富田　夏夫トミタ　ナツオ

研究者基本情報

学歴

•  - 2009年03月, 名古屋市立大学大学院
•  - 2001年03月, 名古屋市立大学

学位

• 博士, 名古屋市立大学大学院医学研究科

所属学協会

• 日本医学放射線学会
• 日本放射線腫瘍学会
• American Society for Radiation Oncology

委員歴

•  - 現在, JROSG 臨床試験審査委員会委員
•  - 現在, JROSG 泌尿器腫瘍委員会委員

経歴

•   2018年07月 - 現在, 名古屋市立大学, 大学院医学研究科 放射線医学分野, 准教授
•   2007年10月 - 2018年06月, 愛知県がんセンター中央病院, 放射線治療部, 医長

研究活動情報

研究分野

• ライフサイエンス, 放射線科学, 放射線治療

研究キーワード

放射線腫瘍学, 放射線治療

論文

• Impact of treatment planning using a structure block function on the target and organ doses related to patient movement in cervical esophageal cancer: A phantom study., Hidetoshi Shimizu, Koji Sasaki, Makoto Ito, Takahiro Aoyama, Hiroyuki Tachibana, Natsuo Tomita, Chiyoko Makita, Hiroshi Tanaka, Yutaro Koide, Tohru Iwata, Takeshi Kodaira, Journal of applied clinical medical physics, 20, (5) 75 - 83,   2019年05月, 査読有り, Helical tomotherapy (HT) can restrict beamlets passing through the virtual contour on computed tomography (CT) image in dose optimization, reducing the dose to organs at risk (OARs). Beamlet restriction limits the incident beamlet angles; thus, the proper planning target volume (PTV) margin may differ from that of the standard treatment plan without beamlet restriction, depending on the patient's movement during dose delivery. Dose distribution changes resulting from patient movement have not been described for treatment plans with beamlet restriction. This study quantified changes in dose distribution to the target and OARs when beamlet restriction is applied to cervical esophageal cancer treatment plan using HT by systematically shifting a phantom. Treatment plans for cervical esophageal cancers with and without beamlet restriction modes [directional block (DB) and nonblock (NB), respectively] were designed for CT images of the RANDO phantom. The PTV margin for the DB mode was set to be the same as that for the NB mode (5 mm). The CT image was intentionally shifted by ±1, ±2, and ±3 voxels in the left-right, anterior-posterior, and superior-inferior directions, and the dose distribution was recalculated for each position using the fluence for the NB or DB mode. When the phantom shift was within the same PTV margin as the NB mode, changes in doses to the targets, lungs, heart, and spinal cord in the DB mode were small as those in the NB mode. In conclusion, the virtual contour shape used in this study would provide safe delivery even with patient movement within the same PTV margin as for the NB mode.
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• Favorable 10-year outcomes of image-guided intensity-modulated radiotherapy combined with long-term androgen deprivation for Japanese patients with nonmetastatic prostate cancer., Tomita N, Soga N, Ogura Y, Furusawa J, Tanaka H, Koide Y, Tachibana H, Kodira T, Asia-Pacific journal of clinical oncology, 15, (1) 18 - 25,   2019年02月, 査読有り
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• Gross tumor volume in sinonasal tract cancer as a predictor of local recurrence after chemoradiotherapy, Suzuki H, Kimura K, Kodaira T, Tachibana H, Tomita N, Koide Y, Tanaka H, Nishikawa D, Koide Y, Beppu S, Hanai N, Jpn J Clin Oncol, In press, (12) 1041 - 1045,   2018年12月, 査読有り
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• Propensity Score Analysis of Radical Hysterectomy Versus Definitive Chemoradiation for FIGO Stage IIB Cervical Cancer., Tomita N, Mizuno M, Makita C, Kondo S, Mori M, Sakata J, Tsubouchi H, Hirata K, Tachibana H, Kodaira T, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 28, ((8)) 1576 - 1583,   2018年10月, 査読有り
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• Repeat stereotactic body radiotherapy (SBRT) for local recurrence of non-small cell lung cancer and lung metastasis after first SBRT., Yasutaka Ogawa, Yuta Shibamoto, Chisa Hashizume, Takuhito Kondo, Hiromitsu Iwata, Natsuo Tomita, Hiroyuki Ogino, Radiation oncology (London, England), 13, (1) 136 - 136,   2018年07月28日, 査読有り, BACKGROUND: This study evaluated the safety and efficacy of repeat SBRT for local recurrence of stage I non-small-cell lung cancer (NSCLC) and solitary lung metastasis. METHODS: Thirty-one patients with in-field local relapse of NSCLC (n = 23) or lung metastasis (n = 8) underwent repeat SBRT. All patients had grade 2 or lower radiation pneumonitis after the first SBRT. Local recurrence was diagnosed with CT and FDG-PET in 17 patients and by biopsy in 14. The median interval between the first and second SBRT was 18 months (range, 4-80). The first SBRT dose was mainly 48-52 Gy in 4 fractions (n = 25) according to the institutional protocols. Second SBRT doses were determined based on the tumor size and distance to organs at risk, and were mostly 48-52 Gy in 4 fractions (n = 13) or 60 Gy in 8 fractions (n = 13). RESULTS: At 3 years, overall survival and local control rates were 36 and 53%, respectively, for all 31 patients. Four patients showed no further recurrence for > 5 years (63-111 months) after the second SBRT. Radiation pneumonitis after the second SBRT was grade 2 in 4 patients, and no grade 3 pneumonitis was observed. CONCLUSION: Repeat SBRT was safe. Local control and survival rates were higher than expected. SBRT should be an important treatment option for local recurrence of NSCLC or lung metastasis after previous local SBRT. TRIAL REGISTRATION: This retrospective study was approved by the ethics committee of our institution (September, 2017; approval number: 27-10).
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• Role of Extensive Lymphadenectomy in Early-Stage Cervical Cancer Patients With Radical Hysterectomy Followed by Adjuvant Radiotherapy., Tomita N, Mizuno M, Kondo S, Mori M, Takeshita S, Sakata J, Tsubouchi H, Kodaira T, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 28, (6) 1211 - 1217,   2018年07月, 査読有り
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• Efficacy of virtual block objects in reducing the lung dose in helical tomotherapy planning for cervical oesophageal cancer: a planning study., Makoto Ito, Hidetoshi Shimizu, Takahiro Aoyama, Hiroyuki Tachibana, Natsuo Tomita, Chiyoko Makita, Yutaro Koide, Daiki Kato, Tsuneo Ishiguchi, Takeshi Kodaira, Radiation oncology (London, England), 13, (1) 62 - 62,   2018年04月04日, 査読有り, BACKGROUND: Intensity-modulated radiotherapy is useful for cervical oesophageal carcinoma (CEC); however, increasing low-dose exposure to the lung may lead to radiation pneumonitis. Nevertheless, an irradiation technique that avoids the lungs has never been examined due to the high difficulty of dose optimization. In this study, we examined the efficacy of helical tomotherapy that can restrict beamlets passing virtual blocks during dose optimization computing (block plan) in reducing the lung dose. METHODS: Fifteen patients with CEC were analysed. The primary/nodal lesion and prophylactic nodal region with adequate margins were defined as the planning target volume (PTV)-60 Gy and PTV-48 Gy, respectively. Nineteen plans per patient were made and compared (total: 285 plans), including non-block and block plans with several shapes and sizes. RESULTS: The most appropriate block model was semi-circular, 8 cm outside of the tracheal bifurcation, with a significantly lower lung dose compared to that of non-block plans; the mean lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and the mean lung dose were 31.3% vs. 48.0% (p <  0.001), 22.4% vs. 39.4% (p <  0.001), 13.2% vs. 16.0% (p = 0.028), and 7.1 Gy vs. 9.6 Gy (p <  0.001), respectively. Both the block and non-block plans were comparable in terms of the homogeneity and conformity indexes of PTV-60 Gy: 0.05 vs. 0.04 (p = 0.100) and 0.82 vs. 0.85 (p = 0.616), respectively. The maximum dose of the spinal cord planning risk volume increased slightly (49.4 Gy vs. 47.9 Gy, p = 0.002). There was no significant difference in the mean doses to the heart and the thyroid gland. Prolongation of the delivery time was less than 1 min (5.6 min vs. 4.9 min, p = 0.010). CONCLUSIONS: The block plan for CEC could significantly reduce the lung dose, with acceptable increment in the spinal dose and a slightly prolonged delivery time.
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• Effects of dose-escalated radiotherapy in combination with long-term androgen deprivation on prostate cancer., Natsuo Tomita, Norihito Soga, Yuji Ogura, Jun Furusawa, Hidetoshi Shimizu, Sou Adachi, Hiroshi Tanaka, Daiki Kato, Yutaro Koide, Chiyoko Makita, Hiroyuki Tachibana, Takeshi Kodaira, The British journal of radiology, 91, (1083) 20170431 - 20170431,   2018年02月, 査読有り, OBJECTIVE: We aimed to examine the effects of a dose escalation for prostate cancer patients receiving long-term androgen deprivation therapy (ADT). METHODS: A retrospective analysis of 605 patients treated with radiotherapy (RT) and long-term ADT (National Comprehensive Cancer Network criteria-defined intermediate-risk, minimum 10 months; high-risk and very-high-risk, minimum 20 months) was performed. The median ADT time was 31 months. Cox's proportional hazards models were used to compare biochemical disease-free survival (bDFS), clinical relapse-free survival (cRFS) and overall survival (OS) between the ≥70, <78 Gy group and 78 Gy group in a univariate analysis and to assess the effects of the dose escalation on bDFS in a multivariate analysis. RESULTS: After a median follow-up of 70 months, 5-year bDFS was significantly better in the 78 Gy group than in the ≥70, <78 Gy group [96 vs 83%; hazard ratio 3.6 (95% confidence interval 2.2-6.1); p < 0.001]. 5-year cRFS and OS were similar between the two groups. The multivariate analysis showed that RT dose was still an independent prognostic factor of bDFS (p = 0.005). CONCLUSION: The results of the present study suggest that dose escalations result in significant improvements in bDFS, even when used in combination with long-term ADT. A longer follow-up is needed to clarify the effects of dose escalations on cRFS and OS. Advances in knowledge: It remains unclear whether high-dose RT is necessary for improving the outcomes of patients receiving long-term ADT. The results suggest that dose escalations result in significant improvements in biochemical control.
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• Comparisons of the clinical outcomes of different postoperative radiation strategies for treatment of head and neck squamous cell carcinoma., Chiyoko Makita, Takeshi Kodaira, Takashi Daimon, Hiroyuki Tachibana, Natsuo Tomita, Yutaro Koide, Yusuke Koide, Yujiro Fukuda, Daisuke Nishikawa, Hidenori Suzuki, Nobuhiro Hanai, Yasuhisa Hasegawa, Japanese journal of clinical oncology, 47, (12) 1141 - 1150,   2017年12月01日, 査読有り, Purpose: We previously reported unfavorable locoregional control with limited field postoperative radiotherapy for head and neck squamous cell carcinoma patients and thus revised the strategy to cover the whole neck. Head and neck squamous cell carcinoma Patients' outcomes were retrospectively analyzed to compare the efficacy of two treatments. Material and methods: Before 2010, the clinical target volume covered the tumor bed and/or involved the neck region. Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate analysis, and propensity score matching were performed. The study included 275 patients: 186 received limited field postoperative radiotherapy and 89 received whole-neck postoperative radiotherapy. The median follow-up time for the entire cohort was 40.8 months. Results: In univariate analysis, the radiation strategy had no significant effect on overall survival and progression-free survival. In multivariate analysis, whole-neck postoperative radiotherapy was a favorable factor for overall survival, progression-free survival, and locoregional control. Propensity score matching resulted in a cohort comprising 118 well-matched patients evenly divided between the limited field postoperative radiotherapy and whole-neck postoperative radiotherapy groups. Whole-neck postoperative radiotherapy group achieved a significantly better 2-year overall survival (56.4% vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P = 0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited field postoperative radiotherapy group developed significantly more locoregional recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0% vs. 0%, P < 0.001) in the matched-pair cohort. Conclusion: Whole-neck postoperative radiotherapy is a more appropriate choice than limited field postoperative radiotherapy to improve overall survival, progression-free survival and locoregional control.
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• Clinical results of definitive chemoradiotherapy for cervical esophageal cancer: Comparison of failure pattern and toxicities between intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy., Ito M, Kodaira T, Tachibana H, Tomita N, Makita C, Koide Y, Kato D, Abe T, Muro K, Tajika M, Niwa Y, Hasegawa Y, Head & neck, 39, (12) 2406 - 2415,   2017年12月, 査読有り
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• Nivolumab Enhances the Inflammation of the Irradiation Field in Advanced Non-Small Cell Lung Cancer, Hiromi Furuta, Tatsuya Yoshida, Junichi Shimizu, Natsuo Tomita, Yasushi Yatabe, Toyoaki Hida, JOURNAL OF THORACIC ONCOLOGY, 12, (11) 1733 - 1736,   2017年11月, 査読有り
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• Very high-risk prostate cancer: stratification by outcomes of radiotherapy and long-term androgen deprivation therapy, Natsuo Tomita, Norihito Soga, Yuji Ogura, Takumi Kageyama, Takeshi Kodaira, ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, 13, (3) 145 - 151,   2017年06月, 査読有り, AimThe definition of very high-risk (VHR) prostate cancer is currently based on the study of radical prostatectomy. We aimed to identify a suitable definition for VHR group following external beam radiation therapy (EBRT) and long-term androgen-deprivation therapy (ADT). MethodsThis retrospective study included 356 high-risk patients treated with EBRT and long-term ADT. A median follow-up time was 68 months. At first, associations of previously described prognostic factors with biochemical disease-free survival (bDFS), clinical relapse-free survival (cRFS) and prostate cancer-specific survival (CSS) were examined. Second, the combination of significant adverse factors in the first analysis served as VHR test definitions. For each factor, a Cox proportional hazards model was used to calculate their hazard ratios for bDFS and cRFS. The logrank test was used to evaluate the association between each factor and CSS. ResultsPrimary Gleason pattern 5, T4 and 5 or 4 cores with Gleason score 8-10 were risk factors associated with bDFS, cRFS and CSS. Eleven VHR test definitions composed of these adverse factors were associated significantly with bDFS, cRFS and CSS. The final definition was described by primary Gleason pattern 5 or T4 or 4 cores with Gleason score 8-10 because of the largest sample size of 38% among 11 test definitions. bDFS, cRFS and CSS of the VHR group were significantly lower compared with other high-risk patients (P < 0.001, P < 0.001 and P = 0.015, respectively). ConclusionThese VHR criteria were best fitted following EBRT with long-term ADT.
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• The Clinical Utility and Safety of Radiofrequency Ablation for Malignant Lung Tumors: Preliminary Results., Hasegawa T, Sato Y, Inaba Y, Kuroda H, Tomita N, Sakao Y, Interventional Radiology, 2, (2) 25 - 32,   2017年06月, 査読有り
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• Analysis of modulation factor to shorten the delivery time in helical tomotherapy, Hidetoshi Shimizu, Koji Sasaki, Hiroyuki Tachibana, Natsuo Tomita, Chiyoko Makita, Kuniyasu Nakashima, Kazushi Yokoi, Takashi Kubota, Manabu Yoshimoto, Tohru Iwata, Takeshi Kodaira, JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS, 18, (3) 83 - 87,   2017年05月, 査読有り, A low modulation factor (MF) maintaining a good dose distribution contributes to the shortening of the delivery time and efficiency of the treatment plan in helical tomotherapy. The purpose of this study was to reduce the delivery time using initial values and the upper limit values of MF. First, patients with head and neck cancer (293 cases) or prostate cancer (181 cases) treated between June 2011 and July 2015 were included in the analysis of MF values. The initial MF value (MFinitial) was defined as the average MFactual value, and the upper limit of the MF value (MFUL) was defined according the following equation: MFUL = 2 x standard deviation of MFactual value + the average MFactual Next, a treatment plan was designed for patients with head and neck cancer (62 cases) and prostate cancer (13 cases) treated between December 2015 and June 2016. The average MFactual value for the nasopharynx, oropharynx, hypopharynx, and prostate cases decreased from 2.1 to 1.9 (p = 0.0006), 1.9 to 1.6 (p < 0.0001), 2.0 to 1.7 (p < 0.0001), and 1.8 to 1.6 (p = 0.0004) by adapting the MFinitial and the MFUL values, respectively. The average delivery time for the nasopharynx, oropharynx, hypopharynx, and prostate cases also decreased from 19.9 s cm(-1) to 16.7 s cm(-1) (p < 0.0001), 15.0 s cm(-1) to 13.9 s cm(-1) (p = 0.025), 15.1 s cm(-1) to 13.8 s cm(-1) (p = 0.015), and 23.6 s cm(-1) to 16.9 s cm(-1) (p = 0.008) respectively. The delivery time was shortened by the adaptation of MFinitial and MFUL values with a reduction in the average MFactual for head and neck cancer and prostate cancer cases.
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• Clinical outcome of definitive radiation therapy for superficial esophageal cancer., Yutaro Koide, Takeshi Kodaira, Hiroyuki Tachibana, Natsuo Tomita, Chiyoko Makita, Makoto Itoh, Tetsuya Abe, Kei Muro, Masahiro Tajika, Yasumasa Niwa, Yoshiyuki Itoh, Shinji Naganawa, Japanese journal of clinical oncology, 47, (5) 393 - 400,   2017年05月01日, 査読有り, Objective: To analyze the clinical outcome of concurrent chemoradiotherapy in superficial esophageal cancer patients. Methods: We retrospectively analyzed data for 123 patients with superficial esophageal cancer who received external beam radiotherapy without intracavitary brachytherapy plus systemic chemotherapy during 1998-2015. Elective nodal irradiation was not performed. The dosage to planning treatment volume was 60 Gy in 30 fractions. The main outcome measure was overall survival. Results: Patient characteristics were as follows: median age, 66 (41-83) years; male/female ratio, 106/17; squamous cell carcinoma/other, 122/1; cT1a/cT1b, 27/96; cervical esophagus/upper thoracic esophagus/middle thoracic esophagus/lower thoracic esophagus, 7/9/66/41 and concurrent chemoradiotherapy/radiotherapy alone, 100/23. Cisplatin and 5-fluorouracil were the most commonly used agents (85%). At the last follow-up (median 60.5 months), 91 (74%) patients were alive. Complete response was achieved in 116 (94.4%) patients. The 5-year overall survival, progression-free survival and local control rates were 77.0, 46.9 and 62.7%, respectively, similar to that in the elderly patients (P = 0.878, 0.754 and 0.648, respectively). There were 55 failures: 42 local, 10 regional and 3 distant failures. Nine local and seven regional failures developed out-of-field. Thirty-eight local failures (90%) were successfully salvaged, of which 30 (71%) were salvaged via endoscopic removal; only 2 regional failures (20%) were salvaged. Fifteen G3 acute toxicities occurred. One pneumonitis (G3), one pneumothorax (G3) and two pericardial effusion (G2) were the late toxicities observed. There were no G4 toxicities or treatment-related deaths. Conclusions: Concurrent chemoradiotherapy without intracavitary brachytherapy was effective and safe for superficial esophageal cancer, even in elderly patients.
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• The Charlson comorbidity index is a prognostic factor in sinonasal tract squamous cell carcinoma, Hidenori Suzuki, Nobuhiro Hanai, Daisuke Nishikawa, Yujiro Fukuda, Yusuke Koide, Takeshi Kodaira, Hiroyuki Tachibana, Natsuo Tomita, Chiyoko Makita, Yasuhisa Hasegawa, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 46, (7) 646 - 651,   2016年07月, 査読有り, Objective: High Charlson comorbidity index values have been reported to be associated with shorter overall survival in various types of cancer. We investigated whether Charlson comorbidity index values were correlated with overall survival in patients with resectable sinonasal tract squamous cell carcinoma. Methods: Seventy-nine patients with resectable sinonasal tract squamous cell carcinoma were treated with curative intent. The Charlson comorbidity index values were calculated by the summation of the weight scores of 19 medical conditions (other than sinonasal tract squamous cell carcinoma) before treatment. The survival rate was analyzed according to the Kaplan-Meier method. Univariate and multivariate survival analyses were performed using the Wilcoxon test and the Cox proportional hazards model, respectively. Results: According to a univariate analysis, a Charlson comorbidity index value >= 6 was found to be significantly correlated with shorter overall survival (P < 0.02). In the multivariate survival analysis with adjustment for the clinical T and N classification, age, sex, anatomical location, treatment group (radiotherapy/surgery) and chemotherapy (presence/absence), a Charlson comorbidity index value >= 6 was found to be associated with the significantly shorter overall survival. Conclusions: These results suggest that the Charlson comorbidity index functions as a prognostic factor in cases of resectable sinonasal tract squamous cell carcinoma.
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• High-dose radiotherapy with helical tomotherapy and long-term androgen deprivation therapy for prostate cancer: 5-year outcomes, Natsuo Tomita, Norihito Soga, Yuji Ogura, Norio Hayashi, Takumi Kageyama, Makoto Ito, Yutaro Koide, Maiko Yoshida, Kana Kimura, Chiyoko Makita, Hiroyuki Tachibana, Takeshi Kodaira, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 142, (7) 1609 - 1619,   2016年07月, 査読有り, We aimed to examine outcomes of high-dose radiotherapy with helical tomotherapy (HT) and long-term androgen deprivation therapy (ADT) for T1-4N0M0 prostate cancer.A total of 391 patients treated with HT between June 2006 and December 2013 were included in this retrospective study. All patients received neoadjuvant ADT for a median duration of 10 months followed by HT at a median dose of 78 Gy [interquartile range (IQR) 78-78]. The times of median adjuvant and total ADT were 19 and 27 months (IQR 20-31), respectively. The risk stratification followed the 2015 National Comprehensive Cancer Network criteria. Biochemical disease-free survival (bDFS) followed the Phoenix definition. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale.Median follow-up from HT start was 60 months (IQR 42-81). Five-year bDFS rates for low-, intermediate-, high-, and very-high-risk groups were 100, 98.2, 97.7, and 87.9 %, respectively. We observed clinical relapse in nine very-high-risk patients and one high-risk patient, resulting in a 5-year clinical relapse-free survival of 100, 100, 99.4, and 91.7 %, respectively, for each risk group. Three patients died of prostate cancer, resulting in a 5-year prostate cancer-specific survival of 99.6 %. The late grade 2 or higher gastrointestinal and genitourinary toxicities were 9.7 and 10.7 %. No cardiovascular fatal events were observed.This report confirmed the excellent outcomes with acceptable late toxicities with the combination of HT and long-term ADT. Longer follow-up is crucial to further determine the treatment effect and toxicity.
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• Retrospective analysis of the clinical efficacy of definitive chemoradiotherapy for patients with hypopharyngeal cancer, Keiichi Takehana, Takeshi Kodaira, Hiroyuki Tachibana, Kana Kimura, Arisa Shimizu, Chiyoko Makita, Natsuo Tomita, Daisuke Nishikawa, Hidenori Suzuki, Hitoshi Hirakawa, Nobuhiro Hanai, Yasuhisa Hasegawa, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 46, (4) 344 - 349,   2016年04月, 査読有り, A retrospective analysis was performed to evaluate the clinical efficacy of definitive chemoradiotherapy including intensity-modulated radiotherapy for patients with hypopharyngeal cancer. Previously untreated 204 patients with hypopharyngeal cancer were treated with definitive chemoradiotherapy. Of note, 66-70 Gy was delivered to the primary and involved nodes and 36-54 Gy was delivered to the prophylactic lymph node using standard fractionated radiotherapy. One hundred and forty-six patients received induction chemotherapy as a larynx preservation strategy, followed by definitive radiotherapy with or without concurrent chemotherapy. Intensity-modulated radiotherapy was also performed after 2006. The median follow-up time of this cohort was 43.4 months (range; 6.9-151.0). The 3-year overall survival, progression-free survival and larynx preservation survival rates were 78.8% (95% confidence interval; 73.0-85.0), 58.4% (95% confidence interval; 51.8-65.9) and 67.5% (95% confidence interval; 61.0-74.7), respectively. Multivariate analyses identified the following significant prognostic factors: an advanced age, the T category and N category for overall survival, the T category and N category for progression-free survival and the T category for larynx preservation survival. Acute toxicities of Grade 3 or higher were observed in 47 patients (23.0%). Two patients (1.0%) had Grade 4 pharyngeal edema. Suspicious treatment-related death due to lethal pharyngeal hemorrhage occurred in 1 (0.4%) patient. The rates of Grade 2 xerostomia in patients treated with intensity-modulated radiotherapy were 28.1, 17.4 and 9.5% at 6 months, 1 and 2 years after the completion of radiotherapy, respectively. The efficacy and safety of definitive chemoradiotherapy are considered feasible with sufficient laryngeal preservation.
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• Clinical results of definitive intensity-modulated radiation therapy for oropharyngeal cancer: retrospective analysis of treatment efficacy and safety, Kana Kimura, Takeshi Kodaira, Natsuo Tomita, Hiroyuki Tachibana, Chiyoko Makita, Maiko Yoshida, Daisuke Nishikawa, Hitoshi Hirakawa, Hidenori Suzuki, Nobuhiro Hanai, Yasuhisa Hasegawa, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 46, (1) 78 - 85,   2016年01月, 査読有り, To evaluate the clinical outcomes of intensity-modulated radiotherapy for patients with oropharyngeal carcinoma. Ninety-three oropharyngeal carcinoma patients histopathologically diagnosed with squamous cell carcinoma and treated with definitive intensity-modulated radiotherapy using helical tomotherapy between January 2006 and December 2013 were analyzed. Planning target volume primary and involved nodes was delivered 66-70 Gy at 2 Gy per fraction, while planning target volume prophylactic was delivered 54 Gy using the simultaneous integrated boost technique. The median follow-up period among the surviving patients was 40 months (range, 13-96). There were 76 males and 17 females with a median age of 60 years (range, 34-80). The disease was Stage II in 13%, Stage III in 10% and Stage IV in 77% of patients. Ninety-two patients received chemotherapy (99%); 68 patients received induction chemotherapy (73%), while 21 received concurrent chemotherapy (23%). The 3-year overall survival, progression-free survival and locoregional control rates were 80, 68 and 79%, respectively. Multivariate analysis identified an advanced T-category (T3-4), having double cancer, and smoking habit as significantly unfavorable factors for overall survival, progression-free survival and both progression-free survival and locoregional control, respectively. Only two patients who achieved disease control required percutaneous endoscopic gastrostomy tubes in the last follow-up. The rate of Grade 2 xerostomia at 2 years was 23%. Intensity-modulated radiotherapy using helical tomotherapy for patients with oropharyngeal carcinoma provided not only sufficient efficacy, but also preserved parotid function.
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• International prostate symptom score (IPSS) change and changing factor in intensity-modulated radiotherapy combined with androgen deprivation therapy for prostate cancer., Natsuo Tomita, Isao Oze, Hidetoshi Shimizu, Maiko Yoshida, Kana Kimura, Keiichi Takehana, Arisa Shimizu, Chiyoko Makita, Hiroyuki Tachibana, Takeshi Kodaira, Norihito Soga, Yuji Ogura, Norio Hayashi, Nagoya journal of medical science, 77, (4) 637 - 46,   2015年11月, 査読有り, The purposes of this study on prostate cancer are to demonstrate the time course of International Prostate Symptom Score (IPSS) after intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) and to examine the factor associated with the IPSS change. This study included 216 patients treated with IMRT between 2006 and 2010. Patients were evaluated in three groups according to baseline IPSS as defined by the American Urological Association classification, where IPSSs of 0 to 7, 8 to 19, and 20 to 35 represent mild (n = 124), moderate (n = 70), and severe (n = 22) symptom groups, respectively. The average IPSSs ± standard deviation at baseline vs. those at 24 months after IMRT were 3.5 ± 2.1 vs. 5.1 ± 3.6 in the mild group (P < 0.001), 12.6 ± 3.4 vs. 10.0 ± 6.0 in the moderate group (P = 0.0015), and 23.8 ± 2.9 vs. 14.4 ± 9.1 in the severe group (P < 0.001). Among factors of patient and treatment characteristics, age, IPSS classification, pretreatment GU medications, and positive biopsy rates were associated with the IPSS difference between baseline and 24 months (P = 0.023, < 0.001, 0.044, and 0.028, respectively). In conclusion, patients with moderate to severe urinary symptoms can exhibit improvement in urinary function after IMRT, whereas patients with mild symptoms may have slightly worsened functions. Age, baseline IPSS, GU medications, and tumor burden in the prostate can have an effect on the IPSS changes.
• Efficacy of palliative radiotherapy for gastric bleeding in patients with unresectable advanced gastric cancer: a retrospective cohort study, Chihiro Kondoh, Kohei Shitara, Motoo Nomura, Daisuke Takahari, Takashi Ura, Hiroyuki Tachibana, Natsuo Tomita, Takeshi Kodaira, Kei Muro, BMC PALLIATIVE CARE, 14,   2015年08月, 査読有り, Background: Bleeding negatively impacts quality of life in patients with unresectable advanced gastric cancer and has the potential to be lethal. When blood transfusion and endoscopic hemostasis are unsuccessful to stop bleeding, radiation to stomach is selected in patients with unsuitable condition for surgery. We performed a retrospective cohort study to clarify the utility of radiotherapy in treating gastric bleeding, particularly for patients with limited life expectancy. Methods: We evaluated the efficacy and safety of palliative radiotherapy in patients with advanced gastric cancer between January 2007 and December 2012 in Aichi Cancer Center Hospital. All patients had gastric bleeding requiring blood transfusion. We defined hemostasis as an increase in hemoglobin level to more than 7.0 g/dL together with the cessation of melena or hematemesis for at least 1 week. Results: During the study period, 313 advanced gastric cancer patients treated in our institution. Of these 17 patients received gastric radiotherapy to stop bleeding. Two patients were excluded from analysis due to combined treatment of intravascular embolization. Eleven out of 15 patients ( 73 %) had undergone two or more previous chemotherapy regimens. Ten patients ( 67 %) had an Eastern Cooperative Oncology Group performance status of 3 and 14 patients ( 93 %) were in palliative prognostic index group B or C. The median total planned radiation dose was 30 Gy in 10 fractions. At a median interval of 2 days after initiation of radiotherapy, 11 patients ( 73 %) achieved hemostasis; rebleeding was observed in four patients ( 36 %). The median hemoglobin level before radiotherapy was significantly increased from 6.0 to 9.0 g/dL ( p < 0.0001). The median volume of red blood cell transfusion was significantly decreased from 1120 to 280 mL ( p = 0.007). The median rebleeding-free survival interval was 27 days, with a median overall survival of 63 days. The cause of death was bleeding in 1 patient ( 7 %) and cancer progression without bleeding in 12 patients ( 80 %). There were no severe adverse events attributable to radiotherapy. Conclusions: Palliative radiotherapy for gastric bleeding achieves hemostasis within a short time frame. This appears to be a useful treatment option, especially for patients with end-stage, unresectable advanced gastric cancer.
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• A case of severe hemoptysis after stereotactic body radiotherapy for peripherally located stage I non-small cell lung cancer, Kana Kimura, Natsuo Tomita, Arisa Shimizu, Yozo Sato, Chiyoko Makita, Takeshi Kodaira, JAPANESE JOURNAL OF RADIOLOGY, 33, (6) 370 - 374,   2015年06月, 査読有り, In stereotactic body radiotherapy (SBRT) for centrally located non-small cell lung carcinoma (NSCLC), severe hemoptysis has been reported in several studies. We report here a rare case of hemoptysis after SBRT even though the lung tumor was peripherally located. A lung nodule of a 79-year-old man was accidentally found at the periphery of the left upper lobe. A computed tomography-guided biopsy of this nodule provided confirmation of the diagnosis of poorly differentiated adenocarcinoma. The clinical diagnosis was T1bN0M0, stage I primary lung cancer. The patient was treated with SBRT using helical tomotherapy at a dose of 60 Gy in 6 fractions (i.e., BED10 = 120). He obtained a complete response and did not experience recurrence. However, the patient suffered massive hemoptysis 4.5 years after SBRT. As hypervascularity of a left bronchial artery was observed at the left lung in accordance with SBRT field on bronchial arteriography, a bronchial artery embolization (BAE) procedure was performed. The patient has had no episodes of hemoptysis after BAE. Although SBRT for early stage NSCLC is usually safe and efficient, it is necessary to be careful for late-onset bronchial hemorrhage in SBRT, even for a peripheral tumor.
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• Clinical Efficacy of Alternating Chemoradiotherapy by Conformal Radiotherapy Combined with Intracavitary Brachytherapy for High-risk Cervical Cancer, Kimiko Hirata, Takeshi Kodaira, Natsuo Tomita, Yukihiko Ohshima, Junji Ito, Hiroyuki Tachibana, Toru Nakanishi, Nobukazu Fuwa, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 44, (6) 556 - 563,   2014年06月, 査読有り, The purpose of this study was to assess the outcome of alternating chemoradiotherapy in patients with high-risk cervical cancer. We performed definitive alternating chemoradiotherapy in cervical cancer patients with at least one high-risk factor such as International Federation of Gynecology and Obstetrics III or IVA disease, primary tumor diameter a parts per thousand yen50 mm, positive pelvic node, and positive para-aortic node. Our chemoradiotherapy protocol was as follows: (i) alternating chemoradiotherapy with 5-fluorouracil and nedaplatin; (ii) whole pelvic radiotherapy with the dynamic conformal technique combined with intracavitary brachytherapy; (iii) prophylactic irradiation to the para-aortic region for International Federation of Gynecology and Obstetrics III/IVA or positive pelvic node and full-dose radiotherapy for positive para-aortic node. Between 1998 and 2010, 121 patients were treated with this protocol. The median follow-up period was 53.7 months (7.6-162.2). International Federation of Gynecology and Obstetrics stages were IB; (9.1%), IIA; 6 (5.0%), IIB; 53 (43.8%), IIIA; 7 (5.8%), IIIB; 37 (30.6%) and IVA; 7 (5.8%), respectively. Nodal involvement was reported in 77 patients (63.6%) at the pelvis and 25 (20.7%) at the para-aortic region. The 5-year overall survival and progression-free survival rates were 80.0 and 63.4%, respectively. Regarding Grade a parts per thousand yen3 late toxicities, three patients developed urinary and three developed intestinal toxicities. We encountered no treatment-related death. The clinical results of our alternating chemoradiotherapy protocol for high-risk cervical cancer are promising.
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• Japanese Structure Survey of High-precision Radiotherapy in 2012 Based on Institutional Questionnaire about the Patterns of Care, Natsuo Tomita, Takeshi Kodaira, Teruki Teshima, Kazuhiko Ogawa, Yu Kumazaki, Chikako Yamauchi, Takafumi Toita, Takashi Uno, Minako Sumi, Hiroshi Onishi, Masahiro Kenjo, Katsumasa Nakamura, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 44, (6) 579 - 586,   2014年06月, 査読有り, The purpose of this study was to clarify operational situations, treatment planning and processes, quality assurance and quality control with relevance to stereotactic radiotherapy, intensity-modulated radiotherapy and image-guided radiotherapy in Japan. We adopted 109 items as the quality indicators of high-precision radiotherapy to prepare a questionnaire. In April 2012, we started to publicly open the questionnaire on the website, requesting every institution with radiotherapy machines for response. The response ratio was 62.1% (490 out of 789 institutions responded). Two or more radiotherapy technologists per linear accelerator managed linear accelerator operation in similar to 90% of the responded institutions while medical physicists/radiotherapy quality managers were engaged in the operation in only 64.9% of the institutions. Radiotherapy certified nurses also worked in only 18.4% of the institutions. The ratios of the institutions equipped for stereotactic radiotherapy of lung tumor, intensity-modulated radiotherapy and image-guided radiotherapy were 43.3, 32.6 and 46.8%, respectively. In intensity-modulated radiotherapy planning, radiation oncologists were usually responsible for delineation while medical physicists/radiotherapy quality managers or radiotherapy technologists set up beam in 33.3% of the institutions. The median time required for quality assurance of intensity-modulated radiotherapy at any site of brain, head and neck and prostate was 4 h. Intensity-modulated radiotherapy quality assurance activity had to be started after clinical hours in > 60% of the institutions. This study clarified one major issue in the current high-precision radiotherapy in Japan. A manpower shortage should be corrected for high-precision radiotherapy, especially in the area relevant to quality assurance/quality control.
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• Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer, Natsuo Tomita, Norihito Soga, Yuji Ogura, Norio Hayashi, Hidetoshi Shimizu, Takashi Kubota, Junji Ito, Kimiko Hirata, Yukihiko Ohshima, Hiroyuki Tachibana, Takeshi Kodaira, JOURNAL OF RADIATION RESEARCH, 54, (5) 919 - 924,   2013年09月, 査読有り, The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between <= Grade 1 and >= Grade 2 toxicity groups using the Student's t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student's t-test) was performed. The median follow-up time was 35 months. Late Grade 2-3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the >= Grade 2 toxicity group were significantly higher than in those of the <= Grade 1 toxicity group (P = 0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose-volume modeling to predict rectal complications after HT.
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• Clinical Outcome and Patterns of Recurrence of Head and Neck Squamous Cell Carcinoma with a Limited Field of Postoperative Radiotherapy, Yoko Goto, Takeshi Kodaira, Kazuhisa Furutani, Hiroyuki Tachibana, Natsuo Tomita, Junji Ito, Nobuhiro Hanai, Taijiro Ozawa, Hitoshi Hirakawa, Hidenori Suzuki, Yasuhisa Hasegawa, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 43, (7) 719 - 725,   2013年07月, 査読有り, Postoperative radiotherapy is the standard treatment for head and neck squamous cell carcinoma having high-risk features in surgical specimens. However, its severe toxicity can be a significant problem. This study was undertaken to evaluate the efficacy of our limited-field postoperative radiotherapy with the aim of reducing morbidity by minimizing the radiation field. Between 2000 and 2009, 154 patients with head and neck squamous cell carcinoma received limited-field postoperative radiotherapy. The reason for postoperative radiotherapy was close/positive margins in 33 patients and extracapsular extension in 91. The median radiation dose was 50 Gy (3066.4). The radiation field covered the tumor bed without lymph node regions for close/positive margins and only involved sites of the neck region were irradiated for multiple nodes or extracapsular extension. With a median follow-up of 43 months for surviving patients, the 3-year overall survival and progression-free survival rates were 53.7 and 42.1, respectively. The 3-year rates of progression-free survival of the group having major risks (i.e. close/positive margins and/or extracapsular extension) and the group with other risks were 34.7 and 62.8, respectively (P 0.01). Thirty-one local recurrences (20), of which 22 were located out-of-field, and 44 regional recurrences (29), of which 16 were located out-of-field, developed. Late toxicity of grade 3 or greater developed in only six patients (3.8). Although the toxicities associated with limited-field postoperative radiotherapy could be kept to lower levels, the locoregional control rate did not seem to be sufficient. We should arrange the radiation field depending on risk factors.
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• Alternating chemoradiotherapy in patients with nasopharyngeal cancer: prognostic factors and proposal for individualization of therapy, Yoko Goto, Takeshi Kodaira, Nobukazu Fuwa, Nobutaka Mizoguchi, Rie Nakahara, Motoo Nomura, Natsuo Tomita, Hiroyuki Tachibana, JOURNAL OF RADIATION RESEARCH, 54, (1) 98 - 107,   2013年01月, 査読有り, The purpose of this study is to assess the efficacy of alternating chemoradiation in patients with nasopharyngeal cancer. From 1990-2006, 100 patients with nasopharyngeal cancer were treated with alternating chemoradiation at the Aichi Cancer Center. Of these, 4, 2, 23, 34, 13 and 23 patients were staged as I, IIA, IIB, III, IVA and IVB, respectively. The median radiation doses for primary tumors and metastatic lymph nodes were 66.6 Gy (range, 50.4-80.2 Gy) and 66 Gy (range, 40.4-82.2 Gy), respectively. A total of 82 patients received chemotherapy with both cisplatin and 5-fluorouracil (5-FU), while 14 patients received nedaplatin (CDGP) and 5-FU. With a median follow-up of 65.9 months, the 5-year rates of overall survival (OAS) and progression-free survival (PFS) were 78.1% and 68.3%, respectively. On multivariate analysis (MVA), elderly age, N3, and WHO type I histology proved to be significantly unfavorable prognostic factors of OAS. As for PFS, there were T4, N3, and WHO type I histology in MVA. Acute toxicities of hematologic and mucositis/dermatitis >= Grade 3 were relatively high (32%); however, they were well-managed. Late toxicities of >= Grade 3 were three (3%) mandibular osteomyelitis and one (1%) lethal mucosal bleeding. Results for alternating chemoradiation for nasopharyngeal carcinoma are promising. In order to improve outcomes, usage of intensity-modulated radiation therapy and application of active anticancer agents are hopeful treatments, especially for groups with poor prognosis factors with WHO type I histopathology, T4 and/or N3 disease.
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• Regression curves of brain metastases after gamma knife irradiation: Difference by tumor and patient characteristics, Katsura Kosaki, Yuta Shibamoto, Tatsuo Hirai, Manabu Hatano, Natsuo Tomita, Tatsuya Kobayashi, Yoshimasa Mori, CANCER SCIENCE, 103, (11) 1967 - 1973,   2012年11月, 査読有り, Regression curves and local control rates of brain metastases after gamma knife treatment were evaluated to investigate differences in tumor response to radiation. A total of 203 metastases were serially evaluated using contrast-enhanced MRI (or computed tomography) at 1, 2, 3, 4.5 and 6 months after a 20-Gy dose. Differences were evaluated in regression curves and control rates between tumors >= 10 mm and tumors < 10 mm in mean diameter, among three major histological subtypes of lung cancer, among adenocarcinomas of the lung, breast and colorectum, and between tumors in patients with above and below median hemoglobin levels. Smaller tumors shrank faster and yielded better control rates than larger tumors. Metastases from small cell and squamous cell carcinomas of the lung shrank faster than those from lung adenocarcinoma, but 6-month control rates were not different. Breast adenocarcinomas tended to shrink faster than lung adenocarcinomas, but the control rates were not different among adenocarcinomas of the lung, breast and colorectum. Tumors in patients with higher hemoglobin levels tended to shrink faster but the control rates were not different. Small cell and squamous cell carcinomas of the lung regress more rapidly than adenocarcinomas, although local control rates might not differ significantly. (Cancer Sci 2012; 103: 1967-1973)
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• Treatment outcomes of definitive chemoradiotherapy for patients with hypopharyngeal cancer, Rie Nakahara, Takeshi Kodaira, Kazuhisa Furutani, Hiroyuki Tachibana, Natsuo Tomita, Haruo Inokuchi, Nobutaka Mizoguchi, Yoko Goto, Yoshiyuki Ito, Shinji Naganawa, JOURNAL OF RADIATION RESEARCH, 53, (6) 906 - 915,   2012年11月, 査読有り, We analyzed the efficacy of definitive chemoradiotherapy (CRT) for patients with hypopharyngeal cancer (HPC). Subjects comprised 97 patients who were treated with definitive CRT from 1990 to 2006. Sixty-one patients (62.9%) with resectable disease who aimed to preserve the larynx received induction chemotherapy (ICT), whereas 36 patients (37.1%) with resectable disease who refused an operation or who had unresectable disease received primary alternating CRT or concurrent CRT (non-ICT). The median dose to the primary lesion was 66 Gy. The median follow-up time was 77 months. The 5-year rates of overall survival (OS), progression-free survival (PFS), local control (LC), and laryngeal preservation were 68.7%, 57.5%, 79.1%, and 70.3%, respectively. The T-stage was a significant prognostic factor in terms of OS, PFS and LC in both univariate and multivariate analyses. The 5-year rates of PFS were 45.4% for the ICT group and 81.9% for the non-ICT group. The difference between these groups was significant with univariate analysis (P = 0.006). Acute toxicity of Grade 3 to 4 was observed in 34 patients (35.1%). Grade 3 dysphagia occurred in 20 patients (20.6%). Twenty-nine (29.8%) of 44 patients with second primary cancer had esophageal cancer. Seventeen of 29 patients had manageable superficial esophageal cancer. The clinical efficacy of definitive CRT for HPC is thought to be promising in terms of not only organ preservation but also disease control. Second primary cancer may have a clinical impact on the outcome for HPC patients, and special care should be taken when screening at follow-up.
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• Preliminary results of intensity-modulated radiation therapy with helical tomotherapy for prostate cancer, Natsuo Tomita, Norihito Soga, Yuji Ogura, Norio Hayashi, Hidetoshi Shimizu, Takashi Kubota, Junji Ito, Kimiko Hirata, Yukihiko Ohshima, Hiroyuki Tachibana, Takeshi Kodaira, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 138, (11) 1931 - 1936,   2012年11月, 査読有り, We present the preliminary results of intensity-modulated radiation therapy with helical tomotherapy (HT) for clinically localized prostate cancer. Regularly followed 241 consecutive patients, who were treated with HT between June 2006 and December 2010, were included in this retrospective study. Most patients received both relatively long-term neoadjuvant and adjuvant androgen deprivation therapy (ADT). Patients received 78 Gy in the intermediate high-risk group and 74 Gy in the low-risk group. Biochemical disease-free survival (bDFS) followed the Phoenix definition. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale. The median follow-up time from the start date of HT was 35 months. The rates of acute Grade 2 gastro-intestinal (GI) and genitor-urinary (GU) toxicities were 11.2 and 24.5 %. No patients experienced acute Grade 3 or higher symptoms. The rates of late Grade 2 and 3 GI toxicities were 6.6 and 0.8 %, and those of late Grade 2 and 3 GU toxicities were 8.3 % and 1.2 %. No patients experienced late Grade 4 toxicity. The 3-year bDFS rates for low, intermediate, and high-risk group patients were 100, 100, and 95.8 %, respectively. We observed clinical relapse in two high-risk patients, resulting in a 3-year clinical DFS of 99.4 %. This preliminary report confirms the feasibility of HT in a large number of patients. We observed that HT is associated with low rates of acute and late toxicities, and HT in combination with relatively long-term ADT results in excellent short-term bDFS.
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• Patterns of Radiotherapy Practice for Patients With Cervical Cancer in Japan, 2003-2005: Changing Trends in the Pattern of Care Process, Natsuo Tomita, Takafumi Toita, Takeshi Kodaira, Atsunori Shinoda, Takashi Uno, Hodaka Numasaki, Teruki Teshima, Michihide Mitsumori, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 83, (5) 1506 - 1513,   2012年08月, 査読有り, Purpose: The patterns of care study (PCS) of radiotherapy for cervical cancer in Japan over the last 10 years was reviewed. Methods and Materials: The Japanese PCS working group analyzed data from 1,200 patients (1995-1997, 591 patients; 1999-2001, 324 patients; 2003-2005, 285 patients) with cervical cancer treated with definitive radiotherapy in Japan. Results: Patients in the 2001-2003 survey were significantly younger than those in the 1999-2001 study (p < 0.0001). Histology, performance status, and International Federation of Gynecology and Obstetrics stage were not significantly different among the three survey periods. Use of combinations of chemotherapy has increased significantly during those periods (1995-1997, 24%; 1999-2001, 33%; 2003-2005, 54%; p < 0.0001). The ratio of patients receiving concurrent chemotherapy has also dramatically increased (1995-1997, 20%; 1999-2001, 54%; 2003-2005, 83%; p < 0.0001). As for external beam radiotherapy (EBRT), the application rate of four-field portals has greatly increased over the three survey periods (1995-1997, 2%; 1999-2001, 7%; 2003-2005, 21%; p < 0.0001). In addition, the use of an appropriate beam energy for EBRT has shown an increase (1995-1997, 67%; 1999-2001, 74%; 2003-2005, 81%; p = 0.064). As for intracavitary brachytherapy (ICBT), an iridium source has become increasingly popular (1995-1997, 27%; 1999-2001, 42%; 2003-2005, 84%; p < 0.0001). Among the three surveys, the ratio of patients receiving ICBT (1995-1997, 77%; 1999-2001, 82%; 2003-2005, 78%) has not changed. Although follow-up was inadequate in each survey, no significant survival differences were observed (p = 0.36), and rates of late Grade 3 or higher toxicity were significantly different (p = 0.016). Conclusions: The Japanese PCS has monitored consistent improvements over the past 10 years in the application of chemotherapy, timing of chemotherapy, and EBRT methods. However, there is still room for improvement, especially in the clinical practice of ICBT. (C) 2012 Elsevier Inc.
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• Predictive factors for radiation pneumonitis in oesophageal cancer patients treated with chemoradiotherapy without prophylactic nodal irradiation, M. Nomura, T. Kodaira, K. Furutani, H. Tachibana, N. Tomita, Y. Goto, BRITISH JOURNAL OF RADIOLOGY, 85, (1014) 813 - 818,   2012年06月, 査読有り, Objective: The objective of this study was to identify clinical and dosimetric factors for the development of radiation pneumonitis (RP) among patients with oesophageal cancer treated with three-dimensional radiotherapy without prophylactic nodal irradiation. Methods: 125 patients with oesophageal cancer had undergone dose-volume histogram (DVH) metrics and received chemoradiotherapy (CRT). Several clinical and dosimetric factors with regard to the lung were evaluated as predictive factors for the development of symptomatic RP. Results: 26 patients (20.8%) developed symptomatic RP classified as greater than or equal to Grade 2. By univariate analysis, body weight loss, tumour length, Stage IV, response to treatment and all DVH parameters proved to be significant factors for the development of RP (p<0.05). By multivariate analysis, Stage IV and all dosimetric factors were independent predictive factors for the development of symptomatic RP (p<0.05). Recursive partitioning analysis indicated that V10 values of 24.8% or more and Stage IV were associated with higher development of RP (odds ratio 6.53). Conclusions: Our study demonstrated that severe RP was also developed in patients treated with the minimal radiation field. Stage IV and the dosimetric factors were identified as independent predictive factors for symptomatic RP in oesophageal cancer patients treated with CRT without prophylactic nodal irradiation.
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• A case of cervical multicentric Castleman disease treated with intensity-modulated radiation therapy using helical tomotherapy, Natsuo Tomita, Takeshi Kodaira, Takuya Tomoda, Kosei Nakajima, Takayuki Murao, Kunio Kitamura, JAPANESE JOURNAL OF RADIOLOGY, 30, (4) 349 - 353,   2012年05月, 査読有り, Castleman disease (CD) is a rare lymphoproliferative disorder. Two clinical entities are described: a unicentric form with disease confined to a single lymph node region and a multicentric form characterized by generalized lymphadenopathy and systemic symptoms. Although surgery is regarded as standard therapy for the unicentric form, no consensus has been reached concerning the standard treatment for multicentric CD. We report here a case of cervical multicentric CD treated with intensity-modulated radiation therapy (IMRT), using helical tomotherapy to minimize xerostomia in comparison with conventional radiotherapy. A 29-year-old woman complained of neck swelling. Computed tomography showed lymphadenopathy in both sides of the neck. The patient was diagnosed with the plasma cell subtype of CD on biopsy. After initial treatment with prednisone, IMRT was planned to avoid normal structures, for example the parotid gland. The cervical lymphadenopathy shrank gradually during IMRT with 44 Gy in 22 fractions. Four years and 3 months after IMRT, regrowth of cervical lymph nodes has not been detected. The parotid function improved dramatically on quantitative salivary scintigraphy between 3 and 12 months after IMRT. Radiotherapy could be an option for multicentric CD, and IMRT is an effective means of minimizing xerostomia in head and neck lesions.
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• Evaluation of Parotid Gland Function using Equivalent Cross-relaxation Rate Imaging Applied Magnetization Transfer Effect, Hidetoshi Shimizu, Shigeru Matsushima, Yasutomi Kinosada, Hiroki Miyamura, Natsuo Tomita, Takashi Kubota, Hikaru Osaki, Masashi Nakayama, Manabu Yoshimoto, Takeshi Kodaira, JOURNAL OF RADIATION RESEARCH, 53, (1) 138 - 144,   2012年01月, 査読有り, Safe imaging modalities are needed for evaluating parotid gland function. The aim of this study was to validate the utility of a magnetic resonance imaging (MRI) tool, equivalent cross-relaxation rate imaging (ECRI), as a measurement of parotid gland function after chemoradiotherapy. Subjects comprised 18 patients with head-neck cancer who underwent ECRI and salivary gland scintigraphy. First, we calculated ECR values (signal intensity on ECRI), maximum uptake rate (MUR) and washout rate (WOR) from salivary gland scintigraphy data at the parotid glands. Second, we investigated correlations between ECR values and each parameter of MUR (uptake function) and WOR (secretory function) obtained by salivary gland scintigraphy at the parotid gland. Next, we investigated each dose-response for ECR, MUR and WOR at the parotid gland. A correlation was detected between ECR values and MUR in both the pre- (r = -0.55, p < 0.01) and post-treatment (r = -0.50, p < 0.05) groups. A significant post-treatment correlation was detected between the percentage change in ECR values at 3-5 months after chemoradiotherapy and median dose to the parotid gland (Pearson correlation, r = -0.62, p < 0.05). However, no correlations were detected between median dose to the parotid gland and either MUR or WOR. ECRI is a new imaging tool for evaluating the uptake function of the parotid gland after chemoradiotherapy.
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• Radiobiological Evaluation of the Radiation Dose as Used in High-precision Radiotherapy: Effect of Prolonged Delivery Time and Applicability of the Linear-quadratic Model, Yuta Shibamoto, Shinya Otsuka, Hiromitsu Iwata, Chikao Sugie, Hiroyuki Ogino, Natsuo Tomita, JOURNAL OF RADIATION RESEARCH, 53, (1) 1 - 9,   2012年01月, 査読有り, Since the dose delivery pattern in high-precision radiotherapy is different from that in conventional radiation, radiobiological assessment of the physical dose used in stereotactic irradiation and intensity-modulated radiotherapy has become necessary. In these treatments, the daily dose is usually given intermittently over a time longer than that used in conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. This phenomenon is almost universarily observed in vitro. In in vivo tumors, however, this decrease in effect can be counterbalanced by rapid reoxygenation, which has been demonstrated in a laboratory study. Studies on reoxygenation in human tumors are warranted to better evaluate the influence of prolonged radiation delivery. Another issue related to radiosurgery and hypofractionated stereotactic radiotherapy is the mathematical model for dose evaluation and conversion. Many clinicians use the linear-quadratic (LQ) model and biologically effective dose (BED) to estimate the effects of various radiation schedules, but it has been suggested that the LQ model is not applicable to high doses per fraction. Recent experimental studies verified the inadequacy of the LQ model in converting hypofractionated doses into single doses. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when it is used for tumor responses in vivo, since it does not take reoxygenation into account. For normal tissue responses, improved models have been proposed, but, for in vivo tumor responses, the currently available models are not satisfactory, and better ones should be proposed in future studies.
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• Changing trend in the patterns of pretreatment diagnostic assessment for patients with cervical cancer in Japan, Natsuo Tomita, Takafumi Toita, Takeshi Kodaira, Atsunori Shinoda, Takashi Uno, Hodaka Numasaki, Teruki Teshima, Michihide Mitsumori, GYNECOLOGIC ONCOLOGY, 123, (3) 577 - 580,   2011年12月, 査読有り, Objective. Cancer staging systems should be responsive to the development of diagnostic tools. The International Federation of Gynecology and Obstetrics (FIGO) cervical cancer guidelines were modified in 2009 regarding the pretreatment assessment. We report the recent Japanese patterns of pretreatment workup for cervical cancer. Methods. The Japanese Patterns of Care Study (PCS) working group analyzed the pretreatment diagnostic assessment data of 609 patients with cervical cancer treated with definitive radiotherapy in the two survey periods (1999-2001, 324: 2003-2005, 285) in Japan. Sixty-one of 640 institutions were selected for this survey using a stratified two-staged cluster sampling method. Results. The use of optional examinations in the latest FIGO guidelines such as intravenous urography, cystoscopy, and proctoscopy was gradually decreasing. Surgical staging was rarely performed in either survey period. Computed tomography (CT) and magnetic resonance imaging (MRI) were widely used, and MRI has become increasingly prevalent even between the two survey periods. Primary lesion size and pelvic lymph node status was evaluated by CT/MRI for most patients in both surveys. Conclusions. The use of CT/MRI that is encouraged in the latest FIGO staging guidelines already replaced intravenous urography, cystoscopy, and proctoscopy in Japan. Japanese patients received the potential benefit of CT/MRI because prognostic factors such as primary lesion size and pelvic lymph node status were evaluated by these modalities. The use of cystoscopy and proctoscopy should be continuously monitored in the future PCS survey because only CT/MRI could lead to the stage migration for patients on suspicion of bladder/rectum involvement on CT/MRI. (C) 2011 Elsevier Inc. All rights reserved.
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• Factors associated with nodal metastasis in nasopharyngeal cancer: an approach to reduce the radiation field in selected patients, N. Tomita, N. Fuwa, Y. Ariji, T. Kodaira, N. Mizoguchi, BRITISH JOURNAL OF RADIOLOGY, 84, (999) 265 - 270,   2011年03月, 査読有り, Objectives: The purpose of this study was to investigate factors associated with lymph node (LN) metastasis to identify which nasopharyngeal cancer (NPC) patients can undergo a reduction in the prophylactic radiation field. MRI of biopsy-proven NPC patients was evaluated to determine primary tumour extension and the existence of LN metastasis. Methods: Sex, age, pathological type, T stage, primary tumour size, existence beyond the midline of the nasopharynx at the primary site and parapharyngeal extension of the primary tumour were assessed regarding their impact on the laterality of LN metastasis using the chi(2) test. Results: Of the 167 patients, 149 (89%) showed nodal involvement. The existence beyond the midline of the nasopharynx was significantly associated with the laterality of LN metastasis (p<0.0001). Most patients (82%) with primary tumour presence within the midline showed only ipsilateral LN metastasis or no LN metastasis. In addition, contralateral LN metastases were seen only at Level II and the retropharyngeal LN among most of other patients. Conclusion: These results suggest that LN areas other than Level II and the retropharyngeal LN on the contralateral side could be omitted in patients with primary tumour presence within the midline and without the contralateral Level II or the retropharyngeal LN. Whether disease control is compromised by reducing the radiation field for subclinical diseases is a problem that should be solved in the future by prospective study.
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• CLINICAL USEFULNESS OF [(18)F] FLUORO-2-DEOXY-D-GLUCOSE UPTAKE IN 178 HEAD-AND-NECK CANCER PATIENTS WITH NODAL METASTASIS TREATED WITH DEFINITIVE CHEMORADIOTHERAPY: CONSIDERATION OF ITS PROGNOSTIC VALUE AND ABILITY TO PROVIDE GUIDANCE FOR OPTIMAL SELECTION OF PATIENTS FOR PLANNED NECK DISSECTION, Haruo Inokuchi, Takeshi Kodaira, Hiroyuki Tachibana, Tatsuya Nakamura, Natsuo Tomita, Rie Nakahara, Akinori Takada, Nobutaka Mizoguchi, Tsuneo Tamaki, Nobukazu Fuwa, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 79, (3) 747 - 755,   2011年03月, 査読有り, Purpose: To evaluate the clinical effectiveness of pretreatment [(18)F] fluoro-2-deoxy-D-glucose-positron emission tomography for head-and-neck squamous cell carcinoma patients with nodal metastasis treated with chemoradiotherapy. Methods and Materials: Between March 2002 and December 2006, 178 patients with head-and-neck squamous cell carcinoma and nodal metastasis underwent fluoro-2-deoxy-D-glucose positron emission tomography before chemoradiotherapy. Fluoro-2-deoxy-D-glucose uptake by both the primary lesion and the neck node was measured using the standard uptake value (SUV). The overall survival, disease-free survival, local control, nodal progression-free survival, and distant metastasis-free survival rates were calculated, and several prognostic factors were evaluated. Results: The patients with a nodal SUV >= 6.00 had a significantly lower 3-year disease-free survival rate than those with a lower SUV (44% vs. 69%, p =.004). On multivariate analysis, a high SUV of nodal disease also proved to be a significantly unfavorable factor for disease-free survival (p =.04, 95% confidence interval [CI], 1.02-3.23), nodal progression-free survival (p =.05; 95% CI, 1.00-4.15), and distant metastasis-free survival (p =.016; 95% CI, 1.25-8.92). Among the patients with a greater nodal SUV (>= 6.00), those treated with planned neck dissection had better nodal progression-free survival than those in the observation group (p =.04, hazard ratio, 2.36; 95% CI, 1.00-5.85). Conclusion: Among head-and-neck squamous cell carcinoma patients treated with chemoradiotherapy, the pretreatment SUV of nodal disease was one of the strongest prognostic factors and also provided important information for the selection of patients suitable for planned neck dissection. (C) 2011 Elsevier Inc.
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• Dosimetric Comparison of Three-Dimensional Conformal Radiotherapy in Salvage Radiotherapy for PSA Relapse after Radical Prostatectomy, Natsuo Tomita, Hidetoshi Shimizu, Takeshi Kodaira, JOURNAL OF RADIATION RESEARCH, 51, (5) 581 - 587,   2010年09月, 査読有り, The purpose of this study is to compare three-dimensional conformal radiotherapy (3D-CRT) plans in a setting of salvage radiotherapy after radical prostatectomy (RP) and to simulate whether dose escalation is possible with the most adequate 3D-CRT technique. This study included consecutive 10 patients underwent salvage radiotherapy (RT) for biochemical relapse of prostate cancer after RP. Normal structures included the rectum, bladder, and femoral head. For each patient, four different treatment plans including four fields RT (4F-RT), dynamic conformal arc radiotherapy (DCAT), six fields RT (6F-RT), and DCAT with rectum hollow-out technique (DCAT-HO), were created to entire the prostate bed. The parameters of the maximum and mean doses received by organs at risk (OAR), target coverage, dose homogeneity for the planning target volume (PTV) were compared. All plans were considered to be clinically tolerable for PTV coverage and dose homogeneity. The rectum sparing at the high dose area for DCAT-HO was considered to be the most superior to those for other three techniques by comparison of the dose delivered to a 1%, 5%, and 10% volume of the rectum. In the simulation of dose escalation to 70 Gy with DCAT-HO, OAR met a requirement of the dose-volume constraints. However, in the simulation of dose escalation to 72 Gy, the rectum that receives 60 to 65 Gy and bladder that receives 65 Gy exceeded the optimal dose-volume constraints. DCAT-HO was considered to be one of the most appropriate techniques in 3D-CRT if dose escalation to 70 Gy might be needed in a setting of salvage RT after RP in the future.
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• Helical tomotherapy for solitary lung tumor: feasibility study and dosimetric evaluation of treatment plans., Natsuo Tomita, Takeshi Kodaira, Masayuki Matsuo, Kazuhisa Furutani, Hiroyuki Tachibana, Takashi Daimon, Hidetoshi Shimizu, Technology in cancer research & treatment, 9, (4) 407 - 15,   2010年08月, 査読有り, The purpose of this study is to evaluate the feasibility of and treatment plans for helical tomotherapy (HT) for solitary lung tumors. Nine patients with stage IA non-small-cell lung cancer (NSCLC) and three patients with solitary lung metastasis were treated with HT. All patients were immobilized with the BodyFIX system, and the target volume shown on computed tomography in the 3 respiration phases were superimposed onto the 3-dimensional radiation treatment planning system to represent the internal target motion. All patients were treated with 54-60 Gy in 12 fractions over 8 to 13 days. The median follow-up time was 14 months (range: 3-16 months). The overall response rate was 92%. The local control rate at 1 year was 100% with no difference between NSCLC and metastasis. Of 12 patients, one patient experienced Grade 2 radiation pneumonitis (RP), and the other patient with severe interstitial pneumonia and emphysema experienced Grade 5 RP. The mean lung dose (MLD) and the dose-volume histogram (DVH) for the normal lung volumes were converted into normalized total dose with an alpha/beta ratio of 3 Gy. The DVH of the normal lung volumes demonstrated that the mean volumes of V(10), V(30), V(50), and V(70) were 40.4 +/- 9.4%, 21.3 +/- 6.4%, and 12.8 +/- 4.6%, and 9.3 +/- 4.2% in all patients, 28.8%, 18.7%, 12.3%, and 10.5% in the patient with Grade 2 RP, and 29.3%, 17.9%, 7.7%, and 5.4% in the patient with Grade 5 RP. The mean MLD of all patients was 13.5 +/- 3.9 Gy, and those values of patients with Grade 2 and 5 RP were 12.9 and 21.8 Gy, respectively. Our study found that only the MLD was significantly correlated with RP >Grade 2 (p = 0.030) using the Student's t-test. Our study found the conformity index value of 1.48 +/- 0.15 and the homogeneity index value of 1.066 +/- 0.023, which suggested the feasibility of using HT to treat lung tumors with hypofractionation. In conclusion, HT is a feasible non-invasive technique for treating solitary lung tumors and achieves high accuracy in terms of dose conformity and homogeneity. The decision of the indications for HT might be required caution in cases in which a severe pulmonary toxicity is predicted from the high MLD, especially in cases involving a severe pulmonary comorbidity.
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• Retrospective analysis of definitive radiotherapy for patients with superficial esophageal carcinoma: Consideration of the optimal treatment method with a focus on late morbidity, Takeshi Kodaira, Nobukazu Fuwa, Hiroyuki Tachibana, Tatsuya Nakamura, Natsuo Tomita, Rie Nakahara, Haruo Inokuchi, Nobutaka Mizoguchi, Akinori Takada, RADIOTHERAPY AND ONCOLOGY, 95, (2) 234 - 239,   2010年05月, 査読有り, Purpose: To evaluate the clinical efficacy of definitive radiotherapy for patients with superficial esophageal cancer. Material and methods: From 1990 through 2006, 97 patients with stage I disease were treated with radiotherapy with or without chemotherapy. All patients were diagnosed with panesophagoscopy and computed tomography. Chemotherapy was added in 61 patients, and intra-cavitary brachytherapy (ICBT) was used in 27 patients. Results: The patients were 90 men and seven women with a median age of 65.7 years (range; 41-89). At last follow-up with a median follow-up duration of 35.7 months, 3 year-overall and progression-free survival (PFS) rates were 81.5% (95% C.I. = 73.3-89.7%) and 55.8% (95% C.I. = 45.2-66.4%), respectively. Shorter tumor length was a significantly favorable factor for the PFS rate (P = 0.02) and local failure-free (LFF) rate (P = 0.007) on both univariate and multivariate analyses. Although the addition of ICBT had no apparent benefit for survival or tumor control, the rate of severe adverse effects including lethal esophageal ulcers, showed a higher tendency in patients receiving ICBT. Conclusions: Our results regarding efficacy from the viewpoint of organ preservation are promising. Special care would be taken for the use of ICBT for patients with superficial esophageal cancer, especially if they have received chemoradiotherapy. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 95 (2010) 234-239
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• Long-term follow-up and a detailed prognostic analysis of patients with oropharyngeal cancer treated with radiotherapy, Natsuo Tomita, Takeshi Kodaira, Kazuhisa Furutani, Hiroyuki Tachibana, Yasuhisa Hasegawa, Akihiro Terada, Kenji Hanai, Taijirou Ozawa, Tatsuya Nakamura, Nobukazu Fuwa, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 136, (4) 617 - 623,   2010年04月, 査読有り, To find a prognostic factor for patients with oropharyngeal cancer (OPC) who were followed for long term after definitive radiotherapy. OPC patients that had been treated with radiotherapy at our institution were reviewed. Sex, age, performance status (PS), subsite, disease stage, T-stage, N-stage, RT dose, concurrent chemotherapy, the duration of RT, hemoglobin concentration before any treatment, and a double cancer were assessed for their impact on overall survival (OS) and locoregional control (LRC). Among a total of 141 patients enrolled into this retrospective study, the disease of most patients (81%) was stage III or IV. The median follow-up time of the surviving patients was 56 months (range 5-175 months). Radiotherapy was administered in conventional fractionation, and the median RT dose was 66 Gy. Most patients (90%) received systemic chemotherapy. The 5-year estimates of progression-free survival, LRC, and OS were 66.0, 72.7, and 65.1%, respectively. In the univariate analysis, LRC and OS in the lateral wall at the primary site, T-stage a parts per thousand currency sign3, and PS a parts per thousand currency sign1 groups were significantly superior to those in the other groups, and OS in age a parts per thousand currency sign60 or the hemoglobin level > 13.0 g/dL groups were also significantly superior to those in the other groups. In the multivariate analysis, age and T-stage remained significant factors for OS. Primary radiotherapy was recommended for OPC patients with the lateral wall at the primary site because of good LRC. The treatment method to the older population and T4 tumor is future tasks.
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• THE IMPACT OF RADIATION DOSE AND FRACTIONATION ON OUTCOMES FOR LIMITED-STAGE SMALL-CELL LUNG CANCER, Natsuo Tomita, Takeshi Kodaira, Toyoaki Hida, Hiroyuki Tachibana, Tatsuya Nakamura, Rie Nakahara, Haruo Inokuchi, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 76, (4) 1121 - 1126,   2010年03月, 査読有り, Purpose: To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients and to compare the outcomes among three groups in which the total radiation doses were 45 Gy with accelerated hyperfractionation (AHF), <54 Gy with standard fractionation (SF), and >= 54 Gy with SF. Methods and Materials: LS-SCLC patients that had been treated with chemoradiotherapy between 1997 and 2007 at Aichi Cancer Center Hospital were reviewed in this study. Of the 127 eligible patients, there were 37 patients in the AHF group, 29 in the SF <54 Gy group, and 61 in the SF >= 54 Gy group. Results: Fifty-five patients (43%) were alive at the time of this analysis, and the median follow-up time of the surviving patients was 33 months. The median survival times were 30.0 months (95% confidence interval [CI] 16.3-43.7) for the AHF group, 14.0 months (CI 6.6-21.4) for the SF <54 Gy group, and 41.0 months (CI 33.9-48.1) for the SF >= 54 Gy group. As for the local control rates, and the overall and progression-free survival rates, all outcomes were significantly lower in the SF <54 Gy group than in the other two groups, although no significant difference was found between the AHF and SF >= 54 Gy groups. Conclusions: These results suggest the importance of a high dose of radiation when using once-daily regimen. This study will support future prospective studies to establish optimal radiation doses and fractionation. (C) 2010 Elsevier Inc.
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• Early salvage radiotherapy for patients with PSA relapse after radical prostatectomy, Natsuo Tomita, Takeshi Kodaira, Kazuhisa Furutani, Hiroyuki Tachibana, Rie Nakahara, Nobutaka Mizoguchi, Norio Hayashi, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 135, (11) 1561 - 1567,   2009年11月, 査読有り, To assess the effectiveness of early salvage radiotherapy (RT) for patients with prostate-specific antigen (PSA) relapse after radical prostatectomy (RP) retrospectively. Fifty-one patients underwent salvage RT for biochemical relapse of prostate cancer initially treated with RP. All patients had persistent or rising PSA > 0.20 ng/ml at some point after surgery, or three successive PSA elevations after a postoperative nadir if PSA was a parts per thousand currency sign0.20 ng/ml. Most (96%) of pre-RT PSA were less or equal to 0.50 ng/ml, and median value was 0.25 ng/ml (range, 0.05-0.90 ng/ml). Median RT dose was 60 Gy (range, 50-66 Gy). Multivariate Cox regression analysis was performed for PSA before RP and salvage RT, margin status, seminal vesicle involvement, extracapsular invasion, Gleason score, PSA doubling time (PSADT), and RT dose to identify significant predictors of biochemical outcome. Median follow-up was 36 months. The 3-year biochemical no evidence of disease rate (bNED) was 55.1%. On multivariate analysis only the following factors were significantly associated with improved bNED: PSADT > 3.0 months (P = 0.008), Gleason score a parts per thousand currency sign7 (P = 0.01), and RT dose a parts per thousand yen60 Gy (P = 0.028). Although a total dose of 60 Gy was effective at a low pre-RT PSA levels with short follow-up, an RT dose a parts per thousand yen60 Gy resulted in superior biochemical outcomes even in patients with a pre-RT PSA a parts per thousand currency sign0.50 ng/ml.
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• ESTIMATION OF ERRORS ASSOCIATED WITH USE OF LINEAR-QUADRATIC FORMALISM FOR EVALUATION OF BIOLOGIC EQUIVALENCE BETWEEN SINGLE AND HYPOFRACTIONATED RADIATION DOSES: AN IN VITRO STUDY, Hiromitsu Iwata, Yuta Shibamoto, Rumi Murata, Natsuo Tomita, Shiho Ayakawa, Hiroyuki Ogino, Masato Ito, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 75, (2) 482 - 488,   2009年10月, 査読有り, Purpose: To investigate the reliability of the linear-quadratic (LQ) formalism and the magnitude of errors associated with its use in assessing biologic equivalence between single, high radiation doses and hypofractionated radiation doses. Methods and Materials: V79 and EM76 single cells received single doses of 2-12 Gy or two or three fractions of 4 or 5 Gy, each at 4-h intervals. Single and fractionated doses to actually reduce the cell survival to the same level were determined by a colony assay. The alpha/beta ratio was obtained from the cell survival curves. Using the alpha/beta ratio and the LQ formalism, equivalent single doses for the hypofractionated doses were calculated. They were then compared with the actually determined equivalent single doses for the hypofractionated doses. The V79 spheroids received single doses of 5-26 Gy or two to five fractions of 5-12 Gy at 2 or 4-h interval, and then were assayed for cell survival. Next, equivalent single doses for the hypofractionated doses were determined, as were done for the single cells. Results: The alpha/beta ratio was 5.1 Gy for the V79 single cells and 0.36 Gy for EMT6. In V79, the equivalent single doses for the hypofractionated doses calculated using the LQ formalism were 12-19% lower than the actually measured biologically equivalent single doses. In the EMT6 cells, this trend was also seen, but the differences were not significant. In the V79 spheroids, the calculated doses were 18-30% lower than the measured doses. Conclusion: Conversion of hypofractionated radiation doses to single doses using the LQ formalism could underestimate the effect of hypofractionated radiation by <= 30%. (C) 2009 Elsevier Inc.
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• A comparison of radiation treatment plans using IMRT with helical tomotherapy and 3D conformal radiotherapy for nasal natural killer/T-cell lymphoma, N. Tomita, T. Kodaira, H. Tachibana, T. Nakamura, R. Nakahara, H. Inokuchi, N. Mizoguchi, A. Takada, BRITISH JOURNAL OF RADIOLOGY, 82, (981) 756 - 763,   2009年09月, 査読有り, The purpose of this study was to compare radiation treatment plans (RTPs) that used intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) or three-dimensional conformal radiation therapy (3D-CRT) for nasal natural killer/T-cell lymphoma (NNKTL). We created RTPs that used IMRT with HT or 3D-CRT for eight NNKTL patients previously treated at our institution and conducted a pilot comparison between the two modalities using the parameters of the target coverage and homogeneity for the planning target volume (PTV) and the maximum and mean doses for organs at risk (OARs). The clinical target volume (CTV) included the gross tumour volume with an additional margin of 1.5 cm and the nasopharynx, palates and nasal cavity; the PTV with the CTV plus a 2 mm margin received a total dose of 50 Gy. IMRT achieved significantly better PTV coverage, with more than 99% of the PTV receiving 90% and 95% of the prescribed dose, whereas 3D-CRT could not provide adequate coverage of the PTV, with 89.1 +/- 2.6% and 84.5 +/- 2.7% of the PTV receiving 90% and 95% of the prescribed dose, respectively (both p <0.0001). The homogeneity index was 0.29 +/- 0.06 for IMRT and 0.046 +/- 0.022 for 3D-CRT, which was statistically significant (p <0.0001). IMRT tended to provide equivalent or slightly better OAR avoidance than 3D-CRT. In conclusion, 3D-CRT could not provide adequate coverage of the PTV because the PTV was close to many OARs. IMRT should be used for NNKTL because a lack of optimal RTPs could cause local failure.
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• Clinical outcome of oropharyngeal carcinoma treated with platinum-based chemoradiotherapy, Tatsuya Nakamura, Takeshi Kodaira, Hiroyuki Tachibana, Natsuo Tomita, Jun-ichi Yokouchi, Nobukazu Fuwa, ORAL ONCOLOGY, 45, (9) 830 - 834,   2009年09月, 査読有り, To determine the efficacy, feasibility, and toxicity of treated with platinum-based chemoradiotherapy for oropharyngeal carcinoma. A retrospective survey of 91 patients who underwent platinum-based chemotherapy and radiotherapy for oropharyngeal cancer at Aichi Cancer Center Hospital between 1971 and 2003. The radiotherapy dose ranged from 50 to 74 Gy (median, 66 Gy). Nine patients who had a tumor in the base of the tongue were also treated with arterial infusion chemotherapy. At a median follow-up of 63 months (range, 2-190 months), 26 (29%) patients developed recurrence. Five patients (5%) developed distant metastases. The 5-year overall survival was 66%, and the relapse-free survival was 51.6%. The 5-year local control rate was 79%. The 5-year local control rate for each subsite was: anterior wall, 90%; lateral wall, 80%; posterior wall, 67%; and superior wall, 64%. The 5-year overall survival was 85% for stage I-II and 62% for stage III-IV. Two patients developed grade 3 (mandibular bone necrosis) or 4 (laryngeal edema) late toxicities. No acute or late grade 5 toxicities were observed. In this study, platinum-based chemoradiotherapy provided good local control for oropharyngeal carcinoma. Although acute and late toxicities occurred, they were considered tolerable. (c) 2009 Elsevier Ltd. All rights reserved.
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• Antitumor effects of a cyclooxygenase-2 inhibitor, meloxicam, alone and in combination with radiation and/or 5-fluorouracil in cultured tumor cells, Shiho Ayakawa, Yuta Shibamoto, Chikao Sugie, Masato Ito, Hiroyuki Ogino, Natsuo Tomita, Masaoki Kumagai, Hiromi Murakami, Hiroki Sawa, MOLECULAR MEDICINE REPORTS, 2, (4) 621 - 625,   2009年07月, 査読有り, To ascertain whether meloxicam used in a clinical setting as a non-steroidal anti-inflammatory drug (NSAID) warrants preclinical in vivo evaluation as an anticancer agent, we investigated its antitumor effects alone and in combination with radiation and/or 5-fluorouracil (5-FU) in cultured cells. Seven cell lines were examined for cyclooxygenase-2 (COX-2) protein expression by immunoblot analysis, and the HeLaS3, SCCVII and EMT6 cell lines were selected, expressing relatively high, intermediate, and relatively low COX-2 levels, respectively. Antitumor effects were examined using a colony assay. Among the three cell lines, the effect of meloxicam alone was strongest in SCCVII cells. With 24 h of drug exposure, meloxicam at concentrations of 250 and 1250 mu M had a definite antitumor effect, dependent on the drug exposure time. The effect of meloxicam in combination with radiation and/or 5-FU was also investigated in the SCCVII cells. At a meloxicam concentration of 250 mu M, the antitumor effect in combination with radiation or 5-FU was increased compared to the effect of radiation or 5-FU alone however, the combined effect appeared to be additive. At lower concentrations, meloxicam had no radiosensitizing effect, nor did it enhance the effect of 5-FU. A meloxicam concentration of 250 mu M is considerably higher than concentrations obtained in humans taking meloxicam as an NSAID. In conclusion, the antitumor effect of meloxicam was not correlated with the level of COX-2 protein expression. The effect of meloxicam in combination with radiation and/or 5-FU appeared to be additive. To evaluate the possibility of using meloxicam as an anticancer agent, in vivo investigations at clinically relevant drug dose levels are required.
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• Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results, Fumiya Baba, Yuta Shibamoto, Natsuo Tomita, Chisa Ikeya-Hashizume, Kyota Oda, Shiho Ayakawa, Hiroyuki Ogino, Chikao Sugie, RADIATION ONCOLOGY, 4,   2009年05月, 査読有り, Background: In stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO(2)) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system. Methods: Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO(2) levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days. Results: By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO(2) did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients. Conclusion: Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO(2) level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.
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• Dynamic conformal arc radiotherapy with rectum hollow-out technique for localized prostate cancer, Natsuo Tomita, Takeshi Kodaira, Hiroyuki Tachibana, Tatsuya Nakamura, Takuya Tomoda, Rie Nakahara, Haruo Inokuchi, Norio Hayashi, Nobukazu Fuwa, RADIOTHERAPY AND ONCOLOGY, 90, (3) 346 - 352,   2009年03月, 査読有り, Purpose: To report the feasibility of dynamic conformal arc radiotherapy with rectum hollow-out technique (DCAT-HO) for localized prostate cancer. Methods and materials: Between October 2000 and April 2007, 204 patients with clinically localized or locally advanced prostate cancer were treated with DCAT-HO. All patients were given neoadjuvant total androgen deprivation (AD) therapy (median 6 months, range 2-27 months). All patients with T3 or T4 stage received post-irradiation AD for 24 months. A total of 128 patients (63%) were treated with 70 Gy, and 76 patients (37% were treated with 74 Gy. Acute and late toxicities were scored by the Radiation therapy Oncology Group morbidity grading scales. PSA relapse was defined as three successive PSA elevations after a post-treatment nadir. The median follow-up was 37 months. Result : Both the acute Grade 2 rectal and urinary toxicities were 1.0%, and no patients experienced acute Grade 3 or higher symptoms. The 3-year rate of both >= late Grade 2 rectal and urinary toxicities were 34%. The 3-year PSA relapse-free survival for low, intermediate, and high-risk group patients treated with 70 Gy were 54%, 75%, and 87%, respectively. Conclusions: These findings demonstrate the feasibility of DCAT-HO in a large number of patients with shore follow-up. DCAT-HO reduced the volume of the rectum exposed to higher doses and this led to all overall reduction in late rectal toxicity. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 90 (2009) 346-352
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• AICHI CANCER CENTER INITIAL EXPERIENCE OF INTENSITY MODULATED RADIATION THERAPY FOR NASOPHARYNGEAL CANCER USING HELICAL TOMOTHERAPY, Takeshi Kodaira, Natsuo Tomita, Hiroyuki Tachibana, Tatsuya Nakamura, Rie Nakahara, Haruo Inokuchi, Nobukazu Fuwa, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 73, (4) 1129 - 1134,   2009年03月, 査読有り, Purpose: To assess the feasibility of helical tomotherapy (HT) for patients with nasopharyngeal carcinoma. Methods and Materials: From June 2006 to June 2007, 20 patients with nasopharyngeal carcinoma were treated with HT with (n = 18) or without (n = 2) systemic chemotherapy. The primary tumor and involved lymph node (PTV 1) were prescribed 70 Gy and the prophylactic region 54 Gy at D95, respectively. The majority of patients received 2 Gy per fraction for PTV1 In 35 fractions. Parotid function was evaluated using quantitative scintigraphy at pretreatment, and posttreatment at 3 months and 1 year later. Results: The median patient age was 53 years, ranging from 15 to 83. Our cohort included 5,8,4, 2, and I patients with disease Stages IIB, III, IVA, IVB, and IVC, respectively. Histopathological record revealed two for World Health Organization Type I and 18 for Type 2 or 3. The median duration time for treatment preparation was 9.5 days, and all plans were thought to be acceptable regarding dose constraints of both the planning target volume and organ at risk. All patients completed their treatment procedure of intensity-modulated radiation therapy (IMRT). All patients achieved clinical remission after IMRT. The majority of patients had Grade 3 or higher toxicity of skin, mucosa, and neutropenia. At the median follow-tip of 10.9 months, two patients recurred, and one patient died from cardiac disease. Parotid gland function at 1 year after completion of IMRT was significantly improved compared with that at 3 months. Conclusion: HT was clinically effective in terms of IMRT planning and utility for patients with nasopharyngeal cancer. (C) 2009 Elsevier Inc.
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• Favorable outcomes of radiotherapy for early-stage mucosa-associated lymphoid tissue lymphoma, Natsuo Tomita, Takeshi Kodaira, Hiroyuki Tachibana, Tatsuya Nakamura, Nobutaka Mizoguchi, Akinori Takada, RADIOTHERAPY AND ONCOLOGY, 90, (2) 231 - 235,   2009年02月, 査読有り, Purpose: The aim of this study was to evaluate the efficacy of radiation therapy (RT) for early-stage mucosa-associated lymphoid tissue (MALT) lymphoma. Materials and methods: Patients with stage IE (n = 48) and stage I IE (a = 2) MALT lymphoma treated with RT were reviewed. The primary tumor originated in the stomach in 20 patients, in the orbit in 9 patients, in the conjunctiva or eyelid and the parotid glands in 6 patients each, and 9 patients in the others. The median total RT dose was 32 Gy (range, 25.6-50 Gy). The median follow-up time was 50 months. Results: Although disease did not recur in the RT field in any patient regardless of the total dose, disease recurred outside the RT field in the seven patients. As all recurrences were localized, salvage RT was performed for each recurrence and achieved complete response without recurrence in the field. The 5-year overall survival, local control, and progression-free survival rates were 96.6%, 100%, and 82.2%, respectively. Conclusions: A total dose of 25-30 Gy is appropriate for local control of MALT lymphoma. RT is also an effective salvage therapy in cases of localized recurrence. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 90 (2009) 231-235
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• Determination of the Irradiation Field for Clinical T1-T3N0M0 Thoracic/Abdominal Esophageal Cancer Based on the Postoperative Pathological Results, Tatsuya Nakamura, Syunzo Hatooka, Takeshi Kodaira, Hiroyuki Tachibana, Natsuo Tomita, Rie Nakahara, Haruo Inokuchi, Nobutaka Mizoguchi, Akinori Takada, Masayuki Shinoda, Nobukazu Fuwa, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 39, (2) 86 - 91,   2009年02月, 査読有り, In patients with thoracic/abdominal esophageal cancer with no clinical evidence of lymph node metastasis, there is no consensus about whether the irradiation field should include regional lymph nodes. In this study, the extent of the irradiation field for clinical stage T1-3N0M0 esophageal cancer was determined based on the postoperative pathological results. From July 1989 to June 2008, 103 patients diagnosed with clinical stage T1-3N0M0 thoracic/abdominal esophageal cancer underwent standard esophagectomy and regional lymph node dissection at the Aichi Cancer Center Hospital. Of these 103 patients, the pathological results of the resected specimens could be confirmed in 95 (92%) patients. The pathological lymphatic spread was reviewed retrospectively, and the extent of the irradiation field was determined based on the postoperative pathological results. Of 95 patients with clinical stage T1-3N0M0 esophageal cancer, 40 (42.1%) had pathological lymph node metastases, and the frequency of nodal metastases was studied by tumor location. The rates of lymph node metastases for the upper, middle, lower and abdominal esophagus were 37.5%, 32.5%, 46% and 70%, respectively. Pathological lymph nodes metastases are often seen after operation in clinical stage T1-3N0M0 esophageal cancer. In the present study, the optimal lymph nodes to be included in the irradiation field were determined according to the primary site in the esophagus.
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• PROSPECTIVE STUDY OF ALTERNATING CHEMORADIOTHERAPY CONSISTING OF EXTENDED-FIELD DYNAMIC CONFORMATIONAL RADIOTHERAPY AND SYSTEMIC CHEMOTHERAPY USING 5-FU AND NEDAPLATIN FOR PATIENTS IN HIGH-RISK GROUP WITH CERVICAL CARCINOMA, Takeshi Kodaira, Nobukazu Fuwa, Toru Nakanishi, Hiroyuki Tachibana, Tatsuya Nakamura, Natsuo Tomita, Rie Nakahara, Haruo Inokuchi, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 73, (1) 251 - 258,   2009年01月, 査読有り, Purpose: To assess the efficacy of alternating chemoradiotherapy combined with extended-field conformal radiotherapy for patients with high-risk cervical cancer. Methods and Materials: Patients with previously untreated cervical cancer, with Stage III/IVA disease, or Stage IB/ II with high-risk factor (primary tumor diameter >= 50 mm or positive lymph node) were entered into this study. Three cycles of chemotherapy with 3,500 mg/m(2) of 5-fluorouracil (5-FU) and nedaplatin (NDP) were accompanied with pelvic irradiation of 45.6-51.3 Gy in 24-27 fractions over 6 weeks. Prophylactic (36 Gy/20 fractions) or definitive (45-56 Gy) irradiation for para-aortic region was followed by pelvic irradiation. Results: Between 1998 and 2004, 40 patients were recruited for this protocol study. Eighteen patients from Phase I setting were registered. Twenty-two patients were treated with NDP of 140 mg/m2 (the recommended dose) in the Phase II segment. Twenty-five patients had T3 disease, and 25 patients had nodal disease including para-aortic involvement (n = 5). Overall/progression-free survival rates at 5 years were 78.8 and 66.5%, respectively. The median follow-up time was 61.8 months (25.5-106.7). Hematologic and gastrointestinal Grade 3 or more toxicities were relatively high rate (27.5-45%); however, they were well manageable. Two for bladder toxicity of Grade 3 were noted. Comparing the data from historical control group evaluated by magnetic resonance imaging, alternating chemoradiotherapy revealed a significant favorable factor for survival and disease recurrence in multivariate analysis (p < 0.05). Conclusion: Acquired results from our unique protocol for cervical cancer with high-risk factor were thought to be promising, considering that the majority of our cohort consisted of high-risk population. (C) 2009 Elsevier Inc.
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• Helical Tomotherapy for Brain Metastases: Dosimetric Evaluation of Treatment Plans and Early Clinical Results, Natsuo Tomita, Takeshi Kodaira, Hiroyuki Tachibana, Tatsuya Nakamura, Rie Nakahara, Haruo Inokuchi, Yuta Shibamoto, TECHNOLOGY IN CANCER RESEARCH & TREATMENT, 7, (6) 417 - 424,   2008年12月, 査読有り, The purpose of this study was to evaluate the feasibility and treatment plans of intensity-modulated radiation therapy using helical tomotherapy (HT) for brain metastases. Twenty-three patients with 1 to 4 brain metastases were treated with HT. In combination with whole-brain radiotherapy (simultaneous plans), metastatic lesions, and the whole brain were treated with 50 Gy and 30 Gy, respectively, in 10 fractions, with a simultaneous integrated boost technique. In patients treated for brain metastases alone (focal plans), metastatic lesions were treated with 35 or 37.5 Gy in 5 fractions. The treatment plans were compared regarding the conformation number (CN) and homogeneity index (HI), and differences in these indexes between simultaneous and focal plans were examined by Student's t-test. Seven and 16 patients were treated with simultaneous plans and focal plans, respectively. The mean +/- SD of CN and HI values were 0.75 +/- 0.13 and 0.063 +/- 0.042, respectively, for simultaneous plans, and 0.73 +/- 0.12 and 0.052 +/- 0.023, respectively, for focal plans. The CN and HI between the two plans were not significantly different. Response rates in 13 patients with follow-up imaging were approximately 90% for both plans and the local control rate at 1 year was 69%. One patient with a huge tumor (34.0 cc) and WHO performance status 3 treated with focal plans experienced severe headache, requiring prolongation of the treatment time, and died at 8 days after completion of treatment. The exact cause of deterioration was uncertain as no radiological investigation was performed in this patient. No late complications were observed during follow-up periods up to 20 months. HT is a viable non-invasive technique for treatment of brain metastases and achieves high accuracy in terms of dose conformity and homogeneity.
• Chemoradiotherapy for Locally Recurrent Nasopharyngeal Carcinoma: Treatment Outcome and Prognostic Factors, Tatsuya Nakamura, Takeshi Kodaira, Hiroyuki Tachibana, Natsuo Tomita, Takuya Tomoda, Rie Nakahara, Haruo Inokuchi, Nobutaka Mizoguchi, Akinori Takada, Nobukazu Fuwa, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 38, (12) 803 - 809,   2008年12月, 査読有り, To evaluate the treatment outcome of patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with re-irradiation and chemotherapy. Between 1991 and 2004, 36 patients with locally recurrent NPC received re-irradiation and chemotherapy. The median re-irradiation dose was 37.9 Gy; the median total dose of prior irradiation and re-irradiation was 104.4 Gy. The outcome is studied retrospectively and also evaluated the prognostic factors and toxicities. With a median follow-up of 40 months, 3-year overall survival (OS) was 58.3% and 3-year progression-free survival (PFS) was 25.0%. Patients aged < 50 and of early stage at recurrence had a significantly better OS and PFS. Over Grade 3 of late toxicities were seen in patients received a total dose of > 110 Gy. Age and stage at recurrence were identified as prognostic factors for OS and PFS. Patients received external beam radiation therapy at a total dose of more than 110 Gy should be careful for severe late toxicities, and it is thought to be the optimal dose for recurrent tumor.
  DOI
• Long-term observation of 64 patients with roentgenographically occult lung cancer treated with external irradiation and intraluminal irradiation using low-dose-rate iridium., Nobukazu Fuwa, Takeshi Kodaira, Hiroyuki Tachibana, Tatsuya Nakamura, Natsuo Tomita, Takashi Daimon, Japanese journal of clinical oncology, 38, (9) 581 - 8,   2008年09月, 査読有り, OBJECTIVE: Therapeutic results of intraluminal irradiation were analyzed in 64 patients with roentgenographically occult lung cancer (ROLC). METHODS: The subjects were 64 patients who underwent intraluminal irradiation between 1987 and 2003. Radiotherapy was performed by combining external irradiation with intraluminal irradiation using low-dose-rate iridium (four 370-MBq wires) through a catheter with a spacer. The doses of radiation were 0-70 Gy (median value 46 Gy) by external irradiation and 10-60 Gy (median value 29.3 Gy) by intraluminal irradiation. RESULTS: The therapeutic effect was CR in 63 patients and PR in 1 patient, and local recurrence was observed in a PR case and in seven of the 63 patients who showed CR. The 5-year overall and relapse-free survival rates were 56 (95% CI, 43-69%) and 55% (95% CI, 43-68%), respectively. Fatal pulmonary hemorrhage was observed in one case. CONCLUSIONS: Considering the facts that ROLC often occurs as multiple cancers and that many patients with ROLC have reduced lung function, radiation therapy by a combination of intraluminal and external irradiation may replace surgery as the first choice for the treatment of this disease.
  DOI
• Effect of low-dose total-body irradiation on transplantability of tumor cells in syngeneic mice, Masato Ito, Yuta Shibamoto, Shiho Ayakawa, Natsuo Tomita, Chikao Sugie, Hiroyuki Ogino, JOURNAL OF RADIATION RESEARCH, 49, (2) 197 - 201,   2008年03月, 査読有り, The effect of pretreatment with various low doses of total-body irradiation (TBI) on tumor cell transplantability in syngeneic mice was investigated. Two cell lines, EMT6 and SCCVII, and two strains of mice, were used. First, Balb/c mice were sham-irradiated or irradiated at 200 mGy, and 6-48 h later, 1000 EMT6 cells were inoculated in the hind legs. Based on the results, 0-1500 mGy of TBI was given 6 h before inoculation of 100 or 1000 cells in the subsequent experiments. All mice were observed for 50 days after transplantation. Tumors were judged as grown when the volume of palpable nodules exceeded 200 mm 3. Tumor transplantability rate was significantly higher in the groups irradiated at 1500 mGy than in the sham-irradiated groups in both Balb/c and C3H/He mice. There were no differences in transplantability rates between the control group and the groups irradiated at various doses of 50-500 mGy. However, the mean time to tumor appearance was significantly elongated in Balb/c mice receiving TBI at 200 mGy and inoculated with 100 or 1000 EMT6 cells 6 h later. This phenomenon was also observed in Balb/c mice receiving 100 mGy TBI and inoculated with 1000 EMT6 cells. The present study might suggest that low-dose TBI to mice may delay tumor growth under certain conditions.
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• Biological effect of intermittent radiation exposure in vivo: Recovery from sublethal damage versus reoxygenation, Natsuo Tomita, Yuta Shibamoto, Masato Ito, Hiroyuki Ogino, Chikao Sugie, Shiho Avakawa, Hiromitsu Iwata, RADIOTHERAPY AND ONCOLOGY, 86, (3) 369 - 374,   2008年03月, 査読有り, Purpose: In vivo effects of intermittent irradiation are influenced by recovery from sublethal damage (SLDR) and reoxygenation, so contribution of the two factors were investigated using murine tumors. Methods and materials: 1-cm-diameter SCCVII tumors growing in the legs of C3H/HeN mice were used. First, effects of 5 fractions of 6 Gy given at intervals of 2.5-15 min were compared using an in vivo-in vitro assay, by clamping the tumor-bearing legs to exclude the influence of reoxygenation. In the second and third experiments, changes in the hypoxic fraction at 0-15 min after 13 or 5 Gy were assessed by a paired cell survival method. Fourth, effects of 5 fractions of 5 Gy given at intervals of 3-10 min under conditions of limited reoxygenation were compared using a growth delay assay. Results: Cell survival from clamped tumors tended to increase with elongation of the intervals, but not significantly. The hypoxic fraction tended to decrease at 5-15 min from the level immediately after irradiation. Effects on tumor growth tended to decrease with elongation of the intervals. Conclusions: Reoxygenation occurring within 5-15 min appeared to compensate for SLDR in SCCVII tumors. When reoxygenation was limited, the decrease of radiation effect occurred due to SLDR. (c) 2007 Elsevier Ireland Ltd. Ali rights reserved.
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• Invasive thymoma: postoperative mediastinal irradiation, and low-dose entire hemithorax irradiation in patients with pleural dissemination., Sugie C, Shibamoto Y, Ikeya-Hashizume C, Ogino H, Ayakawa S, Tomita N, Baba F, Iwata H, Ito M, Oda K, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 3, (1) 75 - 81,   2008年01月, 査読有り
  DOI
• Low-dose whole-body irradiation induced radioadaptive response in C57BL/6 mice, Masato Ito, Yuta Shibamoto, Shiho Ayakawa, Natsuo Tomita, Chikao Sugie, Hiroyuki Ogino, JOURNAL OF RADIATION RESEARCH, 48, (6) 455 - 460,   2007年11月, 査読有り, Radioadaptive survival responses after relatively low doses of radiation were investigated in C57BL/6 mice. The 8-week-old mice received whole-body mid-lethal challenging irradiation (5.9 Gy) at various intervals after conditioning whole-body irradiation with 50-400 mGy. Thereafter, survival of the mice was observed for 30 days. The mice receiving 400 mGy at 6 It before the challenging dose had a lower survival rate than the control group, but it was not observed when the conditioning 400-mGy irradiation was given 24 It beforehand. The conditioning doses of 100 and 200 mGy did not influence the survival of mice after the challenging dose. The mice receiving 50 mGy at I day, 3 days or I week before the challenging dose had a higher survival rate than the control, although this adaptive response was not observed when 50 mGy was given 6 h, 12 h, 3.5 weeks, or 5 weeks beforehand. When 50 mGy was given 2 weeks before the challenging dose, the adaptive response was observed in an experiment in which the mice were caged in our laboratory at the age of 5 weeks, whereas it was not observed in another experiment in which the mice were caged at 3 weeks. This study confirmed the presence of radioadaptive survival responses at the dose of 50 mGy given relatively shortly before the challenging dose.
  DOI
• Influence of contrast materials on dose calculation in radiotherapy planning using computed tomography for tumors at various anatomical regions: A prospective study, Yuta Shibamoto, Asaka Naruse, Hiroshi Fukuma, Shiho Ayakawa, Chikao Sugie, Natsuo Tomita, RADIOTHERAPY AND ONCOLOGY, 84, (1) 52 - 55,   2007年07月, 査読有り, Influences of iodinated contrast media on dose calculation were studied in 26 patients. Mean increases in monitor units by contrast media administration were less than 1% and considered negligible in planning of whole-brain, whole-neck, mediastinal, and whole-pelvic irradiation. However, mean increases over 2% were seen in planning of upper-abdominal radiotherapy. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
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• Treatment results of stage I oral tongue cancer with definitive radiotherapy, Y Ichimiya, N Fuwa, M Kamata, T Kodaira, K Furutani, H Tachibana, N Tomita, S Hidano, ORAL ONCOLOGY, 41, (5) 520 - 525,   2005年05月, 査読有り, The medical records of 133 patients with Stage I tongue cancer treated by definitive radiotherapy between 1966 and 2001 were reviewed. Overall survival rate (OS), progression free survival rate (PFS), and survival rate after recurrence were calculated according to the Kaplan-Meier method. We investigated prognostic factors for local control and risk factors of late neck LN metastasis. The 5-year OS was 81.8% and the 5-year PFS was 67.2%. The 5-year OS after local recurrence was 100% by salvage operation, and that after neck LN metastasis was 40.7% despite radical neck dissection. Tumor thickness over 5 mm and treatment without interstitial irradiation were prognostic factors for local control. Tumor diameter over 15 mm and tumor thickness over 5 mm were risk factors of Late neck LN metastasis. We should consider prophylactic treatment for neck LN for high risk patients with Stage I tongue cancer in order to improve treatment results further. (c) 2005 Elsevier Ltd. All rights reserved.
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MISC

• 前立腺癌に対する放射線治療の予後予測因子としてのGP scoreの有用性, 景山 拓海, 曽我 倫久人, 小倉 友二, 富田 夏夫, 古平 毅, 泌尿器科紀要, 63, (7) 279 - 279,   2017年07月, 査読有り
• 喉頭癌治療における要点と注意点 放射線治療の場合, 古平毅, 立花弘之, 富田夏夫, 牧田智誉子, 竹花恵一, 清水亜里紗, 木村香菜, 吉田舞子, JOHNS, 31,   2015年
• トモセラピー強度変調放射線治療専用機について, 富田夏夫, 立花弘之, 古平毅, Rad Fan, 10,   2012年, 招待有り
• 頭頸部癌IMRT症例の唾液腺機能評価の検討, 古平毅, 清水秀年, 古谷和久, 立花弘之, 富田夏夫, 後藤容子, 野村基雄, 伊藤淳二, 臨床放射線, 56,   2011年
• 放射線治療の現況 PCSより, 古平毅, 戸板孝文, 篠田充功, 宇野隆, 富田夏夫, 光森通英, 沼崎穂高, 手島昭樹, 臨床放射線, 56,   2011年
• 子宮頸癌 手術症例 医療実態調査研究(PCS)から見た子宮頸癌手術(術後照射)症例における放射線治療の現状, 篠田 充功, 戸板 孝文, 古平 毅, 宇野 隆, 富田 夏夫, 沼崎 穂高, 五十野 優, 手島 昭樹, 光森 通英, 癌の臨床, 56, (2) 149 - 154,   2011年
• Tomotherapyを用いた上咽頭癌局所再発に対しての再照射例の検討, 後藤 容子, 野村 基雄, 溝口 信貴, 中原 理絵, 富田 夏夫, 立花 弘之, 古谷 和久, 古平 毅, 臨床放射線, 55, (8) 1018 - 1024,   2010年08月, 著者らは2006〜2009年に遠隔転移を伴わない上咽頭癌の局所再発に対しhelical tomotherapyによるIMRTを行った。適応となった症例は13症例(40〜77歳)であった。1) 全例、化学療法が併用され、最終観察時点での追跡期間の中央値は6.8ヵ月で、生存11例中担癌生存6例、無増悪生存5例であった。一方、死亡は他病死1例、癌死1例であった。2)局所領域の再再発は7例に認められ、うち3例は遠隔転移も伴っていた。1年の全生存率は88%で、無増悪生存率は41.7%であった。3)急性有害事象としてはGrade 1〜2の粘膜炎、Grad 3、Grade 4の白血球減少を各1例に認められた。また、晩期有害事象はGrade 2とGrade 3の聴力障害を各1例にみられた。4)1991〜2004年に三次元原体照射法で再照射を施行した36例では、重篤な晩期有害事象を2例で認められ、致死的な出血と上咽頭壊死が観察されたが、IMRTでは最終観察時点で、こうした例は認められなかった。
• 高精度放射線治療におけるSLD修復と再酸素化, 芝本雄太, 杉江愛生, 荻野浩幸, 富田夏夫, 放射線生物研究, 45,   2010年
• 日本PCS子宮頸癌作業部会 医療実態調査研究（PCS）から見た子宮頸癌非手術（根治的治療）症例における放射線 治療の現状と問題点, 古平毅, 戸板孝文, 篠田充功, 宇野隆, 富田夏夫, 沼崎穂高, 五十野優, 手島昭樹, 光森通英, 癌の臨床, 56,   2010年
• 再発上咽頭癌に対しての放射線治療 - トモセラピーによる強度変調放射線治療の有用性の検討, 古平 毅, 後藤 容子, 野村 基雄, 富田 夏夫, 立花 弘之, 古谷 和久, 耳鼻と臨床, 56, (Suppl.1) 46 - 53,   2010年
• 喉頭癌・副鼻腔癌の放射線治療, 古平 毅, 古谷 和久, 立花 弘之, 富田 夏夫, 中原 理絵, 溝口 信貴, 野村 基雄, 後藤 容子, 臨床放射線, 54, (10) 1217 - 1226,   2009年10月, 喉頭癌や副鼻腔癌に対する化学放射線療法は治療成績の改善だけでなく、臓器及び機能温存という視点が重要である。化学療法の併用、非通常分割照射による局所治療効果の向上が実現され、有効な薬剤療法の併用により局所・遠隔病変制御が可能になった。反面、治療強度の上昇は嚥下機能低下、誤嚥、音声機能低下といった機能損失をもたらす。強度変調放射線治療(IMRT)に代表される高精度放射線治療を紹介した。
• TomoTherapyを用いた強度変調放射線治療の実践, 古平毅, 立花弘之, 中村達也, 富田夏夫, 中原理絵, 井口治男, 溝口信貴, 高田彰憲, 臨床放射線, 54,   2009年
• Treatment results of floor of mouth cancer with definitive radiotherapy, Ichimiya, Y, Fuwa, N, Kodaira, T, Furutani, K, Tachibana, H, Tomita, N, Hidano, S, Journal of JASTRO, 17, (2) 103 - 107,   2005年06月, 査読有り
  DOI
• EBMに基づく放射線治療：脳腫瘍, 芝本雄太, 富田夏夫, 河野太郎, 辻浩子, 南光寿美礼, 谷口裕子, 癌と化学療法, 30, (3) 348 - 353,   2003年, 査読有り

書籍等出版物

• Intensity-Modulated Radiation Therapy，Nishimura Y and Komaki R （Ed.）, Shibamoto Y, Sugie C, Ogino H, Tomita N, 共著, 43−57, Radiobiology for IMRT, Springer,   2015年
• McDermott MW (ed): Radiosurgery., Mori Y, Hashizume C, Shibamoto Y, Kobayashi T, Hayashi N, Tomita N, Yoshida J, 共著, volume 7, 378–383, Preliminary Results of Stereotactic Radiotherapy for Spinal Lesions using the Novalis System, Karger,   2010年

受賞

•   2012年07月, 第25回日本高精度放射線外部照射研究会, 優秀ポスター賞

競争的資金

• 放射線生物学的基礎実験に基づく定位照射の最適照射間隔の確立, 文部科学省: 科学研究費補助金: 基盤研究(C),   2019年04月 - 2022年03月
• 前立腺癌に対する画像誘導下強度変調放射線治療における危険臓器線量制約の確立, 文部科学省: 科学研究費補助金: 若手研究(B),   2013年04月 - 2015年03月
• 限局期前立腺癌に対する直腸打ち抜き原体照射の治療成績, がん研究振興財団, 海外派遣研究助成金,   2008年 - 2008年