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石倉 聡イシクラ サトシ

所属部署医学研究科共同研究教育センター
職名准教授
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Last Updated :2020/06/03

研究者基本情報

学歴

  •  - 1989年, 京都大学, 医学部
  •  - 1989年, 京都大学

学位

  • 医学博士, 京都大学

研究活動情報

研究分野

  • ライフサイエンス, 放射線科学

研究キーワード

    放射線腫瘍学, Radiation Oncology

論文

  • Chemoradiotherapy in elderly patients with non-small cell lung cancer: long-term follow-up of a randomized trial (JCOG0301)., Atagi S, Mizusawa J, Ishikura S, Takahashi T, Okamoto H, Tanaka H, Goto K, Nakagawa K, Harada M, Takeda Y, Nogami N, Fujita Y, Kasai T, Kishi K, Sawa T, Takeda K, Tomii K, Satouchi M, Seto T, Ohe Y, Clic Lung Cancer,   2018年05月, 査読有り
  • Results of a multi-institutional, randomized, non-inferiority, phase 3 trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group study (JCOG0701)., Kodaira T, Kagami Y, Shibata T, Shikama N, Nishimura Y, Ishikura S, Nakamura K, Saito Y, Matsumoto Y, Teshima T, Ito Y, Akimoto T, Nakata K, Toshiyasu T, Nakagawa K, Nagata Y, Nishimura T, Uno T, Kataoka M, Yorozu A, Hiraoka M, Radiation Therapy Study Group of the, Japan Clinical, Oncology Group, Ann Oncol, 29, 992 - 997,   2018年04月, 査読有り
  • Nimotuzumab combined with concurrent chemoradiotherapy in Japanese patients with esophageal cancer: a phase I study., Kato K, Ura T, Koizumi W, Iwasa S, Katada C, Azuma M, Ishikura S, Nakao Y, Onuma H, Muro K, Cancer Sci, 109, 785 - 793,   2018年03月, 査読有り
  • A virtual dosimetry audit – Towards transferability of gamma index analysis between clinical trial QA groups., Hussein M, Clementel E, Eaton D, Greer P, Haworth A, Ishikura S, Kry S, Lehmann J, Lye J, Monti A, Nakamura M, Hurkmans C, Clark C, Radiother Oncol, 125, 398 - 404,   2017年12月, 査読有り
  • Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303), Tatsuya Okuno, Masashi Wakabayashi, Ken Kato, Masayuki Shinoda, Hiroshi Katayama, Hiroyasu Igaki, Yasuhiro Tsubosa, Takashi Kojima, Hiroshi Okabe, Yusuke Kimura, Tatsuyuki Kawano, Shinichi Kosugi, Yasushi Toh, Hoichi Kato, Kenichi Nakamura, Haruhiko Fukuda, Satoshi Ishikura, Nobutoshi Ando, Yuko Kitagawa, INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 22, (6) 1042 - 1049,   2017年12月, 査読有り, Background The aim of this study was to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) for patients with unresectable locally advanced esophageal squamous cell carcinoma (LAESCC) treated with chemoradiotherapy. Methods One hundred forty-two patients were enrolled in JCOG0303 and assigned to the standard cisplatin and 5-fluorouracil (PF)-radiotherapy (RT) group or the low-dose PF-RT group. One hundred thirty-one patients with sufficient data were included in this analysis. A Cox regression model was used to analyze the prognostic factors of patients with unresectable LAESCC treated with PF-RT. The GPS was classified based on the baseline C-reactive protein (CRP) and serum albumin levels. Patients with CRP <=>1.0 mg/dL and albumin >= 3.5 g/dL were classified as GPS0. If only CRP was increased or only albumin was decreased, the patients were classified as GPS1, and the patients with CRP > 1.0 mg/dL and albumin < 3.5 g/dL were classified as GPS2. Results The patients' backgrounds were as follows: median age (range), 62 (37-75); male/female, 119/12; ECOG PS 0/1/2, 64/65/2; and clinical stage (UICC 5th) IIB/III/IVA/IVB, 3/75/22/31. Multivariable analyses indicated only esophageal stenosis as a common factor for poor prognosis. In addition, overall survival tended to decrease according to the GPS subgroups (median survival time (months): GPS0/GPS1/GPS2 16.1/14.9/8.7). Conclusions Esophageal stenosis was identified as a candidate stratification factor for randomized trials of unresectable LAESCC patients. Furthermore, GPS represents a prognostic factor for LAESCC patients treated with chemoradiotherapy.
  • A phase I/II study on stereotactic body radiotherapy with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm for lung tumors, Hiromitsu Iwata, Satoshi Ishikura, Taro Murai, Michio Iwabuchi, Mitsuhiro Inoue, Koshi Tatewaki, Seiji Ohta, Naoki Yokota, Yuta Shibamoto, INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 22, (4) 706 - 714,   2017年08月, 査読有り, Background In this phase I/II study, we assessed the safety and initial efficacy of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm. Methods Study subjects had histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the incidence of Grade >= 3 radiation pneumonitis (RP) within 180 days of the start of SBRT. The secondary endpoint was local control and overall survival rates. Five patients were initially enrolled at level 1 [50 Gy/4 fractions (Fr)]; during the observation period, level 0 (45 Gy/4 Fr) was opened. The dose was escalated to the next level when grade >= 3 RP was observed in 0 out of 5 or 1 out of 10 patients. Virtual quality assurance planning was performed for 60 Gy/4 Fr; however, dose constraints for the organs at risk did not appear to be within acceptable ranges. Therefore, level 2 (55 Gy/4 Fr) was regarded as the upper limit. After the recommended dose (RD) was established, 15 additional patients were enrolled at the RD. The prescribed dose was normalized at the 95% volume border of the planning target volume based on the Monte Carlo algorithm. Results Between September 2011 and September 2015, 40 patients (primary 30; metastasis 10) were enrolled. Five patients were enrolled at level 0, 15 at level 1, and 20 at level 2. Only one grade 3 RP was observed at level 1. Two-year local control and overall survival rates were 98 and 81%, respectively. Conclusion The RD was 55 Gy/4 Fr. SBRT with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm was tolerated well and appeared to be effective for solitary lung tumors.
  • Randomized phase II trial of weekly dose-intensive chemotherapy or amrubicin plus cisplatin chemotherapy following induction chemoradiotherapy for limited-disease small cell lung cancer (JCOG1011), Ikuo Sekine, Hideyuki Harada, Noboru Yamamoto, Masashi Wakabayashi, Haruyasu Murakami, Koichi Goto, Naoyuki Nogami, Takashi Seto, Fumihiro Oshita, Hiroaki Okamoto, Hiroshi Tanaka, Tomohide Tamura, Satoshi Ishikura, Yuichiro Ohe, LUNG CANCER, 108, 232 - 237,   2017年06月, 査読有り, Objectives: The objective of this study was to select, for a phase III trial, the more promising of weekly-dose intensive chemotherapy or amrubicin + cisplatin chemotherapy as subsequent therapy after induction chemoradiotherapy for previously untreated limited-disease small cell lung cancer (LD-SCLC). Materials and Methods: Patients aged 20-70 years with untreated clinical stage Will LD-SCLC were eligible. After one cycle of accelerated hyperfractionation thoracic radiotherapy with etoposide plus cisplatin, patients without progression were randomized to either 3 cycles of cisplatin 25 mg/m(2) (days 1, 8), doxorubicin 40 mg/m2 (day 1), etoposide 80 mg/m2 (days 1-3), and vincristine 1 mg/m2 (day 8) every 2 weeks (CODE) or amrubicin 40 mg/m2 (days 1-3) and cisplatin 60 mg/m2 (day 1) every 3 weeks (AP). The primary endpoint was the one-year progression free survival (PFS). The sample size was 72 to select the arm yielding a better one-year PFS (55% vs. 65%) with a probability of 80%. Results: From March 2011 to February 2014, 85 patients were registered. After the induction chemoradiotherapy, 75 patients were randomized to CODE (n = 39) or AP (n = 36). The one-year PFS (95% confidence interval) was 41.0% (25.7-55.8) in the CODE group and 54.3% (36.6-69.0) in the AP group. Grade 4 neutropenia/grade 3 febrile neutropenia occurred in 47%/16% in the CODE group and 78%/42% in the AP group. Conclusion: The one-year PFS was better in the AP group, but it did not reach the expected 55%. Therefore, neither regimen is suitable for a phase III trial.
  • Phase I study of stereotactic body radiation therapy for peripheral T2N0M0 non-small cell lung cancer (JCOG0702): Results for the group with PTV⩾100cc., Onimaru R, Onishi H, Shibata T, Hiraoka M, Ishikura S, Karasawa K, Matsuo Y, Kokubo M, Shioyama Y, Matsushita H, Ito Y, Shirato H, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 122, (2) 281 - 285,   2017年02月, 査読有り
  • A randomized Phase III trial of comparing two dose-fractionations stereotactic body radiotherapy (SBRT) for medically inoperable Stage IA non-small cell lung cancer or small lung lesions clinically diagnosed as primary lung cancer: Japan Clinical Oncology, Kimura T, Nagata Y, Eba J, Ozawa S, Ishikura S, Shibata T, Ito Y, Hiraoka M, Nishimura Y, Radiation Oncology Study Group of the, Japan Clinical, Oncology Group, Japanese journal of clinical oncology,   2017年01月, 査読有り
  • Stereotactic body radiotherapy versus lobectomy for operable clinical stage IA lung adenocarcinoma: comparison of survival outcomes in two clinical trials with propensity score analysis (JCOG1313-A), Junko Eba, Kenichi Nakamura, Junki Mizusawa, Kenji Suzuki, Yasushi Nagata, Teruaki Koike, Masahiro Hiraoka, Shun-ichi Watanabe, Satoshi Ishikura, Hisao Asamura, Haruhiko Fukuda, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 46, (8) 748 - 753,   2016年08月, 査読有り, Objective: No randomized controlled trials comparing stereotactic body radiotherapy and lobectomy for operable early-stage non-small-cell lung cancer have been successfully conducted. This study compared survival outcomes in two multi-institutional clinical trials for stereotactic body radiotherapy ( Japan Clinical Oncology Group JCOG0403) and lobectomy ( Japan Clinical Oncology Group JCOG0201) with propensity score analysis. Methods: Inclusion criteria were operable, cT1N0M0 and adenocarcinoma diagnosed prior to registration of each trial. Forty of 169 patients from JCOG0403 and 219 of 811 patients from JCOG0201 were included. The primary endpoint was overall survival adjusted with propensity score analysis. The patient selection factors included in the logistic model to estimate the propensity score were age, sex, tumor diameter and consolidation/tumor ratio. Results: Among patient selection factors, age distribution was quite different with little overlap: the median was 79 ( interquartile range: 74.5-83.5) in stereotactic body radiotherapy and 62 ( interquartile range: 55-68) in lobectomy. In propensity score analysis, 21 patients from each group were matched and the hazard ratio for stereotactic body radiotherapy over lobectomy was 9.00 ( 95% confidence interval: 1.14-71.04). In the post hoc subgroup analysis with propensity score analysis of inverse probability of treatment weighting, patients were limited to be aged 75 or younger because JCOG0201 only included them when aged 75 or younger. Thirteen patients for stereotactic body radiotherapy and 219 for lobectomy were compared, and the hazard ratio for stereotactic body radiotherapy over lobectomy was 1.19 ( 95% confidence interval: 0.38-3.73). Conclusions: The point estimates of hazard ratio favored lobectomy over stereotactic body radiotherapy in the limited number of patients. A randomized controlled study is needed for valid comparison.
  • An on-site audit system for dosimetry credentialing of intensity-modulated radiotherapy in Japanese Clinical Oncology Group (JCOG) clinical trials, Mitsuhiro Nakamura, Toshiyuki Minemura, Satoshi Ishikura, Teiji Nishio, Yuichiro Narita, Yasumasa Nishimura, PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS, 32, (8) 987 - 991,   2016年08月, 査読有り, Purpose: This study was undertaken to analyze the results of intensity-modulated radiotherapy (IMRT) dosimetry credentialing using a phantom in the Japanese Clinical Oncology Group clinical trials. Methods: All measurements were performed on-site. The IMRT phantom consisted of a phantom shell and a module. Two types of structures, including a C-shaped planning target volume (PTV) around a column-shaped organ at risk (OAR), were included in the module. Each participating institution was asked to image, plan, and treat the phantom. A prescription dose of 2 Gy should cover 95% of the PTV. The plan should limit the maximum doses to the PTV and OAR to less than 110% and 60%, respectively. The pass criteria were +/- 3% in terms of chamber dosimetry and a difference in profile position <= 2 mm in the high-dose gradient area of film dosimetry. The positional difference was defined as the largest distance between the measured and calculated positions at doses of 60% or 80%. These tolerances were based on the Japanese Society for Radiation Oncology IMRT guidelines. Results: Credentialing was performed on a total of 44 treatment machines in 32 institutions from 2009 to 2015. All differences between measured and planned doses at the measurement points of the PTV were within 3%. The means +/- standard deviations of the positional differences were 1.0 +/- 0.4 mm and 0.9 +/- 0.3 mm without and with the phantom shell, respectively. Conclusions: The dose differences and positional differences met the desired criteria in all institutions. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
  • In Regard to Nagata et al., Nagata Y, Shibata T, Ishikura S, International journal of radiation oncology, biology, physics, 95, (4) ,   2016年07月, 査読有り
  • Inter-institutional survival heterogeneity in chemoradiation therapy for esophageal cancer: exploratory analysis of the JCOG0303 study, Yasuo Hamamoto, Junki Mizusawa, Hiroshi Katayama, Kenichi Nakamura, Ken Kato, Yasuhiro Tsubosa, Satoshi Ishikura, Hiroyasu Igaki, Masayuki Shinoda, Haruhiko Fukuda, Yuko Kitagawa, Nobutoshi Ando, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 46, (4) 389 - 392,   2016年04月, 査読有り, It is important to examine variation in the treatment effects of patients with esophageal cancer in order to generalize treatment outcomes. We aimed to investigate the range of prognostic differences among hospitals in the treatment of locally advanced esophageal cancer. The JCOG0303 study compared the efficacy of radiotherapy plus low-dose cisplatin and 5-fluorouracil with that of high-dose cisplatin and 5-fluorouracil for unresectable esophageal cancer. Of 32 institutions participating in the JCOG0303 study, the 18 institutions that enrolled three or more patients were included in this study. We predicted the 1-year survival in each institution by using a mixed-effect model. We found that the predicted 1-year survival in the 18 institutions with three or more patients was a median of 60.9%, with a range of 60.9-60.9%. This study is the first to investigated heterogeneity of survival in patients who received definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.
  • Feasibility study of chemoradiotherapy followed by amrubicin and cisplatin for limited-disease small cell lung cancer, Ikuo Sekine, Minako Sumi, Miyako Satouchi, Kayoko Tsujino, Makoto Nishio, Takuyo Kozuka, Seiji Niho, Keiji Nihei, Nobuyuki Yamamoto, Hideyuki Harada, Satoshi Ishikura, Tomohide Tamura, CANCER SCIENCE, 107, (3) 315 - 319,   2016年03月, 査読有り, To evaluate the feasibility of amrubicin plus cisplatin (AP) following chemoradiotherapy for limited-disease small-cell lung cancer, chemo-naive patients aged 20-70 years with a performance status of 0 or 1 and normal organ functions were treated with etoposide 100 mg/m(2) on days 1-3, cisplatin 80 mg/m(2) on day 1 and concurrent thoracic radiotherapy at 45 Gy/30 fractions (EP-TRT), followed by three cycles of amrubicin 40 mg/m(2) on days 1-3 and cisplatin 60 mg/m(2) on day 1 every 3 weeks. The EP-TRT could be completed in 21 patients (15 male and 6 female patients with a median age of 62 years). Of these, 2, 1 and 18 (86%) patients received one, two and three cycles of AP, respectively. Sixteen (76%) patients required granulocyte-colony stimulating factor (G-CSF) support. Grade 3/4 neutropenia occurred in all patients. Grade 3 febrile neutropenia was observed in 9 patients, lasting for 1 day in 5 patients. The incidences of grade 3/4 thrombocytopenia and anemia were 43 and 24%, respectively. Grade 3 infection and anorexia occurred in 2 and 3 patients, respectively. The response rate was 95%. The median (95% confidence interval [CI]) progression-free survival (PFS) was 41.9 (0-102) months, and the 5-year PFS rate (CI) was 41.9% (20.4-63.4%). The median overall survival (OS) has not been reached yet, and the 5-year OS rate (CI) was 57.8% (35.2-80.4%). In conclusion, EP-TRT followed by AP therapy was well-tolerated, although a large number of patients required G-CSF support.
  • Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403, Yasushi Nagata, Masahiro Hiraoka, Taro Shibata, Hiroshi Onishi, Masaki Kokubo, Katsuyuki Karasawa, Yoshiyuki Shioyama, Rikiya Onimaru, Takuyo Kozuka, Etsuo Kunieda, Tsutomu Saito, Keiichi Nakagawa, Masato Hareyama, Yoshihiro Takai, Kazushige Hayakawa, Norio Mitsuhashi, Satoshi Ishikura, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 93, (5) 989 - 996,   2015年12月, 査読有り, Purpose: To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC). Methods and Materials: Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients. Results: Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed. Conclusions: Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC. (C) 2015 Elsevier Inc. All rights reserved.
  • A questionnaire-based survey on 3D image-guided brachytherapy for cervical cancer in Japan: advances and obstacles., Ohno T, Toita T, Tsujino K, Uchida N, Hatano K, Nishimura T, Ishikura S, Journal of radiation research, 56, (6) 897 - 903,   2015年11月, 査読有り
  • Phase I study of stereotactic body radiation therapy for peripheral T2N0M0 non-small cell lung cancer with PTV < 100 cc using a continual reassessment method (JCOG0702), Rikiya Onimaru, Hiroki Shirato, Taro Shibata, Masahiro Hiraoka, Satoshi Ishikura, Katsuyuki Karasawa, Yukinori Matsuo, Masaki Kokubo, Yoshiyuki Shioyama, Haruo Matsushita, Yoshinori Ito, Hiroshi Onishi, RADIOTHERAPY AND ONCOLOGY, 116, (2) 276 - 280,   2015年08月, 査読有り, Purpose: To estimate the maximum tolerated dose (MTD) and to determine the recommended dose (RD) of stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinoma (NSCLC) with target volume (PTV) < 100 cc. Materials and methods: The continual reassessment method (CRM) was used to determine the dose level that patients should be assigned to and to estimate the MTD. Dose limiting toxicity (DLT) was grade 3 radiation pneumonitis (RP) within 180 days after the start of SBRT, grade 2 RP was used as a surrogate DLT. The RD was equal to the MTD. The dose was prescribed at D-95 of the PTV. Results: Fifteen patients were accrued. Only 1 experienced grade 2 RP at 60 Gy in 4 fractions. It was difficult to fulfill the dose constraints at 60 Gy in 4 fractions, and the maximum dose level assigned by CRM was changed to 55 Gy in 4 fractions. The lower limit of 95% of the credible interval exceeded the adjacent level, and the RD was determined as 55 Gy in 4 fractions. Conclusions: The RD of SBRT for peripheral T2N0M0 NSCLC with PTV < 100 cc was determined to be 55 Gy in 4 fractions. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Dose calculation accuracies in whole breast radiotherapy treatment planning: a multi-institutional study., Hatanaka S, Miyabe Y, Tohyama N, Kumazaki Y, Kurooka M, Okamoto H, Tachibana H, Kito S, Wakita A, Ohotomo Y, Ikagawa H, Ishikura S, Nozaki M, Kagami Y, Hiraoka M, Nishio T, Radiological physics and technology, 8, (2) 200 - 208,   2015年07月, 査読有り
  • Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303)., Shinoda M, Ando N, Kato K, Ishikura S, Kato H, Tsubosa Y, Minashi K, Okabe H, Kimura Y, Kawano T, Kosugi S, Toh Y, Nakamura K, Fukuda H, Japan Clinical, Oncology Group, Cancer science, 106, (4) 407 - 412,   2015年04月, 査読有り
  • Definitive radiotherapy for head and neck squamous cell carcinoma: update and perspectives on the basis of EBM., Kodaira T, Nishimura Y, Kagami Y, Ito Y, Shikama N, Ishikura S, Hiraoka M, Japanese journal of clinical oncology, 45, (3) 235 - 243,   2015年03月, 査読有り
  • A new two-step accurate CT-MRI fusion technique for post-implant prostate cancer, Hiroaki Kunogi, Hidehiro Hojo, Yoshiaki Wakumoto, Anneyuko I. Saito, Satoshi Ishikura, Yuki Yamashiro, Ryouhei Kuwatsuru, Keisuke Sasai, JOURNAL OF CONTEMPORARY BRACHYTHERAPY, 7, (2) 117 - 121,   2015年03月, 査読有り, Purpose: To develop an accurate method of fusing computed tomography (CT) with magnetic resonance imaging (MRI) for post-implant dosimetry after prostate seed implant brachytherapy. Material and methods: Prostate cancer patients were scheduled to undergo CT and MRI after brachytherapy. We obtained the three MRI sequences on fat-suppressed T1-weighted imaging (FST1-WI), T2-weighted imaging (T2-WI), and T2*-weighted imaging (T2*-WI) in each patient. We compared the lengths and widths of 450 seed source images in the 10 study patients on CT, FST1-WI, T2-WI, and T2*-WI. After CT-MRI fusion using source positions by the leastsquares method, we decided the center of each seed source and measured the distance of these centers between CT and MRI to estimate the fusion accuracy. Results: The measured length and width of the seeds were 6.1 +/- 0.5 mm (mean standard deviation) and 3.2 +/- 0.2 mm on CT, 5.9 +/- 0.4 mm, and 2.4 +/- 0.2 mm on FST1-WI, 5.5 +/- 0.5 mm and 1.8 +/- 0.2 mm on T2-WI, and 7.8 +/- 1.0 mm and 4.1 +/- 0.7 mm on T2*-WI, respectively. The measured source location shifts on CT/FST1-WI and CT/T2-WI after image fusion in the 10 study patients were 0.9 +/- 0.4 mm and 1.4 +/- 0.2 mm, respectively. The shift on CT/FST1-WI was less than on CT/T2-WI (p = 0.005). Conclusions: For post-implant dosimetry after prostate seed implant brachytherapy, more accurate fusion of CT and T2-WI is achieved if CT and FST1-WI are fused first using the least-squares method and the center position of each source, followed by fusion of the FST1-WI and T2-WI images. This method is more accurate than direct image fusion.
  • Global Harmonization of Quality Assurance Naming Conventions in Radiation Therapy Clinical Trials, Christos Melidis, Walther R. Bosch, Joanna Izewska, Elena Fidarova, Eduardo Zubizarreta, Kenneth Ulin, Satoshi Ishikura, David Followill, James Galvin, Annette Haworth, Deidre Besuijen, Clark H. Clark, Elizabeth Miles, Edwin Aird, Damien C. Weber, Coen W. Hurkmans, Dirk Verellen, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 90, (5) 1242 - 1249,   2014年12月, 査読有り, Purpose: To review the various radiation therapy quality assurance (RTQA) procedures used by the Global Clinical Trials RTQA Harmonization Group (GHG) steering committee members and present the harmonized RTQA naming conventions by amalgamating procedures with similar objectives. Methods and Materials: A survey of the GHG steering committee members' RTQA procedures, their goals, and naming conventions was conducted. The RTQA procedures were classified as baseline, preaccrual, and prospective/retrospective data capture and analysis. After all the procedures were accumulated and described, extensive discussions took place to come to harmonized RTQA procedures and names. Results: The RTQA procedures implemented within a trial by the GHG steering committee members vary in quantity, timing, name, and compliance criteria. The procedures of each member are based on perceived chances of noncompliance, so that the quality of radiation therapy planning and treatment does not negatively influence the trial measured outcomes. A comparison of these procedures demonstrated similarities among the goals of the various methods, but the naming given to each differed. After thorough discussions, the GHG steering committee members amalgamated the 27 RTQA procedures to 10 harmonized ones with corresponding names: facility questionnaire, beam output audit, benchmark case, dummy run, complex treatment dosimetry check, virtual phantom, individual case review, review of patients' treatment records, and protocol compliance and dosimetry site visit. Conclusions: Harmonized RTQA harmonized naming conventions, which can be used in all future clinical trials involving radiation therapy, have been established. Harmonized procedures will facilitate future intergroup trial collaboration and help to ensure comparable RTQA between international trials, which enables meta-analyses and reduces RTQA workload for intergroup studies. (C) 2014 Elsevier Inc.
  • Toxicities of organs at risk in the mediastinal and hilar regions following stereotactic body radiotherapy for centrally located lung tumors., Nishimura S, Takeda A, Sanuki N, Ishikura S, Oku Y, Aoki Y, Kunieda E, Shigematsu N, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 9, (9) 1370 - 1376,   2014年09月, 査読有り
  • Randomized Phase II/III Trial of Post-operative Chemoradiotherapy Comparing 3-Weekly Cisplatin with Weekly Cisplatin in High-risk Patients with Squamous Cell Carcinoma of Head and Neck: Japan Clinical Oncology Group Study (JCOG1008), Futoshi Kunieda, Naomi Kiyota, Makoto Tahara, Takeshi Kodaira, Ryuichi Hayashi, Satoshi Ishikura, Junki Mizusawa, Kenichi Nakamura, Haruhiko Fukuda, Masato Fujii, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 44, (8) 770 - 774,   2014年08月, 査読有り, A randomized Phase II/III study was launched in Japan to evaluate the non-inferiority of concurrent chemoradiotherapy with weekly cisplatin (40 mg/m(2)) compared with concurrent chemoradiotherapy with 3-weekly cisplatin (100 mg/m(2)) for post-operative high-risk patients with locally advanced squamous cell carcinoma of head and neck. This study began in October 2012, and a total of 260 patients will be accrued from 18 institutions within 5 years. The primary endpoint of the Phase II part is proportion of treatment completion and that of the Phase III part is overall survival. The secondary endpoints are relapse-free survival, local relapse-free survival, nutrition-support-free survival, non-hospitalized treatment period during permissible treatment period and adverse events. This trial was registered at the UMIN Clinical Trials Registry as UMIN 000009125 [http://www.umin.ac.jp/ctr/].
  • Radiation therapy quality assurance in clinical trials - Global harmonisation group, Christos Melidis, Walter R. Bosch, Joanna Izewska, Elena Fidarova, Eduardo Zubizarreta, Satoshi Ishikura, David Followill, James Galvin, Ying Xiao, Martin A. Ebert, Tomas Kron, Catharine H. Clark, Elizabeth A. Miles, Edwin G. A. Aird, Damien C. Weber, Kenneth Ulin, Dirk Verellen, Coen W. Hurkmans, RADIOTHERAPY AND ONCOLOGY, 111, (3) 327 - 329,   2014年06月, 査読有り
  • Toxicity and efficacy of three dose-fractionation regimens of intensity-modulated radiation therapy for localized prostate cancer, Yoshihiko Manabe, Yuta Shibamoto, Chikao Sugie, Fumiya Baba, Shiho Ayakawa, Aiko Nagai, Shinya Takemoto, Akihiro Hayashi, Noriyasu Kawai, Mitsuru Takeuchi, Satoshi Ishikura, Kenjiro Kohri, Takeshi Yanagi, JOURNAL OF RADIATION RESEARCH, 55, (3) 494 - 501,   2014年05月, 査読有り, Outcomes of three protocols of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. A total of 259 patients treated with 5-field IMRT between 2005 and 2011 were analyzed. First, 74 patients were treated with a daily fraction of 2.0 Gy to a total of 74 Gy (low risk) or 78 Gy (intermediate or high risk). Then, 101 patients were treated with a 2.1-Gy daily fraction to 73.5 or 77.7 Gy. More recently, 84 patients were treated with a 2.2-Gy fraction to 72.6 or 74.8 Gy. The median patient age was 70 years (range, 54-82) and the follow-up period for living patients was 47 months (range, 18-97). Androgen deprivation therapy was given according to patient risk. The overall and biochemical failure-free survival rates were, respectively, 96 and 82% at 6 years in the 2.0-Gy group, 99 and 96% at 4 years in the 2.1-Gy group, and 99 and 96% at 2 years in the 2.2-Gy group. The biochemical failure-free rate for high-risk patients in all groups was 89% at 4 years. Incidences of Grade a parts per thousand yen2 acute genitourinary toxicities were 9.5% in the 2.0-Gy group, 18% in the 2.1-Gy group, and 15% in the 2.2-Gy group (P = 0.29). Cumulative incidences of Grade a parts per thousand yen2 late gastrointestinal toxicity were 13% in the 2.0-Gy group at 6 years, 12% in the 2.1-Gy group at 4 years, and 3.7% in the 2.2-Gy group at 2 years (P = 0.23). So far, this stepwise shortening of treatment periods seems to be successful.
  • Design, development of water tank-type lung phantom and dosimetric verification in institutions participating in a phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer: Japan Clinical Oncology Group trial (JCOG0702), Teiji Nishio, Hiroki Shirato, Masayori Ishikawa, Yuki Miyabe, Satoshi Kito, Yuichirou Narita, Rikiya Onimaru, Satoshi Ishikura, Yoshinori Ito, Masahiro Hiraoka, JOURNAL OF RADIATION RESEARCH, 55, (3) 600 - 607,   2014年05月, 査読有り, A domestic multicenter phase I study of stereotactic body radiotherapy (SBRT) for T2N0M0 non-small cell lung cancer in inoperable patients or elderly patients who refused surgery was initiated as the Japan Clinical Oncology Group trial (JCOG0702) in Japan. Prior to the clinical study, the accuracy of dose calculation in radiation treatment-planning systems was surveyed in participating institutions, and differences in the irradiating dose between the institutions were investigated. We developed a water tank-type lung phantom appropriate for verification of the exposure dose in lung SBRT. Using this water tank-type lung phantom, the dose calculated in the radiation treatment-planning system and the measured dose using a free air ionization chamber and dosimetric film were compared in a visiting survey of the seven institutions participating in the clinical study. In all participating institutions, differences between the calculated and the measured dose in the irradiation plan were as follows: the accuracy of the absolute dose in the center of the simulated tumor measured using a free air ionization chamber was within 2%, the mean gamma value was <= 0.47 on gamma analysis following the local dose criteria, and the pass rate was >87% for 3%/3 mm from measurement of dose distribution with dosimetric film. These findings confirmed the accuracy of delivery doses in the institutions participating in the clinical study, so that a study with integration of the institutions could be initiated.
  • Survey of Advanced Radiation Technologies Used at Designated Cancer Care Hospitals in Japan, Naoto Shikama, Kayoko Tsujino, Katsumasa Nakamura, Satoshi Ishikura, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 44, (1) 72 - 77,   2014年01月, 査読有り, Our survey assessed the use of advanced radiotherapy technologies at the designated cancer care hospitals in Japan, and we identified several issues to be addressed. We collected the data of 397 designated cancer care hospitals, including information on staffing in the department of radiation oncology (e.g. radiation oncologists, medical physicists and radiation therapists), the number of linear accelerators and the implementation of advanced radiotherapy technologies from the Center for Cancer Control and Information Services of the National Cancer Center, Japan. Only 53 prefectural designated cancer care hospitals and 16 regional designated cancer care hospitals have implemented intensity-modulated radiotherapy for head and neck cancers, and 62 prefectural designated cancer care hospitals and 23 regional designated cancer care hospitals use intensity-modulated radiotherapy for prostate cancer. Seventy-four percent prefectural designated cancer care hospitals and 40 regional designated cancer care hospitals employ stereotactic body radiotherapy for lung cancer. Our multivariate analysis of prefectural designated cancer care hospitals which satisfy the institutes qualifications for advanced technologies revealed the number of radiation oncologists (P 0.01) and that of radiation therapists (P 0.003) were significantly correlated with the implementation of intensity-modulated radiotherapy for prostate cancer, and the number of radiation oncologists (P 0.02) was correlated with the implementation of stereotactic body radiotherapy. There was a trend to correlate the number of medical physicists with the implementation of stereotactic body radiotherapy (P 0.07). Only 175 (51) regional designated cancer care hospitals satisfy the institutes qualification of stereotactic body radiotherapy and 76 (22) satisfy that of intensity-modulated radiotherapy. Seventeen percent prefectural designated cancer care hospitals and 13 regional designated cancer care hospitals had a quality assurance committee. The numbers of radiation oncologists and other operating staff might be essential factors in the implementation of advanced radiotherapy technologies. Small proportions of regional designated cancer care hospitals satisfy the institutes qualifications of advanced technologies.
  • Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study, Kaoru Kubota, Toyoaki Hida, Satoshi Ishikura, Junki Mizusawa, Makoto Nishio, Masaaki Kawahara, Akira Yokoyama, Fumio Imamura, Koji Takeda, Shunichi Negoro, Masao Harada, Hiroaki Okamoto, Nobuyuki Yamamoto, Tetsu Shinkai, Hiroshi Sakai, Kaoru Matsui, Kazuhiko Nakagawa, Taro Shibata, Nagahiro Saijo, Tomohide Tamura, LANCET ONCOLOGY, 15, (1) 106 - 113,   2014年01月, 査読有り, Background Four cycles of etoposide plus cisplatin and accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard of care for limited-stage small-cell lung cancer (SCLC). Irinotecan plus cisplatin significantly improved overall survival compared with etoposide plus cisplatin for extensive-stage SCLC. We compared these regimens for overall survival of patients with limited-stage SCLC. Methods We did this phase 3 study in 36 institutions in Japan. Eligibility criteria included age 20-70 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate organ functions. Eligible patients with previously untreated limited-stage SCLC received one cycle of etoposide plus cisplatin (intravenous etoposide 100 mg/m(2) on days 1-3; intravenous cisplatin 80 mg/m(2) on day 1) plus AHTRT (1.5 Gy twice daily, 5 days a week, total 45 Gy over 3 weeks). Patients without progressive disease following induction therapy were randomised (1: 1 ratio, using a minimisation method with biased-coin assignment balancing on ECOG performance status [0 vs 1], response to induction chemoradiotherapy [complete response plus near complete response vs partial response and stable disease], and institution) to receive either three further cycles of consolidation etoposide plus cisplatin or irinotecan plus cisplatin (intravenous irinotecan 60 mg/m(2) on days 1, 8, 15; intravenous cisplatin 60 mg/m(2) on day 1). Patients, physicians, and investigators were aware of allocation. The primary endpoint was overall survival after randomisation; primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00144989, and the UMIN Clinical Trials Registry, number C000000095. Findings 281 patients were enrolled between Sept 1, 2002, and Oct 2, 2006. After induction etoposide plus cisplatin and AHTRT, 258 patients were randomised to consolidation etoposide plus cisplatin (n=129) or irinotecan plus cisplatin (n=129). In the etoposide plus cisplatin group, median overall survival was 3.2 years (95% CI 2.4-4.1). In the irinotecan and cisplatin group, median overall survival was 2.8 years (95% CI 2.4-3.6); overall survival did not differ between the two groups (hazard ratio 1.09 [95% CI 0.80-1.46], one-sided stratified log-rank p=0.70). The most common adverse events of grade 3 or 4 were neutropenia (120 [95%] in the etoposide plus cisplatin group vs 101 [78%] in the irinotecan plus cisplatin group), anaemia (44 [35%] vs 50 [39%]), thrombocytopenia (26 [21%] vs six [5%]), febrile neutropenia (21 [17%] vs 18 [14%]), and diarrhoea (two [2%] vs 13 [10%]). There was one treatment-related adverse event leading to death in each group (radiation pneumonitis in the etoposide plus cisplatin group; brain infarction in the irinotecan plus cisplatin group). Interpretation Four cycles of etoposide plus cisplatin and AHTRT should continue to be the standard of care for limited-stage SCLC.
  • Changes in volume of stage I non-small-cell lung cancer during stereotactic body radiotherapy, Kotoha Tatekawa, Hiromitsu Iwata, Takatsune Kawaguchi, Satoshi Ishikura, Fumiya Baba, Shinya Otsuka, Akifumi Miyakawa, Maho Iwana, Yuta Shibamoto, RADIATION ONCOLOGY, 9,   2014年01月, 査読有り, Background: The overall treatment time of stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer is usually 3 to over 10 days. If it is longer than 7 days, tumor volume expansion during SBRT may jeopardize the target dose coverage. In this study, volume change of stage I NSCLC during SBRT was investigated. Methods: Fifty patients undergoing 4-fraction SBRT with a total dose of 48 Gy (n = 36) or 52 Gy (n = 14) were analyzed. CT was taken for registration at the first and third SBRT sessions with an interval of 7 days in all patients. Patient age was 29-87 years (median, 77), and 39 were men. Histology was adenocarcinoma in 28, squamous cell carcinoma in 17, and others in 5. According to the UICC 7th classification, T-stage was T1a in 9 patients, T1b in 27, and T2a in 14. Tumor volumes on the first and 8th days were determined on CT images taken during the exhalation phase, by importing the data into the Dr. View/LINAX image analysis system. After determining the optimal threshold for distinguishing tumor from pulmonary parenchyma, the region above -250 HU was automatically extracted and the tumor volumes were calculated. Results: The median tumor volume was 7.3 ml (range, 0.5-35.7) on day 1 and 7.5 ml (range, 0.5-35.7) on day 8. Volume increase of over 10% was observed in 16 cases (32%); increases by >10 to <= 20%, >20 to <= 30%, and >30% were observed in 9, 5, and 2 cases, respectively. The increase in the estimated tumor diameter was over 2 mm in 3 cases and 1-2 mm in 6. A decrease of 10% or more was seen in 3 cases. Among the 16 tumors showing a volume increase of over 10%, T-stage was T1a in 2 patients, T1b in 9, and T2a in 5. Histology was adenocarcinoma in 10 patients, squamous cell carcinoma in 5, and others in 1. Conclusions: Volume expansion >10% was observed in 32% of the tumors during the first week of SBRT, possibly due to edema or sustained tumor progression. When planning SBRT, this phenomenon should be taken into account.
  • Dose-escalation study of three-dimensional conformal thoracic radiotherapy with concurrent S-1 and cisplatin for inoperable stage III non-small-cell lung cancer., Harada H, Nishio M, Murakami H, Ohyanagi F, Kozuka T, Ishikura S, Naito T, Kaira K, Takahashi T, Horiike A, Nishimura T, Yamamoto N, Clinical lung cancer, 14, (4) 440 - 445,   2013年07月, 査読有り
  • Distribution patterns of metastatic pelvic lymph nodes assessed by CT/MRI in patients with uterine cervical cancer, Goro Kasuya, Takafumi Toita, Kazuhisa Furutani, Takeshi Kodaira, Tatsuya Ohno, Yuko Kaneyasu, Ryouichi Yoshimura, Takashi Uno, Akira Yogi, Satoshi Ishikura, Masahiro Hiraoka, RADIATION ONCOLOGY, 8,   2013年06月, 査読有り, Background: To investigate the three-dimensional (3D) distribution patterns of clinically metastatic (positive) lymph nodes on pretreatment computed tomography (CT)/magnetic resonance imaging (MRI) images of patients with locally advanced cervical cancer. Methods: We enrolled 114 patients with uterine cervical cancer with positive nodes by CT/MRI (>= 10 mm in the shortest diameter). Pretreatment CT/MRI data were collected at 6 institutions. The FIGO stage was IB1 in 2 patients (2%), IB2 in 6 (5%), IIA in 3 (3%), IIB in 49 (43%), IIIB in 50 (44%), and IVA in 4 (4%) patients. The median cervical tumor diameter assessed by T2-weighted MRI was 55 mm (range, 10-87 mm). The anatomical distribution of the positive nodes was evaluated on CT/MRI images by two radiation oncologists and one diagnostic radiologist. Results: In these patients, 273 enlarged nodes were assessed as positive. The incidence of positive nodes was 104/114 (91%) for the obturator region, 31/114 (27%) for the external iliac region, 16/114 (14%) for the internal iliac region, 22/114 (19%) for the common iliac region, and 6/114 (5%) for the presacral region. The external iliac region was subdivided into four sub-regions: lateral, intermediate, medial, and caudal. The obturator region was subdivided into two sub-regions: cranial and caudal. The majority of patients had positive nodes in the cranial obturator and/or the medial external iliac region (111/114). In contrast, few had positive nodes in the lateral external iliac, caudal external iliac, caudal obturator, internal iliac and presacral regions. All cases with positive nodes in those low-risk regions also had positive nodes in other pelvic nodal regions concomitantly. The incidence of positive nodes in the low-risk regions/sub-regions was significantly related to FIGO stage (p=0.017) and number of positive nodes (p<0.001). Conclusions: We demonstrated the 3D distribution patterns of clinical metastatic pelvic lymph nodes on pretreatment CT/MRI images of patients with locally advanced cervical cancer. These findings might contribute to future individualization of the clinical target volume of the pelvic nodes in patients with cervical cancer.
  • Phase II Study of Cetuximab Plus Concomitant Boost Radiotherapy in Japanese Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck, Susumu Okano, Takayuki Yoshino, Masato Fujii, Yusuke Onozawa, Takeshi Kodaira, Hirofumi Fujii, Tetsuo Akimoto, Satoshi Ishikura, Masahiko Oguchi, Sadamoto Zenda, Barbara de Blas, Makoto Tahara, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 43, (5) 476 - 482,   2013年05月, 査読有り, We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck. Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab (400 mg/m(2) initial dose then 250 mg/m(2) weekly) for 7 weeks plus concomitant boost radiotherapy (weeks 27: once daily [1.8 Gy] for 3.6 weeks, then twice daily [1.8 Gy morning and 1.5 Gy afternoon] for 2.4 weeks). The primary endpoint was treatment completion rate (the rate of treated patients completing 70 of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule). Twenty-two patients were evaluable. The treatment completion rate was 100 (95 confidence interval 85100). The response rate 8 weeks post-radiotherapy was 82 (95 confidence interval 6095). The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation (73); dermatitis (27); and infection, radiation skin injury and stomatitis (23 each). Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck.
  • Multi-institutional comparison of treatment planning using stereotactic ablative body radiotherapy for hepatocellular carcinoma - benchmark for a prospective multi-institutional study, Takahisa Eriguchi, Atsuya Takeda, Yohei Oku, Satoshi Ishikura, Tomoki Kimura, Shuichi Ozawa, Takeo Nakashima, Yukinori Matsuo, Mitsuhiro Nakamura, Yasuo Matsumoto, Sadanori Yamazaki, Naoko Sanuki, Yoshinori Ito, RADIATION ONCOLOGY, 8,   2013年05月, 査読有り, Introduction: Several single institution phase I and phase II trials of stereotactic ablative body radiotherapy (SABR) for liver tumors have reported promising results and high local control rates of over 90%. However, there are wide variations in dose and fractionation due to different prescription policies and treatment methods across SABR series that have been published to date. This study aims to assess and minimize inter-institutional variations in treatment planning using SABR for hepatocellular carcinoma (HCC) in preparation for a prospective multi-institutional study. Methods: Four institutions (A-D) participated in this study. Each institution was provided with data from four cases, including planning and diagnostic CT images and clinical information, and asked to implement three plans (a practice plan and protocol plans 1 and 2). Practice plans were established based on the current treatment protocols at each institution. In protocol plan 1, each institution was instructed to prescribe 40 Gy in five fractions within 95% of the planning target volume (PTV). After protocol plan 1 was evaluated, we made protocol plan 2, The additional regulation to protocol plan 1 was that 40 Gy in five fractions was prescribed to a 70% isodose line of the global maximum dose within the PTV. Planning methods and dose volume histograms (DVHs) including the median PTV D50 (D(m)50) and the median normal liver volume that received 20 Gy or higher (V(m)20) were compared. Results: In the practice plan, D(m)50 was 48.4 Gy (range, 43.6-51.2 Gy). V(m)20 was 15.9% (range, 12.2-18.9%). In protocol plan 1, the D(m)50 at institution A was higher (51.2 Gy) than the other institutions (42.0-42.2 Gy) due to differences in dose specifications. In protocol plan 2, variations in DVHs were reduced. The D(m)50 was 51.9 Gy (range, 51.0-53.1 Gy), and the V(m)20 was 12.3% (range, 10.4-13.2%). The homogeneity index was nearly equivalent at all institutions. Conclusions: There were notable inter-institutional differences in practice planning using SABR to treat HCC. The range of PTV and normal liver DVH values was reduced when the dose was prescribed to an isodose line within the PTV. In multi-institutional studies, detailed dose specifications based on collaboration are necessary.
  • Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301), Shinji Atagi, Masaaki Kawahara, Akira Yokoyama, Hiroaki Okamoto, Nobuyuki Yamamoto, Yuichiro Ohe, Toshiyuki Sawa, Satoshi Ishikura, Taro Shibata, Haruhiko Fukuda, Nagahiro Saijo, Tomohide Tamura, LANCET ONCOLOGY, 13, (7) 671 - 678,   2012年07月, 査読有り, Background It is unknown whether combined chemoradiotherapy improves overall survival in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess whether radiotherapy plus carboplatin results in longer survival than radiotherapy alone in elderly patients with NSCLC. Methods This was a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Patients older than 70 years with unresectable stage III NSCLC were randomly assigned to chemoradiotherapy (60 Gy plus concurrent low-dose carboplatin [30 mg/m(2) per day, 5 days a week for 20 days]) or radiotherapy alone, using a minimisation method with biased-coin assignment balancing on Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), stage (IIIA vs IIIB), and institution. The primary endpoint was overall survival, which was analysed for the eligible population and stratified by ECOG performance status, stage, and institution. The trial was stopped early as a result of the second planned interim analysis. This study is registered with UMIN Clinical Trials Registry, number C000000060, and ClinicalTrials.gov, number NCT00132665. Findings 200 patients were enrolled from Sept 1, 2003 to May 27, 2010: 100 in the chemoradiotherapy group and 100 in the radiotherapy group. The second planned interim analysis was done 10 months after completion of patient accrual. At this time, median follow-up for censored cases was 19.4 months (IQR 10.3-33.5). In accordance with the prespecified stopping rule, the JCOG data and safety monitoring committee recommended early publication of this trial because the difference in overall survival favoured the chemoradiotherapy group. Median overall survival for the chemoradiotherapy and radiotherapy alone groups were 22.4 months (95% CI 16.5-33.6) and 16.9 months (13.4-20.3), respectively (hazard ratio 0.68, 95.4% CI 0.47-0.98, stratified log-rank test one-sided p value=0.0179). More patients had grade 3-4 haematological toxic effects in the chemoradiotherapy group than in the radiotherapy alone group, including leucopenia (61 [63.5%] vs none), neutropenia (55 [57.3%] vs none), and thrombocytopenia (28 [29.2%] vs two [2.0%]). Grade 3 infection was more common with chemoradiotherapy (12 patients [12.5%]) than with radiotherapy (four patients [4.1%]). Incidences of grade 3-4 pneumonitis and late lung toxicity were similar between groups. There were seven treatment-related deaths: three of 100 patients (3.0%) in the chemoradiotherapy group and four of 100 (4.0%) in the radiotherapy group. Interpretation For a select group of elderly patients with locally advanced NSCLC, combination chemoradio therapy provides a clinically significant benefit over radiotherapy alone, and should be considered for this population.
  • Radiotherapy quality assurance review for a multi-center randomized trial of locally advanced esophageal cancer: the Japan Clinical Oncology Group (JCOG) trial 0303, Naoko Sanuki, Satoshi Ishikura, Masayuki Shinoda, Yoshinori Ito, Kazushige Hayakawa, Nobutoshi Ando, INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 17, (2) 105 - 111,   2012年04月, 査読有り, The purpose of this study was to evaluate the radiotherapy (RT) quality assurance (QA) for JCOG 0303. JCOG 0303 was a multi-center phase II/III trial that compared two types of chemotherapy administered concomitantly with RT for locally advanced esophageal cancer. RT requirements included a total dose of 60 Gy in 30 fractions and CTV with a 2-cm margin cranio-caudally to the primary tumor. The QA assessment was given as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable following predefined criteria for quality parameters. A total of 142 cases were accrued. After excluding 36 incomplete/not evaluable, 106 (75%) were fully evaluable for RT quality review. Of these 106, there were 4 VU (4%) and overall RT compliance (PP + DA) was 96%. Comparing the incidence of VU based on the numbers enrolled by institution, the highest quarter of enrollment (a parts per thousand yen7 cases) had no VU, while all VU (4; 11%) were from institutions enrolling < 7 patients. The results of the RTQA assessment for JCOG 0303 were sufficient to provide reliable results. Additional improvements will be needed for institutions with low accrual rates.
  • Stereotactic body radiotherapy using a radiobiology-based regimen for stage I nonsmall cell lung cancer, Yuta Shibamoto, Chisa Hashizume, Fumiya Baba, Shiho Ayakawa, Yoshihiko Manabe, Aiko Nagai, Akifumi Miyakawa, Taro Murai, Hiromitsu Iwata, Yoshimasa Mori, Mikio Mimura, Satoshi Ishikura, CANCER, 118, (8) 2078 - 2084,   2012年04月, 査読有り, BACKGROUND: The most common regimen of stereotactic body radiotherapy (SBRT) for stage I nonsmall cell lung cancer in Japan is 48 grays (Gy) in 4 fractions over 4 days. Radiobiologically, however, higher doses are necessary to control larger tumors, and interfraction intervals should be >24 hours to take advantage of reoxygenation. In this study, the authors tested the following regimen: For tumors that measured <1.5 cm, 1.5 to 3.0 cm, and >3.0 cm in greatest dimension, radiation doses of 44 Gy, 48 Gy, and 52 Gy, respectively, were given in 4 fractions with interfraction intervals of =3 days. METHODS: Among 180 patients with histologically proven disease who entered the study, 120 were medically inoperable, and 60 were operable. The median patient age was 77 years (range, 29-92 years). SBRT was performed with 6-megavolt photons using 4 noncoplanar beams and 3 coplanar beams. Isocenter doses of 44 Gy, 48 Gy, and 52 Gy were received by 4 patients, 124 patients, and 52 patients, respectively. RESULTS: The overall survival rate for all 180 patients was 69% at 3 years and 52% at 5 years. The 3-year survival rate was 74% for operable patients and 59% for medically inoperable patients (P.080). The 3-year local control rate was 86% for tumors > 3 cm (44/ 48 Gy) and 73% for tumors > 3 cm (52 Gy; P.050). Grade >= 2 radiation pneumonitis developed in 13% of patients (10% of the 44-Gy/ 48-Gy group and 21% of the 52-Gy group; P.056). All other grade 2 toxicities developed in < 4% of patients. CONCLUSIONS: The SBRT protocol used in this study yielded reasonable local control and overall survival rates and acceptable toxicity. Dose escalation is being investigated. Cancer 2012; 118: 2078-84. VC 2011 American Cancer Society.
  • Optimal radiotherapy for non-small-cell lung cancer: current progress and future challenges., Ishikura S, General thoracic and cardiovascular surgery, 60, (3) 127 - 131,   2012年03月, 査読有り
  • PHASE II STUDY OF CHEMORADIOTHERAPY WITH 5-FLUOROURACIL AND CISPLATIN FOR STAGE II-III ESOPHAGEAL SQUAMOUS CELL CARCINOMA: JCOG TRIAL (JCOG 9906), Ken Kato, Kei Muro, Keiko Minashi, Atsushi Ohtsu, Satoshi Ishikura, Narikazu Boku, Hiroya Takiuchi, Yoshito Komatsu, Yoshinori Miyata, Haruhiko Fukuda, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 81, (3) 684 - 690,   2011年11月, 査読有り, Purpose: In this Phase II study, we evaluated the efficacy and toxicity of chemoradiotherapy (CRT) with cisplatin (CDDP) and 5-fluorouracil (5-FU) for Stage II-III esophageal squamous cell carcinoma (ESCC). Patients and Methods: Patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) thoracic ESCC were enrolled between April 2000 and March 2002. Chemotherapy comprised two courses of protracted infusion of 5-FU (400 mg/m(2)/day) on Days 1-5 and 8-12, and 2-h infusion of CDDP (40 mg/m(2)) on Days 1 and 8; this regimen was repeated every 5 weeks. Concurrent radiotherapy involved 60-Gy irradiation (30 fractions) for 8 weeks with a 2-week break. Responders received two courses of 5-FU (800 mg/m(2)/day) on Days 1-5 and CDDP (80 mg/m(2)) on Day 1. Final analysis was conducted in March 2007. Survival and late toxicities were monitored for 5 years. Results: The characteristics of the 76 patients enrolled were as follows: median age, 61 years; male/female, 68/8; performance status 0/1, 59/17 patients; Stage IIA/IIB/III, 26/12/38 patients. Of the 74 eligible patients, 46(62.2%) achieved complete response. Median survival time was 29 months, with 3- and 5-year survival rates of 44.7% and 36.8%, respectively. Acute toxicities included Grade 3/4 esophagitis (17%), nausea (17%), hyponatremia (16%), and infection without neutropenia (12%). Late toxicities comprised Grade 3/4 esophagitis (13%), pericardial (16%) and pleural (9%) effusion, and radiation pneumonitis (4%), causing 4 deaths. Conclusions: CRT is effective for Stage II-III ESCC with manageable acute toxicities and can provide a nonsurgical treatment option. However, further improvement is required for reduction in late toxicity. (C) 2011 Elsevier Inc.
  • JCOG Radiation Therapy Study Group: History and Achievements, Satoshi Ishikura, Yoshinori Ito, Masahiro Hiraoka, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 41, (11) 1241 - 1243,   2011年11月, 査読有り, The Radiation Therapy Study Group (RTSG) of the Japan Clinical Oncology Group (JCOG) was established in 2003. The missions of this group are to develop new standards of care with innovative, advanced technology radiation therapy, both for single-and multi-modality cancer treatment, and to improve radiation therapy quality and outcomes of JCOG trials conducted by other organ-oriented groups. In 2004, the first RTSG trial, a Phase II study of stereotactic body radiation therapy for Stage IA non-small cell lung cancer (JCOG 0403), was initiated. Four other trials are currently open for accrual. JCOG 0702 is a Phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer. JCOG 0701 is a Phase III study comparing accelerated fractionation with conventional fractionation radiation therapy for T1-2N0M0 glottic cancer. JCOG 0906 is a multicenter safety trial of hypofractionated radiation therapy after breast-conserving surgery in patients with margin-negative invasive breast cancer. JCOG 1015 is a Phase II study of intensity-modulated radiation therapy with chemotherapy for loco-regionally advanced nasopharyngeal cancer. Other RTSG activities include a medical physics working group responsible for dosimetry audits; a genetic analysis working group involved in accompanying research to analyze single-nucleotide polymorphisms to identify predictors of radiation toxicities; a working group that has developed atlases of clinical target volumes for uterine cervical cancer; and participation in the Harmonisation Group to promote global harmonization of radiotherapy and radiotherapy quality assurance among trial groups. Further efforts to improve radiation therapy quality and outcomes of cancer treatment are necessary.
  • A Consensus-based Guideline Defining Clinical Target Volume for Primary Disease in External Beam Radiotherapy for Intact Uterine Cervical Cancer, Takafumi Toita, Tatsuya Ohno, Yuko Kaneyasu, Tomoyasu Kato, Takashi Uno, Kazuo Hatano, Yoshiki Norihisa, Takahiro Kasamatsu, Takeshi Kodaira, Ryoichi Yoshimura, Satoshi Ishikura, Masahiro Hiraoka, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 41, (9) 1119 - 1126,   2011年09月, 査読有り, Objective: To develop a consensus-based guideline to define clinical target volume for primary disease (clinical target volume primary) in external beam radiotherapy for intact uterine cervical cancer. Methods: The working subgroup of the JCOG Radiation Therapy Study Group began developing a guideline for primary clinical target volume in November 2009. The group consisted of 10 radiation oncologists and 2 gynecologic oncologists. The process started with comparing the contouring on computed tomographic images of actual cervical cancer cases among the members. This was followed by a comprehensive literature review that included primary research articles and textbooks as well as information on surgical procedures. Extensive discussion occurred in face-to-face meetings (three occasions) and frequent e-mail communications until a consensus was reached. Results: The working subgroup reached a consensus on the definition for the clinical target volume primary. The clinical target volume primary consists of the gross tumor volume, uterine cervix, uterine corpus, parametrium, vagina and ovaries. Definitions for these component structures were determined. Anatomical boundaries in all directions were defined for the parametrium. Examples delineating these boundaries were prepared for the posterior border of the parametrium for various clinical situations (i.e. central tumor bulk, degree of parametrial involvement). Conclusions: A consensus-based guideline defining the clinical target volume primary was developed for external beam radiotherapy for intact uterine cervical cancer. This guideline will serve as a template for radiotherapy protocols in future clinical trials. It may also be used in actual clinical practice in the setting of highly precise external beam radiotherapy, including intensity-modulated radiotherapy.
  • Radiotherapy quality assurance of the Japanese Gynecologic Oncology Group study (JGOG1066): a cooperative phase II study of concurrent chemoradiotherapy for uterine cervical cancer, Takafumi Toita, Shingo Kato, Satoshi Ishikura, Kayoko Tsujino, Takeshi Kodaira, Takashi Uno, Kazuo Hatano, Hideyuki Sakurai, Yuzuru Niibe, Tomoko Kazumoto, Tetsuo Nishimura, Ryo Kitagawa, Miki Fukutani, Masahiko Oguchi, Kenji Umayahara, Yasuyuki Hirashima, Yoichi Aoki, Ken Takizawa, INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 16, (4) 379 - 386,   2011年08月, 査読有り, Background To assess radiotherapy protocol compliance in a multi-institutional phase II study of concurrent chemoradiotherapy for patients with locally advanced cancer of the uterine cervix (JGOG1066). Methods For study protocol development, various radiotherapy parameters were examined and consensus was reached by Japanese radiation oncologists with cervical cancer treatment expertise. Quality assurance (QA) was also discussed and included in the protocol. A credentialing process was used to select institutions for participation in the study. Individual case reviews referring to 18 QA items were undertaken for each patient. Radiotherapy data were submitted to the Japanese Gynecologic Oncology Group (JGOG) data center and reviewed by the members of the radiotherapy committee. The QA evaluation was classed as per protocol, deviation, and violation. Results Individual case reviews were performed on 69 of 72 patients entered in the study. In 24 patients (35%), there were no deviations for any QA items. There were also no deviations seen for 5 of the 18 items in 69 patients evaluated. Deviations of 64 QA items were seen in 45 cases, and violations were seen in 4 cases (4 items). The most common deviation concerned appropriate application for the external beam radiotherapy (EBRT) boost to involved nodes or parametrium (32 cases). The 4 violations were identified in the QA items regarding high-dose rate intracavitary brachytherapy. Conclusions Radiotherapy protocol compliance was favorable except for the EBRT boost indications. The results of this study validate the quality of radiotherapy in JGOG1066, and indicate that the final analysis will provide meaningful results.
  • A Consensus-based Guideline Defining the Clinical Target Volume for Pelvic Lymph Nodes in External Beam Radiotherapy for Uterine Cervical Cancer, Takafumi Toita, Tatsuya Ohno, Yuko Kaneyasu, Takashi Uno, Ryouichi Yoshimura, Takeshi Kodaira, Kazuhisa Furutani, Goro Kasuya, Satoshi Ishikura, Toshiharu Kamura, Masahiro Hiraoka, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 40, (5) 456 - 463,   2010年05月, 査読有り, To develop a consensus-based guideline as well as an atlas defining pelvic nodal clinical target volumes in external beam radiotherapy for uterine cervical cancer. A working subgroup to establish the consensus-based guideline on clinical target volumes for uterine cervical cancer was formulated by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July 2008. The working subgroup consisted of seven radiation oncologists. The process resulting in the consensus included a comparison of contouring on CT images among the members, reviewing of published textbooks and the relevant literature and a distribution analysis of metastatic nodes on computed tomography/magnetic resonance imaging of actual patients. The working subgroup defined the pelvic nodal clinical target volumes for cervical cancer and developed an associated atlas. As a basic criterion, the lymph node clinical target volume was defined as the area encompassed by a 7 mm margin around the applicable pelvic vessels. Modifications were made in each nodal area to cover adjacent adipose tissues at risk of microscopic nodal metastases. Although the bones and muscles were excluded, the bowel was not routinely excluded in the definition. Each of the following pelvic node regions was defined: common iliac, external iliac, internal iliac, obturator and presacral. Anatomical structures bordering each lymph node region were defined for six directions; anterior, posterior, lateral, medial, cranial and caudal. Drafts of the definition and the atlas were reviewed by members of the JCOG Gynecologic Cancer Study Group (GCSG). We developed a consensus-based guideline defining the pelvic node clinical target volumes that included an atlas. The guideline will be continuously updated to reflect the ongoing changes in the field.
  • VARIATIONS IN TARGET VOLUME DEFINITION FOR POSTOPERATIVE RADIOTHERAPY IN STAGE III NON-SMALL-CELL LUNG CANCER: ANALYSIS OF AN INTERNATIONAL CONTOURING STUDY, Femke O. B. Spoelstra, Suresh Senan, Cecile Le Pechoux, Satoshi Ishikura, Francesc Casas, David Ball, Allan Price, Dirk De Ruysscher, John R. van Sornsen de Koste, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 76, (4) 1106 - 1113,   2010年03月, 査読有り, Purpose: Postoperative radiotherapy (PORT) in patients with completely resected non small-cell lung cancer with mediastinal involvement is controversial because of the failure of earlier trials to demonstrate a survival benefit. Improved techniques may reduce toxicity, but the treatment fields used in routine practice have not been well studied. We studied routine target volumes used by international experts and evaluated the impact of a contouring protocol developed for a new prospective study, the Lung Adjuvant Radiotherapy Trial (Lung ART). Methods and Materials: Seventeen thoracic radiation oncologists were invited to contour their routine clinical target volumes (CTV) for 2 representative patients using a validated CD-ROM based contouring program. Subsequently, the Lung ART study protocol was provided, and both cases were contoured again. Variations in target volumes and their dosimetric impact were analyzed. Results: Routine CTVs were received for each case from 10 clinicians, whereas six provided both routine and protocol CTVs for each case. Routine CTVs varied up to threefold between clinicians, but use of the Lung ART protocol significantly decreased variations. Routine CTVs in a postlobectomy patient resulted in V(20) values ranging from 12.7% to 54.0%, and Lung ART protocol CTVs resulted in values of 20.6% to 29.2%. Similar results were seen for other toxicity parameters and in the postpneumectomy patient. With the exception of upper paratracheal nodes, protocol contouring improved coverage of the required nodal stations. Conclusion: Even among experts, significant interclinician variations are observed in PORT fields. Inasmuch as contouring variations can confound the interpretation of PORT results, mandatory quality assurance procedures have been incorporated into the current Lung ART study. (C) 2010 Elsevier Inc.
  • A phase I study of palliative chemoradiation therapy with paclitaxel and cisplatin for local symptoms due to an unresectable primary advanced or locally recurrent gastric adenocarcinoma., Takaki Yoshikawa, Akira Tsuburaya, Naoki Hirabayashi, Kazuhiro Yoshida, Naoki Nagata, Yasuhiro Kodera, Naoto Takahashi, Koji Oba, Masayuki Kimura, Satoshi Ishikura, Yumi Miyashita, Junichi Sakamoto, Cancer chemotherapy and pharmacology, 64, (6) 1071 - 7,   2009年11月, 査読有り, PURPOSE: To establish the maximum tolerated dose and dose-limiting toxicity of chemoradiation with paclitaxel (PTX) and cisplatin (CDDP) for patients with local symptoms due to unresectable primary advanced or locally recurrent gastric adenocarcinoma located at left-upper abdomen. METHODS: Chemotherapy consisted of PTX at escalating doses of 40-80 mg/m(2) per day and CDDP at escalating doses of 20-25 mg/m(2) per day on days 1, 15, and 29. Concurrent radiation was administered up to a dose of 45 Gy for 5 weeks. RESULTS: A total of nine patients were enrolled, of which six were into level 1 (PTX 60 mg/m(2) and CDDP 20 mg/m(2)) and three into level -1 (PTX 50 mg/m(2) and CDDP 20 mg/m(2)). At level 1, one patient developed grade 3 fatigue, and the other experienced grade 5 DIC, grade 5 pneumonia, grade 4 thrombocytopenia, grade 3 hyponatremia, and grade 3 esophagitis as dose-limiting toxicities. A palliative effect was observed in eight of nine patients; six of six patients at level 1 and two of three at level -1. CONCLUSION: PTX 50 mg/m(2) and CDDP 20 mg/m(2) given biweekly with concurrent radiation therapy of 45 Gy were well tolerated.
  • Phase I/II Study of Concurrent Chemoradiotherapy for Localized Nasal Natural Killer/T-Cell Lymphoma: Japan Clinical Oncology Group Study JCOG0211, Motoko Yamaguchi, Kensei Tobinai, Masahiko Oguchi, Naoki Ishizuka, Yukio Kobayashi, Yasushi Isobe, Kenichi Ishizawa, Nobuo Maseki, Kuniaki Itoh, Noriko Usui, Izumi Wasada, Tomohiro Kinoshita, Koichi Ohshima, Yoshihiro Matsuno, Takashi Terauchi, Shigeru Nawano, Satoshi Ishikura, Yoshikazu Kagami, Tomomitsu Hotta, Kazuo Oshimi, JOURNAL OF CLINICAL ONCOLOGY, 27, (33) 5594 - 5600,   2009年11月, 査読有り, Purpose To explore a more effective treatment for localized nasal natural killer (NK)/T-cell lymphoma, we conducted a phase I/II study of concurrent chemoradiotherapy. Patients and Methods Treatments comprised concurrent radiotherapy (50 Gy) and 3 courses of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC). Patients with a newly diagnosed stage IE or contiguous IIE disease with cervical node involvement and a performance status (PS) of 0 to 2 were eligible for enrollment. The primary end point of the phase II portion was a 2-year overall survival in patients treated with the recommended dose. Results Of the 33 patients enrolled, 10 patients were enrolled in the phase I portion and a two thirds dose of DeVIC was established as the recommended dose. Twenty-seven patients (range, 21 to 68; median, 56 years) treated with the recommended dose showed the following clinical features: male: female, 17: 10; stage IE, 18; stage IIE, 9; B symptoms present, 10; elevated serum lactate dehydrogenase, 5; and PS 2, 2. With a median follow-up of 32 months, the 2-year overall survival was 78% (95% CI, 57% to 89%). This compared favorably with the historical control of radiotherapy alone (45%). Of the 26 patients assessable for a response, 20 (77%) achieved a complete response, with one partial response. The overall response rate was 81%. The most common grade 3 nonhematologic toxicity was mucositis related to radiation (30%). No treatment-related deaths were observed. Conclusion Concurrent chemoradiotherapy using multidrug resistance-nonrelated agents and etoposide is a safe and effective treatment for localized nasal NK/T-cell lymphoma and warrants further investigation.
  • A Phase II Trial of Chemoradiotherapy for Stage I Esophageal Squamous Cell Carcinoma: Japan Clinical Oncology Group Study (JCOG9708), Hoichi Kato, Akihiro Sato, Haruhiko Fukuda, Yoshikazu Kagami, Harushi Udagawa, Akihiko Togo, Nobutoshi Ando, Otsuo Tanaka, Masayuki Shinoda, Hideaki Yamana, Satoshi Ishikura, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 39, (10) 638 - 643,   2009年10月, 査読有り, Objective: The study objective was to evaluate the efficacy and toxicity of chemoradiotherapy with 5-fluorouracil (5-FU) plus cisplatin in patients with Stage I esophageal squamous cell carcinoma (ESCC). The primary endpoint was proportion of complete response (%CR). Methods: Patients with Stage I (T1 NOMO) ESCC, aged 20-75 years, without indication of endoscopic mucosal resection were eligible. Treatment consisted of cisplatin 70 mg/m(2) (day 1) and 5-FU 700 mg/m(2)/day (days 1-4) combined with 30 Gy radiotherapy (2 Gy/day, 5 days/week, days 1-21). The cycle was repeated twice with 1-week split. Salvage surgery was recommended for residual tumor or local recurrence. Results: From December 1997 to June 2000, 72 patients were enrolled. No ineligible patient or major protocol violation was observed. There were 63 CRs for %CR of 87.5% [95% confidence interval (CI): 77.6-94.1]. Six patients with residual tumor successfully underwent esophagectomy. There was no Grade 4 toxicity. Four-year survival proportion was 80.5% (95% CI: 71.3-89.7), and 4-year major relapse-free survival proportion was 68% (95% CI: 57.3-78.8) (mucosal recurrence removed by endoscopy was not counted as an event). Conclusions: High CR proportion and survival proportion with mild toxicity suggest that this regimen could be considered as a candidate of new standard treatment to be compared with surgery in patients with Stage I ESCC.
  • Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus, Masakatsu Onozawa, Keiji Nihei, Satoshi Ishikura, Keiko Minashi, Tomonori Yano, Manabu Muto, Atsushi Ohtsu, Takashi Ogino, RADIOTHERAPY AND ONCOLOGY, 92, (2) 266 - 269,   2009年08月, 査読有り, Background and purpose: There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer. Materials and methods: Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60 Gy in 30 fractions. Up to 40 Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI. Results: One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years: male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0-5.3%) patient experienced elective nodal failure without any other site of recurrence. Conclusion: In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 92 (2009) 266-269
  • Radiotherapy quality assurance review in a multi-center randomized trial of limited-disease small cell lung cancer: the Japan Clinical Oncology Group (JCOG) trial 0202, Naoko Sanuki-Fujimoto, Satoshi Ishikura, Kazushige Hayakawa, Kaoru Kubota, Yutaka Nishiwaki, Tomohide Tamura, RADIATION ONCOLOGY, 4,   2009年06月, 査読有り, Background: The purpose of this study was to analyze the radiotherapy (RT) quality assurance (QA) assessment in Japan Clinical Oncology Group (JCOG) 0202, which was the first trial that required on-going RT QA review in the JCOG. Methods: JCOG 0202 was a multi-center phase III trial comparing two types of consolidation chemotherapy after concurrent chemoradiotherapy for limited-disease small cell lung cancer. RT requirements included a total dose of 45 Gy/30 fx (bis in die, BID/twice a day) without heterogeneity correction; elective nodal irradiation (ENI) of 30 Gy; at least 1 cm margin around the clinical target volume (CTV); and interfraction interval of 6 hours or longer. Dose constraints were defined in regards to the spinal cord and the lung. The QA assessment was classed as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable (I/NE). Results: A total of 283 cases were accrued, of which 204 were fully evaluable, excluding 79 I/NE cases. There were 18 VU in gross tumor volume (GTV) coverage (8% of 238 evaluated); 4 VU and 23 DA in elective nodal irradiation (ENI) (2% and 9% of 243 evaluated, respectively). Some VU were observed in organs at risk (1 VU in the lung and 5 VU in the spinal cord). Overall RT compliance (PP + DA) was 92% (187 of 204 fully evaluable). Comparison between the former and latter halves of the accrued cases revealed that the number of VU and DA had decreased. Conclusion: The results of the RT QA assessment in JCOG 0202 seemed to be acceptable, providing reliable results.
  • Quality assurance of radiotherapy in cancer treatment: toward improvement of patient safety and quality of care., Ishikura S, Japanese journal of clinical oncology, 38, (11) 723 - 729,   2008年11月, 査読有り
  • Accelerated fractionation versus conventional fractionation radiation therapy for glottic cancer of T1-2N0M0 Phase III study: Japan Clinical Oncology Group study (JCOG 0701)., Nakamura K, Kodaira T, Shikama N, Kagami Y, Ishikura S, Shibata T, Hiraoka M, Japanese journal of clinical oncology, 38, (5) 387 - 389,   2008年05月, 査読有り
  • Feasibility study of glass dosimeter postal dosimetry audit of high-energy radiotherapy photon beams., Mizuno H, Kanai T, Kusano Y, Ko S, Ono M, Fukumura A, Abe K, Nishizawa K, Shimbo M, Sakata S, Ishikura S, Ikeda H, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 86, (2) 258 - 263,   2008年02月, 査読有り
  • A Japan clinical oncology group trial for stereotactic body radiation therapy of non-small cell lung cancer., Hiraoka M, Ishikura S, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2, (7 Suppl 3) S115 - 7,   2007年07月, 査読有り
  • Interinstitutional variations in planning for stereotactic body radiation therapy for lung cancer, Yukinori Matsuo, Kenji Takayama, Yasushi Nagata, Etsuo Kunieda, Kunihiko Tateoka, Naoki Ishizuka, Takashi Mizowaki, Yoshiki Norihisa, Masato Sakamoto, Yuichiro Narita, Satoshi Ishikura, Masahiro Hiraoka, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 68, (2) 416 - 425,   2007年06月, 査読有り, Purpose: The aim of this study was to assess interinstitutional variations in planning for stereotactic body radiation therapy (SBRT) for lung cancer before the start of the Japan Clinical Oncology Group (JCOG) 0403 trial. Methods and Materials: Eleven. institutions created virtual plans for four cases of solitary lung cancer. The created plans should satisfy the target definitions and the dose constraints for the JCOG 0403 protocol. Results: FOCUS/XiO (CMS) was used in six institutions, Eclipse (Varian) in 3, Cadplan (Varian) in one, and Pinnacle3 (Philips/ADAC) in one. Dose calculation algorithms of Clarkson with effective path length correction and superposition were used in FOCUS/XiO; pencil beam convolution with Batho power law correction was used in Eclipse and Cadplan; and collapsed cone convolution superposition was used in Pinnacle3. For the target volumes, the overall coefficient of variation was 16.6%, and the interinstitutional variations were not significant. For maximal dose, minimal dose, D95, and the homogeneity index of the planning target volume, the interinstitutional variations were significant. The dose calculation algorithm was a significant factor in these variations. No violation of the dose constraints for the protocol was observed. Conclusion: There can be notable interinstitutional variations in planning for SBRT, including both interobserver variations in the estimate of target volumes as well as dose calculation effects related to the use of different dose calculation algorithms. (C) 2007 Elsevier Inc.
  • [Field Survey Results on Output for X-ray Therapeutic Accelerators in Radiotherapy Institutions of Saitama and Tochigi Prefectures.]., Enokido Y, Okamoto H, Kiyomiya Y, Furuya T, Fujimori K, Kusano Y, Touyama N, Goka T, Ooyama M, Minemura T, Kutsutani-Nakamura Y, Shimbo M, Tabushi K, Ishikura S, Endou M, Ikeda H, Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics, 27, (2) 71 - 77,   2007年, 査読有り
  • Dosimetric verification in participating institutions in a stereotactic body radiotherapy trial for stage I non-small cell lung cancer: Japan clinical oncology group trial (JCOG0403), Teiji Nishio, Etsuo Kunieda, Hiroki Shirato, Satoshi Ishikura, Hiroshi Onishi, Kunihiko Tateoka, Masahiro Hiraoka, Yuichirou Narita, Masataka Ikeda, Tomonori Goka, PHYSICS IN MEDICINE AND BIOLOGY, 51, (21) 5409 - 5417,   2006年11月, 査読有り, A multicentre phase II trial of stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer was initiated in Japan as the Japan Clinical Oncology Group trial (JCOG0403). Before starting the trial, a decision was made to evaluate the treatment machine and treatment planning in participating institutions to minimize the variations of the prescription dose between the institutions. We visited the 16 participating institutions and examined the absolute dose at the centre of a simulated spherical tumour of 3.0 cm diameter in the lung using the radiation treatment planning systems in each institution. A lung phantom for stereotactic body radiotherapy (SBRT) was developed and used for the treatment planning and film dosimetry. In the JCOG radiotherapy study group, the no model-based calculation algorithm or the model-based calculation algorithm with a dose kernel unscaled for heterogeneities were selected for use in the initial SBRT trials started in 2004, and the model-based calculation algorithm with a dose kernel scaled for heterogeneities was selected for the coming trial. The findings of this study suggest that the clinical results of lung SBRT trials should be carefully evaluated in comparison with the actual dose given to patients.
  • Docetaxel consolidation therapy following cisplatin, vinorelbine, and concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer., Sekine I, Nokihara H, Sumi M, Saijo N, Nishiwaki Y, Ishikura S, Mori K, Tsukiyama I, Tamura T, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 1, (8) 810 - 815,   2006年10月, 査読有り
  • High-dose proton beam therapy for stage I non-small-cell lung cancer, K Nihei, T Ogino, S Ishikura, H Nishimura, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 65, (1) 107 - 111,   2006年05月, 査読有り, Purpose: To evaluate retrospectively the safety and efficacy of high-dose proton beam therapy (PBT) for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Between 1999 and 2003, 37 patients were treated in our institution. The indications for PBT were pathologically proven NSCLC, clinical Stage 1, tumor size <= 5 cm, medically inoperable or refusal of surgery, and written informed consent. A total dose of 70-94 GY(E) was delivered in 20 fractions (3.5-4.9 Gy, per fraction). Results: Patient characteristics (number of patients) were as follows: Stage IA/IB, 17 of 20; medically inoperable/refusal of surgery, 23/14; total dose 70/80/88/94 Gy(E), 3/17/16/1. With a median follow-up period of 24 months, the 2-year local progression-free and overall survival rates were 80% and 84%, respectively. The 2-year locoregional relapse-free survival rates in Stage IA and Stage IB were 79% and 60%, respectively. No serious acute toxicity was observed. Late Grades 2 and 3 pulmonary toxicities were observed in 3 patients each. Of these 6 patients, 5 had Stage IB disease. Conclusions: Proton beam therapy is a promising treatment modality for Stage I NSCLC, though locoregional relapse and late pulmonary toxicities in Stage IB patients were substantial. Further investigation of PBT for Stage I NSCLC is warranted. (c) 2006 Elsevier Inc.
  • Epstein-Barr virus involvement is a predictive factor for the resistance to chemoradiotherapy of gastric diffuse large B-cell lymphoma, T Yoshino, S Nakamura, Y Matsuno, A Ochiai, T Yokoi, Y Kitadai, J Suzumiya, K Tobinai, Y Kobayashi, Oda, I, K Mera, A Ohtsu, S Ishikura, CANCER SCIENCE, 97, (2) 163 - 166,   2006年02月, 査読有り, Primary gastric diffuse large B-cell lymphomas are generally well controlled by non-surgical treatment with combination chemotherapy followed by radiotherapy. We have previously reported that over 90% of patients achieved complete response (CR) with this therapeutic strategy: three cycles of cyclophosphamide, adriamycin, vincristine and prednisone followed by radiotherapy (40.5 Gy). Although the CR rate was very high, some patients still showed resistance to this combination therapy. In order to clarify the factors related to therapy resistance, we examined the relationship between Epstein-Barr virus (EBV), which was examined using an in situ hybridization technique, and the patients' clinical courses. Out of the 50 patients, four were EBV positive; over half of lymphoma cells were positive for EBV by in situ hybridization. Of the three EBV-positive patients, two showed progressive disease and one achieved partial response (PR). Two of the patients died of disease progression. The other patient achieved CR, but the lymphoma recurred with distant metastasis in the cerebellum 3 months after remission. In the present study, eight patients did not achieve CR or they relapsed, four patients showed progressive disease, one patient achieved PR, and three patients achieved CR with recurrence. Therefore, half of these unfavorable patients were EBV positive. This finding strongly indicated that EBV-associated gastric diffuse large B-cell lymphomas frequently show resistance to standard chemoradiotherapy, although some other adverse factors remain unclear.
  • Phase II feasibility study of high-dose radiotherapy for prostate cancer using proton boost therapy: First clinical trial of proton beam therapy for prostate cancer in Japan, K Nihei, T Ogino, S Ishikura, M Kawashima, H Nishimura, S Arahira, M Onozawa, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 35, (12) 745 - 752,   2005年12月, 査読有り, Objective: To assess the feasibility of high-dose radiotherapy for prostate cancer using proton boost therapy following photon radiotherapy. Methods: The primary endpoint was acute grade 3 or greater genitourinary (GU) and gastrointestinal (GI) toxicities. The study included patients with clinical stage T1-3N0M0 prostate cancer. Radiotherapy consisted of 50 Gy/25 fx photon irradiation to the prostate and the bilateral seminal vesicles followed by proton boost of 26 Gy(E)/13 fx to the prostate alone. Hormonal therapy was allowed before and during the radiation therapy. Results: Between January 2001 and January 2003, 30 patients were enrolled in this study. Acute grade 1/2 GU and GI toxicities were observed in 20/4 and 17/0 patients, respectively. With the median follow-up period of 30 months (range 20-45), late grade 1/2 GU and GI toxicities occurred in 2/3 and 8/3 patients, respectively. No grade 3 or greater acute or late toxicities were observed. All patients were alive, but six patients relapsed biochemically after 7-24 months. Conclusions: Proton boost therapy following photon radiotherapy for prostate cancer is feasible. To evaluate the efficacy and safety of proton beam therapy, a multi-institutional phase II trial is in progress in Japan.
  • Japanese multicenter phase II study of CHOP followed by radiotherapy in stage I-II, diffuse large B-cell lymphoma of the stomach, S Ishikura, K Tobinai, A Ohtsu, S Nakamura, T Yoshino, Oda, I, T Takagi, K Mera, Y Kagami, K Itoh, Y Tamaki, J Suzumiya, M Taniwaki, S Yamamoto, CANCER SCIENCE, 96, (6) 349 - 352,   2005年06月, 査読有り, CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) followed by radiotherapy is regarded as standard care for localized aggressive lymphoma; however, prospective confirmation of its applicability to localized primary gastric lymphoma is inadequate, and most patients in Japan have been initially treated with gastrectomy. We conducted a multicenter phase II study to evaluate the feasibility and efficacy of the non-surgical treatment. Eligibility criteria required primary gastric diffuse large B-cell lymphoma, stage I-II1, age 20-75, performance status 0-1 and adequate organ function. Treatment consisted of three cycles of CHOP followed by radiotherapy 40.5 Gy. Fifty-five patients were enrolled between December 1999 and February 2003, and 52 eligible patients were analyzed. Patient characteristics were as follows: median age, 61 years; 28 men, 24 women; 36 with stage 1, 16 with stage 11, 47 with a low International Prognostic Index (IPI) and five with a low-intermediate IPI. All but one patient completed planned treatment. No serious complications including massive hemorrhage or perforation were observed. A complete response was achieved in 48 of the 52 patients (92%, 95% confidence interval: 82-98%) and progressive disease in three. Two patients underwent salvage gastrectomy due to disease persistence or recurrence. With a median follow-up period of 28 months, 2-year progression-free and overall survivals were 88 and 94%, respectively. CHOP followed by radiotherapy is safe and highly effective in localized gastric diffuse large B-cell lymphoma. This organ-preserving treatment should be considered as a very reasonable therapeutic option.
  • Clinical impact of criteria for complete response (CR) of primary site to treatment of esophageal cancer, M Tahara, A Ohtsu, S Hironaka, N Boku, S Ishikura, Y Miyata, T Ogino, S Yoshida, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 35, (6) 316 - 323,   2005年06月, 査読有り, Background: With the development of chemoradiotherapy for esophageal cancer, the complete response (CR) rate would become an important surrogate end-point. However, the Response Evaluation Criteria in Solid Tumors (RECIST) do not provide criteria for a response at the primary site of esophageal cancer. The objective of this study was to assess the validity of the endoscopic CR criteria for the primary site of esophageal cancer treated with chemoradiotherapy. Methods: We reviewed 139 patients with T1-T4, N0-1, M0-1 a esophageal cancer treated with definitive chemoradiotherapy from August 1992 to April 1999. CR was tentatively defined upon endoscopic observation of the entire esophagus as: (i) disappearance of the tumor lesion; (ii) disappearance of ulceration (slough); and (iii) absence of cancer cells in biopsy specimens. Results: CR at the primary site (primary-CR) was achieved in 80 patients (58%). Of these, 71 (89%) were evaluated as having primary-CR within 6 months from the start of therapy. With a median follow-up of 53 months, a remarkable difference in the 5-year survival rate was observed between patients evaluated as having primary-CR and having non-CR (46 and 6%, P < 0.0001). Local failure was observed in 15 patients and the local control rate in patients with primary-CR was 78% at 5 years. Conclusions: These criteria appear to represent an appropriate surrogate end-point because they are convenient to apply, require only a short time before a primary-CR can be declared and their fulfillment can predict long-term survival. It is recommended that RECIST include precise endoscopic findings for primary lesions in esophageal cancer in the CR criteria.
  • Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer: a phase III trial of the Japan Clinical Oncology Group (JCOG9812), S Atagi, M Kawahara, T Tamura, K Noda, K Watanabe, A Yokoyama, T Sugiura, H Senba, S Ishikura, H Ikeda, N Ishizuka, N Saijo, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 35, (4) 195 - 201,   2005年04月, 査読有り, Background: The purpose of this study was to evaluate whether radiotherapy with carboplatin would result in longer survival than radiotherapy alone in elderly patients with unresectable stage III non-small cell lung cancer (NSCLC). Methods: Eligible patients were 71 years of age or older with unresectable stage III NSCLC. Patients were randomly assigned to the radiotherapy alone (RT) arm, irradiation with 60 Gy; or the chemoradiotherapy (CRT) arm, the same radiotherapy and additional concurrent use of carboplatin 30 mg/m(2) per fraction up to the first 20 fractions. Results: This study was terminated early when 46 patients were registered from November 1999 to February 2001. Four patients (one in the RT arm, three in the CRT arm) were considered to have died due to treatment-related causes. The JCOG Radiotherapy Committee assessed these treatment-related deaths (TRDs) and the compliance with radiotherapy in this trial. They found that 60% of the cases corresponded to protocol deviation and 7% were protocol violation in dose constraint to the normal lung, two of whom died due to radiation pneumonitis. As to the effectiveness for the 46 patients enrolled, the median survival time was 428 days [95% confidence interval (CI) = 212-680 days] in the RT arm versus 554 days (95% CI = 331 to not estimable) in the CRT arm. Conclusions: Due to the early termination of this study, the effectiveness of concurrent use of carboplatin remains unclear. We re-planned and started a study with an active quality control program which was developed by the JCOG Radiotherapy Committee.
  • A phase II study of hyperfractionated accelerated radiotherapy (HART) after induction cisplatin (CDDP) and vinorelbine (VNR) for stage III non-small-cell lung cancer (NSCLC), S Ishikura, Y Ohe, K Nihei, K Kubota, R Kakinuma, H Ohmatsu, K Goto, S Niho, Y Nishiwaki, T Ogino, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 61, (4) 1117 - 1122,   2005年03月, 査読有り, Purpose: The purpose was to assess the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HART) after induction chemotherapy for Stage III non-small-cell lung cancer. Methods and Materials: Treatment consisted of 2 cycles of cisplatin 80 mg/m(2) on Day 1 and vinorelbine 25 mg/m(2) on Days 1 and 8 every 3 weeks followed by HART, 3 times a day (1.5, 1.8, 1.5 Gy, 4-h interval) for a total dose of 57.6 Gy. Results: Thirty patients were eligible. Their median age was 64 years (range, 46-73 years), 24 were male, 6 were female, 8 had performance status (PS) 0, 22 had PS 1, 9 had Stage IIIA, and 21 had Stage IIIB. All but 1 patient completed the treatment. Common grade >= 3 toxicities during the treatment included neutropenia, 25; infection, 5; esophagitis, 5; and radiation pneumonitis, 3. The overall response rate was 83%. The median survival was 24 months (95% confidence interval [CI], 13-34 months), and the 2-year overall survival was 50% (95% CI, 32-68%). The median progression-free survival was 10 months (95% CI, 8-20 months). Conclusion: Hyperfractionated accelerated radiotherapy after induction of cisplatin and vinorelbine was feasible and promising. Future investigation employing dose-intensified radiotherapy in combination with chemotherapy is needed. (c) 2005 Elsevier Inc.
  • Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T2-3Nany M-0 squamous cell carcinoma of the esophagus, S Hironaka, A Ohtsu, N Boku, M Muto, F Nagashima, H Saito, S Yoshida, M Nishimura, M Haruno, S Ishikura, T Ogino, S Yamamoto, A Ochiai, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 57, (2) 425 - 433,   2003年10月, 査読有り, Purpose: To compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus and to identify useful clinicopathologic and biologic markers to select better treatment. Methods and Materials: Between August 1992 and April 1999, 98 consecutive patients were selected for this study; 53 were treated with chemoradiotherapy and 45 with surgery. The patients in the chemoradiotherapy group received 5-fluorouracil combined with cisplatin plus 60 Gy of radiation, and those in the surgery group received an esophagectomy with radical node dissection. Biologic markers were investigated immunohistochemically using pretreatment biopsy specimens. Results: The baseline clinical TNM stage was more advanced in the chemoradiotherapy group than in the surgery group. With a median follow-up period of 43 months, the 5-year survival rate was 46% in the chemoradiotherapy and 51% in the surgery group, without statistical significance (p = 0.47, log-rank test). Cox regression analysis for prognosis revealed that epidermal growth factor receptor positivity, high microvessel density, and cyclin D1 positivity yielded a low value for relative risk (0.66, 0.54, and 0.62, respectively), which favored chemoradiotherapy over surgery, without statistical significance. Conclusion: This nonrandomized study showed a trend for the chemoradiotherapy in the treatment of esophageal carcinoma, but the results need to be confirmed by additional study. (C) 2003 Elsevier Inc.
  • [Controversies in the treatment of esophageal cancer from the viewpoint of medical oncology]., Ohtsu A, Muto M, Mera K, Ishikura S, Gan to kagaku ryoho. Cancer & chemotherapy, 30, (9) 1230 - 1237,   2003年09月, 査読有り
  • EMR as salvage treatment for patients with locoregional failure of definitive chemoradiotherapy for esophageal cancer, S Hattori, M Muto, A Ohtsu, N Boku, T Manabe, T Doi, S Ishikura, S Yoshida, GASTROINTESTINAL ENDOSCOPY, 58, (1) 65 - 70,   2003年07月, 査読有り, Background: Definitive chemoradiotherapy is recognized as a standard treatment for esophageal cancer. Although most failures of this combined modality are locoregional, without distant metastasis, there are few curative treatment options available in such cases except salvage esophagectomy. Methods: Experience with 16 patients with squamous cell carcinoma of the esophagus who underwent EMR as a salvage treatment after locoregional failure of definitive chemoradiotherapy was reviewed retrospectively. EMR was performed by using the mucosal strip technique. Eight patients had local recurrence at the primary site after a complete response to chemoradiotherapy, 5 had metachronous multiple cancers, and 3 had residual tumor after completing chemoradiotherapy. Results: In all patients, the EMR-treated tumors were histopathologic stage T1 and were clinical stage NOMO as defined by EUS and CT. No serious complication was observed in any patient. At a median follow-up of 33 months (range 11-73 months) from the initiation of chemoradiotherapy, 3 patients (38%) with local recurrence at the primary site, 3 (40%) with metachronous multiple cancers, and two (67%) with residual cancer were still alive and disease-free after salvage EMR, for periods of 30 to 63 months. The 3-year survival rate from the initiation of salvage EMR for all patients was 56%. Conclusions: Long-term survival can be achieved with salvage EMR for locoregional failure after definitive chemoradiotherapy for esophageal cancer without serious complications. EMR may be a salvage treatment option when a recurrent or residual tumor is superficial or local.
  • Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus, S Ishikura, K Nihei, A Ohtsu, N Boku, S Hironaka, K Mera, M Muto, TG Ogino, S Yoshida, JOURNAL OF CLINICAL ONCOLOGY, 21, (14) 2697 - 2702,   2003年07月, 査読有り, Purpose: To assess the long-term toxicity after definitive chemoradiotherapy (CRT) for squamous cell carcinoma (SCC) of the esophagus. Patients and Methods: Patients newly diagnosed with SCC of the esophagus and treated with definitive CRT between 1992 and 1999 in our institution were recruited from our database an the basis of the following criteria: age :5 75 years, performance status (PS; based on the Eastern Cooperative Oncology Group scale) 0 to 2, and clinical tumor-node-metastasis system stage I to IVA. The CRT consisted of two cycles of cisplatin 40 mg/m(2) on days 1 and 8, and continuous infusion of fluorouracil 400 mg/m(2)/d on days 1 to 5 and 8 to 12, repeated every 5 weeks with concurrent radiotherapy of 60 Gy in 30 fractions. For the assessment of toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme was adopted. Results: A total of 139 patients were recruited, and their characteristics were as follows: median age, 62 years (range, 38 to 75 years); 121 males and 18 females; 96 patients PS 0, 42 patients PS 1, and one patient PS 2; 15 patients T1, 11 patients T2, 60 patients T3, and 53 patients T4; and 101 patients M0, 38 patients M1a. With a median follow-up of 53 months, the median survival time and 5-year survival rate were 21 months and 29%, respectively. Of 78 patients with complete remission, two patients died as a result of acute myocardial infarction. Grade 2, 3, and 4 late toxicities occurred with the following incidences: pericarditis in eight patients, seven patients, and one patient, respectively, heart failure in zero, zero, and two patients; pleural effusion in seven, eight, and zero patients; and radiation pneumonitis in one patient, three patients, and zero patients, respectively. Conclusion: Definitive CRT for SCC of the esophagus is effective with substantial toxicities. Additional investigation to minimize the normal tissue toxicities is warranted. (C) 2003 by American Society of Clinical Oncology.
  • Efficacy of chemoradiotherapy on pain relief in patients with intrapelvic recurrence of rectal cancer, Y Ito, A Ohtsu, S Ishikura, N Boku, K Nihei, T Ogino, H Ikeda, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 33, (4) 180 - 185,   2003年04月, 査読有り, Purpose: To assess the efficacy of chemoradiotherapy on pain relief in patients with intrapelvic recurrence of rectal cancer. Methods: The records of 30 patients treated with radiotherapy with or without chemotherapy for intrapelvic recurrence of rectal cancer between September 1993 and February 1999 were retrospectively reviewed. There were 17 patients in the chemoradiotherapy (CRT) group and 13 patients in the radiotherapy alone (RTA) group. Simultaneous extrapelvic distant metastases were found in 11 patients in the CRT group and in seven patients in the RTA group. Radiotherapy was administered with a median total dose of 50 Gy in both groups. In the CRT group, 15 patients received 5-fluorouracil by continuous infusion and two patients received irinotecan in a biweekly infusion schedule during the course of radiotherapy. The response rate and duration of pain relief were evaluated and were compared between the two groups. Results: The response rate of pain relief in the CRT and RTA was 100 and 77%, respectively. The median duration of pain relief in the CRT and RTA groups was 7.8 and 4.0 months, respectively and there was a significant difference between the two groups (P = 0.019). The median survival time from the start of radiotherapy was 15.1 and 9.3 months in the CRT and RTA groups, respectively, and there was a significant difference between the two groups (P 0.046). Conclusions: The results suggest that chemoradiotherapy for intrapelvic recurrence of rectal cancer for the purpose of pain relief appears to be more effective than radiotherapy alone.
  • Short-course palliative radiotherapy for airway stenosis in non-small cell lung cancer., Nihei K, Ishikura S, Kawashima M, Ogino T, Ito Y, Ikeda H, International journal of clinical oncology, 7, (5) 284 - 288,   2002年10月, 査読有り
  • Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus, S Ishikura, T Ogino, J Furuse, M Satake, S Baba, M Kawashima, K Nihei, Y Ito, Y Maru, H Ikeda, AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 25, (2) 189 - 193,   2002年04月, 査読有り, Transcatheter arterial chemoembolization (TACE) is used in the treatment of hepatocellular carcinoma; however, it has limited effect on portal vein tumor thrombus (PVTT). The purpose of this study was to assess the feasibility and efficacy of radiotherapy targeting the PVTT after TACE for the tumor in the hepatic parenchyma. TACE was performed using epirubicin hydrochloride, iodized poppy seed oil, and gelatin sponge particles. Radiotherapy was performed targeting the PVTT to a total dose of 50 Gy in 25 fractions during 5 weeks. Twenty consecutive patients were treated with this combined treatment. Sixteen of 20 patients could complete the planned radiotherapy. Partial response was observed in 10, no change in 4, and progression in 6. The response rate was 50% (95% Cl 28-72%). The 1-year overall survival rate was 25% (95% Cl 6-44%), and the median survival time was 5.3 months. It was difficult to determine the late toxicities because of disease progression and additional TACE, and only one patient died without disease progression. Radiotherapy after TACE is feasible for patients with hepatocellular carcinoma and PVTT, The survival figure, however, is still dismal, and further investigation is needed to establish the best combination of treatment modalities.
  • Advanced esophageal cancer with esophago-bronchial fistula successfully treated by chemoradiation therapy with additional endoscopic resection: A case report, M Morihiro, N Boku, A Ohtsu, S Miyamoto, S Ishikura, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 32, (2) 59 - 63,   2002年02月, 査読有り, Chemoradiation is potentially curative for esophageal cancer in various stages, but local failure is a major problem. The present case was a 49-year-old male diagnosed with advanced esophageal cancer with an esophago-bronchial fistula and lymph node metastasis. Histological diagnosis by biopsy was adenosquamous cell carcinoma. Chemoradiotherapy comprising intravenous infusion of cisplatin and continuous infusion of 5-fluorouracil with concurrent radiation was initiated in July 1997. In December 1997, after four courses of therapy, partial remission was obtained and the fistula closed with a remnant polypoid lesion at the primary site, which remained even after six courses of treatment. In February 1998, endoscopic polypectomy was performed for the remnant lesion and histological examination revealed that it contained adenocarcinoma cells. Thereafter, no additional treatment was performed and the patient has been disease-free for 3.5 years. This case suggests that additional endoscopic resection is an optional treatment for local failure after chemoradiation.

受賞

  •   2016年11月, 日本放射線腫瘍学会, 優秀教育講演賞
  •   2015年05月, 15th International Congress of Radiation Research, 優秀ポスター賞
  •   2009年, 国立がんセンター, 田宮記念賞
  •   1999年06月, 日本食道疾患研究会, 会長賞


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