Details of a Researcher - Shiraishi, Yutaka

Papers - Shiraishi, Yutaka

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Effect of adding androgen deprivation therapy to permanent iodine-125 implantation with or without external beam radiation therapy on the outcomes in patients with intermediate-risk prostate cancer: A propensity score–matched analysis

Sutani S., Yorozu A., Toya K., Shiraishi Y., Nishiyama T., Yagi Y., Nakamura K., Saito S.

Brachytherapy (Brachytherapy) 20 ( 1 ) 10 - 18 2021.01

ISSN 15384721

Purpose: The purpose of the study was to evaluate the effect of adding androgen deprivation therapy (ADT) to brachytherapy with or without external beam radiation therapy on oncological outcomes in prostate cancer. Methods and Materials: Overall, 1,171 patients with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy with or without ADT between 2003 and 2013 were identified. Propensity score matching was used to counter biases between the ADT and non-ADT groups. The biochemical failure-free rate (bFFR), local recurrence-free rate, and overall survival rate were evaluated using Kaplan–Meier curves, and predictors were identified using Cox proportional hazards regression models. Results: After propensity score matching, 405 patients were included in each group. The median followup duration was 9.1 years; the median ADT duration was 6 months. In the ADT versus non-ADT groups, the 9-year bFFR, local recurrence-free rate, and overall survival rate were 93.4% versus 87.8% (p = 0.016), 96.9% versus 98.1% (p = 0.481), and 88.1% versus 90.4% (p = 0.969), respectively. On multivariate analyses, Gleason score (hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 1.58–4.03) and ADT use (HR: 0.55, 95% CI: 0.34–0.89) were associated with biochemical failure. Supplemental external beam radiation therapy use (HR: 0.38, 95% CI: 0.16–0.91) was associated with lower local recurrence rates. Age (HR: 1.12, 95% CI: 1.08–1.16) and comorbidities (HR: 1.56, 95% CI: 1.04–2.34) were associated with all-cause mortality. Conclusions: A risk-benefit assessment between bFFR improvement and the potential side effects of adding ADT to brachytherapy-based radiotherapy is warranted before incorporating ADT as routine practice.

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Time to achieve a prostate-specific antigen nadir of ≤0.2 ng/mL and related factors after permanent prostate brachytherapy

Soyano T., Yorozu A., Natsume N., Hanada T., Shiraishi Y., Toya K., Saito S.

Brachytherapy (Brachytherapy) 20 ( 1 ) 29 - 37 2021.01

ISSN 15384721

Purpose: The purpose of this study was to identify the time to achieve a prostate-specific antigen (PSA) nadir of ≤0.2 ng/mL and the related factors to achieve this goal. Materials and Methods: We retrospectively reviewed 2218 Japanese prostate cancer patients who received 125I brachytherapy with or without external beam radiotherapy between 2003 and 2013 at one institution. Among them, patients followed up for ≥72 months and without luteinizing hormone–releasing hormone (LH-RH) agonist/antagonist were included (total of 1089 patients). The time to a PSA nadir of ≤0.2 ng/mL (months) was defined as the time between the date of implantation and the first time the lowest PSA value reached ≤0.2 ng/mL. Biochemical recurrence (BCR) was determined using the Phoenix definition. Multivariate linear regression analysis was performed to detect the related factors to achieve this nadir. Results: We assigned 409, 592, and 88 patients to the low-, intermediate-risk, and high-risk groups, respectively. The median followup time was 9.5 years. The median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 (95% confidence interval: 42.3–45.7) months. The percentage of patients that achieved the nadir was 89.1%. BCR was noted in 107 (9.8%) patients. In the multivariate analysis of patients without BCR, younger age, larger prostate volume at implantation, higher initial PSA level, and monotherapy were significantly associated with longer time to achieve the PSA nadir. Conclusion: The median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 months. Some patients, however, may require a lengthy period of time to do so.

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Prediction of Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer: Development and Validation of a Pretreatment Nomogram

van Rossum P.S.N., Deng W., Routman D.M., Liu A.Y., Xu C., Shiraishi Y., Peters M., Merrell K.W., Hallemeier C.L., Mohan R., Lin S.H.

Practical Radiation Oncology (Practical Radiation Oncology) 10 ( 1 ) e16 - e26 2020.01

ISSN 18798500

Introduction: In patients with esophageal cancer, occurrence of severe radiation-induced lymphopenia during chemoradiation therapy has been associated with worse progression-free and overall survival. The aim of this study was to develop and validate a pretreatment clinical nomogram for the prediction of grade 4 lymphopenia. Methods and Materials: A development set of consecutive patients who underwent chemoradiation therapy for esophageal cancer and an independent validation set of patients from another institution were identified. Grade 4 lymphopenia was defined as an absolute lymphocyte count nadir during chemoradiation therapy of <0.2 × 103/μL. Multivariable logistic regression analysis was used to create a prediction model for grade 4 lymphopenia in the development set, which was internally validated using bootstrapping and externally validated by applying the model to the validation set. The model was presented as a nomogram yielding 4 risk groups. Results: Among 860 included patients, 322 (37%) experienced grade 4 lymphopenia. Higher age, larger planning target volume in interaction with lower body mass index, photon- rather than proton-based therapy, and lower baseline absolute lymphocyte count were predictive in the final model (corrected c-statistic, 0.76). External validation in 144 patients, among whom 58 (40%) had grade 4 lymphopenia, yielded a c-statistic of 0.71. Four nomogram-based risk groups yielded predicted risk rates of 10%, 24%, 43%, and 70%, respectively. Conclusions: A pretreatment clinical nomogram was developed and validated for the prediction of grade 4 radiation-induced lymphopenia during chemoradiation therapy for esophageal cancer. The nomogram can risk stratify individual patients suitable for lymphopenia-mitigating strategies or potential future therapeutic approaches to ultimately improve survival.

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A multidisciplinary approach to soft-tissue sarcoma of the extremities

Nakayama R., Mori T., Okita Y., Shiraishi Y., Endo M.

Expert Review of Anticancer Therapy (Expert Review of Anticancer Therapy) 2020

ISSN 14737140

Introduction: Soft-tissue sarcoma (STS) denotes a group of rare and highly heterogeneous malignant tumors of mesenchymal origin. Accurate histological diagnosis is critical for selecting appropriate treatment. Complete tumor resection is the primary treatment for STS, and the efficacies of radiotherapy and chemotherapy have been tested in the adjuvant setting to improve oncological outcomes. Because most STS lesions arise in the extremities, preserving limb function and managing limb impairment after radical local treatment represent significant challenges. Areas covered: This article reviews the current front-line treatments for patients with extremity STS and discusses the multidisciplinary team-based efforts needed to improve oncological outcomes and survivorship. Expert opinion: Given the rarity, variety, and complexity of STS, a multidisciplinary approach involving experts in various disciplines is vital for improving outcomes in patients ranging from diagnosis to survivorship. A major challenge is building a sustainable system in each region permitting all patients with extremity STS to be treated at high-volume centers with multidisciplinary teams dedicated to this rare and complex disease.

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Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy

Shiraishi Y., Fang P., Xu C., Song J., Krishnan S., Koay E., Mehran R., Hofstetter W., Blum-Murphy M., Ajani J., Komaki R., Minsky B., Mohan R., Hsu C., Hobbs B., Lin S.

Radiotherapy and Oncology (Radiotherapy and Oncology) 128 ( 1 ) 154 - 160 2018.07

ISSN 01678140

© 2017 Elsevier B.V. Background and purpose: Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). Material and methods: EC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. Results: Among the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P < 0.0001). On multivariable analysis, PBT was significantly associated with a reduction in grade 4 lymphopenia risk (odds ratio, 0.29; 95% confidence interval, 0.16–0.52; P < 0.0001). Conclusion: PBT is associated with significant risk reduction in grade 4 lymphopenia during nCRT in esophageal cancer.

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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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Definitive Chemoradiation Therapy for Esophageal Cancer in the Elderly

Xu Cai, Xi Mian, Moreno Amy, Shiraishi Yutaka, Hobbs Brian P., Huang Meilin, Komaki Ritsuko, Lin Steven H.

International Journal of Radiation Oncology Biology Physics (International Journal of Radiation Oncology Biology Physics) 98 ( 4 ) 811 - 819 2017.07

ISSN 0360-3016

Purpose The optimal treatment approach for patients ≥80 years (“elderly”) with esophageal cancer is not well established. We assessed the clinical outcomes in elderly patients treated with definitive chemoradiation therapy (CCRT) at our institution. Methods and Materials 56 consecutive patients ≥80 years with esophageal cancer treated with conventional CCRT between 2001 and 2016 were propensity score matched 1:2 to generate 2 younger patient cohorts treated with CCRT without surgery: “intermediate” (65-79 years, n=112) and “younger” (<65 years, n=112). Treatment related toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. The rates of overall survival (OS) and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. Results The median ages of the 3 cohorts were 81 years (elderly, 80-92 years), 71 years (intermediate, 65-79 years), and 58 years (younger, 20-64 years). The elderly cohort was more likely to have cardiac comorbidities. Although the clinical complete response (cCR) rate deviated significantly among the 3 cohorts, (78%, 72%, and 56%; P=.004), the data failed to identify statistically significant differences among RFS, 2-year, and 5-year OS, or in median survival, which was 15.5 months, 23.6 months, and 20.2 months (P=.468), respectively. The overall severe toxicity rates were 38%, 32%, and 30%, respectively (P=.644), including comparable rate of radiation pneumonitis (P>.05). The elderly cohort, however, did show statistically significant evidence of an increased rate of severe radiation pneumonitis (grade ≥3) which was observed to be 11% versus 4% and 0%, respectively (P=.003). Conclusions The studied elderly population showed evidence of similar long-term clinical efficacy after definitive CCRT when compared with cohorts of younger patients with similar prognostic status. An increased rate of pulmonary toxicity was identified, without evidence of differences for nonpulmonary severe adverse events. Understanding the prognostic risk factors of pulmonary toxicity after CCRT may effectuate improved long-term outcomes for elderly population.

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Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer

Shiraishi Yutaka, Fang Penny, Xu Cai, Song Juhee, Krishnan Sunil, Koay Eugene J., Mehran Reza J., Hofstetter Wayne L., Blum-Murphy Mariela, Ajani Jaffer A., Komaki Ritsuko, Minsky Bruce, Mohan Radhe, Hsu Charles C., Hobbs Brian P., Lin Steven H.

Radiotherapy and Oncology 2017.01

ISSN 0167-8140

Background and purpose: Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). Material and methods: EC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. Results: Among the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P < 0.0001). On multivariable analysis, PBT was significantly associated with a reduction in grade 4 lymphopenia risk (odds ratio, 0.29; 95% confidence interval, 0.16-0.52; P < 0.0001). Conclusion: PBT is associated with significant risk reduction in grade 4 lymphopenia during nCRT in esophageal cancer.

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Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or Intensity-modulated radiation therapy

Shiraishi Yutaka, Xu Cai, Yang Jinzhong, Komaki Ritsuko, Lin Steven H.

Radiotherapy and Oncology (Radiotherapy and Oncology) 125 ( 1 ) 48 - 54 2017

ISSN 0167-8140

Purpose: To compare heart and cardiac substructure radiation exposure using intensity-modulated radiotherapy (IMRT) vs. proton beam therapy (PBT) for patients with mid- to distal esophageal cancer who received chemoradiation therapy. Methods and materials: We identified 727 esophageal cancer patients who received IMRT (n = 477) or PBT (n = 250) from March 2004 to December 2015. All patients were treated to 50.4. Gy with IMRT or to 50.4 cobalt Gray equivalents with PBT. IMRT and PBT dose-volume histograms (DVHs) of the whole heart, atria, ventricles, and four coronary arteries were compared. For PBT patients, passive scattering proton therapy (PSPT; n = 237) and intensity-modulated proton therapy (IMPT; n = 13) DVHs were compared. Results: Compared with IMRT, PBT resulted in significantly lower mean heart dose (MHD) and heart V5, V10, V20, V30, and V40. as well as lower radiation exposure to the four chambers and four coronary arteries. Compared with PSPT, IMPT resulted in significantly lower heart V20, V30, and V40 but not MHD or heart V5 or V10. IMPT also resulted in significantly lower radiation doses to the left atrium, right atrium, left main coronary artery, and left circumflex artery, but not the left ventricle, right ventricle, left anterior descending artery, or right coronary artery. Factors associated with lower MHD included PBT (P <. 0.001), smaller planning target volume (PTV; P <. 0.001), and gastroesophageal junction (GEJ) tumor (P <. 0.001). Among PBT patients, factors associated with lower MHD included IMPT (P = 0.038), beam arrangement other than AP/PA (P <. 0.001), smaller PTV (P <. 0.001), and GEJ tumor (P <. 0.001). Conclusions: In patients with mid- to distal esophageal cancer, PBT results in significantly lower radiation exposure to the whole heart and cardiac substructures than IMRT. Long-term studies are necessary to determine how this cardiac sparing effect impacts the development of coronary artery disease and other cardiac complications.

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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 (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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Management of morbidity with radiotherapy for prostate cancer

Yorozu Atsunori, Kota Ryuichi, Takagawa Yoshiaki, Shiraishi Yutaka, Toya Kazuhito

Nihon rinsho. Japanese journal of clinical medicine (Nihon rinsho. Japanese journal of clinical medicine) 74 514 - 519 2016.05

ISSN 0047-1852

Urinary toxicity after prostate brachytherapy

Yorozu A., Kota R., Toya K., Eriguchi T., Kuroiwa N., Takagawa Y., Tanaka T., Shiraishi Y.

Japanese Journal of Clinical Radiology (Japanese Journal of Clinical Radiology) 61 ( 9 ) 1082 - 1088 2016

ISSN 0009-9252

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 (Brachytherapy) 15 ( 3 ) 288 - 295 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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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 (Radiotherapy and Oncology) 117 ( 2 ) 270 - 276 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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Permanent prostate brachytherapy with or without supplemental external beam radiotherapy as practiced in Japan

Yorozu Atsunori, Kuroiwa Nobuko, Takahashi Akane, Toya Kazuhito, Saito Shiro, Nishiyama Toru, Yagi Yasuto, Tanaka Tomoki, Shiraishi Yutaka, Ohashi Toshio

Brachytherapy (Brachytherapy) 14 ( 2 ) 111 - 117 2015.03

ISSN 1538-4721

Purpose: To report outcomes for men treated with iodine-125 (¹²⁵I) prostate brachytherapy (BT) at a single institution in Japan. Methods and Materials: Between 2003 and 2009, 1313 patients (median age, 68years) with clinically localized prostate cancer were treated with ¹²⁵I BT. Median prostate-specific antigen level was 7.6ng/mL (range, 1.1-43.3). T-stage was T1c in 60%, T2 in 39%, and T3 in 1% of patients. The Gleason score was <7, 7, and >7 in 49%, 45%, and 6% of patients, respectively. Neoadjuvant androgen deprivation therapy was used in 40% of patients and combined external beam radiotherapy of 45Gy in 48% of patients. Postimplant dosimetry was performed after 30days after implantation, with total doses converted to the biologically effective dose. Survival functions were calculated by the Kaplan-Meier method and Cox hazard model. Results: Median followup was 67months (range, 6-126). The 7-year biochemical freedom from failure for low-, intermediate-, and selected high-risk prostate cancers were 98%, 93%, and 81%, respectively (. p<0.001). Multivariate analysis identified the Gleason score, initial prostate-specific antigen level, positive biopsy rate, dose, and neoadjuvant androgen deprivation therapy as predictors for biochemical freedom from failure. The 7-year actuarial developing Grade 3+ genitourinary and gastrointestinal toxicity was 2% and 0.3%, respectively. Forty-four percent patients with normal baseline potency retained normal erectile function at 5years. Conclusions: ¹²⁵I prostate BT is a highly effective treatment option for low-, intermediate-, and selected high-risk prostate cancers. Side effects were tolerable. An adequate dose may be required to achieve successful biochemical control.

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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 (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 (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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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 (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. © 2014 Ohashi et al.; licensee BioMed Central Ltd.

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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 (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. © 2013 Elsevier Inc.

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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 (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. © 2013 Elsevier Ireland Ltd. All rights reserved.

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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 (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. © 2013 Elsevier Inc.

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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 (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. © The Author 2013. Published by Oxford University Press. All rights reserved.

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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 (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. © 2013 Elsevier Inc. All rights reserved.

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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 (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. © 2012 American Brachytherapy Society.

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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. © 2012 by The Keio Journal of Medicine.

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%).

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

Sugawara A., Nakashima J., Kunieda E., Nagata H., Mizuno R., Takeda A., Seki S., Shiraishi Y., Kouta R., Oya M., Shigematsu N.

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

ISSN 00229717

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. © 2012 by The Keio Journal of Medicine.

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Result of salvage radiotherapy for post-operative PSA failure of prostate cancer: Evaluation of predictive factors

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

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

ISSN 00099252

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%).

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 (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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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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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 (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. © 2011 Elsevier Inc.

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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 (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. © 2011 Sugawara et al; licensee BioMed Central Ltd.

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