia using a newly developed 8‐MHz radiofrequency (RF) capacitive heating device (Thermotron RF‐8; developed in cooperation with Yamamoto Vinyter Co. of Osaka) was performed under collaboration of seven institutions. Radiation with 4 Gy twice a week for a total of 40 Gy or 2 Gy five times a week for a total of 50 Gy was delivered. After irradiation, hyperthermia at 42.5°C ± 0.5°C for 40 to 60 minutes was given twice a week for a total of 10 times. Tumors examined in this trial were located in various depths in the body, and included those which were considered refractory to conventional treatments or radioresistant such as malignant melanoma and soft tissue tumors. Of the 63 tumors treated, 52.4% showed complete regression (CR); 19.0% more than 80% regression (PRa); 20.6%, 80% to 50% regression (PRb); and 8.0% no regression (NR). Our joint clinical trial demonstrated that hyperthermia with the use of the Thermotron RF‐8 is safe and effective in the treatment of radioresistant tumors located in superficial, subsurface, and in some cases deep regions, if the surface cooling is properly managed by the temperature‐controlled saline pad and electrodes of appropriate size are paired.

Treatment results of intracranial germinoma as a function of the irradiated volume

Between 1962 and 1986, 70 patients were treated with radiation for confirmed or suspected intracranial germinoma at our hospital. The diagnosis was based on histology in 30 cases, cerebrospinal fluid (CSF) cytology in 12 cases, and on clinical and radiological findings in the remaining 28 cases. The target of radiation was the primary tumor site in 34 cases (Group A), the entire neuraxis in 22 cases (Group B), the whole brain in 4 cases (Group C), and the ventricle plus spine in 6 cases (Group D). Four patients were not included in the above groups for various reasons. The average radiation dose was 50-55 Gy to the tumor, 30 Gy to the whole brain, and 24 Gy to the spinal axis. The 5- and 10-year survival rates of the 68 primary cases in which radiotherapy was completed were 86% and 79%, respectively. The survival and relapse-free survival rates for the above 4 groups did not differ significantly, although slightly better results were seen in Groups B and C. Five cases in Groups A and D developed intracranial recurrence, 4 adjacent to the primary site but 1 distant from it, whereas no intracranial recurrence was found in the whole-brain-treated groups (B and C). One patient in Group B developed spinal metastasis, which was possibly due to inadequate radiation fields, and another in Group B developed abdominal metastasis via the shunt tube. Craniospinal irradiation should be administered to the patients with demonstrated meningeal seeding or with a positive CSF cytology. For cytology-negative cases with no evident metastasis, irradiation of the tumor plus a wide margin is usually sufficient, but craniospinal irradiation should be considered when the disease extends along the ventricular walls or is present in both pineal and suprasellar regions.

Supratentorial low-grade astrocytoma. Correlation of computed tomography findings with effect of radiation therapy and prognostic variables.

Background. In supratentorial low‐grade astrocytoma, radiation therapy effects and prognostic factors, especially with respect to computed tomography (CT) findings, are not yet well established. A retrospective analysis of 119 patients with this disease (histologically confirmed ordinary astrocytoma) therefore was conducted.

Clinical experiences with intraoperative radiotherapy of locally advanced cancers.

Clinical results of intraoperative radiotherapy in neoplasms of the stomach, colon, pancreas, biliary tract, bladder, prostate, lung, mediastinum and brain, and soft-tissue sarcomas are reported. After resectable lesions were removed at surgery, residual cancer nests were sterilized by irradiation before surgical closure. Since the lesion can be exposed directly to radiation and sensitive normal structures are positioned outside the treatment volume, a cancerocidal dose can be safely and precisely delivered to the cancer without affecting normal structure. The great advantage of the intraoperative electron beam therapy lies in the treatment of radioresistant tumors and lesions located near radiosensitive organs. Several patients with unresectable tumors were treated by the intraoperative technique and are alive after more than 5 years.

Clinical results of radiofrequency hyperthermia combined with radiation in the treatment of radioresistant cancers

Clinical results of radiothermotherapy applied to 40 radioresistant tumors in 36 patients were reported. Hyperthermia was administered locally using two radiofrequency (RF) capacitive heating equipment systems developed in our institution under the collaboration of Yamamoto Vinyter Co. Ltd. Hyperthermia was given twice weekly immediately after irradiation. Intratumor temperatures of 41°C to 44°C were maintained for 30 to 60 minutes. Radiation doses varied from 32 Gy to 60 Gy. Of the 40 tumors treated, 21 (53%) showed complete response, 16 (40%) partial response, and 3 (7%) no response when the tumor response was assessed by tumor size measurement. Of eight patients who had matched tumors treated with either radiation alone or radiation plus hyperthermia, six patients showed better response in tumors treated with radiothermotherapy than in tumors treated with radiation alone. Skin reactions following radiothermotherapy and radiation alone were comparable. The tumor response was greatly dependent on the tumor size. Greater response was observed in small tumors, although histologic examinations and long‐term follow‐up studies revealed an excellent effect of radiothermotherapy on the large tumors as well as on the small tumors. Tumor responses correlated with tumor center temperatures but not with histologic features. Our clinical results indicate that RF hyperthermia combined with radiation has a therapeutic benefit in the treatment of radioresistant cancers.

Radiofrequency Capacitive Hyperthermia for Deep-seated Tumors I. Studies on Thermometry

The thermometry results of radiofrequency (RF) capacitive hyperthermia for 60 deep‐seated tumors in 59 patients are reported. Hyperthermia was administered regionally using two RF capacitive heating equipments which the authors have developed in cooperation with Yamamoto Vinyter Company Ltd., (Osaka, Japan). Intratumor temperatures were measured by thermocouples inserted through angio‐catheters which were placed 5 cm to 12 cm deep into the tissues. Tumor center temperatures were measured for 307 treatments in all tumors; thermal distributions within tumors and surrounding normal tissues were obtained for 266 treatments of 53 tumors by microthermocouples.

Techniques, Indications and Results of Intraoperative Radiotherapy of Advanced Cancers

After removing resectable lesions at operation, residual cancer nests were sterilized by irradiation before surgical closure. The great advantage of intraoperative radiotherapy lies in the treatment of lesions such as gastric cancers located near radiosensitive organs, and radioresistant tumors, such as soft-tissue sarcoma. Since the lesion is exposed directly to irradiation, a cancerocidal dose can be delivered without affecting normal structures. Clinical results have shown that cure can be expected following excision of the primary mass.

External and intraoperative radiotherapy for resectable and unresectable pancreatic cancer: Analysis of survival rates and complications

PURPOSE Clinical results of intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for both resectable and unresectable pancreatic cancer were analyzed. METHODS AND MATERIALS Between 1980 and 1995, 332 patients with pancreatic cancer were treated with surgery and/or radiation therapy (RT). Of the 332 patients, 157 patients were treated with surgical resection of pancreatic tumor, and the remaining 175 patients had unresectable pancreatic tumors. Among the 157 patients with resected pancreatic cancer, 62 patients were not treated with RT, while 40 patients were treated with EBRT alone (mean RT dose; 46.3 Gy) and 55 patients with IORT (25.2 Gy) +/- EBRT (44.0 Gy). On the other hand, among the 175 patients with unresectable pancreatic cancer, 58 patients were not treated with RT, 46 patients were treated with EBRT alone (39.2 Gy), and the remaining 71 patients with IORT (29.3 Gy) +/- EBRT (41.2 Gy). RESULTS For 87 patients with curative resection, the median survival times (MSTs) of the no-RT, the EBRT, and the IORT +/- EBRT groups were 10.4, 13.0, and 15.5 months, respectively, without significant difference. For 70 patients with noncurative resection, the MSTs of the no-RT, the EBRT, and the IORT +/- EBRT groups were 5.3, 8.7, and 6.5 months, respectively. When the EBRT and the IORT +/- EBRT groups were combined, the survival rate was significantly higher than that of the no RT group for noncuratively resected pancreatic cancers (log rank test; p = 0.028). The 2-year survival probability of the IORT +/- EBRT group (16%) was higher than that of the EBRT group (0%). For unresectable pancreatic cancer, the MSTs of 52 patients without distant metastases were 6.7 months for palliative surgery alone, 7.6 months for EBRT alone, and 8.2 months for IORT +/- EBRT. The survival curve of the IORT +/- EBRT group was significantly better than that of the no-RT group (p < 0.05), and the difference between the IORT +/- EBRT and the EBRT alone groups was marginally significant (p = 0.056). In addition, the 2-year survival probability for the IORT +/- EBRT group was 14%, while no 2-year survival was observed in the no RT or the EBRT groups. Multivariate analysis using the Cox proportional hazards model revealed that tumor size, stage (Stages 1, 2 vs. Stages 3, 4), and curability of resection were significant variables for resectable pancreatic cancer, while distant metastases and performance of IORT were significant variables for unresectable pancreatic cancer. The dose of EBRT was a marginally significant factor for both resectable and unresectable tumors (both p = 0.06). In terms of complications, ulcers of gastrointestinal tract were noted in 14% of the 126 patients treated with IORT. CONCLUSION Although prolongation of the MST by IORT was not remarkable, long survivals (>2 years) were obtained by IORT +/- EBRT for noncuratively resected and unresectable pancreatic cancer. IORT combined with EBRT is indicated for noncurative resected or unresectable pancreatic cancer without distant metastases.

CT simulator: A new 3-D planning and simulating system for radiotherapy: Part 1. Description of system

A real time CT-linked 3-D treatment planning system, called a CT simulator, has been developed. The basic system consists of a CT scanner, a multi-image display component, a treatment planning device with real time visual optimization, and a laser beam projecting component. All the components are connected on line. The system can be conveniently used for 3-D planning and simulation for radiation therapy within a reasonably short period of time.