Yoshihiro Dodo

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.

Improved survival rate in primary intracranial lymphoma treated by high‐dose radiation and systemic vincristine‐doxorubicin‐cyclophosphamide‐prednisolone chemotherapy

Thirty patients with histologically proven primary intracranial non‐Hodgkins lymphoma were treated at Kyoto University. Ten of them were treated prospectively with a radiation‐chemotherapy protocol. All but four specimens were recently reexamined and classified according to the Working Formulation system. The predominant histologic types were diffuse large cell type, large cell immunoblastic type, and diffuse mixed small and large cell type, seen in 38%, 21%, and 21% of cases, respectively. Before 1980, 16 patients were treated with postoperative radiation without definite chemotherapy, and only one has survived more than 5 years. Local recurrence was the most common cause of failure. In 1981, the authors started a protocol in which four to six courses of systemic chemotherapy with vincristine, doxorubicin, cyclophosphamide, and prednisolone (VEPA) was given after whole brain radiation (30–40 Gy) with a local boost up to 50 to 60 Gy. Eight patients completed this protocol, and all of them are alive at 16 to 100 months after diagnosis, with three patients surviving more than 5 years. Only one patient developed recurrence. On the other hand, six patients who did not complete or receive chemotherapy after 1981 are dead or alive with recurrence. Correlation between the Working Formulation subtype and prognosis was not clear because of the variety of treatment. Two patients receiving chemotherapy developed brain necrosis, which was fatal in one case, and the other two patients treated with the protocol are in a poor state without signs of recurrence. Chemotherapy may enhance the radiation effect on normal brain tissue as well as tumor. Combination of radiotherapy and chemotherapy can improve the survival rate, but the optimal dosage needs to be investigated further.

Primary testicular non-Hodgkin's lymphoma : A clinical study and review of the literature

Non-Hodgkins lymphoma (NHL) of the testis is a rare disease, and treatment outcome is generally poor. In this retrospective study, we investigated treatment results for testicular NHL in an attempt to develop an effective treatment policy for this disease. The survival rate and characteristics were retrospectively analyzed in eight patients with NHL of the testis who were treated between 1969 and 1991 at Kyoto University Hospital, Department of Radiology. Four patients were at stage IEA, one at stage IIEA, and three at stage IVEA. Of the eight testicular lymphomas, six were classed as intermediate grade lymphomas and two as high-grade lymphomas according to the Working Formulation. All of the eight patients received orchiectomy. Six patients received combined chemotherapy and radiation therapy as the primary treatment for the disease. One patient each was treated with radiation therapy alone or combination chemotherapy alone. The 5-year overall and disease-free survival rate was 45 and 33%, respectively. Even though almost all of the patients had received combination chemotherapy, high incidence of relapse in the central nervous system (CNS) was observed. Prophylactic treatment against such recurrence may be necessary to improve the treatment outcome of patients with testicular NHL.

Non-Hodgkin's Lymphoma of the Thyroid: A clinical study of twenty-two cases

Non-Hodgkins lymphoma (NHL) of the thyroid gland is a rare disease. In the present study, the survival rate and characteristics were retrospectively analyzed in 22 patients with stage IE and IIE thyroid NHL treated with radiotherapy with or without combination chemotherapy. Seventeen NHL had histological evidence of lymphoma of mucosa-associated lymphoid tissue (MALT) type. The 5-year survival rate was 85% in all patients, with 100% and 63% respectively, for stage IE and stage IIE patients. The highly significant factor correlated with decreased determinate survival was concomitant stridor.

A radiotherapeutic experience for localized extranodal non-Hodgkin's lymphoma: prognostic factors and re-evaluation of treatment modality

Between 1966 and 1988, 149 patients were treated with radiotherapy for localized extranodal lymphoma. The average total dose given was 39.8 Gy for low grade disease and 48.7 Gy for all other disease. Of the 149 patients, 60 also received adjuvant chemotherapy. Twenty-four had low grade lymphoma, 109 had intermediate grade disease, and 16 had high grade disease, histologically. The distribution of histological grade and T/B phenotype varied with the primary site. Low grade lymphomas were found mainly in the orbit, and T-cell lymphomas were found in the nasal cavity and nasopharynx. The 5-year survival rates according to tumor location were 89% for oral cavity, 86% for paranasal sinus, 83% for thyroid, 69% for orbit, 47% for Waldeyers ring (WAR), 44% for testis, 23% for CNS, 21% for nasal cavity and 60% for other sites. Histological grade and T/B phenotype both had prognostic importance. Combined chemotherapy significantly improved the survival rate only for disease with intermediate or high grade histology. Other prognostic factors according to the primary site were the bulk of lymph node for WAR disease, the radiation dose for CNS disease, bone erosion for orbital disease, stridor for disease of the thyroid, and the tumor stage for disease of both the testis and the thyroid.

THE RADIOSENSITIZING EFFECTS OF MISONIDAZOLE (MISO) IN COMBINATION WITH DIETHYL MALEATE (DEM) IN MOUSE MAMMARY TUMORS

Large radiosensitization of C3H/He mouse mammary tumors was obtained with the combination of a non-protein sulfhydryl (NPSH) depletor, diethyl maleate (DEM), and misonidazole (MISO), compared with MISO alone over a range of MISO dose. The difference in enhancement ratios (ERs) for these two treatments was especially prominent at small MISO doses. ERs of 2.06 and 1.44 were obtained, respectively, by combined treatment with DEM (760 mg/kg) and MISO (100 mg/kg) or treatment with MISO alone. Radiosensitization of tumors by DEM alone was observed for doses over 600 mg/kg. When DEM was combined with MISO (100 mg/kg), ERs of the combination were larger than that of MISO alone, for doses over 400 mg/kg of DEM. Similarly, in case of DEM plus MISO (300 mg/kg), the ERs became larger than MISO alone, for doses over 200 mg/kg of DEM. The NPSH content in untreated tumors was 1.08 mmole/kg on the average and no changes in NPSH content was observed after MISO treatment. DEM treatment markedly reduced the NPSH content of tumors as a function of DEM dose and this decrease in NPSH was not significantly affected by MISO treatment. Tumor NPSH was reduced to 24% or less of control by administration of 760 mg/kg of DEM with or without MISO. These results are consistent with competition theory of NPSH and electron affinic radiosensitizers.