Abstract: AIM: To examine the efficacy of major radioactive sources used in brachytherapy and the influence of age. PATIENTS AND METHODS: Six hundred and forty-eight patients with node negative oral tongue cancer (T1-3NOMO; 212T1, 352T2, 84T3) treated at Osaka University Hospital, between 1967 and 1999, were reviewed. RESULTS: The 5-year local control rates for patients treated with Ra-226 and Ir-192 were 85%, and 79% for Ti, 75% and 73% for T2, 62% and 64% for T3 tumors, respectively, and for those in the MicroSelectron-high-dose-rate (MS-HDR) group were 87% for T1, 79% for T2 and 89% for T3. Patients 65 years of age or older attained lower 5-year local control rates (67% for total cases; 72% for Ti, 68% for T2 and 59% for T3) than their younger counterparts (79%, 86%, 77% and 69%; p=0.004). CONCLUSION: The three major radioactive sources produced results that were not significantly different, and age proved to be a factor influencing outcomes.

Abstract: The aim of this study was to examine the interobserver variance in delineating the contour of unresectable pancreatic cancer for chemoradiotherapy. PATIENTS AND METHODS: CT images of two cases of unresectable pancreatic tumors (head and body cancer) were sent to eight radiation therapy facilities in a CD-ROM. Gross tumor volume (GTV) and planning target volume (PTV) were delineated using the radiotherapy treatment planning system (RTP) of the respective facilities. The mean and variance of the GTV and PTV of 11 plans by the eight facilities were analyzed. RESULTS: The respective mean volumes of the GTV of pancreatic head and body cancer cases were 34.8 cm3 (SD, 30.4; median, 31.8; range, 13.5-122 cm3) and 73.4 cm3 (SD, 28.1; median, 67.9; range, 46.3-152 cm3). The ratios of the largest to the smallest contoured GTV were 9 and 3, respectively. The corresponding average volumes of PTV were 148 cm3 (SD, 84.3; median, 129; range, 69.6-363 cm3) and 240 cm3 (SD, 79.8; median, 227; range, 148-420 cm3). The ratios of the largest to the smallest contoured volume were 5 and 2.8 for PTV delineation, respectively. CONCLUSION: Dummy run using CD-ROM is possible on a multi-institute scale but also disclosed interobserver variance. Unified protocol interpretation to reduce inter-observer variance is therefore essential for successful multi-institute clinical trials.

Abstract: PURPOSE: To examine the feasibility of concurrent use of full-dose gemcitabine (GEM) and radiotherapy for advanced pancreatic cancer. PATIENT AND METHODS: 22 patients with advanced pancreatic cancer were subjected to concurrent chemoradiotherapy (GEM 1,000 mg/m(2) weekly, three times during 4 weeks). They received limited-field irradiation by three-dimensional radiotherapy planning. RESULTS: Of the 22 patients, 16 (72%) completed the treatment (50 Gy irradiation and at least three times concurrent administration of 1 g/m(2) GEM). One patient with unresectable tail cancer showed peritonitis carcinomatosa and both chemotherapy and radiotherapy had to be stopped. Dose reduction or omission of GEM was necessary in another four patients. In addition, radiotherapy was discontinued in one patient for fatigue. Grade 3 hematologic toxicity was detected in eight patients (36%), and grade 3 nonhematologic toxicity (anorexia) in one patient (5%). In total, the response rate amounted to 32% (seven partial responses), and the median survival time (MST) was 16 months. Among the twelve patients who received preoperative chemoradiotherapy, nine underwent surgery and showed a survival rate of 78% at 1 year. Another 13 patients without surgery showed 14 months of MST. No regional lymph node failure has appeared so far. CONCLUSION: Limited-field radiotherapy enables the safe concurrent administration of 1,000 mg/m(2) GEM.

Abstract: PURPOSE: For safer treatment of seminal vesicles (SVs), we initiated a new technique using an anchor applicator for high-dose-rate interstitial brachytherapy (HDR-ISBT) of prostate cancer. METHODS AND MATERIALS: Between January 2004 and March 2005, 23 intermediate- to high-risk patients were treated with HDR-ISBT as monotherapy. Transrectal ultrasonography guided implantation of the treatment applicator in and around the prostate gland and proximal SV. We used an "anchor" applicator to prevent posterior displacement of the SV. After insertion of the anchor applicator, the actual treatment applicator was implanted at the best position for optimal SV coverage. SV coverage was analyzed using a dose-volume histogram. RESULTS: Implantation of the applicator on the posterior side of the SV was successful for 43 of 46 SVs (93%). The median percentage of the SVs receiving the prescribed dose was 41% (range 11-86%). Only one case of acute Grade 2 toxicity (3%) was seen. CONCLUSIONS: Our anchor applicator technique for HDR-ISBT can separate the SV from the rectum. This is the first report of dose-volume histogram analysis of the SV for HDR-ISBT.

Abstract: To examine the feasibility of radiotherapy with a full dose of gemcitabine (1000 mg/m2 once a week) for unresectable pancreatic carcinoma, we treated 15 patients with 50 Gy/25 fractions/5 weeks concurrent chemoradiotherapy using a limited irradiation field. Eleven patients completed treatment. No lethal side effects were seen during and after these therapies. Two patients quit therapy because of tumor progression; one patient quit radiotherapy owing to general fatigue and nausea; and the other patient stopped gemcitabine administration owing to a grade 4 hematological adverse event. As only two patients stopped this protocol as a result of untoward effects of treatment, limited-field radiotherapy enabled us to treat pancreatic cancer with full-dose gemcitabine.

Abstract: The purpose of this study was to evaluate the impact of mitochondrial DNA (mtDNA) on the radiation sensitivity of transformed human fibroblast cells. The p+ and p0 human fibroblast cell lines were used, which carry wild-type mtDNA and no mtDNA, respectively. Clonogenic radiosensitivity was evaluated by colony formation assay and micronucleus (MN) formation assay. The ATP assay was then used to address the discrepancy between the results of the former two assays. Despite the lack of a significant difference in survival in the colony formation assay, p+ and p0 cells exhibited high and low radiosensitivities, respectively, in the MN formation assay (P < 0.003). This difference in MN formation correlated with high and low levels of cellular ATP content in p+ and p0 cells (P = 0.004). The addition of antimycin A suppressed differences in both MN formation and cellular ATP content. In the transformed human fibroblast cells we used, mtDNA played an important role in radiation-induced MN formation that was correlated with the levels of cellular ATP content. These results may imply the presence of an MN expression pathway that is dependent on the intrinsic ATP level and that may be compensated and lead to an equivalent level of clonogenic survival.