Mariko Shioya

Treatment results of radiotherapy for malignant lymphoma of the orbit and histopathologic review according to the WHO classification

PURPOSE To analyze the results of radiotherapy (RT) for malignant lymphoma of the orbit and to evaluate them compared with the World Health Organization (WHO) classification published in 2001. METHODS AND MATERIALS The data from 29 patients with malignant lymphoma of the orbit treated with RT at Gunma University Hospital between 1978 and 2001 were retrospectively analyzed. Pathologic slides from 23 cases were available and were reviewed by a hematopathologist according to the WHO classification. The original and reviewed diagnoses, patient characteristics, treatment results, and complications were analyzed. In principle, patients with low-grade or indolent lymphoma were treated with RT alone, using 30 Gy as the tumor dose. Survival data were calculated using the Kaplan-Meier method. RESULTS One case that proved to be a pseudotumor was excluded from evaluation. Of the 28 cases, 25 were Stage IAE, 1 was Stage IIAE, and 2 were Stage IVAE. The median follow-up was 71 months. According to the original classification and the Working Formulation, the 5- and 10-year overall survival rate of patients with low-grade lymphoma was 94% and 73%, respectively. The corresponding rates for those with intermediate-grade lymphoma were 67% and 67% (p = 0.15). In contrast, the WHO classification showed a significant difference in the survival curves. The 5- and 10-year overall survival rate of patients with mucosa-associated lymphoid tissue (MALT) lymphoma was 100% and 88%, respectively; for diffuse large B-cell patients, the rates were both 0% (p < 0.001). In patients with MALT lymphoma, one local and four distant relapses developed; two of them >10 years after initial treatment. All of the relapsed MALT lymphomas were controlled by salvage therapy. CONCLUSION Excellent local control and survival can be achieved for patients with orbital MALT lymphoma using RT alone. A precise histopathologic diagnosis using the WHO classification and long-term follow-up for >10 years is recommended.

The synchronization of chemotherapy to circadian rhythms and irradiation in pre-operative chemoradiation therapy with hyperthermia for local advanced rectal cancer.

Purpose: The therapeutic and adverse effects of pre-operative chrono-chemoradiation with local hyperthermia for patients with rectal adenocarcinoma were evaluated. Materials and methods: Pre-operative radiation therapy of a total dose of 40 Gy (n = 10) or 50 Gy (n = 19) on the whole pelvis and hyperthermia once a week during the radiation therapy for 1 h were performed for patients with T2–T4 rectal adenocarcinoma. Chemotherapy consisted of 5-FU (250 mg m−2 per day) and LV (25 mg m−2 per day) administered by continuous infusion in the night for 5 days a week in the second and fourth weeks of radiation. Results: Grade 3+ toxicities were seen only in two patients (6.9%). A significant down staging was seen in 41.4% of all cases and 52.6% of cases with a radiation dose of 50 Gy. Of the patients who had received surgical resection of a tumour, three (11.1%) had no residue pathologically in the specimen and eight (29.6%) had microscopic lesions. Conclusions: These results yielded a high response rate with minimal toxicities for advanced low-rectal adenocarcinoma. The administration of 5-FU during the sleeping time before irradiation might have an advantage not only as a chronotherapy but also as a radiation sensitizer.

Usefulness of Intraluminal Brachytherapy Combined With External Beam Radiation Therapy for Submucosal Esophageal Cancer: Long-Term Follow-Up Results

PURPOSE To assess the efficacy of radiation therapy (RT) by using intraluminal brachytherapy (IBT) combined with external beam RT (EBRT) for submucosal esophageal cancer. METHODS AND MATERIALS Between 1991 and 2005, 59 consecutive patients received definitive RT without chemotherapy. IBT was performed after patients completed EBRT as a booster therapy for 17 patients, using low-dose-rate Cs-137 sources until 1997, and for 19 patients, using high-dose-rate Ir-192 sources thereafter. The long-term outcomes were investigated with a median follow-up time of 61 months. RESULTS Logoregional recurrences and distant metastases were observed in 14 patients and in 2 patients in the lung, respectively, and 5 patients were rescued by salvage treatments. The 5-year logoregional control and cause-specific survival rates were 75% and 76%, respectively. The 5-year cause-specific survival rate in the EBRT group was 62%, whereas the corresponding rate in the IBT group was 86% (p = 0.04). Multivariate analysis revealed that IBT was the most powerful predictor of survival but did not reach a significant level (p = 0.07). There were five esophageal ulcers in the IBT group, but no ulcers developed with small fractions of 3 Gy. Grade 2 or higher cardiorespiratory complications developed in 2 patients (5.6%) in the IBT group and in 3 patients (13.0%) in the EBRT group. CONCLUSIONS Combining IBT with EBRT is suggested to be one of the preferable treatment modalities for medically inoperable submucosal esophageal cancer because of its preferable local control and survival probabilities, with appreciably less morbidity.

Attenuation of chronic thermotolerance by KNK437, a benzylidene lactam compound, enhances thermal radiosensitization in mild temperature hyperthermia combined with low dose-rate irradiation.

Purpose: We investigated whether the attenuation of chronic thermotolerance by KNK437, a heat shock protein inhibitor, can modify the effect of thermal radiosensitization in mild temperature hyperthermia (MTH) combined with low dose-rate irradiation (LDRI). Materials and methods: The human lung adenocarcinoma cell line A549 was simultaneously exposed to LDRI with MTH at 41°C and KNK437 at a dose of 100 μM. Cell survival was estimated by a clonogenic assay. Cell cycle change during treatment was analyzed by flow cytometry. Expression levels of the heat shock proteins hsp72, hsp27 and heat shock factor 1 (HSF-1) were measured by Western blotting. Results: KNK437 inhibited the expression of inducible hsp72 and hsp27, but produced no change in the mobility shift of HSF-1. The cytotoxicity of LDRI was enhanced by MTH. The survival curve for LDRI + MTH revealed no development of chronic thermotolerance up to 48 h. Simultaneous LDRI and KNK437 treatment also resulted in enhanced cell killing. The radiosensitizing effect of KNK437 was enhanced by simultaneous exposure of the cells to MTH. Flow cytometry analysis of cell cycle progression demonstrated marked G2 arrest and mild G1 arrest with LDRI alone, but mild G1 arrest with MTH alone, and mild G2-M, S-phase accumulation with KNK437 alone. The marked G2 arrest caused by LDRI was partially suppressed by the addition of MTH, and was also suppressed by KNK437 treatment. Conclusions: Exposure of A549 cells to KNK437 caused inhibition of hsp72 and hsp27 expression. The addition of KNK437 increased not only thermosensitivity to MTH, but also radiosensitivity to LDRI. KNK437 also enhanced the MTH-induced radiosensitization under these experimental conditions.

Feasibility study of postoperative intraperitoneal hyperthermochemotherapy by radiofrequency capacitive heating system for advanced gastric cancer with peritoneal seeding

Background: Gastric carcinoma patients with peritoneal dissemination have an extremely poor prognosis. Attempting to improve regional control and decrease the risk of complications related to hyperthermic chemotherapy, we applied a new treatment modality using a combination of gastrectomy with postoperative intraperitoneal hyperthermo-chemotherapy (PIHC) using Thermotron RF-8. The purpose of this study was to evaluate the feasibility of PIHC in advanced gastric carcinoma patients with peritoneal seeding. Patients and methods: Between March 2002 and April 2006, 20 gastric carcinoma patients with peritoneal dissemination were allocated to two groups in the patients selection. The PIHC group (10 patients) received a 60-min PIHC with a cisplatin dose of 80 mg/m2 two weeks after surgery, and the control group (10 patients) received surgery alone. Thermotron RF-8 is a heating device that can raise temperatures in both superficial and deep-seated tumours using 8 MHz radiofrequency electromagnetic waves as a source of heat. Results: No patients in either group had life-threatening complications. The most frequent nonhaematologic toxicity (grade 3) was nausea. The one-, two-, and three-year cumulative survival rates for the PIHC group were 60%, 48%, and 36%, respectively, whereas those for the control group were 40%, 10%, and 0%, respectively. The survival rates for the PIHC group were significantly higher than those for the control group. Conclusion: Although this study was conducted non-randomly with a small number of patients, the PIHC group had a higher survival rate and better prognosis compared with the control group.

Inoperable Pancoast tumors treated with hyperthermia-inclusive multimodality therapies

PURPOSE This study aimed to assess the feasibility, efficacy and complication of hyperthermia-inclusive multimodality therapies for patient with inoperable Pancoast tumor. MATERIAL AND METHODS Five patients with inoperable Pancoast tumor were treated with hyperthermia-inclusive multimodality therapies. They received thermoradiotherapy with/without chemotherapy. Radiation therapy was delivered using 10 MV X-rays with total dose of 68-70 Gy. In the latter half of the radiation therapy hyperthermia was performed for 2-4 sessions once a week with 8 MHz radiofrequency device. RESULTS For primary response, 4 tumors showed partial response to the treatment with the exception of 1 tumor who showed stable disease. Only one patient was with a short follow-up period (9 months), all other patients survived 3 years or more without recurrence. Of them, 2 patients were recognized with local recurrence at 38.7 and 42.7 months after treatment and died at 66.9 and 78.5 months after treatment. The other 2 patients are disease-free survivor for 4 and 5 years after treatment. No severe non-hematological toxicity was observed in each patient. CONCLUSION These data suggested that hyperthermia-inclusive multimodality therapies might be a promising approach for inoperable Pancoast tumor.