Details of a Researcher - Shigematsu, Naoyuki

Papers - Shigematsu, Naoyuki

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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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