Details of a Researcher - Shigematsu, Naoyuki

Papers - Shigematsu, Naoyuki

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Nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS): first analysis on survival

Ito K., Saito S., Yorozu A., Kojima S., Kikuchi T., Higashide S., Aoki M., Koga H., Satoh T., Ohashi T., Nakamura K., Katayama N., Tanaka N., Nakano M., Shigematsu N., Dokiya T., Fukushima M., Takahashi Y., Tsukiyama I., Nasu Y., Harada M., Fukagai T., Yamashita T., Matsubara A., Igawa M., Egawa S., Kakehi Y., Katsuoka Y., Kanetake H., Kubota Y., Kumon H., Yamasaki I., Suzuki K., Deguchi T., Ueno M., Naito S., Namiki M., Baba S., Hayakawa K., Hirao Y., Fujioka T., Horie S., Miki T., Murai M., Yoshida H., Itami J., Inoue T., Imai Y., Kataoka M., Kubo A., Shibuya H., Nishio M., Tanaka H., Tanaka Y., Teramukai S., Harada C., Yamashiro K., Kiba T., Kitagawa S., Uno E., Nishimura T., Kinoshita F., Iida S., Maruo S., Miyakoda K., Daimon T., Kawamoto A., Kaneda H., Yoshidomi M., Nishiyama T., Yagi Y., Namitome R., Toya K., Koike N., Yoshida K., Tabata K., Tsumura H., Kimura M., Ishiyama H., Kotani S., Kondo H., Fujimoto K., Hasegawa M., Tamamoto T., Asakawa I., Nishizawa S., Hashida I., Takezawa Y., Harada K., Tanji S., Sato K., Matsuura T., Ariga H., Ehara S., Nakamura R., Hayashi S., Ohtakara K., Kihara K., Hayashi K., Okamoto K.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 23 ( 6 ) 1148 - 1159 2018.12

ISSN 13419625

© 2018, Japan Society of Clinical Oncology. Background: Investigating oncological outcomes in patients registered in the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS) in terms of biochemical relapse-free survival (bRFS) by the Phoenix and the newly developed J-POPS definitions, exploration of predictive factors for bRFS, and preliminary verification of pitfalls of prostate-specific antigen (PSA) failure definitions. Methods: Between July 2005 and June 2007, 2316 clinically localized patients underwent permanent seed implantation. The primary endpoint was bRFS. One of the secondary endpoints was overall survival (OS). Results: The median age was 69 and performance status was 0 in 99.1% of participants. The median biologically effective dose (BED) was about 180 Gy 2 . During a median follow-up of 60.0 months, 8.4 and 5.9% had PSA failure by the Phoenix and the J-POPS definitions, respectively. The 5-year bRFSs based on the Phoenix and the J-POPS definitions were 89.1 and 91.6%, respectively. The 5-year OS was 97.3%. According to multivariate analyses, only age affected bRFS based on the Phoenix definition, whereas the risk group and BED independently affected bRFS based on the J-POPS definition. A spontaneous PSA decrease was seen in 91.1% of participants after PSA failure based on the Phoenix definition alone, but in only 22.2% after PSA failure based on the J-POPS definition alone. Conclusion: The world’s largest registration study, J-POPS, consisted of patients with longevity, and a highly quality-controlled BED resulted in excellent bRFS and OS. The high likelihood of PSA bounce by the Phoenix definition should be taken into account, especially in younger patients. Clinical trial information: NCT00534196.

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A Highly Advanced Gastric Cancer Maintaining a Clinical Complete Response after Chemoradiotherapy Comprising S-1 and Cisplatin

Yura M., Takahashi T., Fukuda K., Nakamura R., Wada N., Fukada J., Kawakubo H., Takeuchi H., Shigematsu N., Kitagawa Y.

Case Reports in Gastroenterology (Case Reports in Gastroenterology) 12 ( 3 ) 578 - 585 2018.09

© 2018 The Author(s). Published by S. Karger AG, Basel. We report a patient with highly advanced gastric carcinoma who was treated successfully with chemoradiotherapy (CRT) comprising S-1 and cisplatin. The patient was a 71-year-old male who was diagnosed with advanced gastric carcinoma by esophagogastroduodenoscopy (EGD) by medical examination. EGD demonstrated type 3 advanced gastric carcinoma in the posterior wall of the upper gastric body. An abdominal computed tomography (CT) scan showed that the gastric wall was thickened due to gastric primary tumor, and large lymph nodes (LNs) including the lesser curvature LN, anterosuperior LN along the common hepatic artery and some para-aortic LNs were detected. The patient was diagnosed with stage IV advanced gastric carcinoma according to the Japanese classification of gastric carcinoma (cT4a, cN3, cM1 [para-aortic LN], cStage IV). Preoperative CRT was carried out in an attempt to downstage the disease. Remarkable reduction of the primary tumor and metastatic LNs was observed after initial CRT, and radiological examination determined that a partial response had been achieved. Adverse effects included grade 2 anorexia and grade 3 ALP elevation (919 U/ml). No grade 4 or more severe adverse event was observed. After CRT, although we recommended curative surgery, the patient refused surgical treatment and opted for conservative treatment. Thus, we continued S-1 oral administration for 1 year. Five months after beginning CRT, upper endoscopy showed that the tumor had maintained regression and scar formation, in which no cancer cells were detected by endoscopic biopsy. The patient is doing well and has maintained a clinical complete response for more than 42 months without curative surgery. CRT could be considered as an option for treatment of patients with locally advanced gastric carcinoma diagnosed as unresectable, or for those who refuse surgical treatment.

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Nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS)

Ito Kazuto, Saito Shiro, Yorozu Atsunori, Kojima Shinsuke, Kikuchi Takashi, Higashide Satoshi, Aoki Manabu, Koga Hirofumi, Satoh Takefumi, Ohashi Toshio, Nakamura Katsumasa, Katayama Norihisa, Tanaka Nobumichi, Nakano Masahiro, Shigematsu Naoyuki, Dokiya Takushi, Fukushima Masanori, Takahashi Yutaka, Tsukiyama Iwao, Nasu Yasutomo, Harada Masaoki, Fukagai Takashi, Yamashita Takashi, Matsubara Akio, Igawa Mikio, Egawa Shin, Kakehi Yoshiyuki, Katsuoka Youji, Kanetake Hiroshi, Kubota Yoshinobu, Kumon Hiromi, Yamasaki Ichiro, Suzuki Kazuhiro, Deguchi Takashi, Ueno Munehisa, Naito Seiji, Namiki Mikio, Baba Shiro, Hayakawa Kazushige, Hirao Yoshihiko, Fujioka Tomoaki, Horie Shigeo, Miki Tsuneharu, Murai Masaru, Yoshida Hideki, Itami Jun, Inoue Toshihiko, Imai Yutaka, Kataoka Masaaki, Koike Naoyoshi

International Journal of Clinical Oncology 1 - 12 2018.06

ISSN 1341-9625

Background: Investigating oncological outcomes in patients registered in the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS) in terms of biochemical relapse-free survival (bRFS) by the Phoenix and the newly developed J-POPS definitions, exploration of predictive factors for bRFS, and preliminary verification of pitfalls of prostate-specific antigen (PSA) failure definitions. Methods: Between July 2005 and June 2007, 2316 clinically localized patients underwent permanent seed implantation. The primary endpoint was bRFS. One of the secondary endpoints was overall survival (OS). Results: The median age was 69 and performance status was 0 in 99.1% of participants. The median biologically effective dose (BED) was about 180 Gy². During a median follow-up of 60.0 months, 8.4 and 5.9% had PSA failure by the Phoenix and the J-POPS definitions, respectively. The 5-year bRFSs based on the Phoenix and the J-POPS definitions were 89.1 and 91.6%, respectively. The 5-year OS was 97.3%. According to multivariate analyses, only age affected bRFS based on the Phoenix definition, whereas the risk group and BED independently affected bRFS based on the J-POPS definition. A spontaneous PSA decrease was seen in 91.1% of participants after PSA failure based on the Phoenix definition alone, but in only 22.2% after PSA failure based on the J-POPS definition alone. Conclusion: The world’s largest registration study, J-POPS, consisted of patients with longevity, and a highly quality-controlled BED resulted in excellent bRFS and OS. The high likelihood of PSA bounce by the Phoenix definition should be taken into account, especially in younger patients. Clinical trial information: NCT00534196.

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Influence of backscatter radiation on cranial bone fixation devices

Sakamoto Yoshiaki, Koike Naoyoshi, Takei Hideyuki, Ohno Mari, Shigematsu Naoyuki, Kishi Kazuo

Journal of Craniofacial Surgery (Journal of Craniofacial Surgery) 29 ( 4 ) 1094 - 1096 2018.06

ISSN 1049-2275

Postoperative radiation can cause ulcer formation, leading to the denudation of skin over alloplastic materials. The influence of backscatter radiation from fixation devices has not been investigated. The aim of this study is to evaluate backscatter dose variations for different cranial bone fixation devices in an experimental model designed to simulate postoperative radiotherapy. The authors assessed the radiation backscatter doses associated with resorbable (PLLA-PGA) and titanium plates. The samples were irradiated with 6 and 10 MV photon beams from a linear accelerator. Measurements were obtained using an ionization chamber and radiochromic films cut from the same batch. As a result, the backscatter radiation of water and PLLA-PGA proportionally decreased as the depth increased. However, the backscatter radiation of the titanium plate increased just above the plate. This depth lies in the region of the scalp. Each material showed a dose of radioactivity that was higher at 10 MV than that at 6 MV. These devices showed a significant difference, which suggested that these materials amplified the dose compared with water at 6 MV. In conclusion, it is supposed that PLLA-PGA should be used to fix the cranium to decrease the potential for radiation ulcers.

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Long-term results of concurrent chemoradiotherapy with daily-low-dose continuous infusion of 5-fluorouracil and cisplatin (LDFP) for Stage I-II esophageal carcinoma

Kumabe A., Fukada Junichi, Kota R., Koike N., Shiraishi Y., Seki S., Yoshida K., Kitagawa Y., Shigematsu N.

Diseases of the Esophagus (Diseases of the Esophagus) 31 ( 4 ) 2018.04

ISSN 1120-8694

We investigated long-term treatment outcomes and the feasibility of chemoradiotherapy consisting of daily-low-dose 5-fluorouracil and cisplatin (LDFP) chemotherapy plus radiotherapy for Stage I-II squamous cell esophageal cancer. Treatment records from the 2000 through 2008 period were reviewed retrospectively. Fractionated radiotherapy was performed with a total dose of 60 Gy delivered in 2 Gy per fraction. LDFP chemotherapy, as continuous infusion of 200 mg/m² 5-fluorouracil combined with one hour infusion of 4 mg/m² cisplatin, was administered on the same days as radiotherapy. Survival was calculated by the Kaplan-Meier method. Survival, responses, failure patterns, and toxicities were evaluated. Seventy-six (47 stage I and 29 stage II) patients were analyzed with a median follow-up of 93.6 months. The 8-year overall survival (OS), progression-free survival (PFS) and cause-specific survival (CSS) rates were 63.4%, 49.8%, and 76.7%, respectively. The 8-year OS, PFS, and CSS for stage I and stage II patients were 71.0%/56.1%/82.9% and 45.2%/40.2%/66.6%, respectively. Sixty-eight patients (89.5%) completed the treatment regimen. A complete response (CR) was achieved in 68 patients (89.5%). Twenty-five patients (36.8%) experienced recurrence after CR. The failure patterns were (overlap included): local failure (n = 12), nodal metastasis (n = 12), distant metastasis (n = 3), details unknown (n = 2). Salvage therapy was performed for local failure; endoscopic therapy (n = 7) or surgery (n = 2). Six patients remain alive without relapse after salvage endoscopic therapy. Major Grade 3 or higher acute adverse events were leukopenia (22%), anorexia (17%), and esophagitis (11%). Major late toxicities (Grade 3 or 4) involved pericardial effusion (12%), pleural effusion (4%), and esophageal stenosis (3%). Chemoradiotherapy with LDFP provided favorable long-term survival with acceptable toxicity for Stage I-II squamous cell esophageal cancer. The tumor response was excellent, but close endoscopic follow-up is essential for detecting and treating local recurrence.

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Predictive factors of long-term rectal toxicity following permanent iodine-125 prostate brachytherapy with or without supplemental external beam radiation therapy in 2216 patients

Tanaka Tomoki, Yorozu Atsunori, Sutani Shinya, Yagi Yasuto, Nishiyama Toru, Shiraishi Yutaka, Ohashi Toshio, Hanada Takashi, Saito Shiro, Toya Kazuhito, Shigematsu Naoyuki

Brachytherapy (Brachytherapy) 17 ( 5 ) 799 - 807 2018.01

ISSN 1538-4721

Purpose: We analyzed factors associated with rectal toxicity after iodine-125 prostate brachytherapy (BT) with or without external beam radiation therapy (EBRT). Methods and Materials: In total, 2216 prostate cancer patients underwent iodine-125 BT with or without EBRT between 2003 and 2013. The median followup was 6.9 years. Cox proportional hazards modeling was used for univariate and multivariate analyses to assess clinical and dosimetric factors associated with rectal toxicity. Dosimetric parameters from 1 day after implantation (Day 1) and 1 month after implantation (Day 30) were included in the analyses. Results: The 7-year cumulative incidence of Grade 2 or higher rectal toxicity was 5.7% in all patients. The multivariate analysis revealed that antiplatelet or anticoagulant therapy, neoadjuvant androgen deprivation therapy, treatment modality, Day 1 rectal volume receiving 100% of the prescribed dose (RV₁₀₀), and the Day 30 minimal percent of the prescribed dose delivered to 30% of the rectum (RD₃₀) were associated with rectal toxicity. Day 1 RV₁₀₀ was a common predictor in both BT-alone and the BT + EBRT groups. The 5-year cumulative incidence of Grade 2 or higher rectal toxicity was 12.6%, 5.9%, and 1.7% for BT + 3-dimensional conformal radiation therapy, BT + intensity-modulated radiation therapy, and the BT-alone groups, respectively (p < 0.001). Conclusions: Rectal dosimetric parameters in BT were associated with late rectal toxicity. Although the risk of rectal toxicity was higher when EBRT was combined with BT, with proper and achievable rectal dose constraints intensity-modulated radiation therapy yielded less toxicity than 3-dimensional conformal radiation therapy.

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Prostate-specific antigen nadir within 12 months as an early surrogate marker of biochemical failure and distant metastasis after low-dose-rate brachytherapy or external beam radiotherapy for localized prostate cancer

Nishimura Shuichi, Ohashi Toshio, Momma Tetsuo, Sakayori Masanori, Eriguchi Takahisa, Tanaka Tomoki, Yamashita Shoji, Kosaka Takeo, Oya Mototsugu, Shigematsu Naoyuki

Cancer Medicine (Cancer Medicine) 7 ( 5 ) 1794 - 1801 2018.01

Prostate-specific antigen nadir (nPSA) after radiotherapy for localized prostate cancer has been investigated as a predictor. However, nPSA usually requires several years, limiting its clinical utility. We investigated the significance of nPSA within 12 months (nPSA12) after low-dose-rate prostate brachytherapy (LDR-PB) or external beam radiotherapy (EBRT) on treatment outcomes. Between 2006 and 2014, 663 patients with prostate cancer were treated with LDR-PB or EBRT at two institutions. Four hundred and seventy-four men received LDR-PB and 189 men received EBRT, without androgen deprivation therapy. The Kaplan-Meier method was used for biochemical failure (BF)-free survival (BFFS) and distant metastasis (DM)-free survival (DMFS) analyses, and multivariable Cox regression analysis was performed. The median follow-up was 61.3 months. The median nPSA12 in the LDR-PB and EBRT cohorts was 0.7 and 1.0 ng/mL, respectively. The 7-year BFFS and DMFS rates in LDR-PB patients with nPSA12 ≤ 0.7 ng/mL were 99.1% and 99.5%, respectively; when nPSA12 was >0.7 ng/mL, they were 90.2% and 94.8%, respectively. In EBRT patients with nPSA12 ≤ 1.0 ng/mL, BFFS and DMFS rates were 85.4% and 98.5%, respectively; when nPSA12 was >1.0 ng/mL, they were 67.1% and 87.2%, respectively. nPSA12 was an independent predictor of BF and DM in both cohorts (LDR-PB, P = 0.004 and 0.020, respectively; EBRT, P = 0.005 and 0.041, respectively). The nPSA12 after LDR-PB or EBRT is significantly associated with treatment outcomes of prostate cancer. Higher nPSA12 may identify patients at high risk of relapse who might benefit from salvage treatment.

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Plan reproducibility of intraoperatively custom-built linked seeds compared to loose seeds for prostate brachytherapy

Kaneda T., Ohashi T., Sakayori M., Sutani S., Yamashita S., Momma T., Takahashi S., Hanada T., Shigematsu N.

Journal of Contemporary Brachytherapy (Journal of Contemporary Brachytherapy) 10 ( 4 ) 291 - 296 2018

ISSN 1689832X

© 2018 American Public Health Association Inc. All Rights Reserved. Purpose: Few studies have compared the implant quality of linked and loose seeds for prostate brachytherapy. This study aimed to evaluate and compare plan reproducibility of intraoperatively built custom linked seeds and loose seeds for prostate brachytherapy. Material and methods: Between December 2010 and March 2014, 76 localized prostate cancer patients received Iodine-125 brachytherapy with external beam radiotherapy. Linked and loose seeds were implanted in 39 and 37 patients, respectively. The primary endpoint was the mean (± standard deviation) of the absolute change in the minimum dose received by 90% of the prostate volume between intraoperative and post-operative planning (ΔD 90 ) to confirm plan reproducibility. Comparisons between the groups were evaluated using 2-sample t tests. Results: The ΔD 90 values were 6.95 ± 11.6% and -0.41 ± 8.5% for the loose and linked seed groups, respectively (p < 0.01). The linked seed group showed decreased post-operative D 90 (118.8% vs. 127.2%), V 150 (51.7% vs. 66.7%), and RV 100 (0.44 ml vs. 0.61 ml) compared to the loose seed group (p < 0.01), whereas lung migration tended to be reduced (0% vs. 8%). Conclusions: The plan reproducibility of the linked seed group was better than that of the loose seed group. Moreover, the linked seed group showed less migration and lower rectal dose.

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Long-term clinical results of concurrent chemoradiotherapy for patients with cervical esophageal squamous cell carcinoma

Kumabe Atsuhiro, Zenda Sadatomo, Motegi Atsushi, Onozawa Masakatsu, Nakamura Naoki, Kojima Takashi, Daiko Hiroyuki, Shigematsu Naoyuki, Akimoto Tetsuo

Anticancer Research 37 ( 9 ) 5039 - 5044 2017.09

ISSN 0250-7005

Background/Aim: We assessed the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) in patients with squamous cell carcinoma of the cervical esophagus. Patients and Methods: We retrospectively analyzed 37 patients treated with definitive CCRT. The patients received radiotherapy at a fraction dose of 2 Gy (total; 60 or 70 Gy) and concurrent chemotherapy. Adjuvant chemotherapy consisted of 1 to 2 cycles of 5-fluorouracil plus cisplatin or nedaplatin. Results: The median follow-up was 119.0 months, the 10-year overall survival, progression-free survival and laryngectomy-free survival rates were 35.6, 19.9 and 30.2% respectively. In the univariate analysis, T stage (T4 vs. T1-3) was the only prognostic factor for PFS. The most common acute toxicity was leukocytopenia (Grade 3; 27%). As for late toxicities, 4 patients (11%) developed Grade 2 or 3 esophageal strictures. Conclusion: The results of this study demonstrated that CCRT yielded satisfactory clinical outcomes with acceptable toxicities.

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Stereotactic body radiotherapy for operable early-stage non-small cell lung cancer

Eriguchi Takahisa, Takeda Atsuya, Sanuki Naoko, Tsurugai Yuichiro, Aoki Yousuke, Oku Yohei, Hara Yu, Akiba Takeshi, Shigematsu Naoyuki

Lung Cancer 109 62 - 67 2017.07

ISSN 0169-5002

Purpose To analyze outcomes of stereotactic body radiotherapy (SBRT) for operable patients with early-stage non-small cell lung cancer (NSCLC) and to evaluate factors associated with outcomes. Methods We retrospectively analyzed operable patients with NSCLC, staged as cT1-2N0M0, treated with SBRT between 2006 and 2015. Both biopsy-proven and clinically diagnosed NSCLC were included. Local control and survival rates were calculated and compared between subsets of patients. We investigated factors associated with outcomes. Results We identified 88 operable patients among 661 patients with cT1-2N0M0 NSCLC. The median age was 79 years (range: 55–88). The median follow-up time after SBRT was 40 months (range: 4–121). Fifty-nine patients had been pathologically diagnosed and the other 29 had been clinically diagnosed as having NSCLC. Local control, cause-specific survival (CSS) and overall survival (OS) at 3 years were 91%, 97% and 90% for T1, and 100%, 82% and 74% for T2, respectively. The CSS and OS at 3 years were 100% and 100% for GGO and 83% and 59% for solid tumors, respectively (p = 0.005). On univariate analysis, age and T stage were significantly associated with CSS, and age, the Charlson Comorbidity Index (CCI), and opacity were significantly associated with OS. On multivariate analysis, age and CCI were significantly associated with OS. As for toxicities, Grades 0, 1, 2 and 3 radiation pneumonitis occurred in 37.5%, 47.7%, 13.6% and 1.1% of patients, respectively. No Grade 4 or 5 radiation pneumonitis occurred, and no other toxicities of Grade 2 or above were observed. Conclusion Outcomes of SBRT for operable early stage NSCLC were as good as previous SBRT and surgery studies. Further investigation for selecting good SBRT candidates is warranted in high-risk operable patients.

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Quantitative analysis of genitourinary toxicity after iodine-125 brachytherapy for localized prostate cancer

Sakayori Masanori, Ohashi Toshio, Momma Tetsuo, Kaneda Tomoya, Nishimura Shuichi, Sutani Shinya, Yamashita Shoji, Shigematsu Naoyuki

Brachytherapy 2017.03

ISSN 1538-4721

Purpose: To analyze genitourinary toxicity by followup of the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) after prostate brachytherapy. Methods and Materials: Six hundred eighty patients were treated with iodine-125 brachytherapy for localized prostate cancer. IPSS, OABSS, and two categories of IPSS questions (storage symptom score [IPSS-S] and voiding symptom score [IPSS-V]) were evaluated. Results: The median followup was 54 months (range, 24-108). All scales showed rapid increases followed by gradual decreases. The median times to IPSS peak and resolution were 1 and 6 months, respectively. The resolution rates of IPSS, IPSS-S, IPSS-V, and OABSS at the last followup were 84.2%, 86.3%, 89.5%, and 83.0%, respectively. The difference between IPSS baseline and peak was greater for larger preimplant prostate volumes (≥25 mL, p = 0.004). The time to resolution was longer for higher biologic effective dose (BED) (≥210 Gy, p = 0.019 [IPSS]), in those with larger prostate volumes (≥25 mL, p = 0.025 [OABSS]), in younger patients (younger than 70 years, p = 0.043 [IPSS-S]), and in those with androgen deprivation therapy (ADT) use (p = 0.049 [IPSS-V]). Urge incontinence, included in the OABSS, was observed more commonly in older patients (75 years and older, p = 0.018), with ADT use (p < 0.001), and for higher BED (≥210 Gy, p = 0.006). Conclusions: The IPSS and OABSS showed similar patterns of change. Urinary symptoms improved more rapidly in those with high baseline IPSS levels. The OABSS was useful for following urinary symptoms after prostate brachytherapy. Age, ADT use, preimplant prostate volume, and BED were significantly associated with urinary outcomes.

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Evaluation of radiation exposure in Ir-192 brachytherapy for treatment of keloids

Ohta Mao, Nakao Noriaki, Kuribayashi Shigehiko, Miyashita Tsuguhiro, Shigematsu Naoyuki, Hayashizaki Noriyosu

Energy Procedia 131 363 - 370 2017.01

ISSN 1876-6102

Nippon Medical School Hospital recently developed a high dose rate superficial brachytherapy (HDR-SBT) for keloids, which has been carried out since 2008. In this treatment, Ir-192 sources are placed on the affected area through flexible tubes, which has the advantage of providing high dose concentration to complicated shapes. Obviously, unnecessary radiation exposure to high-energy gamma rays must be reduced for vital organs around the affected area. We have developed a system which can evaluate the radiation exposure of tissues and organs in a MIRD-5 phantom using the PHITS Monte Carlo code when the prescribed dose was delivered uniformly to a flat surface based on the actual geometry in HDR-SBT. In the PHITS simulation, an affected area was assumed on the chest of the MIRD-5 phantom, then the dwell time at each dwell position was optimized to deliver 6 Gy uniformly over the affected area in the actual geometry with the lead shields and the bolus. In addition, the radiation exposures of each tissue and organ in the MIRD-5 phantom during the irradiation were calculated. The biologically equivalent dose of the thymus was the highest at 1145.60 mGy followed by the heart at 236.14 mGy and the breasts at 95.32 mGy.

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Influence of backscatter radiation on cranial reconstruction implants

Sakamoto Yoshiaki, Koike Naoyoshi, Takei Hideyuki, Ohno Mari, Miwa Tomoru, Yoshida Kazunari, Shigematsu Naoyuki, Kishi Kazuo

British Journal of Radiology 90 ( 1070 ) 2017

ISSN 0007-1285

Objective: We aimed to evaluate backscatter dose variations in different cranial bone implant materials in an experimental model designed to simulate postoperative radiotherapy. Methods: We assessed the radiation backscatter doses associated with sheet- and mesh-type titanium plates and hydroxyapatite (HAP) samples (porosity: 35%, 50% and 85%). The samples were irradiated with 6- and 10-MV photon beams from a linear accelerator. Measurements were obtained using an ionization chamber and radiochromic films cut from the same batch. Results: At 6MV, the titanium sheet showed the highest peak for backscattered radiation, followed by (in decreasing order) HAP30%, HAP50%, titanium mesh and HAP85%. At 10MV, HAP30% showed the highest peak, followed by HAP50%, titanium sheet, titanium mesh and HAP85%. The peaks were at different depths in the titanium and HAP samples. The thickness of the human scalp is approximately 7mm; therefore, measurements were obtained 0-7mm above the implants to assess the likely dose on the scalp. A comparison of the maximum dose on the scalp showed the titanium sheet had the highest dose at both 6 and 10MV. Conclusion: The backscatter dose differed with the density of the material and the backscatter depth was different for each material. Advances in knowledge: Ulcer formation due to radiotherapy after brain tumour depends on not only radiation but also the implant material. Therefore, the density and type of implant material should be considered when planning radiotherapy and selecting bone reconstruction materials.

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Single-energy metal artifact reduction in postimplant computed tomography for I-125 prostate brachytherapy

Shiraishi Yutaka, Yamada Yoshitake, Tanaka Tomoki, Eriguchi Takahisa, Nishimura Shuichi, Yoshida Kayo, Hanada Takashi, Ohashi Toshio, Shigematsu Naoyuki, Jinzaki Masahiro

Brachytherapy 15 ( 6 ) 768 - 773 2016.11

ISSN 1538-4721

Purpose To evaluate the effectiveness of the single-energy metal artifact reduction (SEMAR) technique for improving the accuracy of I-125 seed identification in postimplant computed tomography (CT) after prostate brachytherapy. Methods and Materials Postimplant CT images of 40 patients treated with I-125 prostate brachytherapy were acquired. For all patients, 2 data sets were reconstructed, 1 with SEMAR algorithms (SEMAR image), and the other without SEMAR algorithms (non-SEMAR image). Seed locations are automatically detected by the automatic seed finder tool, and their locations were compared between the SEMAR and non-SEMAR images. Dosimetric parameters using seed locations as detected were compared. Results The true-positive fraction of properly detected seeds on the SEMAR image as determined from a reference seed distribution defined by one investigator was significantly higher than the true-positive fraction on the non-SEMAR image (p = 0.011). The variabilities in D₉₀ (p = 0.001), V₁₀₀ (p = 0.007), and V₁₅₀ (p = 0.007) were significantly reduced for seed location on the SEMAR image as compared with non-SEMAR image. Conclusions Prostate postimplant CT with SEMAR improved the accuracy of seed localization and postimplant dosimetric parameters.

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In vivo spatial correlation between ¹⁸F-BPA and ¹⁸F-FDG uptakes in head and neck cancer

Kobayashi Kazuma, Kurihara Hiroaki, Watanabe Yoshiaki, Murakami Naoya, Inaba Koji, Nakamura Satoshi, Wakita Akihisa, Okamoto Hiroyuki, Umezawa Rei, Takahashi Kana, Igaki Hiroshi, Ito Yoshinori, Yoshimoto Seiichi, Shigematsu Naoyuki, Itami Jun

Applied Radiation and Isotopes 115 138 - 146 2016.09

ISSN 0969-8043

Background and purpose Borono-2-¹⁸F-fluoro-phenylalanine (¹⁸F-BPA) has been used to estimate the therapeutic effects of boron neutron capture therapy (BNCT), while ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) is the most commonly used positron emission tomography (PET) radiopharmaceutical in a routine clinical use. The aim of the present study was to evaluate spatial correlation between ¹⁸F-BPA and ¹⁸F-FDG uptakes using a deformable image registration-based technique. Material and methods Ten patients with head and neck cancer were recruited from January 2014 to December 2014. All patients underwent whole-body ¹⁸F-BPA PET/computed tomography (CT) and ¹⁸F-FDG PET/CT within a 2-week period. For each patient, ¹⁸F-BPA PET/CT and ¹⁸F-FDG PET/CT images were aligned based on a deformable image registration framework. The voxel-by-voxel spatial correlation of standardized uptake value (SUV) within the tumor was analyzed. Results Our image processing framework achieved accurate and validated registration results for each PET/CT image. In 9/10 patients, the spatial distribution of SUVs between ¹⁸F-BPA and ¹⁸F-FDG showed a significant, positive correlation in the tumor volume. Conclusions Deformable image registration-based voxel-wise analysis demonstrated a spatial correlation between ¹⁸F-BPA and ¹⁸F-FDG uptakes in the head and neck cancer. A tumor sub-volume with a high ¹⁸F-FDG uptake may predict high accumulation of ¹⁸F-BPA.

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Stereotactic body radiotherapy for T3 and T4N0M0 non-small cell lung cancer

Eriguchi Takahisa, Takeda Atsuya, Sanuki Naoko, Nishimura Shuichi, Takagawa Yoshiaki, Enomoto Tatsuji, Saeki Noriyuki, Yashiro Kae, Mizuno Tomikazu, Aoki Yousuke, Oku Yohei, Yokosuka Tetsuya, Shigematsu Naoyuki

Journal of Radiation Research 57 ( 3 ) 265 - 272 2016.06

ISSN 0449-3060

To evaluate the outcomes and feasibility of stereotactic body radiotherapy (SBRT) for cT3 and cT4N0M0 non-small cell lung cancer (NSCLC), 25 patients with localized primary NSCLC diagnosed as cT3 or cT4N0M0, given SBRT between May 2005 and July 2013, were analyzed. All patients had inoperable tumors. The major reasons for tumors being unresectable were insufficient respiratory function for curative resection, advanced age (>80 years old) or technically inoperable due to invasion into critical organs. The median patient age was 79 years (range; 60-86). The median follow-up duration was 25 months (range: 5-100 months). The 2-year overall survival rates for T3 and T4 were 57% and 69%, respectively. The 2-year local control rates for T3 and T4 were 91% and 68%, respectively. As for toxicities, Grade 0-1, Grade 2 and Grade 3 radiation pneumonitis occurred in 23, 1 and 1 patient, respectively. No other acute or symptomatic late toxicities were reported. Thirteen patients who had no local, mediastinal or intrapulmonary progression at one year after SBRT underwent pulmonary function testing. The median variation in pre-SBRT and post-SBRT forced expiratory volume in 1 s (FEV1) values was -0.1 (-0.8-0.8). This variation was not statistically significant (P = 0.56). Forced vital capacity (FVC), vital capacity (VC), %VC and %FEV1 also showed no significant differences. SBRT for cT3 and cT4N0M0 NSCLC was both effective and feasible. Considering the favorable survival and low morbidity rate, SBRT is a potential treatment option for cT3 and cT4N0M0 NSCLC.

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Erectile function status is highly associated with prostate-specific antigen bounce in localized prostate cancer patients treated with permanent prostate brachytherapy

Matsushima Masashi, Kikuchi Eiji, Matsumoto Kazuhiro, Kosaka Takeo, Mizuno Ryuichi, Ohashi Toshio, Mikami Shuji, Miyajima Akira, Shigematsu Naoyuki, Oya Mototsugu

International Journal of Urology 23 ( 3 ) 247 - 252 2016.03

ISSN 0919-8172

Objectives: To examine the relationship between erectile function status and prostate-specific antigen bounce after prostate brachytherapy for localized prostate cancer. Methods: We identified 154 patients who were followed up for at least 24 months after brachytherapy. Erectile function status was assessed prospectively before brachytherapy (baseline), and 3, 6, 12, 18, 24 and 36 months postoperatively using the International Index of Erectile Function-15 questionnaire. Prostate-specific antigen bounce was defined as an increase of at least 0.4 ng/mL from a previous prostate-specific antigen level with a subsequent decline equal to, or less than, the initial nadir without treatment. A logistic regression analysis was used to identify a significant set of independent predictors of prostate-specific antigen bounce after brachytherapy. Results: Prostate-specific antigen bounce was observed in 38 (24.7%) men. The prostate-specific antigen bounce group had a higher erectile function domain score, higher orgasmic function domain score, and higher total International Index of Erectile Function-15 score before (at baseline) and after brachytherapy (3, 6, 12, 18, 24 and 36 months after brachytherapy) than their counterparts (P <0.05). Of the 77 patients who completed the International Index of Erectile Function-15 questionnaire 18 months after brachytherapy (the median time of prostate-specific antigen bounce), sexual desire and intercourse satisfaction domain scores, and total International Index of Erectile Function scores 18 months after brachytherapy correlated with the occurrence of prostate-specific antigen bounce. A multivariate analysis identified the intercourse satisfaction domain score 18 months after brachytherapy as an independent indicator for the occurrence of prostate-specific antigen bounce (P = 0.008). Conclusions: International Index of Erectile Function-15 score seems to be correlated with the prostate-specific antigen bounce in prostate cancer patients undergoing brachytherapy, and an occurrence of prostate-specific antigen bounce seems to be more likely in those who are more sexually active.

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Prospective study of direct radiation exposure measurements for family members living with patients with prostate ¹²⁵I seed implantation

Hanada Takashi, Yorozu Atsunori, Shinya Yukiko, Kuroiwa Nobuko, Ohashi Toshio, Saito Shiro, Shigematsu Naoyuki

Brachytherapy 2016.02

ISSN 1538-4721

Purpose: To broaden the current understanding of radiation exposure and risk and to provide concrete evidence of radiation safety related to ¹²⁵I seed implantation. Methods and Materials: Direct radiation exposure measurements were obtained from dosimeters provided to 25 patients who underwent ¹²⁵I seed implantation, along with their family members. The estimated lifetime exposure dose and the precaution time for holding children near the patient's chest were calculated in two study periods. Results: During the first and second study period, the mean estimated lifetime exposure doses were, respectively, 7.61 (range: 0.45, 20.21) mSv and 6.84 (range: 0.41, 19.20) mSv for patients, and 0.19 (range: 0.02, 0.54) mSv and 0.25 (range: 0.04, 1.00) mSv for family members. The mean ratios of first and second period measurements were 1.05 (range: 0.44, 3.18) for patients and 1.82 (range: 0.21, 7.04) for family members. The corresponding absolute differences between first and second period measurements were -0.77 (range: -11.40, 7.63) mSv and 0.06 (range: -0.26, 0.79) mSv, respectively. Assuming a dose limit of 1 mSv, the precaution times for holding a child every day of the first and second periods were 250.9 (range: 71.3, 849.4) min and 275.2 (range: 75.0, 883.4) min, respectively. Assuming a dose limit of 0.5 mSv, the corresponding precaution times were 179.0 (range: 35.6, 811.5) min and 178.9 (range: 37.5, 1131.8) min, respectively. Conclusions: Our study demonstrated low radiation exposures to family members of patients undergoing ¹²⁵I prostate implantation. It was clear that ¹²⁵I seed implantation did not pose a threat to the safety of family members.

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Dose reconstruction technique using non-rigid registration to evaluate spatial correspondence between high-dose region and late radiation toxicity

Kobayashi Kazuma, Murakami Naoya, Inaba Koji, Wakita Akihisa, Nakamura Satoshi, Okamoto Hiroyuki, Sato Jun, Umezawa Rei, Takahashi Kana, Igaki Hiroshi, Ito Yoshinori, Shigematsu Naoyuki, Itami Jun

Journal of Contemporary Brachytherapy 8 ( 2 ) 156 - 163 2016

ISSN 1689-832X

Purpose: Small organ subvolume irradiated by a high-dose has been emphasized to be associated with late complication after radiotherapy. Here, we demonstrate a potential use of surface-based, non-rigid registration to investigate how high-dose volume topographically correlates with the location of late radiation morbidity in a case of tracheobronchial radiation stenosis. Material and methods: An algorithm of point set registration was implemented to handle non-rigid registration between contour points on the organ surfaces. The framework estimated the global correspondence between the dose distribution and the varying anatomical structure. We applied it to an 80-year-old man who developed tracheobronchial stenosis 2 years after high-dose-rate endobronchial brachytherapy (HDR-EBT) (24 Gy in 6 Gy fractions) and external beam radiotherapy (EBRT) (40 Gy in 2 Gy fractions) for early-stage tracheal cancer. Results and conclusions: Based on the transformation function computed by the non-rigid registration, irradiated dose distribution was reconstructed on the surface of post-treatment tracheobronchial stenosis. For expressing the equivalent dose in a fractional dose of 2 Gy in HDR-EBT, α/β of linear quadratic model was assumed as 3 Gy for the tracheal bronchus. The tracheobronchial surface irradiated by more than 100 Gy_αβ3 tended to develop severe stenosis, which attributed to a more than 50% decrease in the luminal area. The proposed dose reconstruction technique can be a powerful tool to predict late radiation toxicity with spatial consideration.

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Dosimetric variations due to interfraction organ deformation in cervical cancer brachytherapy

Kobayashi Kazuma, Murakami Naoya, Wakita Akihisa, Nakamura Satoshi, Okamoto Hiroyuki, Umezawa Rei, Takahashi Kana, Inaba Koji, Igaki Hiroshi, Ito Yoshinori, Shigematsu Naoyuki, Itami Jun

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 117 ( 3 ) 555 - 558 2015.12

ISSN 0167-8140

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Predictive factors for urinary toxicity after iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy

Eriguchi Takahisa, Yorozu Atsunori, Kuroiwa Nobuko, Yagi Yasuto, Nishiyama Toru, Saito Shiro, Toya Kazuhito, Hanada Takashi, Shiraishi Yutaka, Ohashi Toshio, Shigematsu Naoyuki

Brachytherapy 2015.10

ISSN 1538-4721

Purpose: We examined the factors associated with urinary toxicities because of brachytherapy with iodine-125 with or without supplemental external beam radiotherapy (EBRT) for prostate cancer. Methods and Materials: We investigated 1313 patients with localized prostate cancer treated with iodine-125 brachytherapy with or without supplemental EBRT between 2003 and 2009. The International Prostate Symptom Score (IPSS) and Common Terminology Criteria for Adverse Events data were prospectively determined. Patients, treatment, and implant factors were investigated for their association with urinary toxicity or symptoms. Results: IPSS resolution was not associated with biologically effective dose (BED). Baseline IPSS, total needles, and the minimal dose received by 30% of the urethra had the greatest effect according to multivariate analysis (MVA). Urinary symptom flare was associated with baseline IPSS, age, BED, and EBRT on MVA. Urinary symptom flare and urinary Grade 2 or higher (G2+) toxicity occurred in 51%, 58%, and 67% (p = 0.025) and 16%, 22%, and 20% (p = 0.497) of the 220 Gy BED groups, respectively. Urinary G2+ toxicity was associated with baseline IPSS, neoadjuvant androgen deprivation therapy (NADT), and seed density on MVA. When we divided patients into four groups according to prostate volume (

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Three-dimensional conformal arc radiotherapy using a C-arm linear accelerator with a computed tomography on-rail system for prostate cancer

Kumabe Atsuhiro, Fukuhara Noboru, Utsunomiya Takuji, Kawase Takatsugu, Iwata Kunihiro, Okada Yukinori, Sutani Shinya, Ohashi Toshio, Oya Mototsugu, Shigematsu Naoyuki

Radiation Oncology 10 ( 1 ) 2015.10

Background: We report the feasibility and treatment outcomes of image-guided three-dimensional conformal arc radiotherapy (3D-CART) using a C-arm linear accelerator with a computed tomography (CT) on-rail system for localized prostate cancer. Methods and materials: Between 2006 and 2011, 282 consecutive patients with localized prostate cancer were treated with in-room CT-guided 3D-CART. Biochemical failure was defined as a rise of at least 2.0 ng/ml beyond the nadir prostate-specific antigen level. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: A total of 261 patients were analyzed retrospectively (median follow-up: 61.6 months). The median prescribed 3D-CART dose was 82 Gy (2 Gy/fraction, dose range: 78-86 Gy), and 193 of the patients additionally received hormonal therapy. The 5-year overall survival rate was 93.9 %. Among low-, intermediate-, and high-risk patients, 5-year rates of freedom from biochemical failure were 100, 91.5 and 90.3 %, respectively. Rates of grade 2-3 late gastrointestinal and genitourinary toxicities were 2.3 and 11.4 %, respectively. No patient experienced late grade 4 or higher toxicity. Conclusions: In-room CT-guided 3D-CART was feasible and effective for localized prostate cancer. Treatment outcomes were comparable to those previously reported for intensity-modulated radiotherapy.

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Dose-escalated stereotactic body radiotherapy (SBRT) as a salvage treatment for two cases with relapsed peripheral lung cancer after initial SBRT

Nishimura Shuichi, Takeda Atsuya, Sanuki Naoko, Yoshida Sachiko, Shigematsu Naoyuki

Journal of Thoracic Oncology 10 ( 8 ) e69 - e71 2015.08

ISSN 1556-0864

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Comparison of genitourinary and gastrointestinal toxicity among four radiotherapy modalities for prostate cancer

Sutani Shinya, Ohashi Toshio, Sakayori Masanori, Kaneda Tomoya, Yamashita Shoji, Momma Tetsuo, Hanada Takashi, Shiraishi Yutaka, Fukada Junichi, Oya Mototsugu, Shigematsu Naoyuki

Radiotherapy and Oncology 2015.05

ISSN 0167-8140

Purpose: To compare late genitourinary (GU) and gastrointestinal (GI) toxicity following different prostate cancer treatment modalities. Materials and methods: This study included 1084 consecutive prostate cancer patients treated with conventional radiotherapy, intensity-modulated radiotherapy (IMRT), permanent iodine-125 implantation (PI) alone, and PI combined with external beam radiotherapy (PI + EBRT). The effects of treatment- and patient-related factors on late grade. ≥. 2 (G2+) GU/GI toxicity risk were assessed. Results: The median follow-up was 43. months (range, 12-97. months). Compared to the PI + EBRT, there was significantly less G2+ GU toxicity in the conventional radiotherapy (hazard ratio [HR] = 0.39; 95% CI, 0.20-0.77) and the IMRT (HR = 0.45, 95% CI, 0.27-0.73). Compared to the PI + EBRT, there was significantly more G2+ GI toxicity in the IMRT (HR = 2.38; 95% CI, 1.16-4.87). In PI-related groups, prostate equivalent dose in 2. Gy fractions was a significant predictor of G2+ GU toxicity (p = 0.001), and the rectal volume receiving more than 100% of the prescribed dose was a significant predictor of G2+ GI toxicity (p = 0.001). Conclusion: The differences in the late G2+ GU/GI risk cannot be explained by the differences in treatment modalities themselves, but by the total radiation dose to the GU/GI tract, which had a causal role in the development of late G2+ GU/GI toxicity across all treatment modality groups.

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Nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS)

Saito Shiro, Ito Kazuto, Yorozu Atsunori, Aoki Manabu, Koga Hirofumi, Satoh Takefumi, Ohashi Toshio, Shigematsu Naoyuki, Maruo Shinichiro, Kikuchi Takashi, Kojima Shinsuke, Dokiya Takushi, Fukushima Masanori, Yamanaka Hidetoshi

International Journal of Clinical Oncology 20 ( 2 ) 375 - 385 2015.04

ISSN 1341-9625

Background: To evaluate the safety and efficacy of brachytherapy with permanent iodine-125 seed implantation (PI) for prostate cancer. The nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS) has continued since July 2005. This manuscript presents the rationale, J-POPS study design, and the characteristics of initial participants enrolled in this study from July 2005 to June 2007. Methods: All participants were treated with PI in accordance with the American Brachytherapy Society recommendations. The primary outcome measure was biochemical progression-free survival. Progression-free survival, overall survival, cause-specific survival, longitudinal changes in health-related quality of life, disease-specific quality of life, the International Prostate Symptom Score, and the incidence of adverse events were also investigated as secondary outcome measurements. Results: Overall, 6,927 patients were enrolled by the end of 2010, that is approximately 40 % of all cases treated around the country. During the first 2 years, 2,354 participants were enrolled and 2,339 were actually treated with PI. The age range of participants was 45 to 89 years (median 69 years) and their risk classifications were 1,037 (44.3 %) at low risk, 1,126 (48.1 %) at intermediate risk, and 134 (5.7 %) at high risk, in addition to 16 participants whose classification was unknown. Of all patients, 76.6 % were treated with PI without external beam radiation therapy and 49.3 % received neoadjuvant hormone therapy. Conclusions: The J-POPS, a nationwide prospective cohort study that enrolled approximately 40 % of all PI cases in Japan, will provide highly reliable evidence, including outcomes and quality of life, after long-term follow-up.

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Postmortem radiation safety and issues pertaining to permanent prostate seed implantation in Japan

Satoh Takefumi, Dokiya Takushi, Yamanaka Hidetoshi, Saito Shiro, Ishiyama Hiromichi, Itami Jun, Shibuya Hitoshi, Nakano Takashi, Shigematsu Naoyuki, Aoki Manabu, Egawa Shin, Hashimoto Mitsuyasu, Nishimura Tetsuo, Yorozu Atsunori

Brachytherapy 14 ( 2 ) 136 - 141 2015.03

ISSN 1538-4721

PURPOSE: If a prostate cancer patient treated with (125)I brachytherapy dies within 12 months after the treatment, prostate removal before cremation is recommended to avoid problems related to radioactivity in the ashes, such as inhalation of airborne particulate matter by crematorium staff or nearby residents. To provide guidance for such cases, a manual prepared under the editorial supervision of several professional associations was issued in 2008 in Japan. Herein, we investigated the incidence and causes of death, and the actions taken subsequent to death, among prostate cancer patients who died within 12 months after (125)I brachytherapy over a 10-year period in Japan; and we compared the results before and after the manual was issued.METHODS AND MATERIALS: Data extracted from the Japan Radioisotope Association database for the period from September 2003 to the end of December 2013 were used.RESULTS: Of 27,976 patients who underwent (125)I brachytherapy during the specified period, 79 died within 12 months after implantation, including 3 who died in the 2011 earthquake and tsunami. The prostate and brachytherapy source were retrieved at autopsy from 69 of the 79 patients. Autopsy could not be performed on the other 10 patients, 2 of whom died in the earthquake. Autopsy and retrieval of the brachytherapy source were significantly more common after issuance of the manual than before (22/28 cases before; 47/49 cases after; p=0.021).CONCLUSION: In most cases of early death after (125)I brachytherapy in Japan, the brachytherapy source was retrieved.

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Successful treatment of metastatic rhabdomyosarcoma with radiochemotherapy and allogeneic hematopoietic stem cell transplantation

Yamazaki Fumito, Osumi Tomoo, Shigematsu Naoyuki, Morioka Hideo, Shimada Hiroyuki

Japanese Journal of Clinical Oncology 45 ( 2 ) 225 - 228 2015.02

ISSN 0368-2811

We report a case of a 21-year-old man with alveolar rhabdomyosarcoma primarily in the right hand with lymph node, lung, bone and bone marrow metastases. Complete remission was achieved after intensive chemotherapy and radiotherapy of the primary and metastatic sites, followed by allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning from a single HLA-DR locus-mismatched mother. The patient remained relapse-free for 41 months after the diagnosis. Considering that the conventional treatment for rhabdomyosarcoma with multiple risk factors (old age, bone or bone marrow involvement, unfavorable primary sites and ≥3 metastases) is associated with a poor prognosis (5% probability of a 3-year event-free survival), the graft-versus-tumor effect may have contributed to his sustained relapse-free survival. Allogeneic hematopoietic stem cell transplantation for rhabdomyosarcoma should be done by experienced clinical oncologists on properly designed controlled trials.

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A Dose-response analysis of biochemical control outcomes after ¹²⁵I monotherapy for patients with favorable-risk prostate cancer

Shiraishi Yutaka, Yorozu Atsunori, Ohashi Toshio, Toya Kazuhito, Saito Shiro, Nishiyama Toru, Yagi Yasuto, Shigematsu Naoyuki

International Journal of Radiation Oncology Biology Physics 90 ( 5 ) 1069 - 1075 2014.12

ISSN 0360-3016

Purpose To define the optimal dose for ¹²⁵I prostate implants by correlating postimplantation dosimetry findings with biochemical failure and toxicity.Methods and Materials Between 2003 and 2009, 683 patients with prostate cancer were treated with ¹²⁵I prostate brachytherapy without supplemental external beam radiation therapy and were followed up for a median time of 80 months. Implant dose was defined as the D90 (the minimal dose received by 90% of the prostate) on postoperative day 1 and 1 month after implantation. Therefore, 2 dosimetric variables (day 1 D90 and day 30 D90) were analyzed for each patient. We investigated the dose effects on biochemical control and toxicity.Results The 7-year biochemical failure-free survival (BFFS) rate for the group overall was 96.4% according to the Phoenix definition. A multivariate analysis found day 1 D90 and day 30 D90 to be the most significant factors affecting BFFS. The cutoff points for day 1 D90 and day 30 D90, calculated from ROC curves, were 163 Gy and 175 Gy, respectively. By use of univariate analysis, various dosimetric cutoff points for day 30 D90 were tested. We found that day 30 D90 cutoff points from 130 to 180 Gy appeared to be good for the entire cohort. Greater D90s were associated with an increase in late genitourinary or gastrointestinal toxicity ≥ grade 2, but the increase was not statistically significant.Conclusions Improvements in BFFS rates were seen with increasing D90 levels. Day 30 D90 doses of 130 to 180 Gy were found to serve as cutoff levels. For low-risk and low-tier intermediate-risk prostate cancer patients, high prostate D90s, even with doses exceeding 180 Gy, achieve better treatment results and are feasible.

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Five-year potency preservation after iodine-125 prostate brachytherapy

Nishimura Shuichi, Yorozu Atsunori, Ohashi Toshio, Sakayori Masanori, Yagi Yasuto, Nishiyama Toru, Saito Shiro, Shiraishi Yutaka, Yoshida Kayo, Toya Kazuhito, Shigematsu Naoyuki

International Journal of Clinical Oncology 19 ( 5 ) 940 - 945 2014.10

ISSN 1341-9625

Background: We aimed to evaluate long-term erectile function following prostate brachytherapy, based on patient characteristics and treatment factors.Methods: Between 2003 and 2006, 665 men with localized prostate cancer were treated with ¹²⁵I permanent seed implantation. None was given adjuvant hormone therapy. Erectile function was assessed before treatment, and at 6 months, 1, 2, 3, 4 and 5 years after implantation using the Mount Sinai Erectile Function Score (MSEFS) of 0–3 (0 = no erections, 1 = erections insufficient for intercourse, 2 = suboptimal erections but sufficient for intercourse, 3 = normal erectile function). Potency was defined as score 2 or 3, and 382 men were potent before treatment. Univariate and multivariate analyses were performed on the data from these 382 patients to identify variables associated with potency preservation.Results: In patients who were potent before treatment, the actuarial potency preservation rate fell to 46.2 % at 6 months after brachytherapy, and then slowly recovered reaching 52.0 % at 5 years after brachytherapy. In multivariate logistic regression analysis, patient age (p = 0.04) and pre-treatment MSEFS (p < 0.001) were predictors of 5-year potency preservation. Neoadjuvant hormone therapy affected potency preservation only at 6 months after brachytherapy.Conclusions: Patient age at implantation and pre-treatment erectile function are predictive factors for the development of erectile dysfunction following prostate brachytherapy.

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Correction to Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis -KOGC04- [Radiat Oncol 9 (2014) 9]

Matsuda Satoru, Takahashi Tsunehiro, Fukada Junichi, Fukuda Kazumasa, Kawakubo Hirofumi, Saikawa Yoshiro, Kawaguchi Osamu, Takeuchi Hiroya, Shigematsu Naoyuki, Kitagawa Yuko

Radiation Oncology 9 ( 1 ) 2014.06

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Combined brachytherapy and external beam radiotherapy without adjuvant androgen deprivation therapy for high-risk prostate cancer

Ohashi Toshio, Yorozu Atsunori, Saito Shiro, Momma Tetsuo, Nishiyama Toru, Yamashita Shoji, Shiraishi Yutaka, Shigematsu Naoyuki

Radiation Oncology 9 ( 1 ) 2014.01

Background: To report the outcomes of patients treated with combined iodine-125 (I-125) brachytherapy and external beam radiotherapy (EBRT) for high-risk prostate cancer.Methods: Between 2003 and 2009, I-125 permanent prostate brachytherapy plus EBRT was performed for 206 patients with high-risk prostate cancer. High-risk patients had prostate-specific antigen ≥ 20 ng/mL, and/or Gleason score ≥ 8, and/or Stage ≥ T3. One hundred and one patients (49.0%) received neoadjuvant androgen deprivation therapy (ADT) but none were given adjuvant ADT. Biochemical failure-free survival (BFFS) was determined using the Phoenix definition.Results: The 5-year actuarial BFFS rate was 84.8%. The 5-year cause-specific survival and overall survival rates were 98.7% and 97.6%, respectively. There were 8 deaths (3.9%), of which 2 were due to prostate cancer. On multivariate analysis, positive biopsy core rates and the number of high-risk factors were independent predictors of BFFS. The 5-year BFFS rates for patients in the positive biopsy core rate <50% and ≥50% groups were 89.3% and 78.2%, respectively (p = 0.03). The 5-year BFFS rate for patients with the any single high-risk factor was 86.1%, compared with 73.6% for those with any 2 or all 3 high-risk factors (p = 0.03). Neoadjuvant ADT did not impact the 5-year BFFS.Conclusions: At a median follow-up of 60 months, high-risk prostate cancer patients undergoing combined I-125 brachytherapy and EBRT without adjuvant ADT have a high probability of achieving 5-year BFFS.

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Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis

Matsuda Satoru, Takahashi Tsunehiro, Fukada Junichi, Fukuda Kazumasa, Kawakubo Hirofumi, Saikawa Yoshiro, Kawaguchi Osamu, Takeuchi Hiroya, Shigematsu Naoyuki, Kitagawa Yuko

Radiation Oncology 9 ( 1 ) 2014.01

Background: In patients with highly advanced gastric cancer, the recurrence rate remains high and the prognosis disappointing. We previously reported a phase I study of a neoadjuvant chemoradiotherapy of S-1 plus weekly cisplatin. Although adequate safety and efficacy were reported, myelosuppression was frequently observed, leading to treatment delay in several cases. To decrease toxicity and improve efficacy, we planned a phase I study with a modified chemotherapy regimen with biweekly cisplatin.Methods: Patients with advanced gastric cancer and lymph node metastasis who were treated by our institution between 2011 and 2012 were eligible for inclusion. The initial chemoradiotherapy schedule consisted of 6 weeks of S-1 orally administered on days 1-15 with an escalating dose of cisplatin administered on days 1 and 15. The starting dose (level 1) of cisplatin was 15 mg/m², the second dose (level 2) was 20 mg/m², and the third dose (level 3) was 25 mg/m². Radiation of 40 Gy was administered in 20 fractions. After initial chemoradiotherapy, one cycle of combination chemotherapy with S-1 plus cisplatin was delivered. The second cycle was 42 days in duration and included S-1 administered on days 1-29 plus biweekly cisplatin administered on days 1, 15, and 29. After neoadjuvant treatment, a curative gastrectomy with extended (D2) lymph node dissection was planned.Results: Nine patients were enrolled. At level 3, one patient had dose-limiting grade 3 diarrhea. Another patient experienced grade 3 nausea and intended to discontinue the treatment. Overall, because 2 of 3 patients experienced dose-limiting toxicity at level 3, we confirmed level 3 (Cisplatin 25 mg/m²) as the maximum tolerated dose and level 2 (Cisplatin 20 mg/m²) as the recommended dose (RD). The response rate was 78%, and 8 patients underwent curative gastrectomy. Resected specimens showed a histological response in 6 patients (75%), including one with a pathological complete response.Conclusions: In this phase I trial, RD of cisplatin was identified as 20 mg/m². Generally, S-1 plus biweekly cisplatin can be given safely with concurrent radiation. We have initiated a multicenter phase II trial to further confirm the efficacy and safety of this approach. Trial registration: UMIN000008941.

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Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin

Takabayashi Kaoru, Kashiwagi Kazuhiro, Kawata Tetsuya, Sato Toshiro, Matsuoka Katsuyoshi, Hisamatsu Tadakazu, Takaishi Hiromasa, Hibi Toshifumi, Ogata Haruhiko, Yahagi Naohisa, Kitagawa Yuko, Shigematsu Naoyuki, Kanai Takanori

Cancer Biology and Therapy 15 ( 1 ) 81 - 88 2014.01

ISSN 1538-4047

The efficacy of conventional radiation therapy for gastric cancer is controversial. In this study, we evaluated the in vitro and in vivo effects of continuous low-dose-rate irradiation by I-125 seeds on different histological types of gastric cancer cell lines. Three human gastric cancer cell lines (MKN74, MKN45, and NUGC4) were treated with or without continuous low-dose irradiation by I-125 seeds in vitro and in vivo. Cell viability, apoptosis, caspase-3 assay, and cell-cycle distribution were examined in vitro. Body weight and tumor volumes of BALB/c nude mice bearing MKN74, MKN45, and NUGC4 gastric cancer xenografts were measured, and in vivo cell proliferation and apoptosis assays were performed by Ki67 and TUNEL staining, respectively. Continuous low-dose-rate irradiation by I-125 seeds reduced cell viability and induced cell apoptosis through the activation of caspase-3, and led to the accumulation of cells in the G2/M phase in vitro. It also suppressed the growth of gastric cancer xenografts in nude mice, while inhibiting cell proliferation and inducing apoptosis as demonstrated by Ki67 and TUNEL staining. Therefore, our data suggest that continuous low-dose-rate irradiation by I-125 seeds could be a promising new option for gastric cancer treatment, regardless of histological origin.

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Toxicities of organs at risk in the Mediastinal and Hilar regions following stereotactic body radiotherapy for centrally located lung tumors

Nishimura Shuichi, Takeda Atsuya, Sanuki Naoko, Ishikura Satoshi, Oku Yohei, Aoki Yousuke, Kunieda Etsuo, Shigematsu Naoyuki

Journal of Thoracic Oncology 9 ( 9 ) 1370 - 1376 2014

ISSN 1556-0864

INTRODUCTION: We investigated tolerable doses to organs at risk (OARs) in the mediastinum and pulmonary hilum following stereotactic body radiotherapy for centrally located lung tumors. METHODS: Between 2005 and 2012, 381 patients with lung tumors were treated with stereotactic body radiotherapy of 40 to 60 Gy in five fractions. From among these patients, we extracted those who received greater than 25 Gy irradiation to OARs and analyzed dosimetric factors in relation to grade 3 to 5 toxicities. RESULTS: In total, 398 OARs in 133 patients were analyzed, with a median follow-up of 33 (range, 3-87) months. The numbers receiving greater than 25 Gy irradiation to the aorta, vena cava, pulmonary artery, pulmonary vein, bronchus, trachea, heart, and esophagus were 72, 33, 73, 60, 55, 13, 69, and 23, respectively. The corresponding median Dmax 0.5 ml were 43.8, 32.0, 32.2, 29.1, 28.4, 28.7, 41.1, and 21.7 Gy. Of these patients, two developed grade 5 and one grade 3 hemoptysis, and two had grade 3 obstructive pneumonia. Two patients with grade 5 hemoptysis received high doses at the pulmonary artery and bronchus (59.2 and 54.4 Gy, and 61.3 and 59.6 Gy, respectively). No other grade 3 to 5 toxicities occurred. CONCLUSION: Therapeutic indications and dose-intensity should be carefully determined for patients with central tumors, especially when doses to the pulmonary artery and bronchus in the pulmonary hilum exceed 50 Gy. Tolerable doses for other OARs might, however, be higher than in this study, though longer follow-up is necessary to assess this possibility.

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Assessing protection against radiation exposure after prostate ¹²⁵I brachytherapy

Hanada Takashi, Yorozu Atsunori, Kikumura Riki, Ohashi Toshio, Shigematsu Naoyuki

Brachytherapy 13 ( 3 ) 311 - 318 2014

ISSN 1538-4721

Purpose: To expand the radiation dose rate measurement data set by measuring radiation under various prostate ¹²⁵I brachytherapy situations. Methods and Materials: Measurements were obtained from 63 consecutive unselected patients at Tokyo Medical Center, Japan. Differences in factors during measurements, such as body postures, distances from the skin surface, and measurement directions were considered. Furthermore, shielding effects of lead-lined underwear, consisting mainly of 0.1-mm thickness of lead, were also assessed. Results: Radiation exposure varies according to the patient's body posture, with results differing as much as approximately 40.0% in measured radiation dose rates at 30. cm from the anterior skin surface. Weight, body mass index, and tissue thickness showed good correlations with measured radiation dose rates. The magnitude of radiation exposure attenuation by shielding was approximately 95.8%, similar to the attenuation ratio based on tissue measurements made in the lateral direction. The respective mean times required to reach 1. mSv were 1.2, 7.6, and 65.4 days in the standing position and 0.6, 4.6, and 40.4 days in the supine position at the site of contact, and at 30 and 100. cm from the anterior skin surface. Conclusions: This study obtained supplemental information pertaining to radiological protection and confirmed that shielding can be an effective tool for reducing exposures.

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Efficacy of aprepitant in preventing nausea and vomiting due to high-dose melphalan-based conditioning for allogeneic hematopoietic stem cell transplantation

Sakurai Masatoshi, Mori Takehiko, Kato Jun, Koda Yuya, Kikuchi Taku, Kohashi Sumiko, Saburi Masuho, Toyama Takaaki, Aisa Yoshinobu, Nakazato Tomonori, Beppu Noriko, Tsuda Soichiro, Shigematsu Naoyuki, Okamoto Shinichiro

International Journal of Hematology 99 ( 4 ) 457 - 462 2014

ISSN 0925-5710

High-dose melphalan has been gaining recognition as a highly emetogenic agent used in hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to elucidate the efficacy of aprepitant in preventing high-dose melphalan-induced emesis. Sixty patients who received melphalan (70 mg/m²/day, 2 days) and fludarabine (125 mg/m²/day, 5 days) as conditioning for allogeneic HSCT for hematological malignancies, and who received ondansetron and methylprednisolone as an antiemetic prophylaxis, were eligible. Twenty of these 60 patients also received aprepitant for 5 days (aprepitant group); the remaining 40 patients served as a control. The rates of complete response (CR), defined as no emesis without rescue medications, and complete protection (CP), defined as no emesis with or without rescue medications, were assessed between the two groups. The observation period was 12 days from the first day of melphalan administration. The CR and CP rates were significantly higher in the aprepitant group than in the control group during the observation period (35 % versus 10 %, P < 0.05; 85 % versus 33 %, P < 0.001; respectively). These results suggest that aprepitant in combination with ondansetron and steroid effectively ameliorates nausea and vomiting caused by the high-dose melphalan-based conditioning for allogeneic HSCT.

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A newly introduced comprehensive consultation fee in the national health insurance system in Japan

Igaki Hiroshi, Onishi Hiroshi, Nakagawa Keiichi, Dokiya Takushi, Nemoto Kenji, Shigematsu Naoyuki, Nishimura Yasumasa, Hiraoka Masahiro

Japanese Journal of Clinical Oncology 43 ( 12 ) 1233 - 1237 2013.12

ISSN 0368-2811

Objective: The consultation fee for outpatient radiotherapy was newly introduced in the national health insurance system in Japan in April 2012. We conducted a survey on the use of this consultation fee and its effect on clinical practices. Methods: The health insurance committee of the Japanese Society of Therapeutic Radiology and Oncology conducted a questionnaire survey. The questionnaire form was mailed to 160 councilors of the Society, the target questionees. A total of 94 answers (58% of the target questionees) sent back were used for analyses. Results: The analyses revealed that 75% of the hospitals charged most of the patients who receive radiotherapy in an outpatient setting a consultation fee. The introduction of the consultation fee led to some changes in radiation oncology clinics, as evidenced by the response of 'more careful observations by medical staff' in 37% of questionees and a 12% increase in the number of full-time radiation oncology nurses. It was also shown that the vast majority (92%) of radiation oncologists expected a positive influence of the consultation fee on radiation oncology clinics in Japan. Conclusions: Our questionnaire survey revealed the present status of the use of a newly introduced consultation fee for outpatient radiotherapy, and the results suggested its possible effect on promoting a multidisciplinary medical care system in radiation oncology departments in Japan.

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Symptomatic pericardial effusion after chemoradiation therapy in esophageal cancer patients

Fukada Junichi, Shigematsu Naoyuki, Takeuchi Hiroya, Ohashi Toshio, Saikawa Yoshiro, Takaishi Hiromasa, Hanada Takashi, Shiraishi Yutaka, Kitagawa Yuko, Fukuda Keiichi

International Journal of Radiation Oncology Biology Physics 87 ( 3 ) 487 - 493 2013.11

ISSN 0360-3016

Purpose We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. Methods and Materials We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning in the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. Results The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion. Conclusions Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion.

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Outcomes following iodine-125 prostate brachytherapy with or without neoadjuvant androgen deprivation

Ohashi Toshio, Yorozu Atsunori, Saito Shiro, Momma Tetsuo, Toya Kazuhito, Nishiyama Toru, Yamashita Shoji, Shiraishi Yutaka, Shigematsu Naoyuki

Radiotherapy and Oncology 109 ( 2 ) 241 - 245 2013.11

ISSN 0167-8140

Purpose To report the biochemical failure-free survival (BFFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with iodine-125 (I-125) brachytherapy for clinically localized prostate cancer. Methods and materials Between 2003 and 2009, I-125 permanent prostate brachytherapy without supplemental external-beam radiotherapy was performed for 663 patients with low-risk and low-tier intermediate-risk (defined as organ-confined disease, PSA <10 ng/mL, and Gleason score 3 + 4 with biopsy positive core rate <33%) prostate cancer. Early in the study period, the preplanning method was used in the first 104 patients, and later the real-time planning method was used. Biochemical failure was determined using the American Society for Therapeutic Radiology Oncology (ASTRO) and Phoenix definitions. Results The 7-year BFFS rates for the ASTRO and Phoenix definitions were 96.1% and 95.9%, respectively. The corresponding BFFS rates by risk group were 97.6% and 96.7% for low-risk, and 91.8% and 93.6% for low-tier intermediate-risk disease (p = 0.007 and 0.08, respectively). The median times to biochemical failure in those who failed were 29.5 and 43.9 months according to the ASTRO and Phoenix definitions, respectively. The 7-year CSS and OS were 99.1% and 96.4%. There was no significant difference in CSS or OS between the low-risk and low-tier intermediate-risk groups. In multivariate Cox regression analysis, risk group and prostate D90 were independent predictors of BFFS for the ASTRO definition, while only the prostate D90 was significant for the Phoenix definition. Conclusion I-125 prostate brachytherapy results in excellent 7-year BFFS, CSS, and OS for low-risk and low-tier intermediate-risk prostate cancer.

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Comparison of the repair of potentially lethal damage after low- And high-LET radiation exposure, assessed from the kinetics and fidelity of chromosome rejoining in normal human fibroblasts

Liu Cuihua, Kawata Tetsuya, Zhou Guangming, Furusawa Yoshiya, Kota Ryuichi, Kumabe Atsuhiro, Sutani Shinya, Fukada Junichi, Mishima Masayo, Shigematsu Naoyuki, George Kerry, Cucinotta Francis

Journal of Radiation Research 54 ( 6 ) 989 - 997 2013.11

ISSN 0449-3060

Potentially lethal damage (PLD) and its repair (PLDR) were studied in confluent human fibroblasts by analyzing the kinetics of chromosome break rejoining after X-ray or heavy-ion exposures. Cells were either held in the non-cycling G0 phase of the cell cycle for 12 h, or forced to proliferate immediately after irradiation. Fusion premature chromosome condensation (PCC) was combined with fluorescence in situ hybridization (FISH) to study chromosomal aberrations in interphase. The culture condition had no impact on the rejoining kinetics of PCC breaks during the 12 h after X-ray or heavy-ion irradiation. However, 12 h after X-ray and silicon irradiation, cycling cells had more chromosome exchanges than non-cycling cells. After 6 Gy X-rays, the yield of exchanges in cycling cells was 2.8 times higher than that in non-cycling cells, and after 2 Gy of 55 keV/μm silicon ions the yield of exchanges in cycling cells was twice that of non-cycling cells. In contrast, after exposure to 2 Gy 200-keV/μm or 440-keV/μm iron ions the yield of exchanges was similar in non-cycling and cycling cells. Since the majority of repair in G0/G1 occurs via the non-homologous end joining process (NHEJ), increased PLDR in X-ray and silicon-ion irradiated cells may result from improved cell cycle-specific rejoining fidelity through the NHEJ pathway, which is not the case in high- LET iron-ion irradiated cells.

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Novel parameter predicting grade 2 rectal bleeding after iodine-125 prostate brachytherapy combined with external beam radiation therapy

Shiraishi Yutaka, Hanada Takashi, Ohashi Toshio, Yorozu Atsunori, Toya Kazuhito, Saito Shiro, Shigematsu Naoyuki

International Journal of Radiation Oncology Biology Physics 87 ( 1 ) 182 - 187 2013.09

ISSN 0360-3016

Purpose: To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after ¹²⁵I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter. Methods and Materials: To account for differences among radiation treatment modalities and fractionation schedules, rectal dose-volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUD_sum) was determined by a summation of the brachytherapy and external-beam radiation therapy components. Results: Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUD_sum increased: 2.0% (2 of 102 patients) for <70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for >90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUD_sum (P=.000) as risk factors for grade 2+ rectal bleeding. Conclusions: Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.

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Comparison of preplanning and intraoperative planning for I-125 prostate brachytherapy

Yoshida Kayo, Ohashi Toshio, Yorozu Atsunori, Toya Kazuhito, Nishiyama Toru, Saito Shiro, Hanada Takashi, Shiraishi Yutaka, Shigematsu Naoyuki

Japanese Journal of Clinical Oncology 43 ( 4 ) 383 - 389 2013.04

ISSN 0368-2811

Objective: To compare two widely used permanent prostate brachytherapy techniques, preplanning and intraoperative planning, based on postimplant dosimetry, toxicity and biochemical outcomes. Methods: Between 2003 and 2006, 665 men with localized prostate cancer were treated with permanent interstitial implantation. The first 227 consecutive men were treated with the preplanning technique, followed by 438 men treated with the intraoperative technique. Late toxicity was scored by the Common Terminology Criteria for Adverse Events v.4.0. Biochemical failure was defined as a prostate-specific antigen increase of more than 2 ng/ml above the nadir value excluding a benign bounce. Univariate and multivariate analyses were performed to identify the variables associated with biochemical failure-free survival. Results: Postimplant target coverage was similar in the two groups, with a small difference in risk organ doses. Mean V100 was 96.3 vs. 96.7% (P = 0.205), D90 was 119.6 vs. 119.4% (P = 0.884), urethral D10 was 157.5 vs. 146.1% (P = 0.010), rectal V100 was 0.57 vs. 0.43 cc (P = 0.002) in the preplanning and intraoperative planning groups, respectively. Acute and late Grade 3 genitourinary and gastrointestinal toxicities were , <1% for both methods. The 5-year biochemical failure-free survival rate was 95.4% for the preplanning and 94.0% for the intraoperative planning group (P = 0.776). Multivariate analysis revealed Gleason score, biopsy positive rate and V100 to be predictors of biochemical failure-free survival, while the planning technique was not significant. Conclusion: This large-scale analysis of high-quality implants revealed similar postimplant dosimetry, toxicity profiles and biochemical failure-free survival for the preplanning and intraoperative planning methods.

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Detection of esophageal fiducial marker displacement during radiation therapy with a 2-dimensional on-board imager

Fukada Junichi, Hanada Takashi, Kawaguchi Osamu, Ohashi Toshio, Takeuchi Hiroya, Kitagawa Yuko, Seki Satoshi, Shiraishi Yutaka, Ogata Haruhiko, Shigematsu Naoyuki

International Journal of Radiation Oncology Biology Physics 85 ( 4 ) 991 - 998 2013.03

ISSN 0360-3016

Purpose: To quantify the interfraction displacement of esophageal fiducial markers for primary esophageal cancer radiation therapy. Methods and Materials: Orthogonal 2-dimensional (2D) matching records fused to vertebrae were analyzed in clinically staged T1/2N0 esophageal cancer patients undergoing endoscopic clipping as fiducial metal markers. Displacement of the markers between the digitally reconstructed radiographs and on-board kilovoltage images during radiation therapy was analyzed according to direction and esophageal site. Results: Forty-four patients, with 81 markers (10 proximal, 42 middle, and 29 distal), underwent 367 2D matching sessions during radiation therapy. The mean (SD) absolute marker displacement was 0.26 (0.30) cm in the right-left (RL), 0.50 (0.39) cm in the superior-inferior (SI), and 0.24 (0.21) cm in the anterior-posterior (AP) direction. Displacement was significantly larger in the SI than in the RL and AP directions (P<.0001). In the SI direction, mean absolute displacements of the distal, middle, and proximal esophagus were 0.67 (0.45) cm, 0.42 (0.32) cm, and 0.36 (0.30) cm, respectively. Distal esophagus displacement was significantly larger than those of the middle and proximal esophagus (P<.0001). The estimated internal margin to cover 95% of the cases was 0.75 cm in the RL and AP directions. In the SI direction, the margin was 1.25 cm for the proximal and middle esophagus and 1.75 cm for the distal esophagus. Conclusions: The magnitude of interfraction displacement of esophageal clips was larger in the SI direction, particularly in the distal esophagus, but substantial displacement was observed in other directions and at other esophageal sites. It is practical to take estimated movements into account with internal margins, even if vertebrae-based 2D matching is performed.

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Acceptable toxicity after stereotactic body radiation therapy for liver tumors adjacent to the central biliary system

Eriguchi Takahisa, Takeda Atsuya, Sanuki Naoko, Oku Yohei, Aoki Yousuke, Shigematsu Naoyuki, Kunieda Etsuo

International Journal of Radiation Oncology Biology Physics 85 ( 4 ) 1006 - 1011 2013.03

ISSN 0360-3016

Purpose: To evaluate biliary toxicity after stereotactic body radiation therapy (SBRT) for liver tumors. Methods and Materials: Among 297 consecutive patients with liver tumors treated with SBRT of 35 to 50 Gy in 5 fractions, patients who were irradiated with >20 Gy to the central biliary system (CBS), including the gallbladder, and had follow-up times >6 months were retrospectively analyzed. Toxicity profiles, such as clinical symptoms and laboratory and radiologic data especially for obstructive jaundice and biliary infection, were investigated in relation to the dose volume and length relationship for each biliary organ. Results: Fifty patients with 55 tumors were irradiated with >20 Gy to the CBS. The median follow-up period was 18.2 months (range, 6.0-80.5 months). In the dose length analysis, 39, 34, 14, and 2 patients were irradiated with >20 Gy, >30 Gy, >40 Gy, and >50 Gy, respectively, to >1 cm of the biliary tract. Seven patients were irradiated with >20 Gy to >20% of the gallbladder. Only 2 patients experienced asymptomatic bile duct stenosis. One patient, metachronously treated twice with SBRT for tumors adjacent to each other, had a transient increase in hepatic and biliary enzymes 12 months after the second treatment. The high-dose area >80 Gy corresponded to the biliary stenosis region. The other patient experienced biliary stenosis 5 months after SBRT and had no laboratory changes. The biliary tract irradiated with >20 Gy was 7 mm and did not correspond to the bile duct stenosis region. No obstructive jaundice or biliary infection was found in any patient. Conclusions: SBRT for liver tumors adjacent to the CBS was feasible with minimal biliary toxicity. Only 1 patient had exceptional radiation-induced bile duct stenosis. For liver tumors adjacent to the CBS without other effective treatment options, SBRT at a dose of 40 Gy in 5 fractions is a safe treatment with regard to biliary toxicity.

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A prospective longitudinal survey of erectile dysfunction in patients with localized prostate cancer treated with permanent prostate brachytherapy

Matsushima Masashi, Kikuchi Eiji, Maeda Takahiro, Nakashima Jun, Sugawara Akitomo, Ando Toshiyuki, Mizuno Ryuichi, Nagata Hirohiko, Miyajima Akira, Shigematsu Naoyuki, Oya Mototsugu

Journal of Urology 189 ( 3 ) 1014 - 1018 2013.03

ISSN 0022-5347

Purpose: Few studies have evaluated changes in erectile function with time before and after prostate brachytherapy using the International Index of Erectile Function-15, a sensitive, validated tool for assessing male sexual dysfunction. In this prospective study we evaluated the natural history of erectile function after prostate brachytherapy without supplemental therapy (external beam radiotherapy, phosphodiesterase-5 inhibitors or androgen deprivation therapy) using the International Index of Erectile Function-15. Materials and Methods: We identified 119 patients who were followed at least 12 months after prostate brachytherapy between 2004 and 2010. Sexual and erectile function status were assessed before brachytherapy (baseline), and 3, 6, 12, 18, 24 and 36 months postoperatively using the International Index of Erectile Function-15. Results: Mean total International Index of Erectile Function-15 score, and scores on the erectile function, orgasmic function, sexual desire and intercourse satisfaction domains 3 months after brachytherapy were significantly lower than at baseline (p <0.05). They remained lower until 36 months after prostate brachytherapy. Erectile function was maintained 12 months after brachytherapy in 16 of the 48 men (33.3%) with a baseline erectile function domain score of 11 or greater. There was no significant difference in clinical features except the age of patients who maintained the erectile function domain score and their counterparts 12 months after brachytherapy. Multivariate analysis revealed that age 70 years or greater was the only predictive factor for deteriorating erectile function after brachytherapy (p = 0.035). Conclusions: Findings indicate a global decrease in all domains of the International Index of Erectile Function-15 score 12 months after prostate brachytherapy. Also, patient age may influence the preservation of brachytherapy related potency.

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Dosimetric effects of prone and supine positions on post-implant assessments for prostate brachytherapy

Ohashi Toshio, Momma Tetsuo, Yamashita Shoji, Kanai Kunimitsu, Watanabe Yusuke, Hanada Takashi, Shigematsu Naoyuki

Journal of Contemporary Brachytherapy 5 ( 3 ) 122 - 126 2013

ISSN 1689-832X

Purpose: Post-implant dosimetric assessment is essential for optimal care of patients receiving prostate brachytherapy. In most institutions, post-implant computed tomography (CT) is performed in the supine position. This study aimed to assess variability in dosimetric parameters with postural changes during acquisition of post-implant CT scans. Material and methods: In total, 85 consecutive patients were enrolled in this study. Fifty-three patients underwent seed implantation alone, and the remaining 32 received a combination of seed implantation and external beam radiotherapy. For post-implant analyses, CT scans were obtained in two patient positions, supine and prone. To evaluate differences in dosimetric parameters associated with postural change, the dosimetric data obtained in the supine position were defined as the standard. Results: The median prostate volume was 22.4 ml in the supine and 22.5 ml in the prone position (p = 0.51). The median prostate D₉₀ was 120.1% in the supine and 120.3% in the prone position, not significantly different. The mean prostate V₁₀₀ was 97.1% in the supine and 97.0% in the prone position, again not significantly different. Median rectal V₁₀₀ in supine and prone positions were 0.42 ml and 0.33 ml, respectively (p < 0.01). Rectal D_2cc was also significantly decreased in the prone as compared with the supine position (median, 59.1% vs. 63.6%; p < 0.01). A larger post-implant prostate volume was associated with decreased rectal doses in the prone position. Conclusions: Though there were no significant differences among prostate D₉₀ assessments according to postural changes, our results suggest that post-implant rectal doses decreased in the prone position.

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Multiple myeloma relapse in the irradiated liver

Uetake Akiko, Takeda Atsuya, Shigematsu Naoyuki, Ikeda Eiji, Kametaka Minako, Ohashi Toshio, Kunieda Etsuo

Journal of Radiotherapy in Practice 11 ( 4 ) 271 - 273 2012.12

ISSN 1460-3969

We described a rare case of multiple myeloma in a 60-year-old man, in whom relapse limited to the irradiated area in the left lobe of the liver developed following radiotherapy for lesions in 11th and 12th thoracic spines. Immunohistochemical analysis revealed expression of hepatocyte growth factor (HGF) and hepatocyte growth factor receptor (c-Met) in the hepatocytes in the irradiated area of the liver. We speculate that the malignant plasma cells might have proliferated in response to local increase of HGF production in the irradiated liver. The role of HGF in the extraosseous spread of multiple myeloma and also under the experimental condition of hepatic transplantation is discussed.

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Chemoradiotherapy for advanced gastric cancer

Takahashi Tsunehiro, Saikawa Yoshiro, Fukuda Kazumasa, Wada Norihito, Kawakubo Hirofumi, Takeuchi Hiroya, Fukada Junichi, Kawaguchi Osamu, Takaishi Hiromasa, Shigematsu Naoyuki, Kitagawa Yuko

Japanese Journal of Cancer and Chemotherapy 39 ( 13 ) 2464 - 2468 2012.12

ISSN 0385-0684

In the US and Europe, chemoradiotherapy has become a standard treatment not only for head and neck cancer, esophageal cancer, pancreatic cancer, and rectal cancer, but also for gastric cancer. In particular, chemoradiotherapy has been established as an adjuvant therapy. In Japan, it has not been established as a standard treatment. Its indications are limited, and it is often performed as palliative care. Disadvantages of radiation therapy for gastric cancer include the difficulty of establishing the area to irradiate due to peristaltic movement, risk of perforation and ulceration from high-dose radiation, and ineffectiveness against adenocarcinoma with low radiosensitivity. In recent years, technological advancement of radiation therapy has enabled pinpoint accuracy in the treatment of primary gastric lesions and regional lymph nodes. There has been much anticipation that chemoradiotherapy will become a part of multidisciplinary treatment for advanced cancer. This report describes the current state of chemoradiotherapy for gastric cancer in Japan and overseas, and outlines our approach to locally advanced gastric cancer.

Prostate brachytherapy seed migration to a left varicocele

Sugawara Akitomo, Nakashima Jun, Kunieda Etsuo, Nagata Hirohiko, Mizuno Ryuichi, Seki Satoshi, Shiraishi Yutaka, Kouta Ryuichi, Oya Mototsugu, Shigematsu Naoyuki

Brachytherapy 11 ( 6 ) 502 - 506 2012.11

ISSN 1538-4721

Purpose: To report a rare case of seed migration to a left varicocele after transperineal interstitial prostate brachytherapy with loose iodine-125 (¹²⁵I) seeds. Methods and Materials: A 73-year-old man presented with a serum prostate-specific antigen level of 5.21ng/mL, Gleason score of 7 (3+4), and clinical T1c adenocarcinoma of the prostate. The patient underwent transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds followed by external beam radiation therapy. Two weeks after seed implantation, a followup pelvic radiograph was obtained. One month after seed implantation, a pelvic computed tomography scan for postimplant dosimetric analysis was carried out. Subsequent ultrasound examination of the scrotum was undertaken. Results: Two weeks after seed implantation, an anteroposterior pelvic radiograph showed that a migrated seed was overlapped by the scrotum. Postimplant pelvic computed tomography revealed that a seed had migrated to the left side of the scrotum. Subsequent ultrasound examination of the scrotum revealed that the patient had a left varicocele to which the seed had migrated. The patient had no symptoms related to the migrated seed. Conclusions: This is the first report of seed migration to a left varicocele after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds. For the present case, we suggest that the seed moved from the prostate to the left varicocele through the pelvic veins, bypassing the systemic circulation.

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Impact of MRI-based postimplant dosimetric assessment in prostate brachytherapy using contrast-enhanced T1-weighted images

Ohashi Toshio, Momma Tetsuo, Yamashita Shoji, Nagatsuma Katsumi, Kanai Kunimitsu, Kitagawa Kazuhito, Takahashi Shinichi, Hanada Takashi, Yorozu Atsunori, Shigematsu Naoyuki

Brachytherapy 11 ( 6 ) 468 - 475 2012.11

ISSN 1538-4721

Purpose: To compare contrast-enhanced T1-weighted (CE-T1WI) magnetic resonance imaging (MRI) with computed tomography (CT) for postimplant dosimetry and seed recognition in prostate brachytherapy. Methods and Materials: A total of 245 patients who received ¹²⁵I prostate brachytherapy with or without external beam radiotherapy were enrolled. For postimplant analysis, CT and MRI scans were obtained at 1 month after seed implantation. For MRI-based dosimetry, T2-weighted images were fused with the CE-T1WI; the prostate was delineated on the T2-weighted images, and the seed detection was performed manually on the CE-T1WI. In CT-based dosimetry, the seed detection was essentially performed automatically. The dosimetric results obtained by MRI-based and CT-based dosimetry were compared. Results: The mean prostate D₉₀ (the minimum dose received by 90% of the prostate volume) estimated by MRI-based and CT-based dosimetry were 113% and 115%, respectively, with no significant difference. The mean prostate V₁₀₀ (the percent volume of the postimplant prostate receiving 100% of the prescribed dose) estimated by MRI-based and CT-based dosimetry were 95.2% and 95.8%, respectively, again with no significant difference. The mean prostate V₁₅₀ (the percent volume of the postimplant prostate receiving 150% of the prescribed dose) estimated by MRI-based and CT-based dosimetry were 52.8% and 57.0%, respectively (p<0.01). In all of the 35 patients (14%) in whom the MRI-based V₁₅₀ were at least 10% lower than the CT-based results, the seed detection by CT-based dosimetry was overestimated in highly seed-clustered areas or in the areas close to calcifications because of reconstruction artifacts in CT images. Conclusions: MRI-based dosimetry using CE-T1WI appears to be acceptable. Our results suggest that MRI-based dosimetry is a practical method for estimation of the higher dose distribution, especially if seeds are clustered together or when they are close to calcifications.

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Result of salvage radiotherapy for post-operative PSA failure of prostate cancer

Sakayori M., Ohashi T., Fukada J., Shiraishi Y., Hanada T., Shigematsu N.

Japanese Journal of Clinical Radiology 57 ( 9 ) 1193 - 1199 2012.09

ISSN 0009-9252

Fifty-five patients with PSA failure were treated with salvage radiotherapy. Post-operative and postradiotherapy PSA failure was defined as the PSA elevation (nadir+0.2ng/ml) or the initiation of hormone therapy. The median follow-up period after salvage radiotherapy was 32 months (range ; l-67months). The 3-yrs biochemical free survival and overall survival rate was 66.7% and 100%. Result of salvage radiotherapy for post-operation PSA failure is good and only the dose was significant predictive factor (60Gy vs > 64Gy ; 53.9% vs 862%).

Initial experience of individualized chemoradiotherapy for superficial esophageal cancers based on the sentinel lymph node concept

Kaburagi Takuji, Takeuchi Hiroya, Fujii Hirofumi, Saikawa Yoshiro, Murakami Koji, Fukada Junichi, Shigematsu Naoyuki, Ozawa Soji, Ando Nobutoshi, Kitagawa Yuko

Esophagus 9 ( 3 ) 147 - 152 2012.09

ISSN 1612-9059

Background: Esophageal squamous cell carcinomas (ESCCs) invading the muscularis mucosae (T1a-MM) cause subclinical node metastasis in approximately 10 % of cases. When chemoradiotherapy (CRT) is administered to T1a-MM or deeper ESCC, prophylactic irradiation of areas with a risk of subclinical nodal metastasis may improve disease control. We had an opportunity for clinical observation of the status of lymph nodes in the patients whose hot spots in lymphoscintigraphy before CRT had been included within the irradiation field. Methods: We retrospectively investigated patients selected using following criteria: (1) cT1a-MM and cT1b without previous treatments, or pT1a-MM and pT1b cancers proved by previous endoscopic resections; (2) patients with neither clinical nodal nor distant metastasis; (3) patients whose hot spots detected by lymphoscintigraphy had been included within the irradiation fields. Lymphoscintigraphy had been examined with endoscopic injection of a radioisotope around the primary lesion before CRT. Results: Sixteen patients met the inclusion criteria. Of these patients [T1a-MM (4 cases), T1b-SM1 (2 cases), and T1b-SM2 (10 cases)], there were 9 definitive CRTs and 7 adjuvant CRTs after endoscopic resections. The median dose of irradiation was 60 Gy to the primary tumors and 46 Gy to the hot spots. All patients with definitive CRT achieved complete remission. At the median follow-up of 76.6 months, there was no lymph node recurrence. Conclusions: Prophylactic irradiation of the hot spots in lymphoscintigraphy may be effective. This result warrants further evaluation concerning the validity of irradiation field settings based on lymphoscintigraphic findings in patients with superficial ESCCs.

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Predicting pubic arch interference in prostate brachytherapy on transrectal ultrasonography-computed tomography fusion images.

Fukada Junichi, Shigematsu Naoyuki, Nakashima Jun, Ohashi Toshio, Kawaguchi Osamu, Oya Mototsugu

Journal of Radiation Research 53 ( 5 ) 753 - 759 2012.09

ISSN 0449-3060

We investigated the usefulness of the fusion image created by transrectal ultrasonography (TRUS) and large-bore computed tomography (CT) for predicting pubic arch interference (PAI) during prostate seed brachytherapy. The TRUS volume study was performed in 21 patients, followed by large-bore computed tomography of patients in the lithotomy position. Then, we created TRUS-CT fusion images using a radiation planning treatment system. TRUS images in which the prostate outline was the largest were overlaid on CT images with the narrowest pubic arch. PAI was estimated in the right and left arch separately and classified to three grades: no PAI, PAI positive within 5 mm and PAI of >5 mm. If the estimated PAI was more than 5 mm on at least one side of the arch, we judged there to be a significant PAI. Brachytherapy was performed in 18 patients who were evaluated as not having significant PAI on TRUS. Intra-operative PAI was observed in one case, which was also detected with a fusion image. On the other hand, intra-operative PAI was not observed in one case that had been evaluated as having significant PAI with a fusion image. In the remaining three patients, TRUS suggested the presence of significant PAI, which was also confirmed by a fusion image. Intra-operative PAI could be predicted by TRUS-CT fusion imaging, even when it was undetectable by TRUS. Although improvement of the reproducibility of the patients' position to avoid false-positive cases is warranted, TRUS-CT fusion imaging has the possibility that the uncertainty of TRUS can be supplemented.

Preimplant factors affecting prostate D90 after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds

Sugawara Akitomo, Nakashima Jun, Kunieda Etsuo, Nagata Hirohiko, Mizuno Ryuichi, Takeda Atsuya, Seki Satoshi, Shiraishi Yutaka, Kouta Ryuichi, Oya Mototsugu, Shigematsu Naoyuki

Keio Journal of Medicine 61 ( 3 ) 89 - 94 2012.09

ISSN 0022-9717

The dose received by 90% of the prostate volume (D90) is the key parameter of dosimetric analysis in prostate brachytherapy. The aim of this analysis was to identify preimplant factors affecting prostate D90 after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds. We reviewed the records of 210 patients who underwent transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds for clinical T1/T2 prostate cancer at our institution. Patients who received supplemental external-beam radiation therapy were excluded. One hundred and nine patients (51.9%) received neoadjuvant hormonal therapy (NHT). One month after seed implantation, postimplant computed tomography and dosimetric analysis were performed. Univariate and multivariate analyses were carried out to identify preimplant factors affecting postimplant prostate D90. The postimplant prostate D90 values ranged from 123.3 to 234.1 Gy (mean ± standard error, 177.1 ± 1.4 Gy). Postimplant prostate D90 differed significantly between patients who had and had not undergone NHT (P = 0.001). In addition, simple regression analyses showed positive correlations with the estimated preimplant prostate D90, preimplant prostate volume by transrectal ultrasound (TRUS), total radioactivity, number of needles, and number of seeds. On stepwise multiple regression analysis, postimplant prostate D90 showed significant negative correlations with NHT and preimplant prostate volume by TRUS, and a significant positive correlation with total radioactivity. In conclusion, NHT, preimplant prostate volume by TRUS, and total radioactivity are significant preimplant factors affecting postimplant prostate D90 in prostate cancer patients treated with transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds.

Enhancement of radiosensitivity by a unique novel NF-B inhibitor, DHMEQ, in prostate cancer

Kozakai N., Kikuchi E., Hasegawa M., Suzuki E., Ide H., Miyajima A., Horiguchi Y., Nakashima J., Umezawa K., Shigematsu N., Oya M.

British Journal of Cancer 107 ( 4 ) 652 - 657 2012.08

ISSN 0007-0920

Background: Inducible activation of nuclear factor (NF)-B is one of the principal mechanisms through which resistant prostate cancer cells are protected from radiotherapy. We hypothesised that inactivation of inducible NF-B with a novel NF-B inhibitor, DHMEQ, would increase the therapeutic effects of radiotherapy.Methods:PC-3 and LNCaP cells were exposed to irradiation and/or DHMEQ. Cell viability, cell cycle analysis, western blotting assay, and NF-B activity were measured. The antitumour effect of irradiation combined with DHMEQ in vivo was also assessed.Results:The combination of DHMEQ with irradiation resulted in cell growth inhibition and G2/M arrest relative to treatment with irradiation alone. Inducible NF-B activity by irradiation was inhibited by DHMEQ treatment. The expression of p53 and p21 in LNCaP, and of 14-3-3 in PC-3 cells, was increased in the combination treatment. In the in vivo study, 64 days after the start of treatment, tumour size was 85.1%, 77.1%, and 64.7% smaller in the combination treatment group than that of the untreated control, DHMEQ-treated alone, and irradiation alone groups, respectively.Conclusion:Blockade of NF-B activity induced by radiation with DHMEQ could overcome radio-resistant responses and may become a new therapeutic modality for treating prostate cancer.

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Statistical analysis of 32 patients with nasopharyngeal Carcinoma

Fujii Ryoichi, Imanishi Yorihisa, Tomita Toshiki, Sakamoto Koji, Shigetomi Seiji, Habu Noboru, Ootsuka Kuninori, Sato Yoichiro, Ozawa Hiroyuki, Yamashita Taku, Fujii Masato, Shigematsu Naoyuki, Ogawa Kaoru

Journal of Otolaryngology of Japan 115 ( 8 ) 773 - 782 2012.08

ISSN 0030-6622

In order to assess the clinical outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) who were initially treated in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine between 1997 and 2006, statistical analyses were performed based on the patient medical records. Cause-specific survival (CSS) and disease-free survival (DFS) in all cases (stage I to IV, n = 32) and advanced cases (stage III and IV, n = 22) were estimated using the Kaplan-Meier method. The independent prognostic values of the clinical and therapeutic factors were determined using multivariate Cox proportional hazards models. Results: The 5-year CSS/DFS were 43.4%/34.8% in all cases and 34.596/29.8% in advanced cases. Multivariate analysis revealed that, in all cases, the independent prognostic factors for CSS were age ≥ 61 vs. ≤60, risk ratio (RR) =5.717, p = 0.006), T-stage (3/4 vs. 1/2, RR = 6.957, p = 0.004), and the use of platinum agents (unused vs. used, RR = 3.911, p = 0.012), whereas those for DFS were T-stage (3/4 vs. 1/2, RR=3.499, p = 0.019) and the use of platinum agents (unused vs. used, RR=2.947, p = 0.028). In advanced cases, the use of platinum agents alone was significant for both CSS (RR = 4.503, p = 0.023)and DFS (RR=4.218, p = 0.014). The patients who received neoadjuvant chemotherapy (NAC) showed better CSS and DFS than the patients who did not (p = 0.066 and p = 0.025, respectively) in a univariate analysis (Log-rank test), although no significant difference was seen between these groups in the multivariate analysis. Conclusion: The advantage of the administration of platinum agents in the treatment of NPC was statistically corroborated even in our study with its small sample size. As agents combined with chemoradiotherapy, the efficacy of do-cetaxel alone did not seem comparable to that of platinum agents. The docetaxel-CDDP-5-FU regimen applied as NAC was suggested to be possibly beneficial for advanced cases of NPC.

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Pericardial and pleural effusions after definitive radiotherapy for esophageal cancer

Fukada Junichi, Shigematsu Naoyuki, Ohashi Toshio, Shiraishi Yutaka, Takeuchi Hiroya, Kawaguchi Osamu, Kitagawa Yuko

Journal of Radiation Research 53 ( 3 ) 447 - 453 2012.05

ISSN 0449-3060

Purpose: We investigated the incidences of pericardial and pleural effusions after definitive radiotherapy with or without concurrent chemotherapy were analyzed retrospectively. Methods: One hundred and forty-seven patients with esophageal cancer received definitive radiotherapy or concurrent chemoradiotherapy (CCR). Follow-up chest Computed Tomography scans were reviewed to detect pericardial and pleural effusions. Adverse events were graded according to the Radiation Therapy Oncology Group Common Toxicity Criteria. Results: The median follow-up was 34 (range, 6 to 84) months. Numbers of eligible patients evaluated for pericardial and pleural effusions were 107 and 101, respectively. Pericardial effusions exceeding grade 1 and grade 2 toxicities were observed in 46 (43%) and 15 (14%) patients, respectively. The corresponding numbers for pleura! effusions were 44 (44%) and 18 (18%). Onset of effusion ranged from 1 to 65 months after treatment. Multivariate analysis identified radiation field width of the mediastinum exceeding 8 cm as a significant risk factor for both pericardial and pleural effusions. Age and field length exceeding 20 cm were identified as independent risk factors for pleural effusion. Conclusions: Pericardial and pleural effusions after radiotherapy or CCR are occasionally recognized as adverse events in patients with esophageal cancer. The mediastinal radiation field width can be a simple indicator for predicting those adverse events.

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Comparison of clinical, tumour-relatedand dosimetric factors in grade 0-1, grade2 and grade 3 radiation pneumonitis after stereotactic body radiotherapy for lung tumours

Takeda A., Ohashi T., Kunieda Etsuo, Sanuki N., Enomoto T., Takeda T., Oku Y., Shigematsu N.

British Journal of Radiology 85 ( 1013 ) 636 - 642 2012.05

ISSN 0007-1285

Objective: The aim of this study was to investigate significant clinical, tumour-related and dosimetric factors among patients with grade 0-1, grade 2 and grade 3 radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for lung tumours. Methods: Patients (n=128) with a total of 133 lung tumours treated with SBRT of 50 Gy in 5 fractions were analysed. RP was graded according to the Common Terminology Criteria for Adverse Events v.3.0. Significant factors were identified by univariate and multivariate analyses. Threshold dose-volume histograms (DVHs) were constructed to identify the incidence of RP. Results: The median follow-up period was 12 months (range, 6-45 months). In univariate analyses, gender, operability, forced expiratory volume in 1 s (FEV1), internal target volume, lung volumes treated with doses >5-30 Gy (V5-30) and mean lung dose were significant factors differentiating between grade 0-1 and grade 2 RP, and V15-30 were significant factors differentiating between grade 2 and grade 3. However, no factors were significant between grade 0-1 and grade 3 RP. Multivariate analysis showed that female gender, high FEV1 and high V15 were significant factors differentiating between grade 0-1 and grade 2 RP. Threshold DVH curves were created based on ≤5% and ≤15% risk of grade 2 RP among patients with grade 0-2 RP. Conclusions: Grade 0-2 RP was dose-volume dependent, and female gender and high FEV1 were significant predictive clinical factors for grade 2 RP among patients with grade 0-2 RP. However, incidences of V15-30 in grade 3 RP were significantly lower than those in grade 2 RP, and no significant clinical or tumour-related factors were found. Further studies are needed to identify the mechanism underlying the development of grade 3 RP after SBRT for lung tumours.

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Safety and efficacy of total body irradiation, cyclophosphamide, and cytarabine as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia

Mori Takehiko, Aisa Yoshinobu, Kato Jun, Yamane Akiko, Nakazato Tomonori, Shigematsu Naoyuki, Okamoto Shinichiro

American Journal of Hematology 87 ( 4 ) 349 - 353 2012.04

ISSN 0361-8609

Disease relapse still greatly interferes with the success of allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL). This study retrospectively evaluated the long-term safety and efficacy of a conditioning regimen consisting of total body irradiation (TBI; 12 Gy), cyclophosphamide (CY; 60 mg kg ^-1, two doses), and high-dose cytarabine (Ara-C; 2 g m ^-2; four doses) for patients with ALL. Fifty-five patients (median age: 31-years old) were evaluated. Stem cells were from human leukocyte antigen-identical siblings in 22 patients and from alternative donors in 33. There were no cases of early death before engraftment, and 100-day transplant-related mortality was 7.3%. With a median follow-up period of 9.6 years, 5-year overall and disease-free survival were 63.2% (95% CI: 46.5-79.9%) and 63.6% (95% CI: 47.1-80.1%) in patients with complete remission, respectively, both of which were significantly higher than the values of 27.3% (95% CI: 8.7-46.0%) and 22.7% (95% CI: 5.3-40.1%) for patients in advanced stages (P < 0.01). These results suggest that TBI and CY (TBI-CY) plus Ara-C could be a feasible and effective conditioning regimen for adult patients with ALL both in remission and in advanced stages, and a future study to compare this combination therapy with TBI-CY is required.

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Clinical evidence of particle beam therapy

Shigematsu Naoyuki, Shiraishi Yutaka, Seki Satoshi, Fukada Junichi, Ohashi Toshio

International Journal of Clinical Oncology 17 ( 2 ) 75 - 78 2012.04

ISSN 1341-9625

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Nuclear disaster after the Earthquake and Tsunami of March 11

Shigematsu Naoyuki, Fukada Junichi, Ohashi Toshio, Kawaguchi Osamu, Kawata Tetsuya

Keio Journal of Medicine 61 ( 1 ) 28 - 34 2012.03

ISSN 0022-9717

We would like to explain the effects of radiation on human health and discuss the actual effects of the contamination with radioactive material present in Tokyo. Currently, external exposure doses are within the allowable range in Tokyo and will have no adverse health effects on adults or children. As for internal exposure doses, there will likely be no problems as regards our ordinary dietary intakes. However, hot spots of Cs-134, Sr-90 and others should be monitored further.

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[Allogeneic hematopoietic stem cell transplantation with fludarabine, melphalan, and total body irradiation as a conditioning for elderly patients with myeloid malignancies].

Nakamura Yukinori, Mori Takehiko, Kato Jun, Aisa Yoshinobu, Nakazato Tomonori, Shigematsu Naoyuki, Okamoto Shinichiro

[Rinshō ketsueki] The Japanese journal of clinical hematology 53 ( 3 ) 318 - 322 2012.03

ISSN 0485-1439

A variety of reduced-intensity conditionings have been used in the reported studies of allogeneic hematopoietic stem cell transplantation (HSCT) for elderly patients with myeloid hematological malignancies. This study retrospectively analyzed the outcome of allogeneic HSCT for 10 patients aged 50 years or older with myeloid hematological malignancies after conditioning with fludarabine (125 mg/m(2)), melphalan (140 mg/m(2)) and total body irradiation (TBI; 8 Gy). Median age of the patients was 56.5 years, and diagnoses included acute myelogenous leukemia, advance myelodysplastic syndrome, and secondary myelofibrosis. Sources of stem cells were bone marrow from sibling (n=4) or unrelated donor (n=6). Both overall and disease-free survival rates were 40.0% (95% CI: 10.6~69.4%). Causes of death were relapse (n=2), fungal infection (n=2), and secondary malignancies (n=2). Because of a high incidence of transplant-related mortality, further refinement of this conditioning is required.

Dose constraint for minimizing grade 2 rectal bleeding following brachytherapy combined with external beam radiotherapy for localized prostate cancer

Shiraishi Yutaka, Yorozu Atsunori, Ohashi Toshio, Toya Kazuhito, Seki Satoshi, Yoshida Kayo, Kaneda Tomoya, Saito Shiro, Nishiyama Toru, Hanada Takashi, Shigematsu Naoyuki

International Journal of Radiation Oncology Biology Physics 81 ( 3 ) 2011.11

ISSN 0360-3016

Purpose: To determine the rectal tolerance to Grade 2 rectal bleeding after I-125 seed brachytherapy combined with external beam radiotherapy (EBRT), based on the rectal dose-volume histogram. Methods and Materials: A total of 458 consecutive patients with stages T1 to T3 prostate cancer received combined modality treatment consisting of I-125 seed implantation followed by EBRT to the prostate and seminal vesicles. The prescribed doses of brachytherapy and EBRT were 100 Gy and 45 Gy in 25 fractions, respectively. The rectal dosimetric factors were analyzed for rectal volumes receiving >100 Gy and >150 Gy (R100 and R150) during brachytherapy and for rectal volumes receiving >30 Gy to 40 Gy (V30-V40) during EBRT therapy in 373 patients for whom datasets were available. The patients were followed from 21 to 72 months (median, 45 months) after the I-125 seed implantation. Results: Forty-four patients (9.7%) developed Grade 2 rectal bleeding. On multivariate analysis, age (p = 0.014), R100 (p = 0.002), and V30 (p = 0.001) were identified as risk factors for Grade 2 rectal bleeding. The rectal bleeding rate increased as the R100 increased: 5.0% (2/40 patients) for 0 ml; 7.5% (20/267 patients) for >0 to 0.5 ml; 11.0% (11/100 patients) for >0.5 to 1 ml; 17.9% (5/28 patients) for >1 to 1.5 ml; and 27.3% (6/22 patients) for >1.5 ml (p = 0.014). Grade 2 rectal bleeding developed in 6.4% (12/188) of patients with a V30 ≤35% and in 14.1% (26/185) of patients with a V30 >35% (p = 0.02). When these dose-volume parameters were considered in combination, the Grade 2 rectal bleeding rate was 4.2% (5/120 patients) for a R100 ≤0.5 ml and a V30 ≤35%, whereas it was 22.4% (13/58 patients) for R100 of >0.5 ml and V30 of >35%. Conclusion: The risk of rectal bleeding was found to be significantly volume-dependent in patients with prostate cancer who received combined modality treatment. Rectal dose-volume analysis is a practical method for predicting the risk of development of Grade 2 rectal bleeding.

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Incidence of seed migration to the chest, abdomen, and pelvis after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds

Sugawara Akitomo, Nakashima Jun, Kunieda Etsuo, Nagata Hirohiko, Mizuno Ryuichi, Seki Satoshi, Shiraishi Yutaka, Kouta Ryuichi, Oya Mototsugu, Shigematsu Naoyuki

Radiation Oncology 6 ( 1 ) 2011.10

Background: The aim was to determine the incidence of seed migration not only to the chest, but also to the abdomen and pelvis after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds.Methods: We reviewed the records of 267 patients who underwent prostate brachytherapy with loose ¹²⁵I seeds. After seed implantation, orthogonal chest radiographs, an abdominal radiograph, and a pelvic radiograph were undertaken routinely to document the occurrence and sites of seed migration. The incidence of seed migration to the chest, abdomen, and pelvis was calculated. All patients who had seed migration to the abdomen and pelvis subsequently underwent a computed tomography scan to identify the exact location of the migrated seeds. Postimplant dosimetric analysis was undertaken, and dosimetric results were compared between patients with and without seed migration.Results: A total of 19,236 seeds were implanted in 267 patients. Overall, 91 of 19,236 (0.47%) seeds migrated in 66 of 267 (24.7%) patients. Sixty-nine (0.36%) seeds migrated to the chest in 54 (20.2%) patients. Seven (0.036%) seeds migrated to the abdomen in six (2.2%) patients. Fifteen (0.078%) seeds migrated to the pelvis in 15 (5.6%) patients. Seed migration occurred predominantly within two weeks after seed implantation. None of the 66 patients had symptoms related to the migrated seeds. Postimplant prostate D90 was not significantly different between patients with and without seed migration.Conclusion: We showed the incidence of seed migration to the chest, abdomen and pelvis. Seed migration did not have a significant effect on postimplant prostate D90.

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Prevention of cytarabine-induced kerato-conjunctivitis by eye rinse in patients receiving high-dose cytarabine and total body irradiation as a conditioning for hematopoietic stem cell transplantation

Mori Takehiko, Kato Jun, Yamane Akiko, Aisa Yoshinobu, Kawata Yusuke, Ichimura Mayu, Tsuneyama Chiaki, Yashima Tomoko, Ogawa Yoko, Tsubota Kazuo, Shigematsu Naoyuki, Shimizu Takayuki, Okamoto Shinichiro

International Journal of Hematology 94 ( 3 ) 261 - 265 2011.09

ISSN 0925-5710

We previously reported a high incidence of kerato-conjunctivitis in patients receiving high-dose cytarabine following total body irradiation (TBI) as a conditioning for hematopoietic stem cell transplantation (HSCT) even on prophylaxis with topical corticosteroid. This study aimed to evaluate whether addition of eye rinse, which was designed to remove cytarabine from ocular surface, further reduces the incidence of kerato-conjunctivitis in the same setting. Seventy-six patients receiving cytarabine at a dose of 3 g/m ² every 12 h for 4 days after receiving TBI (12 Gy) as conditioning for HSCT were evaluated. All patients received betamethasone sodium phosphate eye drops. Twenty-three patients were further instructed to rinse their eyes with sterile saline every 10-15 min during and for two additional hours after the completion of each cytarabine infusion. Among 23 patients with eye rinse, Grades 2-3 and 1-3 kerato-conjunctivitis were observed in 4 (17.4%) and 5 patients (21.7%), respectively. These incidences were significantly lower than those [35 (66.0%) and 41 (77.4%)] observed in 53 patients without eye rinse (P<0.001 and P<0.00001, respectively). These results strongly suggest that eye rinse effectively reduces the incidence and severity of cytarabine-induced kerato-conjunctivitis in HSCT recipients who receive high-dose cytarabine following TBI.

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Phase I study of neoadjuvant chemoradiotherapy consisting of S-1 and cisplatin for patients with resectable advanced gastric cancer (KOGC-01)

Takahashi Tsunehiro, Saikawa Yoshiro, Takaishi Hiromasa, Takeuchi Hiroya, Wada Norihito, Oyama Takashi, Fukuda Kazumasa, Fukada Junichi, Kawaguchi Osamu, Shigematsu Naoyuki, Kitagawa Yuko

Anticancer Research 31 ( 9 ) 3079 - 3083 2011.09

ISSN 0250-7005

Background: The prognosis for advanced gastric cancer is poor, with surgery as the only treatment for resectable advanced gastric cancer. Therefore, treatment options that might improve the prognosis are needed. To that end, neoadjuvant chemoradiotherapy with S-1 and cisplatin (CDDP) was investigated. Patients and Methods: The chemotherapy schedule included one cycle repeated after 6 weeks. S-1 was administered orally every day on days 1-21 and CDDP was infused on days 1, 8 and 15. Radiation therapy was started concurrently with chemotherapy and repeated daily on days 1-5, 8-12, 15-19, and 22-26. Results: A total of 10 patients were recruited. The first four patients were entered into level 1 (CDDP, 20 mg/m²). The next six patients were entered into level 0 (15 mg/m²), because of dose-limiting toxicity (delaying the second course of chemotherapy in two patients) that had been observed at level 1. The maximum tolerated dose (MTD) of CDDP was 20 mg/m². Seven patients underwent surgery and all had an R0 (no residual tumor) resection without surgical complications. Conclusion: Neoadjuvant chemoradiotherapy with S-1 and CDDP may cause surgery to be delayed, but shows promise for resectable advanced gastric cancer.

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

Tabuchi Satoshi, Ozawa Soji, Koyanagi Kazuo, Shigematsu Naoyuki, Kubo Atsushi, Ueda Masakazu, Kitajima Yuko Kitagawa, Kitajima Masaki

Experimental and Therapeutic Medicine 2 ( 4 ) 601 - 606 2011.07

ISSN 1792-0981

Esophageal squamous cell carcinoma (ESCC) is more sensitive to radiation and chemotherapy than other cancers of the digestive system, and combined modality therapy may represent a promising treatment method. The radiation-sensitizing effect of docetaxel on ESCC cell lines was investigated. A colony formation assay was performed in which ESCC cell lines (TE2, TE3) and A431 were exposed to docetaxel (from 1.0x10 ¹¹ to 10⁷ M) for 3 h to determine the concentration of docetaxel that was not able to kill individual cells (i.e., the non-cytocidal concentration). Individual cell lines were then exposed to the non-cytocidal concentration of docetaxel prior to, during, and after irradiation to determine whether the timing of docetaxel administration affected cell survival. In addition, flow-cytometry was performed, and the cell cycle was examined prior to and after docetaxel exposure to assess the mechanism of docetaxel as a radiation sensitizer. Docetaxel exhibited a concentration-dependent cytocidal effect, with a different IC₅₀ for each cell type. Almost no cytocidal effect was observed at the following docetaxel concentrations: A431, ≤1.0x10¹⁰ M; TE-2 and TE-3, ≤1.0x10⁹ M. Concurrent treatment with docetaxel and radiation tended to decrease cell survival in all the cell lines compared with docetaxel or radiation alone. Cell survival was lowest when the cells were treated using X-ray irradiation after docetaxel exposure (p<0.05). Flow cytometry revealed that in all three cell lines, docetaxel exposure increased the G2/M cell fraction with a higher increase in the cell line that exhibited the highest radiosensitivity This study demonstrated that the administration of docetaxel at a non-cytocidal concentration prior to radiotherapy produced a synergistic cell-killing effect in SCC cell lines.

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Non-sentinel lymph node status and prognosis of breast cancer patients with micrometastatic sentinel lymph nodes

Onishi T., Jinno H., Takahashi M., Hayashida T., Sakata M., Nakahara T., Shigematsu N., Mukai M., Kitagawa Y.

European Surgical Research 45 ( 3-4 ) 344 - 349 2010.12

ISSN 0014-312X

Background: The prognostic significance of sentinel lymph node (SLN) micrometastases and the need for axillary lymph node dissection (ALND) on patients with micrometastases in SLNs remain controversial. Methods: A prospective database of 657 breast cancer patients who underwent SLN biopsy (SLNB) was analyzed. SLNs were detected using a combined method of isosulfan blue dye and small-sized technetium-99m-labeled tin colloid. Results: Micrometastases in SLNs were found in 50 (7.6%) of 657 patients. Twenty-nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and no further metastases were found in non-sentinel lymph nodes. Among 21 patients (42.0%) with micrometastatic SLNs who decided to forego ALND, no axillary lymph node recurrence has been observed during a median follow-up time of 47 months. There is no significant difference in recurrence-free survival between the patients with micrometastatic and negative SLNs (p = 0.90). Conclusions: These data suggest that it may not be necessary to perform ALND on patients with micrometastases in SLNs and that the presence of micrometastases in SLNs may not be associated with prognosis.

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CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis

Sanuki-Fujimoto N., Takeda A., Ohashi T., Kunieda Etsuo, Iwabuchi S., Takatsuka K., Koike N., Shigematsu N.

British Journal of Radiology 83 ( 996 ) 1063 - 1071 2010.12

ISSN 0007-1285

This study aimed to assess the imaging appearances of focal liver reactions following stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) and to examine relationships between imaging appearance and baseline liver function. We retrospectively studied 50 lesions in 47 patients treated with SBRT (30-40 Gy in 5 fractions) for HCC, who were followed up for more than 6 months. After SBRT, all patients underwent regular follow-ups with blood tests and dynamic CT scans. At a median follow-up of 18.1 months (range 6.2-43.7 months), all lesions but one were controlled. 3 density patterns describing focal normal liver reactions around HCC tumours were identified in pre-contrast, arterial and portal-venous phase scans: iso/iso/iso in 4 patients (Type A), low/iso/iso in 8 patients (Type B) and low/iso (or high)/high in 38 patients (Type C). Imaging changes in the normal liver surrounding the treated HCC began at a median of 3 months after SBRT, peaked at a median of 6 months and disappeared 9 months later. Liver function, as assessed by the Child-Pugh classification, was the only factor that differed significantly between reactions to treatment showing "non-enhanced" (Type A and B) and "enhanced" (Type C) appearances in CT. Hence, liver tissue with preserved function is more likely to be well enhanced in the delayed phase of a dynamic contrast-enhanced CT scan. The CT appearances of normal liver seen in reaction to the treatment of an HCC by SBRT were therefore related to background liver function and should not be misread as recurrence of HCC.

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A comparison of chromosome repair kinetics in G0 and G1 reveals that enhanced repair fidelity under noncycling conditions accounts for increased potentially lethal damage repair

Liu Cuihua, Kawata Tetsuya, Shigematsu Naoyuki, Cucinotta Francis, George Kerry, Saito Masayoshi, Uno Takashi, Isobe Kouichi, Ito Hisao

Radiation Research 174 ( 5 ) 566 - 573 2010.11

ISSN 0033-7587

Potentially lethal damage (PLD) and its repair were studied in confluent human fibroblasts by analyzing the kinetics of chromosome break rejoining and misrejoining in irradiated cells that were either held in noncycling G0 phase or allowed to enter G1 phase of the cell cycle immediately after 6 Gy irradiation. Virally mediated premature chromosome condensation (PCC) methods were combined with fluorescence in situ hybridization (FISH) to study chromosomal aberrations in interphase. Flow cytometry revealed that the vast majority of cells had not yet entered S phase 15 h after release from G0. By this time some 95 of initially produced prematurely condensed chromosome breaks had rejoined, indicating that most repair processes occurred during G1. The rejoining kinetics of prematurely condensed chromosome breaks was similar for each culture condition. However, under noncycling conditions misrepair peaked at 0.55 exchanges per cell, while under cycling conditions (G1) it peaked at 1.1 exchanges per cell. At 12 h postirradiation, complex-type exchanges were sevenfold more abundant for cycling cells (G1) than for noncycling cells (G0). Since most repair in G0/G1 occurs via the non-homologous end-joining (NHEJ) process, increased PLD repair may result from improved cell cycle-specific rejoining fidelity of the NHEJ pathway.

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Preimplant factors affecting postimplant CT-determined prostate volume and the CT/TRUS volume ratio after transperineal interstitial prostate brachytherapy with ¹²⁵I free seeds

Sugawara Akitomo, Nakashima Jun, Kunieda Etsuo, Nagata Hirohiko, Asakura Hirotaka, Oya Mototsugu, Shigematsu Naoyuki

Radiation Oncology 5 ( 1 ) 2010.09

Background: The aim was to identify preimplant factors affecting postimplant prostate volume and the increase in prostate volume after transperineal interstitial prostate brachytherapy with ¹²⁵I free seeds.Methods: We reviewed the records of 180 patients who underwent prostate brachytherapy with ¹²⁵I free seeds for clinical T1/T2 prostate cancer. Eighty-one (45%) of the 180 patients underwent neoadjuvant hormonal therapy. No patient received supplemental external beam radiotherapy. Postimplant computed tomography was undertaken, and postimplant dosimetric analysis was performed. Univariate and multivariate analyses were performed to identify preimplant factors affecting postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.Results: Preimplant prostate volume by transrectal ultrasound, serum prostate-specific antigen, number of needles, and number of seeds implanted were significantly correlated with postimplant prostate volume by computed tomography. The increase in prostate volume after implantation was significantly higher in patients with neoadjuvant hormonal therapy than in those without. Preimplant prostate volume by transrectal ultrasound, number of needles, and number of seeds implanted were significantly correlated with the increase in prostate volume after implantation. Stepwise multiple linear regression analysis showed that preimplant prostate volume by transrectal ultrasound and neoadjuvant hormonal therapy were significant independent factors affecting both postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.Conclusions: The results of the present study show that preimplant prostate volume by transrectal ultrasound and neoadjuvant hormonal therapy are significant preimplant factors affecting both postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.

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Sebaceous carcinoma of the parotid gland

Kumabe Atsuhiro, Kawase Takatsugu, Miura Kouki, Tada Yuichiro, Masubuchi Tatsuo, Kamata Shin Etsu, Tanada Shuji, Kubo Atsushi, Tajima Yasuo, Shigematsu Naoyuki

Clinical Nuclear Medicine 35 ( 4 ) 260 - 262 2010.04

ISSN 0363-9762

Sebaceous carcinoma is a rare malignant tumor typically originating in the skin of the eyelid. We report an unusual case of sebaceous carcinoma originating in the parotid gland of a 23-year-old woman. The patient underwent F-18 2-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (FDG PET/CT) to determine the initial clinical stage. FDG PET/CT revealed strong uptake in the primary lesion but neither regional lymphatic nor distant metastasis were seen. These findings allowed for an accurate prediction of the nodal status, which contributed to precise determination of the initial stage. FDG PET/CT scans may be useful for the initial staging of cutaneous sebaceous carcinomas as well.

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Weekly Low-Dose Docetaxel-Based Chemoradiotherapy for Locally Advanced Oropharyngeal or Hypopharyngeal Carcinoma

Fukada Junichi, Shigematsu Naoyuki, Takeda Atsuya, Ohashi Toshio, Tomita Toshiki, Shiotani Akihiro, Kunieda Etsuo, Kawaguchi Osamu, Fujii Masato, Kubo Atsushi

International Journal of Radiation Oncology Biology Physics 76 ( 2 ) 417 - 424 2010.02

ISSN 0360-3016

Purpose: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m²]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade ≥3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

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Superiority of radioisotope over blue dye for sentinel lymph node detection in breast cancer

Hayashida T., Jinno H., Sakata M., Takahashi M., Onishi T., Seki H., Sato T., Nakahara T., Shigematsu N., Mukai M., Hibi T., Kitajima M., Kitagawa Y.

European Surgical Research 44 ( 2 ) 111 - 116 2010.02

ISSN 0014-312X

Background: Sentinel lymph node biopsy (SLNB) is commonly performed using radioisotopes and/or blue dye. However, it is still undefined which reagent is more suitable for identifying sentinel lymph nodes (SLN). Patients and Methods: A consecutive series of 640 breast cancer patients who had undergone SLNB at the Keio University Hospital from 2001 to 2006 was analyzed. The SLN was identified by a combination of technetium-99m tin colloid and isosulfan blue dye. The correlation between clinicopathological factors and the distribution of radioisotopes and blue dye was analyzed. The single metastatic lymph node revealed by axillary lymph node dissection (ALND) is the 'true SLN', and the distribution of radioisotopes and blue dye to the 'true SLN' was also analyzed. Results: Blue-dye- and radioisotope-positive SLN were identified in 79.6 and 94.7% of the patients, respectively. Taken together, SLN were identified in 625 patients (97.7%) by radioisotope and/or blue dye. No significant correlation was observed between clinicopathological features and the distribution of the reagents. ALND found 73 patients with single lymph node metastasis, and 73 'true SLN' were identified by blue dye in 65.7% (48/73), and by radioisotope in 95.9% (70/73) of the cases. Conclusion: These data suggest that radioisotopes are superior to blue dye in detecting SLN in breast cancer.

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Factors influencing the long-term survival in patients with esophageal cancer who underwent esophagectomy after chemoradiotherapy

Takeuchi Hiroya, Saikawa Yoshiro, Oyama Takashi, Ozawa Soji, Suda Koichi, Wada Norihito, Takahashi Tsunehiro, Nakamura Rieko, Shigematsu Naoyuki, Ando Nobutoshi, Kitajima Masaki, Kitagawa Yuko

World Journal of Surgery 34 ( 2 ) 277 - 284 2010.02

ISSN 0364-2313

Background: Salvage esophagectomy is potentially the only treatment available that can offer a chance of long-term survival when definitive chemoradiotherapy (CRT) fails to achieve local control for patients with esophageal squamous cell carcinoma (ESCC). However, salvage esophagectomy is a highly invasive procedure with various postoperative complications compared to planned esophagectomy after neoadjuvant chemoradiotherapy (CRT). We hypothesize that severe postoperative complications may affect not only surgical mortality but also tumor recurrence and long-term survival for patients with salvage esophagectomy after definitive CRT. Methods: For the present study we reviewed the surgical procedures, postoperative complications, and the prognosis of 65 consecutive patients with thoracic ESCC who underwent the esophagectomy after neoadjuvant (neoadjuvant group: n = 40) or definitive (salvage group: n = 25) CRT. Results: Most patients underwent right-transthoracic extended esophagectomy and reconstruction using gastric conduit by way of subcutaneous route with left cervical anastomosis. The incidence of postoperative pneumonia was found to be higher in the salvage group than in the neoadjuvant group. In both groups, the survival of patients with R0 resection was significantly better than those with R1/R2 resection. Moreover, in the salvage group, the postoperative survival rate of patients with pneumonia or bacteremia/sepsis was significantly lower than that for patients who did not suffer the same complications. In the neoadjuvant group, R0 resection was selected to be the only independent prognostic factor in univariate and multivariate analysis. In contrast, in the salvage group, R0 resection and bacteremia/sepsis remained significant and were independent of the other factors in multivariate analysis. Conclusions: This study reveals that postoperative morbidity affects not only the perioperative mortality but also the long-term survival of patients with ESCC who undergo salvage esophagectomy after definitive CRT.

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Evaluation of the dosimetric parameters for ¹²⁵ brachytherapy determined in prostate medium using CT images

Hanada Takashi, Yorozu Atsunori, Ohashi Toshio, Shigematsu Naoyuki, Maruyama Koichi

Journal of Radiation Research 51 ( 5 ) 553 - 561 2010

ISSN 0449-3060

In the present study, the prostate medium determined from the CT images of 149 patients was developed. The dosimetric parameters such as Λ, GL(r) and F(r, θ) used in TG-43U1-based calculation for an iodine-125 (¹²⁵I) brachytherapy-source were examined using Monte Carlo code Geant4. Clinical dosimetry parameters such as the D₉₀ were evaluated among a subgroup of 50 randomly selected patients who had been treated with permanent brachytherapy between January 2008 and December 2008 at the Tokyo Medical Center. The results show a slight difference in the dose rate constant Λ (within 1.0%). The radial dose function GL(r) exhibits a prominent difference in the region over 3 cm, and this difference is maintained within 2.9% in the region close to the source. The calculated values of F(r, θ) for the prostate medium were similar to values for water (within 1%), except in the longitudinal axis. A comparison of D₉₀ values shows a systematic dose overestimation of 2.8 ± 0.7 GY in water, where the distribution of the differences can be seen with a spread of 1.8 ± 0.3% compared to that in prostate medium. It was concluded that the introduction of any kind of tissue correction for the TG-43U1-based calculation was not necessary to allow for the differences in elemental compositions and densities between water and prostate medium. PACS number: 87.00.00; 87.55.dk; 87.55.K-; 87.56.B-.

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Chemotherapy for head and neck cancer

Tomita Toshiki, Imanishi Yorihisa, Ozawa Hiroyuki, Fujii Ryoichi, Shigetomi Seiji, Habu Noboru, Otsuka Kuninori, Ogawa Kaoru, Fukada Junichi, Shigematsu Naoyuki, Kogashiwa Yasunao, Yamauchi Kohichi, Kohno Naoyuki

Toukeibu Gan 36 ( 3 ) 273 - 277 2010

ISSN 1349-5747

A meta-analysis showed that chemoradiotherapy (CCRT) improved survival in patients with advanced head and neck squamous cell carcinoma (HNSCC). CCRT has become widely used in treating such patients. The purpose of CCRT in the treatment of resectable HNSCC is to improve survival while preserving organs and functions, and so CCRT is a potential alternative to surgery. However, problems regarding CCRT were revealed such as severe dysphasia and difficulty of salvage surgery. Recently, induction chemotherapy has attracted attention again, the purpose of which is to predict the response of subsequent CCRT or to improve outcomes. Moreover, chemotherapy is concurrently used with postoperative radiotherapy or definitively used for recurrent or metastatic HNSCC. In this article, we review the current state of chemotherapy for HNSCC and consider the problems in Japan.

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Early Graphical Appearance of Radiation Pneumonitis Correlates With the Severity of Radiation Pneumonitis After Stereotactic Body Radiotherapy (SBRT) in Patients With Lung Tumors

Takeda Atsuya, Ohashi Toshio, Kunieda Etsuo, Enomoto Tatsuji, Sanuki Naoko, Takeda Toshiaki, Shigematsu Naoyuki

International Journal of Radiation Oncology Biology Physics 77 ( 3 ) 685 - 690 2010

ISSN 0360-3016

Purpose: To investigate factors associated with Grade ≥3 radiation pneumonitis (RP) in patients with lung tumors treated with stereotactic body radiotherapy (SBRT). Methods and Materials: We retrospectively analyzed 128 patients with 133 lung tumors treated with SBRT. RP was graded according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate analyses were used to identify predictive factors for RP. Results: The median follow-up period after SBRT was 12 months (range, 5-45 months). Incidences of Grades 0, 1, 2, and 3 RP were 27%, 52%, 16%, and 5%, respectively. No patients suffered Grade 4 or 5 RP. For all patients with Grade 2 or 3, symptoms occurred either simultaneously with or subsequent to graphical appearances. The latent period was the only significant factor associated with Grade ≥3 RP (p < 0.01). A latent period of 1 or 2 months indicated a 40% (6/15) risk for Grade 3. However, the risk for Grade 3 was 1.2% (1/82) 3 months after SBRT. No pretreatment clinical or dosimetric factors were significantly associated with Grade ≥3 RP. However, 4 of 7 patients with Grade 3 RP had severe pulmonary comorbidities. Conclusion: Only the latency period was a significant factor in the development of RP. No pretreatment clinical or dosimetric factors were significantly associated with Grade ≥3 RP. Patients, especially those with severe pulmonary comorbidities, should be carefully observed for the graphical appearance of RP within a few months during the follow-up period after SBRT.

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Prediction of PSA bounce after permanent prostate brachytherapy for localized prostate cancer

Kanai Kunimitsu, Nakashima Jun, Sugawara Akitomo, Shigematsu Naoyuki, Nagata Hirohiko, Kikuchi Eiji, Miyajima Akira, Nakagawa Ken, Kubo Atsushi, Oya Mototsugu

International Journal of Clinical Oncology 14 ( 6 ) 502 - 506 2009.12

ISSN 1341-9625

Background: We aimed to calculate the frequency and features of the development of a prostate-specific antigen (PSA) bounce after prostate brachytherapy alone, to correlate the bounce with clinical and dosimetric factors and to identify factors that predict PSA bounce. Methods: PSA bounce was evaluated in 86 patients with T1-T2 prostate cancer who underwent radioactive seed implantation using iodine-125 (I-125) without hormonal therapy or external-beam radiation therapy (EBRT) from September 2004 to December 2007. A PSA bounce was defined as a rise of at least 0.4 ng/ml greater than a previous PSA level with a subsequent decline equal to, or less than, the initial nadir. Results: Calculated by the Kaplan-Meier method, the incidence of PSA bounce at a 2-year follow-up was 26%. Median time to the PSA bounce was 15 months. Univariate analysis demonstrated that age, dose received by 90% of the prostate gland (D90), volume of gland receiving 100% of the prescribed dose (V100), and V150 were significantly associated with the PSA bounce, while pretreatment PSA level, Gleason score, pretreatment prostate volume, clinical T stage, and V200 were not. In multivariate analysis, age 67 years or less and D90 more than 180 Gy were identified as independent factors for predicting the PSA bounce (P < 0.05). Conclusion: PSA bounce is not a rare phenomenon after prostate brachytherapy. It is more common in younger patients and patients receiving higher doses of radiation.

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Efficacy of mouth rinse in preventing oral mucositis in patients receiving high-dose cytarabine for allogeneic hematopoietic stem cell transplantation

Mori Takehiko, Hasegawa Kaori, Okabe Ai, Tsujimura Natsuki, Kawata Yusuke, Yashima Tomoko, Kobayashi Naoko, Kondo Sakiko, Aisa Yoshinobu, Kato Jun, Tsunoda Kazuyuki, Nagai Tetsuo, Nakagawa Taneaki, Shigematsu Naoyuki, Kubo Atsushi, Ikeda Yasuo, Okamoto Shinichiro

International Journal of Hematology 88 ( 5 ) 583 - 587 2009.12

ISSN 0925-5710

High-dose cytarabine is one of the major components of the conditioning regimen for hematopoietic stem cell transplantation (HSCT), and frequently causes severe oral mucositis. We have recently demonstrated that cytarabine is excreted into the saliva in patients receiving high-dose cytarabine, and proposed that it might locally and directly contribute to the development of oral mucositis. Therefore, this study was performed to assess whether removing the excreted cytarabine in the saliva by intensive mouth rinse during high-dose cytarabine infusion could reduce the incidence of oral mucositis. Fifteen patients with hematologic malignancies undergoing allogeneic HSCT who received total body irradiation (12 Gy) and high-dose cytarabine at a dose of 3 g/m ² every 12 h for 4 days as a conditioning were evaluated. Patients were instructed to rinse their mouths using ice-cold water every 10 min, starting simultaneously with the 2-h cytarabine infusion and continuing up to 1 h after completion of each infusion. Oral mucositis was graded on a daily basis according to the National Cancer Institute, Common Toxicity Criteria. Thirty-five patients who previously underwent the same conditioning without mouth rinse served as controls. The incidence of Grades 2-3 and Grade 3 oral mucositis was significantly reduced in patients who performed mouth rinse as compared with the controls (40 vs. 80%, P = 0.009; 0 vs. 25. 7%, P = 0.02). In conclusion, mouth rinse during and shortly after high-dose cytarabine infusion could be an effective and inexpensive measure in reducing the incidence of moderate to severe oral mucositis caused by high-dose cytarabine. This finding strongly suggests the role of cytarabine excretion in the saliva in the development of cytarabine-associated oral mucositis.

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Extrapulmonary Soft-Tissue Fibrosis Resulting From Hypofractionated Stereotactic Body Radiotherapy for Pulmonary Nodular Lesions

Kawase Takatsugu, Takeda Atsuya, Kunieda Etsuo, Kokubo Masaki, Kamikubo Yoshifumi, Ishibashi Ryouchi, Nagaoka Tomoaki, Shigematsu Naoyuki, Kubo Atsushi

International Journal of Radiation Oncology Biology Physics 74 ( 2 ) 349 - 354 2009.06

ISSN 0360-3016

Purpose: To clarify the incidence, symptoms, and timing of extrapulmonary fibrosis developing after hypofractionated stereotactic body radiotherapy. Patients and Methods: We analyzed 379 consecutive patients who underwent stereotactic body radiotherapy for lung tumors at four institutions between February 2001 and March 2007. The median follow-up time was 29 months (range, 1-72). We investigated the subjective and objective characteristics of the extrapulmonary masses, redelineated the origin tissue of each on the treatment planning computed tomography scan, and generated dose-volume histograms. Results: In 9 patients (2.4%), extrapulmonary masses were found 3-36 months (median, 14) after irradiation. Coexisting swelling occurred in 3 patients, chest pain in 2, thumb numbness in 1, and arm edema in 1 patient. Extrapulmonary masses occurred in 5 (5.4%) of 92 and 4 (1.4%) of 287 patients irradiated with a 62.5-Gy and 48.0-Gy isocenter dose, respectively. The mean and maximal dose to the origin tissue was 25.8-53.9 Gy (median, 43.7) and 47.5-62.5 Gy (median, 50.2), respectively. In 5 of 9 patients, the standardized uptake values on 18F-fluorodeoxyglucose-positron emission tomography was 1.8-2.8 (median, 2.2). Percutaneous needle biopsy was performed in 3 patients, and all the specimens showed benign fibrotic changes without malignant cells. Conclusion: All patients should be carefully followed after stereotactic body radiotherapy. The findings of any new lesion should prompt an assessment for radiation-induced extrapulmonary fibrosis before an immediate diagnosis of recurrence is made. Careful beam-shape modification and dose prescription near the thoracic outlet are required to prevent forearm neuropathy and lymphedema.

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Dose Distribution Analysis in Stereotactic Body Radiotherapy Using Dynamic Conformal Multiple Arc Therapy

Takeda Atsuya, Kunieda Etsuo, Sanuki Naoko, Ohashi Toshio, Oku Yohei, Sudo Yasunobu, Iwashita Hideo, Ooka Yoshikazu, Aoki Yosuke, Shigematsu Naoyuki, Kubo Atsushi

International Journal of Radiation Oncology Biology Physics 74 ( 2 ) 363 - 369 2009.06

ISSN 0360-3016

Purpose: We have used dynamic conformal multiple arc therapy (DCMAT) for stereotactic body radiotherapy (SBRT) since 2001. We investigated the consistency of DCMAT for SBRT using dose-volume histogram analysis. Methods and Materials: A total of 50 patients with peripheral lung tumors underwent SBRT. The median tumor diameter was 2.4 cm (range, 0.9-5.9). Treatment planning was performed using a superposition algorithm. The prescribed 50 Gy dose was divided into five fractions. The prescribed dose was defined as 80% of the maximal dose in the planning target volume (PTV), and the leaf margins were modified to ensure the PTV was included in the 80% isodose surface. The dose-volume histogram analysis was used to assess the PTV and normal lung volume. Results: The median dose covering 95% of the PTV was 50.27 Gy (range, 46.14-52.67), essentially consistent with the prescribed dose. The median homogeneity and conformity index was 1.41 (range, 1.31-1.53) and 1.73 (range, 1.41-2.21), respectively. The median volume of lung receiving ≥20 Gy (V₂₀) was 4.2% (range, 1.4-10.2%). A linear correlation was found between the tumor diameter and V₂₀, and an even stronger correlation was found between the PTV/(normal lung volume) and V₂₀. The estimated V₂₀ was 7.1% (range, 3.9-10.4%) for a 5-cm-diameter tumor, assumed to be the maximal size limitation for SBRT. Conclusion: SBRT with DCMAT achieved high conformity and delivered adequate doses within the PTV. The median dose covering 95% of the PTV was consistent with the prescribed dose. V₂₀ can be estimated using the tumor diameter and normal lung volume. DCMAT was thus both a feasible and a reproducible method of SBRT delivery.

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Intense accumulation of Tc-99m MDP in pericardial metastasis from breast cancer

Kawase Takatsugu, Fujii Hirofumi, Nakahara Tadaki, Shigematsu Naoyuki, Kubo Atsushi, Kosuda Shigeru

Clinical Nuclear Medicine 34 ( 3 ) 173 - 174 2009.03

ISSN 0363-9762

Extraosseous uptake often seen on Tc-99m methylene diphosphonate bone scintigraphy has clinical significance. In a routine follow-up study on a 54-year-old female patient with breast cancer, we encountered a rare finding of pericardial metastasis clearly demonstrated by Tc-99m methylene diphospho- nate bone scintigraphy. This incidental finding of increased uptake in the periphery of the cardiac contour on a bone scan reflects radionuclide accumulation in pericardium, myocardium, or pericardial effusion itself. In our case, an additional computed tomography examination of the chest was useful for making the definitive diagnosis of dystrophic calcification of the pericardium.

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Stereotactic Body Radiotherapy for Primary Lung Cancer at a Dose of 50 Gy Total in Five Fractions to the Periphery of the Planning Target Volume Calculated Using a Superposition Algorithm

Takeda Atsuya, Sanuki Naoko, Kunieda Etsuo, Ohashi Toshio, Oku Yohei, Takeda Toshiaki, Shigematsu Naoyuki, Kubo Atsushi

International Journal of Radiation Oncology Biology Physics 73 ( 2 ) 442 - 448 2009.02

ISSN 0360-3016

Purpose: To retrospectively analyze the clinical outcomes of stereotactic body radiotherapy (SBRT) for patients with Stages 1A and 1B non-small-cell lung cancer. Methods and Materials: We reviewed the records of patients with non-small-cell lung cancer treated with curative intent between Dec 2001 and May 2007. All patients had histopathologically or cytologically confirmed disease, increased levels of tumor markers, and/or positive findings on fluorodeoxyglucose positron emission tomography. Staging studies identified their disease as Stage 1A or 1B. Performance status was 2 or less according to World Health Organization guidelines in all cases. The prescribed dose of 50 Gy total in five fractions, calculated by using a superposition algorithm, was defined for the periphery of the planning target volume. Results: One hundred twenty-one patients underwent SBRT during the study period, and 63 were eligible for this analysis. Thirty-eight patients had Stage 1A (T1N0M0) and 25 had Stage 1B (T2N0M0). Forty-nine patients were not appropriate candidates for surgery because of chronic pulmonary disease. Median follow-up of these 49 patients was 31 months (range, 10-72 months). The 3-year local control, disease-free, and overall survival rates in patients with Stages 1A and 1B were 93% and 96% (p = 0.86), 76% and 77% (p = 0.83), and 90% and 63% (p = 0.09), respectively. No acute toxicity was observed. Grade 2 or higher radiation pneumonitis was experienced by 3 patients, and 1 of them had fatal bacterial pneumonia. Conclusions: The SBRT at 50 Gy total in five fractions to the periphery of the planning target volume calculated by using a superposition algorithm is feasible. High local control rates were achieved for both T2 and T1 tumors.

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Biodistribution of immunoliposome labeled with Tc-99m in tumor xenografted mice

Kitamura Naoto, Shigematsu Naoyuki, Nakahara Tadaki, Kanoh Momoe, Hashimoto Jun, Kunieda Etsuo, Kubo Atsushi

Annals of Nuclear Medicine 23 ( 2 ) 149 - 153 2009.02

ISSN 0914-7187

Objective: Immunoliposome (PEG, GAH, liposome; PGL), consisting of F(ab)₂ fragment of monoclonal antibody, GAH and polyethyleneglycol- coated (PEGylated) liposome was provided. Immunoliposome, PGL was labeled with technetium-99m (Tc-99m) by two methods: labeling F(ab)₂ fragment with Tc-99m; Tc-99m-PGL, and entrapping Tc-99m into liposome; PGL[Tc-99m]. The objective of this study was to compare the biodistribution of Tc-99m-PGL and PGL[Tc-99m] in human gastric cancer xenografted mice. Methods: Tc-99m-PGL, PGL[Tc-99m], and Tc-99m-entrapped liposome; Lipo[Tc-99m] were prepared. They were injected into human gastric cancer, MKN45, xenografted mice via the tail vein, and their biodistribution was studied. Results: No marked accumulation of either PGL[Tc-99m] or Lipo[Tc-99m] was observed in the stomach. The uptake of Tc-99m-PGL by the liver, spleen, and lung was higher than that by the tumor. On the other hand, the uptake of PGL[Tc-99m] by the lung and spleen was markedly lower as compared with that of Tc-99m-PGL; the accumulation of PGL[Tc-99m] was lower in the lung and higher in the spleen as compared with that of the tumor. Although the liver uptake of PGL[Tc-99m] was markedly decreased as compared with that of Tc-99m-PGL, it was higher than the uptake of the tumor. The Tc-99m-PGL was strongly taken up by the tumor, with a high level of incorporation also seen in the stomach. These findings suggest the need for further study of the labeling stability. Conclusions: PGL[Tc-99m] appears to show promise for high tumor uptake and retention. This is an important implication for the potential application of immunoliposomes entrapped with Re-186, instead of Tc-99m, in internal radiotherapy.

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Dose Distribution Analysis of Axillary Lymph Nodes for Three-Dimensional Conformal Radiotherapy With a Field-in-Field Technique for Breast Cancer

Ohashi Toshio, Takeda Atsuya, Shigematsu Naoyuki, Fukada Junichi, Sanuki Naoko, Amemiya Atsushi, Kubo Atsushi

International Journal of Radiation Oncology Biology Physics 73 ( 1 ) 80 - 87 2009.01

ISSN 0360-3016

Purpose: We previously reported that most of axillary regions could be irradiated by the modified tangential irradiation technique (MTIT). The purpose of this study was to determine whether the three-dimensional conformal radiotherapy (3D-CRT) with a field-in-field technique improves dosimetry for the breast and axillary nodes. Methods and Materials: Fifty patients with left-sided breast cancer were enrolled. With MTIT, we planned the radiation field to be wider in the cranial direction than the standard tangential fields to include the axillary regions. With 3D-CRT, a field-in-field technique was used to spare the heart and contralateral breast to the extent possible by applying the multileaf collimator manually. Dose-volume histograms were compared for the breast, axillary region, heart, lung, and other normal tissues. Results: There were no significant differences in the percent volume of the breast receiving >90% of the prescribed dose (V90) between MTIT and 3D-CRT. The mean V90 of the level I to III axillary regions were increased from 93.7%, 48.2%, and 41.3% with MTIT to 97.6%, 85.8%, and 82.8% with 3D-CRT. 3D-CRT significantly reduced the volume of the heart receiving >30 Gy (mean, 7.6 vs. 15.9 mL), the percent volume of the bilateral lung receiving >20 Gy (7.4% vs. 8.9%), and the volume of other normal tissues receiving >107% of the prescribed dose (0.1 vs. 2.9 mL). Conclusion: The use of 3D-CRT with a field-in-field technique improves axillary node coverage, while decreasing doses to the heart, lungs, and the other normal tissues, compared with MTIT.

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Prediction of seed migration after transperineal interstitial prostate brachytherapy with I-125 free seeds

Sugawara Akitomo, Nakashima Jun, Shigematsu Naoyuki, Kunieda Etsuo, Kubo Atsushi

Brachytherapy 8 ( 1 ) 52 - 56 2009.01

ISSN 1538-4721

Purpose: The present study was undertaken to determine the incidence and predictors of seed migration after transperineal interstitial prostate brachytherapy using I-125 free seeds. Methods and Materials: Between September 2004 and November 2007, 158 patients who underwent transperineal interstitial prostate brachytherapy as monotherapy for clinical T1/T2 carcinoma of the prostate gland were reviewed. Implants had been performed with standard techniques. All 158 patients underwent followup radiographs (orthogonal chest radiographs, a kidney-ureter-bladder radiograph, and a posteroanterior pelvic radiograph) to assess the presence of seed migration at 3 months after transperineal interstitial prostate brachytherapy. Patient characteristics and treatment status were recorded. Univariate and multivariate analyses were performed to identify predictors of seed migration. Results: Seed migration occurred in 35 of 158 patients (22.2%). Univariate analyses revealed that preoperative prostate volume estimated by transrectal ultrasound, the number of needles, the number of seeds implanted, and the presence or absence of pubic arch interference (PAI) were significantly associated with seed migration. These results indicated that larger prostate glands were more likely to have seed migration. However, the absolute difference in prostate size was not overly impressive (22.4 vs. 26.3 cm³). Multivariate analysis revealed that the number of seeds implanted and the presence or absence of PAI were significant predictors of seed migration. Conclusion: The number of seeds implanted and the presence or absence of PAI provide the most predictive information on seed migration.

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Development of a prototype semiconductor gamma-camera system

Ogawa Koichi, Ishikawa Takumi, Shuto Keisei, Kobayashi Hiroaki, Nakahara Tadaki, Shigematsu Naoyuki

3597 - 3601 2009

We made a prototype gamma camera system with CdZnTe semiconductor detectors that work at room temperature. The effective field of view of this detector is 195 x 156 mm² with a pixel size of 2.46 x 2.46 mm². We evaluated the performance of the detector in terms of the energy resolution, intrinsic spatial resolution, system spatial resolution and system sensitivity. The performance of the detector was evaluated with methods based on the NEMA standard (NU1). The results showed that the mean energy resolution was 5.55 % FWHM for ^99mTc, the intrinsic spatial resolution 2.46 mm FWHM, the system spatial resolutions 7.1 mm FWHM (without scatterer) and 7.4 mm FWHM (with scatterer), and the system sensitivity 46.3 cps/MBq. The performance of the system was also evaluated with some SPECT phantoms and the feasibility of the detector was confirmed with the SPECT images.

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Pattern of tumor recurrence in initially nonmetastatic breast cancer patients – distribution and frequency of metastases at unusual sites.

Sanuki-Fujimoto N, Takeda A, Amemiya A, Ofuchi T, Ono M, Yamagami R, Hatayama J, Kunieda E, Shigematsu N

Cancer 113 ( 4 ) 677-682 2008.08

Research paper (scientific journal), Joint Work, Accepted

Phase II study of chemoradiotherapy with S-1 and low-dose cisplatin for inoperable advanced gastric cancer

Saikawa Y, Kubota T, Kumagai K, Nakamura R, Kumai K, Shigematsu N, Kubo A, Kitajima M, Kitagawa Y

Int J Radiation Oncology Biol Phys 71 ( 1 ) 173-179 2008.04

Research paper (scientific journal), Joint Work, Accepted

Possible misinterpretation of demarcated solid patterns of radiation fibrosis on CT scans as tumor recurrence in patients receiving hypofractionated stereotactic radiotherapy for lung cancer.

Takeda A, Kunieda E, Takeda T, Tanaka M, Sanuki N, Fujii H, Shigematsu N, Kubo A

Int J Radiat Oncol Biol Phys 70 ( 4 ) 1057-1065 2008.03

Research paper (scientific journal), Joint Work, Accepted

前立腺癌：1日で終わる放射線治療

SHIGEMATSU NAOYUKI

第84回生涯教育研修セミナー 2008.02

Research paper (conference, symposium, etc.), Single Work

Dose-related fluorodeoxyglucose uptake in acute radiation-induced hepatitis.

Nakahara T, Takagi Y, Takemasa K, Mitsui Y, Tsuyuki A, Shigematsu N, Kubo A

Eur J Gastroenterol Hepatol 20 ( 10 ) 1040-1044 2008

Research paper (scientific journal), Joint Work, Accepted

Hypofractionated stereotactic radiotherapy with and without transarterial chemoembolization for small hepatocellular carcinoma not eligible for other ablation therapies: preliminary results for efficacy and toxicity

Takeda A, Takahashi M, Kunieda E, Takeda T, Sanuki N, Koike Y, Atsukawa K, Ohashi T, Saito H, Shigematsu N, Kubo A

Hepatol Res 38 ( 1 ) 60-69 2008

Research paper (scientific journal), Joint Work

Effects of single or repeated administration of methamphetamine on immune response in mice

Saito M, Terada M, Kawata T, Ito H, Shigemtsu N, Kromkhun P, Yokosuka M, Saito R

Exp Anim 57 ( 1 ) 35-43 2008

Research paper (scientific journal), Joint Work, Accepted

Anti-tumor effects of water-soluble propolis on a mouse sarcoma cell line in vivo and in vitro.

Inoue K, Saito M, Kanai T, Kawata T, Shigematsu N, Uno T, Isobe K, Liu CH, Ito H

Am J Chin Med 36 ( 3 ) 625-634 2008

Research paper (scientific journal), Joint Work, Accepted

Intrafractional gastric motion and interfractional stomach deformity during radiation therapy.

Watanabe M, Isobe K, Takisima H, Uno T, Ueno N, Kawakami H, Shigematsu N, Yamashita M, Ito H

Radiother Oncol 87 ( 3 ) 425-431 2008

Research paper (scientific journal), Joint Work, Accepted

Long-term follow-up of allogeneic hematopoietic stem cell transplantation for de novo acute myelogenous leukemia with a conditioning regimen of total body irradiation and granulocyte colony-stimulating factor-combined high-dose cytarabine.

Mori T, Aisa Y, Watanabe R, Yamazaki R, Kato J, Shimizu T, Shigematsu N, Kubo A, Yajima T, Hibi T, Ikeda Y, Okamoto S

Biol Blood Marrow Transplant 14 ( 6 ) 651-657 2008

Research paper (scientific journal), Joint Work, Accepted

Detection of perineal tumor invasion of the head and neck: clinical use of thallium-201 SPECT/CT image fusion

Nakahara T, Suzuki T, Kunieda E, Momoshima S, Shigematsu N, Kubo A

Clin Nucl Med 33 ( 8 ) 567-570 2008

Research paper (scientific journal), Joint Work, Accepted

Takeda A, Takahashi M, Kunieda E, Takeda T, Sanuki N, Koike Y, Atsukawa K, Ohashi T, Saito H, Shigematsu N, Kubo A

Hepatol Res 38 ( 1 ) 60-69 2008

Research paper (scientific journal), Joint Work, Accepted

Reduced efficacy of topical corticosteroid in preventing cytarabine-induced kerato-conjunctivitis in patients receiving high-dose cytarabine and total body irradiation for allogeneic hematopoietic stem cell transplantation

Mori T, Watanabe M, Kurotori-Sotome T, Ito C, Yamada K, Yashima T, Kobayashi N, Kondo S, Aisa Y, Kato J, Ogawa Y, Tsubota K, Shigematsu N, Kubo A, Ikeda Y, Okamoto S

Bone Marrow Transplant 42 ( 3 ) 197-199 2008

Research paper (scientific journal), Joint Work, Accepted

甲状腺疾患に対する放射線外照射

茂松直之

日本臨床 65 ( 11 ) 2053-2060 2007

Research paper (scientific journal), Joint Work

Repair of Potentially Lethal Damage in Normal Cells and Ataxia Teleangiectasia Cells; Consideration of Non-Homogenous End-Joining.

Kan’o M, Kawata T, Ito H, Shigematsu N, Liu C, Uno T, Isobe K, Kawakami H, Cucinotta F, George K and Kubo A

J Radiat Res 48 31-38 2007

Research paper (scientific journal), Joint Work, Accepted

早期前立腺癌に対するヨウ素125 密封小線源療法

SHIGEMATSU NAOYUKI

慶應医学 84 ( 1 ) 39455 2007

Research paper (scientific journal), Joint Work

Role of salivary gland scintigraphy with Tc-99m pertechnetate in determining treatment of solitary palotid gland tumors: A retrospective study

Nakahara T, Suzuki T, Hashimoto J, Shigematsu N, Tomota T, Ogawa K, Hubo A

Clin Nucl Med 32 ( 5 ) 363-366 2007

Research paper (scientific journal), Joint Work, Accepted

Death related to pleural and pericardial effusions following chemoradiotherapy in a patient with advanced cancers of the esophagus and stomach

Shigematsu N, Kitamura N, Saikawa Y, Ikeda E, Fukada J, Kunieda E, Kitagawa Y, Fukuda K, Okada Y, Kubo A

Keio J Med 56 ( 4 ) 124-129 2007

Research paper (scientific journal), Single Work, Accepted

Comparizon of intraoperative ultrasound with postimplant computed tomography - dosimetric values at day 1 and day 30 after prostate brachytherapy

Ohashi T, Yorozu A, Toya K, Saito S, Momma T, Nagata H, Kosugi M, Shigematsu N, Kubo A

Brachytherapy 6 246-253 2007

Research paper (scientific journal), Joint Work, Accepted

食道sm癌治療の合理的個別化に向けたsentinel node理論の応用

SHIGEMATSU NAOYUKI

消化器外科 43 ( 5 ) 383-388 2006

Research paper (scientific journal), Joint Work

Dose-volume factors predicting radiation pneumonitis in patients receiving salvage radiotherapy for postlobectomy locoregional recurrent non-small-cell lung cancer.

Uno T, Isobe K, Kawakami H, Ueno N, Kawata T, Yamamoto S, Sekine Y, Iyoda A, Iizasa T, Fujikawa T, Shigematsu N, Ito H

Int J Clin Oncol 11 55-59 2006

Research paper (scientific journal), Joint Work, Accepted

Tamoxifen for recurrent desmoid tumor of the chest wall.

Ohashi T, Shigematsu N, Kameyama K, Kubo A

Int J of Clin Oncol 11 150-152 2006

Research paper (scientific journal), Joint Work, Accepted

Value of CT Thallium-201 SPECT fusion imaging over SPECT alone for detection and localization of nasopharngeal and maxillary cancers.

Nakahara T, Shigematsu N, Fujii M, Kunieda E, Suzuki T, Tanaka C, Hashimoto J, Kubo A

AJR 187 825-829 2006

Research paper (scientific journal), Joint Work, Accepted

Rotational and translational reproducibility of newly developed Leksell frame-based relocatable fixiation system.

Kunieda E, Hossain DM, Kitamura M, Kawaguchi O, Shiba H, Takeda A, Kawase T, Seki S, Shigematsu N, Kubo A

Radiat Med 24 503-510 2006

Research paper (scientific journal), Joint Work, Accepted

Unique Treatment Policy for Well-differentiated Thyroid Cancer in Japan: Results of a Questionnaire Distributed to Members of the Japanese Society of Thyroid Surgery and the International Association of Endocrine Surgeons.

Shigematsu N, Takami H, Ito N, Kubo A

Endocrine J 53 829-839 2006

Research paper (scientific journal), Joint Work, Accepted

Radiation Therapy after Breast Conserving Surgery.

Shigematsu N, Takeda A, Fukada J, Sanuki N, Uno T, Kawaguchi O, Kunieda E, Kubo A

Radiat Med 24 388-404 2006

Research paper (scientific journal), Joint Work

胃癌に対するS-1を含めた化学療法と放射線療法の併用

SHIGEMATSU NAOYUKI

癌と化学療法 33 99-105 2006

Research paper (scientific journal), Joint Work

I-125 brachytherapyの治療成績・治療手技・導入経験前立腺密封小線源永久挿入治療初期経験

SHIGEMATSU NAOYUKI

泌尿器外科 19 ( 8 ) 933-935 2006

Research paper (scientific journal), Joint Work

I-125 brachytherapyの治療成績・治療手技・早期前立腺癌に対するI-125を用いた永久挿入密封小線源治療の経験

SHIGEMATSU NAOYUKI

泌尿器外科 19 ( 8 ) 1001-1003 2006

Research paper (scientific journal), Joint Work

日本および外国での高分化甲状腺癌に対する治療方針の相違　−日本甲状腺外科学会と国際内分泌外科学会会員に対するアンケート結果

SHIGEMATSU NAOYUKI

日本医師会雑誌 135 ( 6 ) 1333-1340 2006

Research paper (scientific journal), Joint Work, Accepted

治療計画装置を用いた乳癌術後照射法について（2）

SHIGEMATSU NAOYUKI

臨床放射線 51 ( 1 ) 196-200 2006

Research paper (scientific journal), Joint Work

治療計画装置を用いた乳癌術後照射法について（1）

SHIGEMATSU NAOYUKI

臨床放射線 50 ( 13 ) 1822-1823 2005

Research paper (scientific journal), Joint Work

Postoperative pelvic radiotherapy for cervical cancer patients with positive parametrial invasion.

Uno T, Ito H, Isobe K, Kaneyasu Y, Tanaka N, Mitsuhashi A, Suzuka H, Yamazawa K, Shigematsu N, Itami J

Gynecol Oncol 96 335-340 2005

Research paper (scientific journal), Joint Work, Accepted

Relation between chromosomal aberration and radiation dose during the process of TBI.

Kutsuki S, Ihara N, Shigematsu N, Okamoto S, Kubo A

Radiat Med 23 37-42 2005

Research paper (scientific journal), Joint Work, Accepted

Is chemoradiation effective or harmful for stage IV gastric cancer patients?

Saikawa Y, Kubota T, Takahashi T, Akatsu Y, Nakamura R, Yoshida M, Shigematsu N, Otani Y, Kumai K, Hibi T, Kitajima M

Oncol Rep 13 ( 5 ) 865-870 2005

Research paper (scientific journal), Joint Work, Accepted

Hyperfractionated radiation therapy for locoregionally advanced nasopharyngeal cancer.

Isobe K, Uno T, Kawakami H, Ueno N, Aruga T, Yasuda S, Hanazawa T, Okamoto Y, Ito H, Shigematsu N

Jap J Clin Oncol 35 ( 3 ) 116-120 2005

Research paper (scientific journal), Joint Work, Accepted

Differences in pulmonary function before vs. 1 year after hypofractionated stereotactic radiotherapy for small peripheral lung tumors

Ohashi T, Takeda A, Shigematsu N, Kunieda E, Ishizaka A, Fukada J, Deloar MH, Kawaguchi O, Takeda T, Takemasa K, Isobe K, Kubo A

Int J Radiation Oncology Biol Phys 62 ( 4 ) 1003-1008 2005

Research paper (scientific journal), Joint Work, Accepted

Successful pregnancy and normal delivery after whole craniospinal irradiation in two patients.

Shigematsu N, Shinmoto H, Ito N, Kunieda E, Takeda A, Ohashi T, Kawaguchi O, Kawata T, Ito H, Kuribayashi S, Kubo A

Anticancer Res 25 3481-3487 2005

Research paper (scientific journal), Joint Work, Accepted

Nationwide survey on the treatment policy for well-differentiated thyroid cancer: Results of a questionnaire distributed at the 37th meeting of the Japanese Society of Thyroid Surgery.

Shigematsu N, Takami H, Ito N, Kubo A

Endocrine J 52 479-491 2005

Research paper (scientific journal), Joint Work, Accepted

Small Lung Tumors: Long-Scan-Time CT for Planning of Hypofractionated Stereotactic Radiation Therapy ? Initial Findings.

Takeda A, Kunieda E, Shigematsu N, Hossain DM, Kawase T, Ohashi T, Fukada J, Kawaguchi O, Uematsu M, Takeda T, Takemasa K, Takahashi T, Kubo A

Radiology 237 295-300 2005

Research paper (scientific journal), Joint Work, Accepted

本邦における高分化甲状腺癌の治療方針の実態

SHIGEMATSU NAOYUKI

内分泌外科 22 ( 1 ) 29-39 2005

Research paper (scientific journal), Joint Work, Accepted

新しい放射線治療法の概要

SHIGEMATSU NAOYUKI

臨床外科 60 ( 6 ) 695-702 2005

Research paper (scientific journal), Joint Work

Ｘ線検査：Ｘ線エネルギーの生物作用

SHIGEMATSU NAOYUKI

周産期医学 34 ( 6 ) 823-827 2004

Research paper (scientific journal), Joint Work

Measurment of beam-axis displacement from the isocenter during three-dimensional conformal radiosurgery with a micro-multileaf collimator.

Kunieda E, Kawaguchi O, Saitoh H, Fujisaki T, Takeda A, Kawase T, Deloar HM, Shigematsu N, Kubo, A

Radiother Oncol 70 45-48 2004

Research paper (scientific journal), Joint Work, Accepted

Evaluation of novel modified tangential irradiation technique for breast cancer patients using dose-volume histograms.

Takeda A, Shigematsu N, Ikeda T, Kawaguchi O, Kutski S, Ishibashi R, Kunieda E, Takeda T, Takemasa K, Ito H, Uno T, Jinno H, Kubo A

Int J Radiation Oncology Biol Phys 58 ( 4 ) 1279-1287 2004

Research paper (scientific journal), Joint Work, Accepted

Radiation injury after hypofractionated stereotactic radiotherapy for periphefal small lung tumors: Serial changes on CT.

Takeda T, Takeda A, Kunieda E, Ishizaka A, Takemasa K, Shimada K, Yamamoto S, Shigematsu N, Kawaguchi O, Fukada J, Ohashi T, Kuribayashi S, Kubo A

AJR 182 1123-1128 2004

Research paper (scientific journal), Joint Work, Accepted

Treatment of breast carcinoma in patients with clinically negative axillary lymph nodes using radiotherapy versus axillary dissection.

Fujimoto N, Amemiya A, Kondo M, Takeda A, Shigematsu N

Cancer 101 ( 10 ) 2155-2163 2004

Research paper (scientific journal), Joint Work, Accepted

Adenoid cystic carcinoma with hyperostosis after stereotactic radiosurgery.

Kawaguchi O, Kunieda E, Fujii H, Shigematsu N, Kutsuki S, Ito H, Kubo A

Radiat Med 22 ( 3 ) 198-200 2004

Research paper (scientific journal), Joint Work, Accepted

放射線治療が著効したと考えられる頭蓋内Malignant Peripheral Nerve Sheath Tumorの1例

SHIGEMATSU NAOYUKI

静岡赤十字病院研究報 24 ( 1 ) 117-123 2004

Research paper (bulletin of university, research institution), Joint Work

原発性および転移性肺腫瘍に対する定位放射線治療

国枝悦夫、川瀬貴嗣、武田篤也、笠松智孝、川口修、沓木章二、茂松直之、久保敦司

臨床放射線 48 ( 5 ) 609-612 2003

Research paper (scientific journal), Joint Work

Consolidation radiotherapy following brief chemotherapy for localized diffuse large B-cell lymphoma: A prospective study.

Isobe K, Kawakami H, Tamaru J, Yasuda S, Uno T, Aruga T, Kawata T, Shigematsu N, Takano K, Takagi T, Mikata A Ito H

Leuk Lymph 44 ( 9 ) 1535-1539 2003

Research paper (scientific journal), Joint Work, Accepted

Histological complete response in a case of advanced gastric cancer treated by chemotherapy with S-1 plus low-dose cisplatin and radiation.

Takahashi T, Saikawa Y, Kubota T, Akiba Y, Shigematsu N, Yoshida M, Otani Y, Hibi T, Kitajima M

Jpn J Clin Oncol 33 ( 11 ) 584-588 2003

Research paper (scientific journal), Joint Work, Accepted

マイクロマルチリーフコリメータ（ＭＭＬＣ）によるラジオサージャリー

SHIGEMATSU NAOYUKI

定位的放射線治療 7 25-31 2003

Research paper (scientific journal), Joint Work, Accepted

肛囲にPaget現象を伴った肛門管癌の1例

SHIGEMATSU NAOYUKI

臨床皮膚科 57 ( 6 ) 506-508 2003

Research paper (scientific journal), Joint Work

Induction of chromatin damage and distribution of isochromatid breaks in human fibroblast cells exposed to heavy ions

Kawata Tetsuya, Ito Hisao, Motoori Ken, Ueda Takuya, Shigematsu Naoyuki, Furusawa Yoshiya, Durante Marco, George Kerry, Wu Honglu, Cucinotta Francis A

Journal of radiation research 43 s169-s173 2002.12

Research paper (scientific journal), Joint Work

Intra-arterial CT-Angiography for Cerebral Arteriovenous Malformation Initial Experiences for Treatment Planning of Radiosurgery

Kunieda Etsuo, Kawaguchi Osamu, Onozuka Satoshi, Momoshima Suketaka, Takeda Atsuya, Shigematsu Naoyuki, Hashimoto Subaru, Ohira Takayuki, Kubo Atsushi,

International journal of radiation oncology, biology and physics 54 ( 4 ) 120-132 2002.11

Research paper (scientific journal), Joint Work

油圧式アームを使った定位放射線治療用着脱式固定システムの開発とCTによる精度測定

Kitamura Masayuki, Kunieda Etsuo, Kawaguchi Osamu, Andou Yutaka, Shigematsu Naoyuki, Shiba Hideyuki, Kubo Atsushi

日本放射線腫瘍学会誌 14 ( 2 ) 107-112 2002.06

Research paper (scientific journal), Joint Work

Adjuvant pelvic irradiation in patients with pathologic T2b carcinoma of the uterine cervix

Uno T, Ito H, Itami J, Sato T, Minoura S, Yasuda S, Aruga T, Isobe K, Shigematsu N, Kubo A

International Journal of Gynecological Cancer 12 ( 2 ) 187-191 2002.03

Research paper (scientific journal), Joint Work

Adjuvant pelvic irradiation in patients with node-negative carcinoma of the uterine cervix

Uno T, Ito H, Yasuda S, Aruga T, Isobe K, Kawakami H, Mitsuhashi A, Tanaka N, Yamazawa K, Suzuka K, Sekiya S, Itami J, Shigematsu N, Kubo A

Anticancer Research 22 ( 2B ) 1213-1216 2002.03

Research paper (scientific journal), Joint Work

Death from hypovolemic shock caused by perforation of duodenal ulcer in a patient with angiosarcoma of the scalp

Nishikawa T, Hakuno M, Asano K, Shigematsu N, Shiomi T, Okada Y

The Keio Journal of Medicine 51 ( 1 ) 36-45 2002.03

Research paper (scientific journal), Joint Work

Adjuvant pelvic irradiation in patients with pathologic T2b carcinoma of the uterine cervix

Uno T, Ito H, Itami J, Sato T, Minoura S, Yasuda S, Aruga T, Isobe K, Shigematsu N, Kubo A

International journal of gynecological cancer 12 ( 2 ) 187-191 2002.03

Research paper (scientific journal), Joint Work

A case of intramedulalry spinal cord tumor producing chronic gonadotropin

Sasaki Takahiro, Amano Takahiro, Takao Masaki, Shibata Mamoru, Shigemitsu Naoyuki, Fukuuchi Yasuo

Journal of Neuro-Oncology 56 ( 3 ) 247-250 2002.02

Research paper (scientific journal), Joint Work

Breast-conserving therapy for ductal carcinoma in situ

Takeda A, Shigematsu N, Kondo M, Amemiya A, Kawaguchi O, Kutsuki S, Ishibashi R, Kawata T, Masago K, Fukada J, Kubo A

Oncology Reports 8 ( 4 ) 835-839 2001.08

Research paper (scientific journal), Joint Work

Clinical role of Tc-99m-MIBI scintigraphy in non-Hodgkin's lymphoma

Ohta M, Isobe K, Kuyama J, Uchida Y, Nakao K, Goto S, Uno T, Yasuda S, Shigematsu N, Kawata A, Kitahara H, Ito H

Oncology Reports 8 ( 4 ) 841-845 2001.07

Research paper (scientific journal), Joint Work

Cell killing and mutation induced by heavy ion beams

Shigematsu Naoyuki, Ihara Noriko, Kawata Tetsuya, Kawaguchi Osamu, Takeda Atsuya, Kutsuki Shoji, Kubo Atsushi, Kanai Tatsuaki, Furusawa Yoshiya, Uno Takashi, Ito Hisao

International Journal of Molecular Medicine 7 ( 5 ) 509-513 2001.05

Research paper (scientific journal), Joint Work

Effect of combined treatment with radiation and low dose etoposide on cell survival

Shigematsu Naoyuki, Kawata Tetsuya, Ihara Noriko, Kawaguchi Osamu, Kutsuki Shoji, Ishibashi Ryochi, Kubo Atsushi, Ito Hisao

Anticancer Research 21 ( 1A ) 325-328 2001.01

Research paper (scientific journal), Joint Work

前立腺癌治療の最近の動向―ヨード125組織内照射

Shigematsu Naoyuki，Kubo Atsushi

Radioisotopes 50 ( 9 ) 429-432 2001

Research paper (scientific journal), Joint Work

Effect of combined treatment with radiation and low dose etoposide on cell survival

Shigematsu Naoyuki, Kawata Tetsuya, Kawaguchi Osamu, Kutsuki Shoji, Ishibashi Ryochi, Kubo Atsushi, Ito Hisao

Anticancer Research 21 ( 1A ) 325-328 2001

Research paper (scientific journal), Joint Work

悪性腫瘍放射線療法の晩期合併症

Uno Takashi，Isobe Kouichi，Shigematsu Naoyuki，Itou Hisao

産婦人科の実際 49 ( 11 ) 1647-1654 2000.10

Research paper (scientific journal), Joint Work

子宮頚部腺癌の放射線療法

Itou Hisao，Uno Takashi，Isobe Kouichi，Shigematsu Naoyuki

産科と婦人科 67 ( 9 ) 1175-1180 2000.09

Research paper (scientific journal), Joint Work

Low-dose induction radiotherapy for stomach conservation in patients with massive gastric lymphoma

Sato Michinao, Uematsu Minoru, Hama Y, Kondo Makoto, Kutsuki Shoji, Shigematsu Naoyuki, Ando Yutaka, Kusano S, Kubo A

Tumori 86 ( 4 ) 286-288 2000.07

Research paper (scientific journal), Joint Work

MRIで実測した定位放射線照射の3次元線量分布のDVH解析

Kawase Takatsugu，Kunieda Etsuo，Kawaguchi Osamu，Shigematsu Naoyuki，Kubo Atsushi

定位放射線治療 4 ( 1 ) 143-147 2000.07

Research paper (scientific journal), Joint Work

Postoperative radiation for stage IB-IIB carcinoma of the cervix with poor prognostic factors

Uno Takashi, Ito Hisao, Itami Jun, Yasuda S, Isobe Koichi, Hara R, Sato T, Shigematsu Naoyuki, Kubo Atsushi

Anticancer Research 20 ( 3B ) 2235-2239 2000.05

Research paper (scientific journal), Joint Work

癌の治療戦略─現状と展望─癌の放射線治療

Itou Hisao，Uno Takashi，Isobe Kouichi，Shigematsu Naoyuki

外科治療 82 ( 増刊 ) 672-678 2000.05

Research paper (scientific journal), Joint Work

放射線療法の最近の進歩

Itou Hisao，Uno Takashi，Isobe Kouichi，Shigematsu Naoyuki

産婦人科の実際 49 ( 4 ) 509-515 2000.04

Research paper (scientific journal), Joint Work

Indications of stereotactic irradiation for brain lesions

Shigematsu Naoyuki, Kunieda Etsuo, Kawaguchi Osamu, Takeda Atsuya, Ihara Noriko, Yamashita Shoji, Kubo Atsushi, Ito Hisao

Acta Oncologica 39 ( 5 ) 597-603 2000

Research paper (scientific journal), Joint Work

子宮頚癌の放射線療法─他施設間での比較─

Itou Hisao，Yoshida Hiroshi，Kikuchi Yuuzou，Hareyama Masato，Kaneyasu Yuuko，Shigematsu Naoyuki，Nakano Takashi，Katou Eriko，Chatani Masashi，Takekawa Yoshihiro，Toita Takafumi

日本放射線腫瘍学会誌 12 379-382 2000

Research paper (scientific journal), Joint Work

1日多分割照射法の有効性に関する臨床試験

Kikuchi Yuuzou，Kita Midori，Hamashima Nobuyuki，Hareyama Masato，Nemoto Kenji，Sakai Kunio，Itou Hisao，Hanno Kazuo，Sugawara Tadashi，Ikeda Hiroshi，Karasawa Kumiko，Shigematsu Naoyuki，Sasaki Takehito，Oguchi Masahiko，Itou Yoshiyuki，Nishijima Hiroshi，Nishimura Yasumasa，Hirokawa Hiroshi，Terashima Hiromi，Yoshida Hiroshi，Tamaki Yoshio

日本放射線腫瘍学会誌 12 389-393 2000

Research paper (scientific journal), Joint Work

リンパ節原発低悪性度早期非ホジキンリンパ腫の放射線療法

Kutsuki Shouji，Uematsu Minoru，Kondou Makoto，Shigematsu Naoyuki，Kawaguchi Osamu，Kawase Takatsugu，Sugawara Akitomo，Itou Hisao，Kubo Atsushi

日本放射線腫瘍学会誌 12 131-136 2000

Research paper (scientific journal), Joint Work

放射線抵抗腫瘍についての臨床的総論

伊東久夫、宇野隆、磯部公一、茂松直之

癌の臨床 46 ( 3 ) 215-218 2000

Research paper (scientific journal), Joint Work

Radiotherapy for large hepatocellular carcinoma combined with transcatheter arterial embolization and percutaneous ethanol injection therapy.

Yasuda Shigeo, Ito Hisao, Yoshikawa M, Shinozaki M, Goto N, Fujimoto H, Nasu K, Uno Takashi, Itami J, Isobe Kouichi, Shigematsu Naoyuki, Ebara M, Saito H

International Journal of Oncology 15 ( 3 ) 467-473 1999.09

Research paper (scientific journal), Joint Work

上咽頭癌における新TNM分類の検討

Tokumaru Yutaka, Fujii Masato, Oono Yoshihiro, Imanishi Yorihisa, Kanke Minoru, Tomita Toshiki, Shigematsu Naoyuki, Kubo Atsushi, Kanzaki Hitoshi, Inuyama Masao

頭頚部腫瘍学会誌 25 ( 3 ) 426-432 1999.07

Research paper (scientific journal), Joint Work

原発不明頚部リンパ節転移癌の放射線療法

Hara Ryuusuke, Itou Hisao, Yasuda Shigeo, Machida Namio, Isobe Kouichi, Uno Takashi, Hatano Kazuo, Shigematsu Naoyuki, Kubo Atsushi

日本放射線腫瘍学会誌 11 ( 2 ) 109-115 1999.06

Research paper (scientific journal), Joint Work

Late retinal complications of radiation therapy for nasal and paranasal malignancies: relationship between irradiated-dose area and severity

Takeda Atsuya, Shigematsu Naoyuki, Suzuki Saburosuke, Fujii Masato, Kawata Tetsuya, Kawaguchi Osamu, Uno Takashi, Takano Hideyuki, Kubo Atsushi, Ito Hisao

International Journal of Radiation Oncology, Biology, Physics 44 ( 3 ) 599-605 1999.06

Research paper (scientific journal), Joint Work

Late retinal complications of radiation therapy for nasal and paranasal malignancies: Relationship between irradiated-dose area and severity

Takeda Atsuya, Shigematsu Naoyuki, Suzuki S, Fujii M, Kawata Tetsuya, Kawaguchi Osamu, Uno Takashi, Takano Hideyuki, Kubo Atsushi, Ito Hisao

International Journal of Radiation Oncology Biology Physics 44 ( 3 ) 599-605 1999.06

Research paper (scientific journal), Joint Work

The modified tangenital irradiation technique for breast cancer: How to cover the entire axillary region

Takeda Atsuya, Shigematsu Naoyuki, Kondo Makoto, Amemiya Atsushi, Kawaguchi Osamu, Sato Michinao, Kutsuki Shoji, Toya Kazuhito, Ishibashi Ryochi, Kawase Takatsugu, Tsukamoto Nobuhiro, Kubo Atsushi

International Journal of Radiation Oncology Biology Physics 46 ( 4 ) 815-822 1999

Research paper (scientific journal), Joint Work

3次元静的多門照射による定位的分割照射─空間的及び時間的線量分布の検討

Kunieda Etsuo, Shigematsu Naoyuki, Kawaguchi Osamu, Kitamura Masayuki, Kawase Takatsugu, Kubo Atsushi

定位放射線治療 3 ( 1 ) 97-102 1999

Research paper (scientific journal), Joint Work

上咽頭癌の放射線治療1　―外照射―

Takeda Atsuya, Shigematsu Naoyuki, Fujii Masato

JOHNS 14 ( 11 ) 1565-1568 1998.11

Research paper (scientific journal), Joint Work

Stereotactic irradiationのスケジュール―Repairとcell proliferationの因子を加味した検討

Shigematsu Naoyuki, Kunieda Etsuo, Kawata Tetsuya, Kitamura Masayuki, Kubo Atsushi, Dokiya Takushi, Itou Hisao

日本医学放射線学会雑誌 58 ( 9 ) 516-520 1998.08

Research paper (scientific journal), Joint Work

上咽頭癌の新病期分類に関する検討

Oono Yoshihiro, Fujii Masato, Tokumaru Yutaka, Imanishi Yorihisa, Kanke Minoru, Kanzaki Jin, Shigematsu Naoyuki, Nakayama Toshii

頭頸部腫瘍 24 61-66 1998.05

Research paper (scientific journal), Joint Work

Stereotactic irradiationにおける放射線生物学的考察

Shigematsu Naoyuki, Kunieda Etsuo, Kawata Tetsuya, Kitamura Masayuki, Kubo Atsushi, Dokiya Takushi, Itou Hisao

日本医学放射線学会雑誌 58 ( 6 ) 281-286 1998.05

Research paper (scientific journal), Joint Work

Mutation of human cancer cell-line caused by heavy-ions and X-rays

Kawata Tetsuya, Shigematsu Naoyuki, Ito Hisao, Yamashita Shoji, Toya Kazuhito, Kubo Atsushi, Kanai Tatsuaki

Riken Accel Prog Rep 30 134-134 1998.03

Research paper (scientific journal), Joint Work

Cell death and mutation induction on cultured cells by irradiation of heavy ions and X-rays

Kawada Tetsuya, Shigematsu Naoyuki, Ito Hisao, Yamashita Shouji, Takeda Atsuya, Toya Kazuhito, Ishibashi Ryouchi, Kubo Atsushi, Kanai Tatsuaki, Furusawa Yoshiya, Yatagai Fumio

Riken Accelerator Progress Report 31 149-149 1998.03

Research paper (scientific journal), Joint Work

Advanced nasoparyngeal carcinoma treated with chemotherapy : Distant metastasis and local recurrence

Isobe Kouichi, Ito Hisao, Naoyuki Shigematsu, Kawata Tetsuya, Yasuda Shigeo, Ryuusuke Hara, Machida Namio, Takano Hideyuki, Uchida Yoshitaka, Uno Takashi, Kitahara Hiroshi, Kubo Atsushi

Int J Oncol 12 1183-1187 1998.02

Research paper (scientific journal), Joint Work

汎用医用ライナックは高精度定位的照射に使用可能か?─ガントリーと治療台の回転精度の検討

Kunieda Etsuo, Kitamura Masayuki, Kawaguchi Osamu, Oohira Takayuki, Shigematsu Naoyuki, Tounai Takenori, Andou Yutaka, Kubo Atsushi, Kawase Takeshi

日医放射会誌 58 ( 3 ) 86-90 1998.02

Research paper (scientific journal), Joint Work

放射線治療施設の基準化に関する提案

阿部光幸、永田靖、平岡真寛、井上俊彦、角美奈子、池田恢、茂松直之、土器屋卓志、晴山雅人、山下孝、広川裕

日本放射線腫瘍学会誌 10 249-257 1998

Research paper (scientific journal), Joint Work, Accepted

Advanced nasopharyngeal carcinoma treated with chemotherapy and radiotherapy: Distant metastasis and local recurrence

Isobe K, Ito Hisao, Shigematsu Naoyuki, Kawada Tetsuya, Yasuda S, Hara R, Machida N, Takano H, Uchida Y, Uno T, Kitahara H, Kubo Atsushi

International Journal of Oncology 12 ( 5 ) 1183-1187 1998

Research paper (scientific journal), Joint Work

不整型腫瘤に対する定位的放射線治療の方法

Kawaguchi Osamu, Kunieda Etsuo, Kitamura Masayuki, Shigematsu Naoyuki, Kubo Atsushi

定位的放射線治療 2 115-118 1998

Research paper (scientific journal), Joint Work

Apoptosis induction and cell-cycle change of human cancer cell-line caused by heavy-ion and x-rays

Shigematsu N, Yamashita S, Ihara N, Kawata T, Kutsuki S, Toya K, Kubo A, Ito H, Kanai T, Furusawa Y Yatagai F

Riken Accel Prog Rep 32 152 1998

Research paper (scientific journal), Joint Work, Accepted

膀胱癌に対する化学療法併用多分割放射線治療の経験

Ishibashi Ryouchi, Shigematsu Naoyuki, Kawata Tetsuya, Itou Hisao, Nakayama Toshitake, Andou Yutaka, Kubo Atsushi, Tachibana Masaaki

日放線腫瘍会誌 9 125-130 1997.09

Research paper (scientific journal), Joint Work

Radiotherapy for centrally recurrent cervical cancer of the vaginal stump following hysterectomy

Ito Hisao, Shigematsu Naoyuki, Kawata Tetsuya, Kubo Atsushi

Gnecol Oncol 67 154-161 1997.05

Research paper (scientific journal), Joint Work

子宮頚癌術後照射の意義

Shigematsu Naoyuki, Ito Hisao, Nishiguchi Iku, Kawada Tetsuya, Kutsuki Shouji, Nakayama Toshitake, Kumagai Hideo, Uematsu Minoru, Kubo Atsushi

日癌治療会誌 32 ( 2 ) 141-146 1997.03

Research paper (scientific journal), Joint Work

上咽頭癌の放射線治療成績と進行病期分類

Oki Yousuke, Ito Hisao, Shogematsu Naoyuki, Kawada Tetsuya, Takeda Atsuya, Suzuki Takayuki, Uematsu Minoru, Kubo Atsushi, Fujii Masato, Kanzaki Hitoshi

日本癌治療学会誌 32 ( 2 ) 193-198 1997.03

Research paper (scientific journal), Joint Work

乳癌と肺癌由来の転移に対する放射線治療法の考察--骨転移と脳転移について--

Shigematsu Naoyuki, Ito Hisao, Kutsuki Shouji, Kawada Tetsuya, Toya Kazuhito, Kubo Atsushi

日癌治療会誌 32 ( 2 ) 133-140 1997.03

Research paper (scientific journal), Joint Work

子宮頚癌症例に対する術後照射の予後因子

Shigematsu Naoyuki, Ito Hisao, Nishiguchi Iku, Kawada Tetsuya, Kutsuki Shouji, Nakayama Toshitake, Kumagai Hideo, Uematsu Minoru, Kubo Atsushi

日医放線会誌 57 ( 1 ) 28-33 1997.01

Research paper (scientific journal), Joint Work

X線および重粒子線照射による培養細胞における遺伝子突然変異発生頻度の定量

Toya Kazuhito, Shigematsu Naoyuki, Ito Hisao, Yamashita Shouji, Kubo Atsushi, Kanai Tatsuaki

日医放線会誌 56 ( 11 ) 736-740 1996.09

Research paper (scientific journal), Joint Work

多分割照射法の落とし穴--回復時間の影響に関する理論的考察--

Shigematsu Naoyuki, Itou Hisao, Kubo Atsushi, Dokiya Takushi

日医放線会誌 56 ( 8 ) 61-66 1996.07

Research paper (scientific journal), Joint Work

炭素粒子線のヒト培養細胞に対する細胞致死効果

Ko Weijei, Ito Hisao, Shigematsu Naoyuki, Yamashita Shouji, Kubo Atsushi, Kanai Tatsuaki

日医放線会誌 56 ( 8 ) 669-673 1996.07

Research paper (scientific journal), Joint Work

線量率効果の臨床応用に関する理論的考察--pulsed brachytherapy の検討--

Shigematsu Naoyuki, Ito Hisao, Kubo Atsushi, Dokiya Takushi

日医放線会誌 56 ( 8 ) 57-60 1996.07

Research paper (scientific journal), Joint Work

下咽頭癌の放射線治療成績--放射線療法と術後照射

Suzuki Takayuki, Ito Hisao, Shigematsu Naoyuki, Kawada Tetsuya, Uematsu Minoru, Kubo Atsushi, Fujii Masato, Kanzaki Hitoshi

日癌治療会誌 31 ( 6 ) 395-400 1996.06

Research paper (scientific journal), Joint Work

骨転移に対する放射線的緩和療法

Shigematsu Naoyuki, Ito Hisao, Kubo Atsushi

緩和医療研究会誌 5 ( 1 ) 25-30 1996.06

Research paper (scientific journal), Joint Work

転移性脳腫瘍の放射線治療成績と予後因子

Kutsuki Shouji, Ito Hisao, Shigematsu Naoyuki, Toya Kazuhito, Ko Weijei, Tsukamoto Nobuhiro, Kumagai Hideo, Uematsu Minoru, Kubo Atsushi

日医放線会誌 56 ( 6 ) 426-431 1996.05

Research paper (scientific journal), Joint Work

生物学的側面；LQ model からみた至適線量

茂松直之、川田哲也、土器屋卓志

臨床放射線 41 ( 13 ) 1581-1585 1996

Research paper (scientific journal), Joint Work

Ｘ線および重粒子線照射による培養細胞における遺伝子突然変異発生頻度の定量

戸矢和仁、茂松直之、伊東久夫、山下昌次、久保敦司、金井達明

日本医学放射線学会雑誌 56 ( 11 ) 736-740 1996

Research paper (scientific journal), Joint Work, Accepted

上咽頭癌の放射線治療における予後因子

茂松直之、伊東久夫、沖陽輔、川田哲也、鈴木天之、武田篤也、植松稔、久保敦司、藤井正人、神崎仁

日本医学放射線学会雑誌 56 ( 14 ) 1050-1055 1996

Research paper (scientific journal), Single Work, Accepted

放射線治療後に発生する変異遺伝子の定量による二次発がん予測法の開発

戸矢和仁、茂松直之、伊東久夫

INNERVISION 11 ( 8 ) 64 1996

Research paper (scientific journal), Joint Work

重粒子線照射との対比からみたX線治療難治性がんの解析とX線治療効果改善の検討

Ito Hisao

Innervision 10 ( 9 ) 59 1995.08

Research paper (scientific journal), Joint Work

放射線照射との対比からみたＸ線治療難治性がんの解析とＸ線治療効果改善の検討

伊東久夫、茂松直之、沓木章二

INNERVISION 10 ( 9 ) 59 1995

Research paper (scientific journal), Joint Work

Thiol and disulfide metabolites of the radiation protector and potential chemopriventive WR-2721

Grdina DJ, Shigematsu N, Dale P, Newton GL, Aguelera JA, Fahey RC

Carcinogenesis 16 ( 4 ) 677-681 1995

Research paper (scientific journal), Joint Work

線量率効果の理論的考察と臨床応用；高線量率と低線量率の比較

Shigematsu Naoyuki

臨床放射線 40 ( 6 ) 651-656 1995

Research paper (scientific journal), Joint Work

有痛性骨転移に対する放射線治療の鎮痛効果

Shigematsu Naoyuki

日本医学放射線学会誌 55 ( 9 ) 677-681 1995

Research paper (scientific journal), Joint Work

放射線治療による転移性脳腫瘍症状の改善と関連因子

Kutsuki Shouji

癌の臨床 41 ( 8 ) 876-882 1995

Research paper (scientific journal), Joint Work

食道癌の腔内照射における線量率効果

土器屋卓志、萬篤憲、荻田幹夫、茂松直之

癌の臨床 41 ( 14 ) 1749-1753 1995

Research paper (scientific journal), Joint Work

乳癌根治手術後再発症例の予後因子：治療から再発までの期間とリンパ節転移

柯偉傑、伊東久夫、植松　稔、沓木章二、茂松直之、西口郁、安藤裕、久保敦司、榎本耕治、池田正、北島政樹

日本癌治療学会誌 29 ( 3 ) 613-624 1994

Research paper (scientific journal), Joint Work, Accepted

Protection against radiation-induced mutagenesis at the hprt locus by spermine and N,N"-(dithiodi-2, 1-ethanediyl)bis-1,3-propanediamine (WR33278)

Shigematsu N, Schuwartz JL, Grdina DJ

Mutagenesis 9 355-360 1994

Research paper (scientific journal), Joint Work, Accepted

Radiotherapy for cervical cancer with high-dose rate brachytherapy: correlation between tumor size, dose and failure

Ito H, Kutsuki S, Nishiguchi I, Shigematsu N, Kuribayashi T, Uematsu M, Nakayama T, Wei-Jei Ka, Takemasa K, Ando Y, Kubo A,

Radiother Oncol 31 240-247 1994

Research paper (scientific journal), Joint Work, Accepted

Mutation caused by heavy ion particles and x-rays

Shigematsu N, Ito H, Yamashita S, Toya K, Kubo A, Yatagi F, Kanai T

Riken Accel Prog Rep 28 117 1994

Research paper (scientific journal), Joint Work, Accepted

RBEs of human monolayer cells

Ito H, Yamashita S, Ka w-J, Shigematsu N, Yatagai F, Kanai T

Riken Accel Prog Rep 27 105 1993

Research paper (scientific journal), Joint Work, Accepted

放射線照射を行った腫瘍よりの遠隔転移に関する検討

伊東久夫、茂松直之、西口郁、栗林徹、戸矢和仁、橋本省三

日本医学放射線学会雑誌 52 ( 6 ) 830-837 1992

Research paper (scientific journal), Joint Work, Accepted

ＯＫ－４３２と腫瘍切除による放射線治療後再増殖腫瘍からの転移抑制に関する実験的検討

伊東久夫、西口郁、茂松直之、栗林徹、橋本省三

日本癌治療学会誌 26 ( 11 ) 2420-2426 1991

Research paper (scientific journal), Joint Work, Accepted

High dose rate intracavitary brachytherapy for recurrent cervical cancer of the vaginal stump following hysterectomy

Ito H, Kumagaya H, Shigematsu N, Nishiguchi I, Nakayama T, Hashimoto S

Int J Radiat Oncol Biol Phys 20 927-932 1991

Research paper (scientific journal), Joint Work, Accepted

７施設における頸胸境界部食道癌の放射線治療成績

茶谷正史、又吉嘉伸、真崎規江、西尾正道、荻野尚、唐沢克之、渋谷均、茂松直之、大竹英二

日本放射線腫瘍学会誌 3 41-47 1991

Research paper (scientific journal), Joint Work, Accepted

肺癌の放射線治療

茂松直之、橋本省三

カレントテラピー 8 ( 4 ) 28-33 1990

Research paper (scientific journal), Joint Work

腫瘍の局所照射が自然肺転移におよぼす影響と免疫賦活剤によるその修飾

茂松直之

日本医学放射線学会雑誌 50 ( 9 ) 1139-1146 1990

Research paper (scientific journal), Joint Work, Accepted

ワルダイエル輪の非ホジキンリンパ腫：22年間の治療成績とＣＨＯＰの意義

平松秀子、近藤誠、植松稔、茂松直之、安藤裕、橋本省三

日本癌治療学会誌 25 ( 10 ) 2477-2483 1990

Research paper (scientific journal), Joint Work, Accepted

放射線治療を行ったマウス腫瘍よりの肺転移とOK-432.

伊東久夫、山田佐代子、西口郁、茂松直之、中山俊威、栗林徹、橋本省三>

癌の臨床 36 ( 9 ) 993-997 1990

Research paper (scientific journal), Joint Work

症例検討

茂松直之

臨床放射線 34 ( 6 ) 721-722 1989

Research paper (scientific journal), Single Work

Measurement of lung density by computed tomography: implication for radiotherapy

Kohda E, Shigematsu N

Keio J Med 38 ( 4 ) 454-463 1989

Research paper (scientific journal), Joint Work, Accepted

ホジキン病の治療成績：プロトコール確立と遂行の重要性

平松秀子、近藤誠、植松稔、茂松直之、安藤裕、橋本省三

日本癌治療線学会誌 24 ( 5 ) 1045-1052 1989

Research paper (scientific journal), Joint Work, Accepted

「医療法施行規則」等の改正について

茂松直之

臨床放射線 34 ( 3 ) 353-354 1989

Research paper (scientific journal), Single Work

直流通電療法（ＤＣ療法）の腫瘍増殖抑制効果

伊東久夫、茂松直之、中山俊威、西口郁、安藤裕、橋本省三

日本癌治療学会誌 23 ( 3 ) 696-702 1988

Research paper (scientific journal), Joint Work, Accepted

Prognostic factors of stage I and II non-Hodgkin's lymphomas of the head and neck: the value of the working formulation and need for chemotherapy

Shigematsu N, Kondo M, Kubo A, Mikata A

Int J Radiat Oncol Biol Phys 15 1111-1118 1988

Research paper (scientific journal), Joint Work, Accepted

マウス移植腫瘍に対する直流通電療法の化学療法剤増強効果

伊東久夫、中山俊威、茂松直之、西口郁、橋本省三

癌と化学療法 14 ( 6 ) 1854-1859 1987

Research paper (scientific journal), Joint Work

実験腫瘍（Ca-755）における放射線照射と5-FU系薬剤の併用療法について

宮本宏、土器屋卓志、冨永紳一、国枝悦夫、茂松直之、橋本省三

癌と化学療法 13 ( 3 ) 570-577 1986

Research paper (scientific journal), Joint Work

Value of gallium scans and lymph-angiography in non-Hodgkin's lymphoma of the Waldeyer's ring

Shigematsu N, Kondo M, Kubo A, Hashimoto S

Cancer 58 ( 12 ) 2622-2624 1986

Research paper (scientific journal), Joint Work, Accepted

Treatment of non-Hodgkin's lymphomas in the nasal cavities and paranasal sinus: a failure analysis

Kondo M, Mikata A, Inuyama Y, Uematsu M, Shigematsu N, Nishiguchi I, Hashimoto S

Acta Radiol Oncol 25 91-97 1986

Research paper (scientific journal), Joint Work, Accepted

核医学診断,67Gaシンチグラフィ

久保敦司、中山俊威、茂松直之

臨床放射線 30 ( 11 ) 1301-1309 1985

Research paper (scientific journal), Joint Work

Prognostic factors influencing relapse of squamous cell carcinoma of the makillary sinus

Kondo M. Ogawa K, Inuyama Y, Yamashita S, Tominaga S, Shigematsu N, Nishiguchi I, Hashimoto S

Cancer 55 190-196 1985

Research paper (scientific journal), Joint Work, Accepted

ＣＨＯＰ療法（Full Dose）：Feasibility と放射線治療への影響

冨永紳一、近藤誠、安藤　裕、山下昌次、植松稔、茂松直之、西口郁、橋本省三

日本癌治療学会誌 20 ( 7 ) 1327-1333 1985

Research paper (scientific journal), Joint Work, Accepted

放射線治療に対するツムラ十全大補湯の使用効果について

宮本宏、茂松直之、山下昌次、冨永紳一、近藤　誠、橋本省三

診断と治療 73 ( 7 ) 153-159 1985

Research paper (scientific journal), Joint Work

悪性リンパ腫に対する抗腫瘍剤大量投与時におけるデキサメタゾンの併用経験

冨永紳一、近藤誠、安藤裕、山下昌次、茂松直之、西口郁、橋本省三>

医学と薬学 12 ( 3 ) 333-337 1984

Research paper (scientific journal), Joint Work

Skin metastasis within the previous radiation field after prophylactic postoperative radiotherapy for breast cancer

Ito H, Kubo A, Shigematsu N, Hashimoto S

Clin Expl Metastasis 2 ( 3 ) 235-239 1984

Research paper (scientific journal), Joint Work, Accepted

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