Kazushige Tsutsui

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.

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.

Extranodal non-Hodgkin's lymphoma of the head and neck. A clinicopathologic study in the kyoto-nara area of japan

The clinicopathologic features of 114 Japanese patients with extranodal non‐Hodgkins lymphoma of the head and neck region were analyzed. The median age was 60.5 years and the male:female ratio was 1.5:1. The most common site of involvement was Waldeyers ring, followed by the oral cavity, thyroid gland, paranasal sinuses, nasal cavity, and larynx. Seventy‐five percent of the patients were in Stage I or Stage II at admission. Histologically, diffuse lymphoma accounted for 94% and follicular lymphoma for 6% of cases. The histologic grade according to the Working Formulation System of the National Cancer Institute was low in 11%, intermediate in 75%, and high in 14% of cases. Immunohistochemical study showed that the majority of the cases were of B‐cell type and only 13 cases (11%) were of the T‐cell type. Peripheral T‐cell lymphomas (eight cases) mainly occurred in the nasopharynx and nasal cavity, whereas four of five thymic T‐cell lymphomas were found in the palatine tonsil. The over‐all 5‐year survival rate was 54%, and the factors affecting survival were sex, histologic grade, T/B phenotype, clinical stage, and the site of initial presentation. Five‐year survival with nasal cavity and Waldeyers ring lymphoma was 24% and 46%, respectively. The poor prognosis of lymphomas at these sites might result from the predominance of T‐cell lymphoma, the paucity of low grade lymphoma, and the relatively high incidence of cases that were in an advanced stage at presentation. In Stage II, patients treated with combined therapy tended to have a better 5year survival rate than those treated with radiotherapy alone.

Esophageal cancer treated with radiotherapy: Impact of total treatment time and fractionation

PURPOSE Local control rate and survival rate of esophageal cancer treated with radical radiation therapy (RT) were analyzed with special respect to total treatment time and fractionation. METHODS AND MATERIALS Between 1979 and 1992, 88 patients with Stages I-III esophageal cancer were treated radically with RT at Kyoto University Hospital and Wakayama Red Cross Hospital. Of the 88 patients, 52 patients were treated with conventional fractionation (1.7-2.0 Gy/day, five times/week), and the remaining 36 patients were treated with accelerated hyperfractionation (AHF). In 1989, we started AHF regimen for esophageal cancer. Daily fractionations were 2.0 Gy and 1.2 Gy (field-in-field), or 1.5 Gy and 1.5 Gy at 5- to 6-h interval. Most of the patients treated with AHF received the total radiation dose of 64-68 Gy. Twenty-seven patients were treated with intraluminal brachytherapy (IBT) as boost therapy following external RT. Fourteen patients were treated with IBT following AHF. RESULTS The median of treatment time of AHF was approximately 2 weeks shorter than that of conventional fractionation. Local control rate at 1 year were 47% for AHF, which was significantly higher than that for conventional fractionation (22%, p < 0.05). The improvement of local control by AHF was responsible for a trend to an improved cause-specific survival (p = 0.07). Local control rates at 1 year were plotted as a function of total treatment time. The slope of the linear regression line was -2.3 +/- 0.5% per day (p < 0.025) for patients treated with external RT alone, indicating a 2.3% per day loss in local control. Pretreatment and treatment parameters were evaluated in a multivariate analysis for the end point of local control. T stage (T1, 2 vs. T3, 4; p = 0.003) and fractionation schedule (p = 0.03) were independent of prognostic significance. Patients could tolerate the AHF well, although esophageal stenosis was noted frequently as a late toxicity. CONCLUSION Accelerated hyperfractionation was the most important treatment-related variable in this patient population. Total treatment time may have a significant impact on the treatment outcome for esophageal cancer.

Chemosensitization by buthionine sulfoximine in vivo

The in vivo effects of buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, on the cytotoxicity of cyclophosphamide (CYM), cisplatin (CDDP) and bleomycin (BLM), were examined by monitoring the changes of non-protein thiols (NPSH) in normal tissues and in the NFSa fibrosarcoma. We used the lung colony assay as a measure of tumor response and the spleen colony assay as a measure of normal tissue response to CYM. In this study, 5 mmol/kg of BSO was subcutaneously injected four times every 12 hr before administration of the above anti-neoplastic drugs. GSH levels in subcutaneous NFSa tumors decreased to 2% of the control 12 hr after the last administration of BSO, but in the bone marrow, had recovered to 41%. In the colony assays, BSO increased the anti-cancer effects of the three chemotherapeutic agents, but did not modify the bone marrow suppression by CYM. This finding was a result of the differential response of GSH depletion in the tumor and in the bone marrow. Our study demonstrates that BSO is an effective chemosensitizer of these drugs and may be of therapeutic value when used at an optimal interval.

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.

Three-dimensional treatment planning for maxillary cancer using a CT simulator

PURPOSE The results of three-dimensional treatment planning using a computed tomography simulator were evaluated in patients with maxillary cancer. METHODS AND MATERIALS Treatment planning was done in 25 patients using an x-ray simulator and plain x-ray films (1979-1982, group 1) in 34 patients using an x-ray simulator and computed tomography films (1983-1987, group 2), in 24 patients using a computed tomography simulator (1988-1992, group 3). The number of patients with Stage IV disease increased in the order of group 1 to group 3. RESULTS The average radiation field was smallest in group 3 (66.5 cm2) followed by group 2 (67.4 cm2) and group 1 (72.9 cm2). A radiation dose of more than 30 Gy to the lens of the effected side was delivered to 13% of group 3, 44% of group 2, and 44% of group 1. The dose to the lens on the uneffected side was zero in 56% of group 1, 74% of group 2, and 96% of group 3. A long-term decrease in visual activity on the effected side occurred in 11% of group 3, 32% of group 2, and 44% of group 1. However, a significant increase in survival was only noted between groups 1 and 2, because the three population of patients were different. CONCLUSION The three-dimensional treatment planning results in a better treatment than two-dimensional treatment planning as measured by complication rates and field sizes.

Radiation therapy for nasopharyngeal carcinoma. Retrospective review of 105 patients based on a survey of Kansai Cancer Therapist Group

One hundred five patients with nasopharyngeal carcinoma were treated with radiation therapy combined with or without chemotherapy at 16 of the participating institutes in Kansai Cancer Therapist Group, Japan, from January 1978 to December 1980. The study comprised 77 males and 28 females; their ages ranged from 15 to 80 years (mean, 53 years). Five‐year survival rates according to stage were as follows: Stage I, 100%; Stage II, 67%; Stage III, 44%; and Stage IV, 34%. As far as Stage IV disease was concerned, the radiation therapy only group showed significantly poorer prognosis than the combined radiation and chemotherapy group (P < 0.05). Cancer 57:2267–2271, 1986.