Feasibility and Efficacy of Definitive Radiotherapy with 66 Gy and Concurrent Carboplatin-Paclitaxel Chemotherapy for Stage III Non-Small Cell Lung Cancer.

Purpose/Objectives : This study was conducted to assess the feasibility and efficacy of definitive radiotherapy (RT) with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy for patients (pts) with stage Ⅲ non-small celllung cancer. Materials/Methods : Between April 2007 and December 2013，99 pts with non-small cell lung cancer were treated using RT with concurrent carboplatin-paclitaxel chemotherapy in our hospital. Sixty-eight of them received RT with a total dose of 66 Gy. We analyzed 46 Stage Ⅲ pts who had been treated with RT using three-dimensional radiotherapy treatment planning. The prophylactic mediastinal lymph nodes were included in the clinical target volume for RT. The survival rate after the start of RT was estimated using the Kaplan-Meier method. We estimated the cumulative local failure and distant metastasis rates with the Fine-Gray method. Adverse events were evaluated according to the CTCAE (v.4.0). Results : The median age of the pts was 70.9 (52.8-78.7) years old (y.o.). The performance status (PS) of each pt was fairly good (ECOG PS 0: 25, PS 1: 20, PS 3:1), and their clinical stages (UICC 7th) were twenty-nine Ⅲ A and seventeen Ⅲ B. Diagnoses were pathologically confirmed in 32 pts. The median follow-up period was 35.7 (2.0-82.2) months among all pts, and 55.9 (40.1-82.2) months among survivors. The 3- and 5-year Kaplan-Meier overall survival rates were 52.2 and 34.0%，respectively, and the median survival time was 36.6 months. The 3- and 5-year Kaplan-Meier progression-free survival rates were 29.1 and 21.9%，respectively, and the median progression-free survival time was 9.9 months. The 5-year local failure rate was 37.6%, and the 5-year distant metastasis rate was 49.7%. Sixteen (34.8%) pts required steroid administration because of radiation pneumonitis (CTCAE Grade 2 or higher) and two of them died (Grade 5). No other severe non-hematologic toxicity (Grade 3 or higher) was observed. Conclusion : These results suggest that definitive RT with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy is feasible and may be promising for pts with Stage Ⅲ non-small cell lung cancer

L-Qモデルは転移性脳腫瘍の定位放射線照射に適用可能か?

The biologically effective dose (BED) based on the linear-quadratic (LQ) model has been commonly used to evaluate the dose-effect relationships among the different fractionation schedules, but whether the LQ model is appropriate for hypofractionated (HF) high-dose stereotactic irradiation (STI) is uncertain. The validity of the model at high doses per fraction has been critically examined. In this study, STI of metastatic brain tumors was evaluated to suggest the applicability of the LQ model to HF high-dose radiotherapy. No significant difference was found between stereotactic radiosurgery (SRS) and HF stereotactic radiotherapy (SRT) in the analyses of 151 tumors. Furthermore, no significant differences were found among SRS, HF-SRT, and non-HF SRT in 117 metastatic lung adenocarcinomas. The results of this study suggest that BED calculation is a reasonable approach for careful dose-effect evaluation based on the LQ model for HF high-dose radiotherapy for metastatic brain tumors, especially lung adenocarcinomas.博士（医学）・甲第688号・平成30年9月26

Ⅲ期非小細胞肺癌に対するカルボプラチン・パクリタキセル同時併用66Gy放射線治療の安全性と有効性について

Purpose/Objectives: This study was conducted to assess the feasibility and efficacy of definitive radiotherapy (RT) with a total dose of 66Gy and concurrent carboplatin-paclitaxel chemotherapy for patients (pts) with stage Ⅲ non-small cell lung cancer. Materials/Methods: Between April 2007 and December 2013, 99 pts with non-small cell lung cancer were treated by RT with concurrent carboplatin-paclitaxel chemotherapy in our hospital. Sixty-eight of them received RT with a total dose of 66Gy. We analyzed 46 Stage Ⅲ pts who had been treated with RT using three-dimensional radiotherapy treatment planning. The prophylactic mediastinal lymph nodes were included in the clinical target volume of RT. The survival rate after the beginning of RT was estimated using the Kaplan-Meier method. We estimated the cumulative local failure and distant metastasis rates with the Fine-Gray method. Adverse events were evaluated according to the CTCAE (v.4.0). Results: The median age of the pts was 70.9 (52.8-78.7) years old (y.o.). The performance status (PS) of each pt was fairly good (ECOG PS 0: 25, PS 1: 20, PS3:1), and clinical stages (UICC 7th) consisted of twenty-nine ⅢA and seventeen ⅢB. Diagnoses were pathologically confirmed in 32　pts. The median follow-up period　was 35.7 (2.0-82.2) months among all pts, and 55.9 (40.1-82.2) months among survivors. The 3- and 5-year　Kaplan-Meier overall survival rates were 52.2 and 34.0%, respectively, and the median survival time was 36.6 months. The 3- and 5-year Kaplan-Meier progression-free survival rates were 29.1 and 21.9%, respectively, and the median progression-free survival time was 9.9 months. The 5-year local failure rate was 37.6%, and the 5-year distant metastasis rate was 49.7%. Sixteen (34.8%) pts required steroid administration because of radiation pneumonitis (CTCAE Grade 2 or higher) and two of them died (Grade 5). No other severe non-hematologic toxicity (Grade 3 or higher) was observed. Conclusion: These results suggest that definitive RT with a total dose of 66Gy and concurrent carboplatin-paclitaxel chemotherapy is feasible and may be promising for pts with Stage Ⅲ non-small cell lung cancer.博士（医学）・甲第663号・平成29年3月15

頭皮皮膚血管肉腫に対する根治的な寡分割高線量放射線治療の実行可能性と有効性の検討

Cutaneous angiosarcoma is a rare but highly aggressive vascular tumor resistant to all treatment modalities available. The aim of this study was to analyze the treatment outcomes of patients who received definitive hypofractionated high-dose radiotherapy (RT) for angiosarcoma of the scalp. Between April 2008 and December 2014, 11 patients with histologically proven cutaneous angiosarcoma of the scalp visited our Department of Radiation Oncology, because dermatologists suggested that there was no indication for surgery in those cases. One patient rejected all radical treatments and the other 10 patients were treated by RT with curative intent along with chemotherapy or immunotherapy. Eight patients were treated with 6 - 12 MeV electron beams and the other 2 patients were treated with 4 MV X-ray Intensity Modulated Radiation Therapy (IMRT) and electron beams. The total irradiated dose was 63 - 75 Gy (median: 72.5 Gy) in 26 - 30 fractions, and the fraction size was 2.5 Gy in principle. The median age of the patients treated with RT was 80 years old (range: 73 - 91) and the median follow-up time was 16.5 months (range: 5.6 - 86.3). Four patients are still alive. A complete response (CR) was achieved in 10 patients (100%) and only one patient suffered local relapse 20 months after RT. Medians of overall survival (OS), progression-free survival (PFS), and local relapse-free survival (LRFS) were 38.7, 13.4, and 19.8 months, respectively. Local control rates were 100 and 75% at 1 and 2 years, respectively. Skin ulceration was CTCAE grade 2 in 5 patients (50%) and grade 3 in 5 (50%), alopecia was grade 2 in all patients (100%), but no patient developed grade 4 or more severe adverse events after RT. Hypofractionated high-dose RT was feasible and achieved excellent local control of cutaneous angiosarcoma in the elderly patients.博士（医学）・甲第646号・平成28年3月15日Copyright: © 2015 Shimoda E. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The definitive version is available at " http://clinmedjournals.org/articles/ijccr/international-journal-of-cancer-and-clinical-research-ijccr-2-032.php?jid=ijccr

線形二次曲線モデルの寡分割照射への適用性

Background: The linear-quadratic (LQ) model is used for evaluating fractionation schedules in radiation oncology. It has been suggested that the biologically effective dose based on the LQ model cannot be applied to hypofractionated radiotherapy. Methods: Glioblastoma cells were transplanted into nude mice. Four equivalent dose fractionation schedules (12 Gy/1 fraction (fr). 15.06 Gy/2 fr, 18.16 Gy/4 fr, and 20.96 Gy/8 fr) were calculated based on the LQ model. The tumor size was measured to evaluate the number of days required for the relative tumor volume to double and become five t imes the initial value (TGD₂ and TGD₅, respectively). A histopathological study was performed after the evaluation of growth delay. Result: The mean TGD₂ of the unirradiated control group and 12 Gy/1 fr, 15.06 Gy/2 fr. 18.16/4 fr, and 20.96 Gy/8 fr groups was 5.69, 22.64, 37.26. 36.81, and 28.96 days, respectively. The mean TGD₅ was 17.83, 48.03. 60.30, 60.40, and 64.94 days, respectively. All TGDs of the irradiated groups were longer than those of the control group. However, no significant differences were observed among the four irradiated groups. Histologically, irregular giant cells were found, but there were no significant differences among the four groups. There was no significant difference in the Ki-67 labeling index and the CD133 and CD44 expression among the groups. Conclusion: The four dose fractionation schedules equivalent to 12 Gy/1 fr yielded comparable responses, suggesting that the LQ model may be applicable to hypofractionated radiotherapy, with a high dose per fraction of up to 12 Gy.博士（医学）・甲第756号・令和2年9月30

Is the linear-quadratic model appropriate for stereotactic irradiation of metastatic brain tumors?

The biologically effective dose (BED) based on the linear-quadratic (LQ) model has been commonly used to evaluate the dose-effect relationships among the different fractionation schedules, but whether the LQ model is appropriate for hypofractionated (HF) high-dose stereotactic irradiation (STI) is uncertain. The validity of the model at high doses per fraction has been critically examined. In this study, STI of metastatic brain tumors was evaluated to suggest the applicability of the LQ model to HF high-dose radiotherapy. No significant difference was found between stereotactic radiosurgery (SRS) and HF stereotactic radiotherapy (SRT) in the analyses of 151 tumors. Furthermore, no significant differences were found among SRS, HF-SRT, and non-HF SRT in 117 metastatic lung adenocarcinomas. The results of this study suggest that BED calculation is a reasonable approach for careful dose-effect evaluation based on the LQ model for HF high-dose radiotherapy for metastatic brain tumors, especially lung adenocarcinomas.博士（医学）・甲第688号・平成30年9月26日identifier:Journal of Nara Medical Association Vol.69 No.1,2,3 p.9-15 (2018.6)identifier:13450069identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3496identifier:Journal of Nara Medical Association, 69(1,2,3): 9-1

Feasibility and efficacy of definitive radiotherapy with 66 GY and concurrent carboplatin-paclitaxel chemotherapy for stage Ⅲ non-small cell lung cancer.

Purpose/Objectives: This study was conducted to assess the feasibility and efficacy of definitive radiotherapy (RT) with a total dose of 66Gy and concurrent carboplatin-paclitaxel chemotherapy for patients (pts) with stage Ⅲ non-small cell lung cancer. Materials/Methods: Between April 2007 and December 2013, 99 pts with non-small cell lung cancer were treated by RT with concurrent carboplatin-paclitaxel chemotherapy in our hospital. Sixty-eight of them received RT with a total dose of 66Gy. We analyzed 46 Stage Ⅲ pts who had been treated with RT using three-dimensional radiotherapy treatment planning. The prophylactic mediastinal lymph nodes were included in the clinical target volume of RT. The survival rate after the beginning of RT was estimated using the Kaplan-Meier method. We estimated the cumulative local failure and distant metastasis rates with the Fine-Gray method. Adverse events were evaluated according to the CTCAE (v.4.0). Results: The median age of the pts was 70.9 (52.8-78.7) years old (y.o.). The performance status (PS) of each pt was fairly good (ECOG PS 0: 25, PS 1: 20, PS3:1), and clinical stages (UICC 7th) consisted of twenty-nine ⅢA and seventeen ⅢB. Diagnoses were pathologically confirmed in 32　pts. The median follow-up period　was 35.7 (2.0-82.2) months among all pts, and 55.9 (40.1-82.2) months among survivors. The 3- and 5-year　Kaplan-Meier overall survival rates were 52.2 and 34.0%, respectively, and the median survival time was 36.6 months. The 3- and 5-year Kaplan-Meier progression-free survival rates were 29.1 and 21.9%, respectively, and the median progression-free survival time was 9.9 months. The 5-year local failure rate was 37.6%, and the 5-year distant metastasis rate was 49.7%. Sixteen (34.8%) pts required steroid administration because of radiation pneumonitis (CTCAE Grade 2 or higher) and two of them died (Grade 5). No other severe non-hematologic toxicity (Grade 3 or higher) was observed. Conclusion: These results suggest that definitive RT with a total dose of 66Gy and concurrent carboplatin-paclitaxel chemotherapy is feasible and may be promising for pts with Stage Ⅲ non-small cell lung cancer.博士（医学）・甲第663号・平成29年3月15日identifier:Journal of Nara Medical Association Vol.68 No.1,2,3 p.1-6 (2017.06)identifier:13450069identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3314identifier:Journal of Nara Medical Association, 68(1-2

Feasibility and Efficacy of Definitive Radiotherapy with 66 Gy and Concurrent Carboplatin-Paclitaxel Chemotherapy for Stage III Non-Small Cell Lung Cancer.

Purpose/Objectives : This study was conducted to assess the feasibility and efficacy of definitive radiotherapy (RT) with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy for patients (pts) with stage Ⅲ non-small celllung cancer. Materials/Methods : Between April 2007 and December 2013，99 pts with non-small cell lung cancer were treated using RT with concurrent carboplatin-paclitaxel chemotherapy in our hospital. Sixty-eight of them received RT with a total dose of 66 Gy. We analyzed 46 Stage Ⅲ pts who had been treated with RT using three-dimensional radiotherapy treatment planning. The prophylactic mediastinal lymph nodes were included in the clinical target volume for RT. The survival rate after the start of RT was estimated using the Kaplan-Meier method. We estimated the cumulative local failure and distant metastasis rates with the Fine-Gray method. Adverse events were evaluated according to the CTCAE (v.4.0). Results : The median age of the pts was 70.9 (52.8-78.7) years old (y.o.). The performance status (PS) of each pt was fairly good (ECOG PS 0: 25, PS 1: 20, PS 3:1), and their clinical stages (UICC 7th) were twenty-nine Ⅲ A and seventeen Ⅲ B. Diagnoses were pathologically confirmed in 32 pts. The median follow-up period was 35.7 (2.0-82.2) months among all pts, and 55.9 (40.1-82.2) months among survivors. The 3- and 5-year Kaplan-Meier overall survival rates were 52.2 and 34.0%，respectively, and the median survival time was 36.6 months. The 3- and 5-year Kaplan-Meier progression-free survival rates were 29.1 and 21.9%，respectively, and the median progression-free survival time was 9.9 months. The 5-year local failure rate was 37.6%, and the 5-year distant metastasis rate was 49.7%. Sixteen (34.8%) pts required steroid administration because of radiation pneumonitis (CTCAE Grade 2 or higher) and two of them died (Grade 5). No other severe non-hematologic toxicity (Grade 3 or higher) was observed. Conclusion : These results suggest that definitive RT with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy is feasible and may be promising for pts with Stage Ⅲ non-small cell lung cancer.identifier:Journal of Nara Medical Association Vol.68 No.1,2,3 p.1-6 (2017 Jun)identifier:13450069identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3414identifier:Journal of Nara Medical Association, 68(1,2,3): 1-