川本 泰之 (カワモト ヤスユキ)

医学研究院 内科系部門 内科学分野助教
Last Updated :2025/06/10

■研究者基本情報

学位

  • 博士(医学), 北海道大学, 2012年03月

研究者番号

  • 60755601

研究分野

  • ライフサイエンス, 消化器内科学
  • ライフサイエンス, 腫瘍診断、治療学

担当教育組織

■経歴

学歴

  • 2008年04月 - 2012年03月, 北海道大学, 大学院医学研究科, 日本国
  • 1998年04月 - 2004年03月, 北海道大学, 医学部, 日本国

■研究活動情報

論文

  • Subcutaneous adipose tissue radiodensity as a predictor of poor prognosis in advanced biliary tract cancer
    Ryo Sugiura, Yasuyuki Kawamoto, Masaki Kuwatani, Kazumichi Kawakubo, Kazuaki Harada, Masatsugu Ohara, Hiroki Yonemura, Shunichiro Nozawa, Naoya Sakamoto
    Journal of Hepato-Biliary-Pancreatic Sciences, Wiley, 2025年01月08日
    研究論文(学術雑誌), Abstract

    Background

    High subcutaneous adipose tissue radiodensity (SATr), an indirect surrogate marker of adipose tissue quality, was associated with poor prognosis in various cancers. The present study aimed to assess the association of SATr with survival outcomes in patients with advanced biliary tract cancer (BTC).

    Methods

    This retrospective, single‐center study included patients with unresectable or recurrent BTC who underwent chemotherapy/chemoradiotherapy. Overall survival (OS) and progression‐free survival (PFS) were assessed using the log‐rank test and the Cox proportional hazards model according to the SATr status.

    Results

    The study cohort included 234 patients, including 38 and 196 patients with high and non‐high SATr, respectively. The median OS durations were 10.5 and 17.4 months (HR = 1.72, 95% CI: 1.19–2.49, p < .01) and the median PFS durations were 4.9 and 8.0 months (HR = 1.52, 95% CI: 1.05–2.20, p = .03) in patients with high and non‐high SATr, respectively. By multivariate analysis, high SATr, neutrophil/lymphocyte ratio >5, modified Glasgow prognostic score 1–2, and serum carcinoembryonic antigen >5.0 ng/mL were predictors for OS (HR, 1.66, 2.42, 2.00, and 1.56, respectively; p < .05). By multivariate analysis, metastatic disease status, high SATr, neutrophil/lymphocyte ratio >5, and modified Glasgow prognostic score 1–2 were independent risk factors for worse PFS (HR, 1.56, 1.56, 1.81, and 1.57, respectively; p < .05).

    Conclusions

    High SATr was associated with risk of tumor progression and poor prognosis in patients with advanced BTC treated by palliative chemotherapy/chemoradiotherapy.
  • Normal tissue complication probability model for severe radiation-induced lymphopenia in patients with pancreatic cancer treated with concurrent chemoradiotherapy
    Fuki Koizumi, Norio Katoh, Takahiro Kanehira, Yasuyuki Kawamoto, Toru Nakamura, Tatsuhiko Kakisaka, Miyako Myojin, Noriaki Nishiyama, Akio Yonesaka, Manami Otsuka, Rikiya Takashina, Hideki Minatogawa, Hajime Higaki, Yusuke Uchinami, Hiroshi Taguchi, Kentaro Nishioka, Koichi Yasuda, Naoki Miyamoto, Isao Yokota, Keiji Kobashi, Hidefumi Aoyama
    Physics and Imaging in Radiation Oncology, 100690, 100690, Elsevier BV, 2024年12月
    研究論文(学術雑誌)
  • Efficacy of liposomal irinotecan + 5-FU/LV vs. S-1 in gemcitabine-refractory metastatic pancreatic cancer: a real-world study using inverse probability of treatment weighting.
    Hiroshi Imaoka, Masafumi Ikeda, Satoshi Kobayashi, Akihiro Ohba, Masayuki Ueno, Yuko Suzuki, Hidetaka Tsumura, Nana Kimura, Shinya Kawaguchi, Yasuyuki Kawamoto, Kohei Nakachi, Kunihiro Tsuji, Noritoshi Kobayashi, Reiko Ashida, Naohiro Okano, Kumiko Umemoto, Gou Murohisa, Ayumu Hosokawa, Akinori Asagi, Hiroko Nebiki, Rei Suzuki, Takeshi Terashima, Ryusuke Shibata, Kazuhito Kawata, Toshifumi Doi, Hiroshi Ohyama, Yohei Kitano, Kazuhiko Shioji, Hiroyuki Okuyama, Atsushi Naganuma, Yuji Negoro, Yasunari Sakamoto, Satoshi Shimizu, Chigusa Morizane, Makoto Ueno, Junji Furuse, Hiroaki Nagano
    Journal of gastroenterology, 2024年11月30日, [国内誌]
    英語, 研究論文(学術雑誌), BACKGROUND: S-1 monotherapy had previously been widely used as a second-line treatment for pancreatic cancer (PC) after gemcitabine-based chemotherapy mainly in Japan. Based on the results of the NAPOLI-1 trial, the recommended second-line therapy is now liposomal irinotecan plus fluorouracil/folinic acid (nal-IRI + 5-FU/LV). However, there have been no studies comparing nal-IRI + 5-FU/LV therapy with S-1 monotherapy. METHODS: The main objective of this study was to compare overall survival (OS) in patients treated with nal-IRI + 5-FU/LV and those treated with S-1 monotherapy as second-line treatments, using the inverse probability of treatment weighting (IPTW) method. This study was conducted in 31 institutions participating in Japan Oncology Network in Hepatobiliary and Pancreas. To minimize potential biases due to the retrospective design, IPTW analysis was performed with multiple imputation, and imputed IPTW-adjusted hazard ratios and corresponding 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model and combined into pooled estimates. RESULTS: A total of 463 metastatic PC patients were enrolled in this study (257 in the S-1 monotherapy group and 206 in the nal-IRI + 5-FU/LV group). The median OS was 7.50 months (95% CI 4.18-12.69 months) in the nal-IRI + 5-FU/LV group and 5.72 months (95% CI 2.76-10.79 months) in the S-1 monotherapy group. In the IPTW-adjusted Cox proportional hazards model, nal-IRI + 5-FU/LV was associated with a significant OS benefit (pooled IPTW-adjusted hazard ratio, 0.779; 95% CI 0.399-0.941; p = 0.025). CONCLUSION: These findings support the use of nal-IRI + 5-FU/LV as standard second-line treatment for PC patients after gemcitabine-based chemotherapy.
  • 消化器癌に対するS-1を含む全身化学療法による眼障害に関する前向き観察研究               
    八木澤 允貴, 中村 路夫, 澤田 憲太郎, 川本 泰之, 村中 徹人, 中積 宏之, 太宰 昌佳, 辻 靖, 進藤 吉明, 中野 真太郎, 上林 実, 渡邉 桃子, 原田 一顕, 結城 敏志, 小松 嘉人
    日本癌治療学会学術集会抄録集, 62回, P62, 3, (一社)日本癌治療学会, 2024年10月
    英語
  • 5-Fluorouracil metabolic pathway genes predict recurrence risk following adjuvant S-1 therapy: Results of an ancillary analysis from a phase III trial of resected biliary tract cancer (JCOG1202A1).
    Shuichi Mitsunaga, Masafumi Ikeda, Shogo Nomura, Chigusa Morizane, Akiko Todaka, Naoto Yamamoto, Ken Kamata, Hiroo Yanagibashi, Nobumasa Mizuno, Yasuyuki Kawamoto, Kunihito Gotoh, Hirofumi Shirakawa, Naohiro Okano, Tatsuya Nomura, Kazunari Tanaka, Amane Takahashi, Shintaro Yagi, Koji Ohta, Yukiko Takayama, Haruo Miwa, Hiroaki Nagano, Yasushi Kojima, Terumasa Hisano, Munenori Tahara, Yasunaru Sakuma, Hiroyuki Arai, Ikuo Nakamura, Hiroshi Katayama, Masaru Konishi, Makoto Ueno
    Journal of hepato-biliary-pancreatic sciences, 2024年09月25日, [国内誌]
    英語, 研究論文(学術雑誌), BACKGROUND: S-1, an oral fluoropyrimidine derivative, is standard adjuvant therapy for resected biliary tract cancer (BTC), based on the results of the JCOG1202, a phase III trial evaluating the survival benefit with adjuvant S-1 following curative resection for BTC compared to surgery alone. This multicenter ancillary study of the JCOG1202 aimed to evaluate the prognostic impact of the 5-fluorouracil (5-FU) metabolic pathway genes including thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). METHODS: The 5-FU metabolic pathway genes were measured in tumor cells from formalin-fixed paraffin-embedded resected specimens from 183 patients (surgery alone: n = 94; adjuvant S-1: n = 89). We randomly divided them into training (n = 96) and validation sets (n = 87) for evaluating the interaction between gene levels and RFS benefits in the treatment arm. RESULTS: RFS benefits of adjuvant S-1 were observed in the low DPD (HR = 0.440 and 0.748, respectively in the training and validation sets) and the low TP groups (HR = 0.709 and 0.602, respectively). Clinicopathological characteristics were well balanced between low and high DPD populations. More advanced stage tumors were observed in high TP populations as compared to those in low TP populations (p = .0332). CONCLUSION: The results suggest the RFS benefit of adjuvant S-1 in resected BTC patients with low DPD and low TP gene expressions.
  • Real-world outcomes of FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer: the JSCCR-TRIPON study.
    Yoshiyuki Yamamoto, Hiroki Yukami, Tatsuro Yamaguchi, Hisatsugu Ohori, Sachiko Nagasu, Yoshinori Kagawa, Naotoshi Sugimoto, Hiromichi Sonoda, Kentaro Yamazaki, Atsuo Takashima, Hiroyuki Okuyama, Hiroko Hasegawa, Chihiro Kondo, Eishi Baba, Toshihiko Matsumoto, Yasuyuki Kawamoto, Masato Kataoka, Yoshiaki Shindo, Toshiaki Ishikawa, Taito Esaki, Yosuke Kito, Takeo Sato, Taro Funakoshi, Toshifumi Yamaguchi, Yasuhiro Shimada, Toshikazu Moriwaki
    International journal of clinical oncology, 2024年08月28日, [国内誌]
    英語, 研究論文(学術雑誌), BACKGROUND: FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety. METHODS: We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil. RESULTS: Out of 104 patients who met the criteria, the median age was 58 years (range, 16-72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4-12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8 months (95% CI, 10.6-15.0) and 27.9 months (95% CI 21.6-34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed. CONCLUSION: In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials.
  • Clinical utility of BRCA and ATM mutation status in circulating tumour DNA for treatment selection in advanced pancreatic cancer.
    Kentaro Sudo, Yoshiaki Nakamura, Makoto Ueno, Masayuki Furukawa, Nobumasa Mizuno, Yasuyuki Kawamoto, Naohiro Okano, Kumiko Umemoto, Akinori Asagi, Masato Ozaka, Koushiro Ohtsubo, Satoshi Shimizu, Nobuhisa Matsuhashi, Shinji Itoh, Toshihiko Matsumoto, Taroh Satoh, Hiroyuki Okuyama, Masahiro Goto, Hiroko Hasegawa, Yoshiyuki Yamamoto, Justin I Odegaard, Hideaki Bando, Takayuki Yoshino, Masafumi Ikeda, Chigusa Morizane
    British journal of cancer, 131, 7, 1237, 1245, 2024年08月28日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Identification of homologous recombination deficiency (HRD) remains a challenge in advanced pancreatic cancer (APC). We investigated the utility of circulating tumour DNA (ctDNA) profiling in the assessment of BRCA1/2 and ATM mutation status and treatment selection in APC. METHODS: We analysed clinical and ctDNA data of 702 patients with APC enroled in GOZILA, a ctDNA profiling study using Guardant360. RESULTS: Inactivating BRCA1/2 and ATM mutations were detected in 4.8% (putative germline, 3.7%) and 4.4% (putative germline, 0.9%) of patients, respectively. Objective response (63.2% vs. 16.2%) and PFS (HR 0.55, 95% CI 0.32-0.93) on platinum-containing chemotherapy were significantly better in patients with putative germline BRCA1/2 (gBRCA) mutation than those without. In contrast, putative gBRCA mutation had no impact on the efficacy of gemcitabine plus nab-paclitaxel. In 2 patients treated with platinum-containing therapy, putative BRCA2 reversion mutations were detected. Three of seven patients with somatic BRCA mutations responded to platinum-containing therapy, while only one of four with putative germline ATM mutations did. One-third of somatic ATM mutations were in genomic loci associated with clonal haematopoiesis. CONCLUSION: Comprehensive ctDNA profiling provides clinically relevant information regarding HRD status. It can be a practical, convenient option for HRD screening in APC.
  • A multicenter, prospective, phase II trial of second-line aflibercept plus FOLFIRI in patients with metastatic colorectal cancer refractory to an anti-EGFR antibody: HGCSG1801.
    Hiroshi Nakatsumi, Yoshito Komatsu, Kazuaki Harada, Yasuyuki Kawamoto, Satoshi Yuki, Kentaro Sawada, Atsushi Ishiguro, Susumu Sogabe, Takayuki Ando, Yusuke Sasaki, Ayumu Yoshikawa, Michio Nakamura, Masayoshi Dazai, Miki Tateyama, Osamu Muto, Masahito Kotaka, Tamotsu Sagawa, Tetsuhito Muranaka, Kazuteru Hatanaka, Ryo Takagi, Yu Sakata
    International journal of cancer, 2024年08月14日, [国際誌]
    英語, 研究論文(学術雑誌), Aflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti-epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open-label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin-based chemotherapy plus an anti-EGFR agent. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5-fluorouracil [5-FU] 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression-free survival (PFS) rate at 6 months. Forty three patients were enrolled between November 2019 and October 2022. The primary endpoint was met: 6-month PFS rate was 58.8% (90% confidence interval [CI], 45.7%-72.0%). Median PFS and OS were 7.3 months (95% CI, 5.5-11.0 months) and 18.8 months (95% CI, 12.9-26.6 months), respectively. The overall response rate was 20.9% (95% CI, 10.0-36.0%) and disease control rate was 88.4% (95% CI, 74.9-96.1%). The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%), and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. This study suggests that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese patients with mCRC who failed prior oxaliplatin-based chemotherapy plus an anti-EGFR agent.
  • Trastuzumab Deruxtecan in Human Epidermal Growth Factor Receptor 2-Expressing Biliary Tract Cancer (HERB; NCCH1805): A Multicenter, Single-Arm, Phase II Trial.
    Akihiro Ohba, Chigusa Morizane, Yasuyuki Kawamoto, Yoshito Komatsu, Makoto Ueno, Satoshi Kobayashi, Masafumi Ikeda, Mitsuhito Sasaki, Junji Furuse, Naohiro Okano, Nobuyoshi Hiraoka, Hiroshi Yoshida, Aya Kuchiba, Ryo Sadachi, Kenichi Nakamura, Naoko Matsui, Yoshiaki Nakamura, Wataru Okamoto, Takayuki Yoshino, Takuji Okusaka
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 42, 27, JCO2302010, 3217, 2024年08月05日, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Treatment options for patients with unresectable or recurrent biliary tract cancer (BTC) who progress on a gemcitabine-containing regimen are limited. In addition, the significance of anti-human epidermal growth factor receptor 2 (HER2) therapy in HER2-expressing BTC has not been sufficiently investigated. METHODS: In this phase II trial, participants from five institutions in Japan were enrolled. Eligible patients had pathologically confirmed unresectable or recurrent BTC with centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ or IHC2+ and in situ hybridization [ISH]+) or HER2-low (IHC2+ and ISH-, IHC1+, and IHC0 and ISH+) and were refractory or intolerant to a gemcitabine-containing regimen. The patients received 5.4 mg/kg trastuzumab deruxtecan (T-DXd) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was the confirmed objective response rate (ORR) in HER2-positive BTC by an independent central review (threshold ORR, 15%; expected ORR, 40%). RESULTS: A total of 32 patients were enrolled and treated. Among these patients, 22 with HER2-positive disease comprised the primary efficacy population and had a confirmed ORR of 36.4% (90% CI, 19.6 to 56.1; P = .01), meeting the primary end point. Eight with HER2-low disease comprised the exploratory population and had a confirmed ORR of 12.5%. The most common ≥grade 3 treatment-related adverse events were anemia (53.1%) and neutropenia (31.3%). Eight patients (25.0%) had interstitial lung disease (ILD), including two grade 5 events. CONCLUSION: T-DXd showed promising activity in patients with HER2-positive BTC and a signal of efficacy in patients with HER2-low BTC. Although the safety profile was generally manageable, ILD requires careful monitoring and early intervention.
  • 持続可能な膵がん教室にするための現状と課題
    田辺 睦子, 中村 透, 寺澤 孝男, 伊藤 元, 白岩 剛, 川本 泰之, 桑谷 将城, 加藤 徳雄, 浅野 賢道, 山田 眞佐美, 池澤 賢治, 安保 義恭, 潟沼 朗生, 平手 大輔
    膵臓, 39, 3, A388, A388, (一社)日本膵臓学会, 2024年07月
    日本語
  • Phase II trial of niraparib for BRCA-mutated biliary tract, pancreatic and other gastrointestinal cancers: NIR-B.
    Yasuyuki Kawamoto, Chigusa Morizane, Yoshito Komatsu, Shunsuke Kondo, Makoto Ueno, Satoshi Kobayashi, Masayuki Furukawa, Lingaku Lee, Taroh Satoh, Daisuke Sakai, Masafumi Ikeda, Hiroshi Imaoka, Arisa Miura, Yutaka Hatanaka, Isao Yokota, Yoshiaki Nakamura, Takayuki Yoshino
    Future oncology (London, England), 20, 26, 1, 7, 2024年04月17日, [国際誌]
    英語, 研究論文(学術雑誌), Due to the widespread use of cancer genetic testing in gastrointestinal cancer, the BRCA1/2 genetic mutation has been identified in biliary tract cancer as well as pancreatic cancer. Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor, and PARP inhibitors exert their cytotoxicity against cancer cells in the context of homologous recombination deficiency, such as BRCA mutations, via the mechanism of synthetic lethality. The aim of this phase II NIR-B trial is to evaluate the efficacy and safety of niraparib for patients with unresectable advanced or recurrent biliary tract cancer, pancreatic cancer or other gastrointestinal cancers with germline or somatic BRCA1/2 mutations revealed by genetic testing. The primary end point is an investigator-assessed objective response rate in each cohort.Clinical Trial Registration: jRCT2011200023 (ClinicalTrials.gov).
  • Transitional dynamics in oncology clinical trials: evaluating the impact of Clinical Trials Act on cooperative groups.
    Kenichi Nakamura, Koji Takeda, Akiko M Saito, Miho Kato, Shinya Sato, Satoshi Nakagawa, Yasuyuki Kawamoto, Eiji Oki, Isamu Okamoto, Hiroaki Okamoto, Hiroshi Katayama, Junki Mizusawa, Harumi Kaba, Taro Shibata, Haruhiko Fukuda
    Japanese journal of clinical oncology, 54, 7, 748, 752, 2024年03月26日, [国際誌]
    英語, 研究論文(学術雑誌), OBJECTIVE: large-scale multicentre clinical trials conducted by cooperative groups have generated a lot of evidence to establish better standard treatments. The Clinical Trials Act was enforced on 1 April 2018, in Japan, and it has remarkably increased the operational burden on investigators, but its long-term impact on cancer cooperative groups is unknown. METHODS: a survey was conducted across the nine major cooperative groups that constitute the Japan Cancer Trials Network to assess the impact of Clinical Trials Act on the number of newly initiated trials from fiscal year (from 1 April to 31 March) 2017 to 2022 and that of ongoing trials on 1 April in each year from 2018 to 2023. RESULTS: the number of newly initiated trials dropped from 38 trials in fiscal year 2017 to 26 trials in fiscal year 2018, surged to 50 trials in fiscal year 2019, but then gradually decreased to 25 trials by fiscal year 2022. Specified clinical trials decreased from 32 trials in fiscal year 2019 to 12 trials in fiscal year 2022. The number of ongoing trials was 220 trials in 2018, peaked at 245 trials in 2020, but then gradually decreased to 219 trials by 2023. The number of specified clinical trials has been in consistent decline. By April 2023, of the 20 ongoing non-specified clinical trials, nine adhered to Clinical Trials Act and 11 followed the Ethical Guidelines for Medical and Health Research Involving Human Subjects. CONCLUSION: the number of multicentre clinical trials in oncology gradually decreased after the Clinical Trials Act's enforcement, which underscores the need for comprehensive amendment of the Clinical Trials Act to streamline the operational process.
  • CA125 Kinetics as a Potential Biomarker for Peritoneal Metastasis Progression following Taxane-Plus-Ramucirumab Administration in Patients with Advanced Gastric Cancer
    Akira Ueda, Satoshi Yuki, Takayuki Ando, Ayumu Hosokawa, Naokatsu Nakada, Yosuke Kito, Iori Motoo, Ken Ito, Miho Sakumura, Yurika Nakayama, Yuko Ueda, Shinya Kajiura, Koji Nakashima, Kazuaki Harada, Yasuyuki Kawamoto, Yoshito Komatsu, Ichiro Yasuda
    Cancers, 16, 5, 2024年03月
    研究論文(学術雑誌)
  • CA125 Kinetics as a Potential Biomarker for Peritoneal Metastasis Progression following Taxane-Plus-Ramucirumab Administration in Patients with Advanced Gastric Cancer.
    Akira Ueda, Satoshi Yuki, Takayuki Ando, Ayumu Hosokawa, Naokatsu Nakada, Yosuke Kito, Iori Motoo, Ken Ito, Miho Sakumura, Yurika Nakayama, Yuko Ueda, Shinya Kajiura, Koji Nakashima, Kazuaki Harada, Yasuyuki Kawamoto, Yoshito Komatsu, Ichiro Yasuda
    Cancers, 16, 5, 2024年02月22日, [国際誌]
    英語, 研究論文(学術雑誌), Currently, no established marker exists for predicting peritoneal metastasis progression during chemotherapy, although they are major interruptive factors in sequential chemotherapy in patients with advanced gastric cancer (AGC). This multicenter retrospective study was conducted from June 2015 to July 2019, analyzing 73 patients with AGC who underwent taxane-plus-ramucirumab (TAX/RAM) therapy and had their serum carbohydrate antigen 125 (CA125) concentrations measured. Of 31 patients with elevated CA125 levels above a cutoff of 35 U/mL, 25 (80.6%) had peritoneal metastasis. The CA125 concentrations before TAX/RAM treatment were associated with ascites burden. The overall survival was significantly shorter in the CA125-elevated group. CA125 kinetics, measured at a median of 28 days after chemotherapy, were associated with the ascites response (complete or partial response: -1.86%/day; stable disease: 0.28%/day; progressive disease: 2.33%/day). Progression-free survival in the CA125-increased group, defined by an increase of 0.0067%/day using receiver operating characteristic curve analysis, was significantly poorer among patients with peritoneal metastases. In conclusion, this study highlights that CA125 kinetics can serve as an early predictor for the progression of peritoneal metastasis during TAX/RAM treatment.
  • Efficacy of liposomal irinotecan + 5-FU/LV vs. S-1 in gemcitabine-refractory metastatic pancreatic cancer: a real-world study using inverse probability of treatment weighting
    Hiroshi Imaoka, Masafumi Ikeda, Satoshi Kobayashi, Akihiro Ohba, Masayuki Ueno, Yuko Suzuki, Hidetaka Tsumura, Nana Kimura, Shinya Kawaguchi, Yasuyuki Kawamoto, Kohei Nakachi, Kunihiro Tsuji, Noritoshi Kobayashi, Reiko Ashida, Naohiro Okano, Kumiko Umemoto, Gou Murohisa, Ayumu Hosokawa, Akinori Asagi, Hiroko Nebiki, Rei Suzuki, Takeshi Terashima, Ryusuke Shibata, Kazuhito Kawata, Toshifumi Doi, Hiroshi Ohyama, Yohei Kitano, Kazuhiko Shioji, Hiroyuki Okuyama, Atsushi Naganuma, Yuji Negoro, Yasunari Sakamoto, Satoshi Shimizu, Chigusa Morizane, Makoto Ueno, Junji Furuse, Hiroaki Nagano
    Journal of Gastroenterology, 2024年
    研究論文(学術雑誌)
  • Adjuvant and neoadjuvant chemotherapy for biliary tract cancer: a review of randomized controlled trials.
    Kohei Nakachi, Naoto Gotohda, Etsuro Hatano, Satoshi Nara, Shinichiro Takahashi, Yasuyuki Kawamoto, Makoto Ueno
    Japanese journal of clinical oncology, 53, 11, 1019, 1026, 2023年11月05日, [国際誌]
    英語, 研究論文(学術雑誌), The first randomized controlled trial of adjuvant chemotherapy for biliary tract cancer was reported in 2002. Since then, studies have continued, with efficacy reported for capecitabine in 2018 and S-1 in 2023. Oral fluoropyrimidines have become established as the standard of care. This article reviews the evidence from the randomized controlled trials reported to date and those that are ongoing or from which results have not yet been reported.
  • 胸部食道がん化学放射線療法における重症放射線食道炎に関する後方視的研究
    原田 一顕, 中村 赳晶, 渡辺 亮介, 山村 貴洋, 結城 敏志, 坂本 直哉, 川本 泰之, 小松 嘉人, 打浪 雄介, 田口 大志, 加藤 徳雄, 青山 英史
    北海道医学雑誌, 98, 2, 139, 140, 北海道医学会, 2023年11月
    日本語
  • 胸部食道がん化学放射線療法における重症放射線食道炎に関する後方視的研究
    原田 一顕, 中村 赳晶, 渡辺 亮介, 山村 貴洋, 結城 敏志, 坂本 直哉, 川本 泰之, 小松 嘉人, 打浪 雄介, 田口 大志, 加藤 徳雄, 青山 英史
    北海道医学雑誌, 98, 2, 139, 140, 北海道医学会, 2023年11月
    日本語
  • The Short- and Long-Term Surgical Results of Consecutive Hepatopancreaticoduodenectomy for Wide-Spread Biliary Malignancy
    Yasunori Yoshimi, Takehiro Noji, Keisuke Okamura, Kimitaka Tanaka, Aya Matsui, Yoshitsugu Nakanishi, Toshimichi Asano, Toru Nakamura, Takahiro Tsuchikawa, Yasuyuki Kawamoto, Kazuaki Harada, Kanako Fuyama, Kazuhumi Okada, Satoshi Hirano
    Annals of Surgical Oncology, 31, 1, 90, 96, Springer Science and Business Media LLC, 2023年10月29日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Cancer-free resection (R0) is one of the most important factors for the long-term survival of biliary carcinoma. For some patients with widespread invasive cancer located between the hilar and intrapancreatic bile duct, hepatopancreaticoduodenectomy (HPD) is considered a radical surgery for R0 resection. However, HPD is associated with high morbidity and mortality rates. Furthermore, previous reports have not shown lymph node metastasis (LNM) status, such as the location or number, which could influence the prognosis after HPD. In this study, first, we explored the prognostic factors for survival, and second, we evaluated whether the LNM status (number and location of LNM) would influence the decision on surgical indications in patients with widely spread biliary malignancy. METHODS: We retrospectively reviewed the medical records of 54 patients who underwent HPD with hepatectomy in ≥2 liver sectors from January 2003 to December 2021 (HPD-G). We also evaluated 54 unresectable perihilar cholangiocarcinoma patients who underwent chemotherapy from January 2010 to December 2021 (CTx-G). RESULTS: R0 resection was performed in 48 patients (89%). The median survival time (MST) and 5-year overall survival rate of the HPD-G and CTx-G groups were 36.9 months and 31.1%, and 19.6 months and 0%, respectively. Univariate and multivariate analyses showed that pathological portal vein involvement was an independent prognostic factor for survival (MST: 18.9 months). Additionally, patients with peripancreatic LNM had worse prognoses (MST: 13.3 months) than CTx-G. CONCLUSIONS: Patients with peripancreatic LNM or PV invasion might be advised to be excluded from surgery-first indications for HPD.
  • 転移性大腸癌におけるレゴラフェニブの開始用量が治療成績に対する影響               
    胡 慶江, 原田 一顕, 川上 武志, 緒方 貴次, 伏木 邦博, 谷口 浩也, 室 圭, 安藤 幸滋, 南原 翔, 川本 泰之, 小松 嘉人, 沖 英次, 舛石 俊樹, 山崎 健太郎, 結城 敏志
    日本癌治療学会学術集会抄録集, 61回, O15, 5, (一社)日本癌治療学会, 2023年10月
    英語
  • Clinical significance of circulating-tumour DNA analysis by metastatic sites in pancreatic cancer.
    Kumiko Umemoto, Yu Sunakawa, Makoto Ueno, Masayuki Furukawa, Nobumasa Mizuno, Kentaro Sudo, Yasuyuki Kawamoto, Takeshi Kajiwara, Koushiro Ohtsubo, Naohiro Okano, Nobuhisa Matsuhashi, Shinji Itoh, Toshihiko Matsumoto, Satoshi Shimizu, Toru Otsuru, Hiroko Hasegawa, Hiroyuki Okuyama, Hideko Ohama, Toshikazu Moriwaki, Takashi Ohta, Justin I Odegaard, Yoshiaki Nakamura, Hideaki Bando, Takayuki Yoshino, Masafumi Ikeda, Chigusa Morizane
    British journal of cancer, 128, 8, 1603, 1608, 2023年04月, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Liquid biopsy is an alternative to tissue specimens for tumour genotyping. However, the frequency of genomic alterations with low circulating-tumour DNA (ctDNA) shedding is shown in pancreatic ductal adenocarcinoma (PDAC). We, therefore, investigated the prevalence of KRAS mutations and ctDNA fraction by the metastatic site in patients with PDAC. METHODS: This study enrolled previously treated PDAC patients from a plasma genomic profiling study; ctDNA analysis was performed using Guardant360 at disease progression before initiating subsequent treatment. RESULTS: In 512 patients with PDAC, KRAS mutations were detected in 57%. The frequency of KRAS mutation in ctDNA differed depending on the metastatic organ; among patients with single-organ metastasis (n = 296), KRAS mutation detection rate was significantly higher in patients with metastasis to the liver (78%). In addition, the median maximum variant allele frequency (VAF) was higher with metastasis to the liver (1.9%) than with metastasis to the lungs, lymph nodes, peritoneum or with locally advanced disease (0.2%, 0.4%, 0.2% and 0.3%, respectively). CONCLUSION: The prevalence of KRAS mutations and maximum VAF were higher in patients with metastasis to the liver than in those with metastasis to other sites. This study indicated the clinical utility of ctDNA analysis, especially in PDAC with liver metastases.
  • 進行胆嚢癌に対する肝・膵切除術の妥当性               
    野路 武寛, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 原田 一顕, 川本 泰之, 平野 聡
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 132回・126回, 67, 67, 日本消化器病学会-北海道支部, 2023年03月
    日本語
  • 進行胆嚢癌に対する肝・膵切除術の妥当性               
    野路 武寛, 武内 慎太郎, 和田 雅孝, 田中 公貴, 松井 あや, 中西 喜嗣, 浅野 賢道, 中村 透, 土川 貴裕, 原田 一顕, 川本 泰之, 平野 聡
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 132回・126回, 67, 67, 日本消化器病学会-北海道支部, 2023年03月
    日本語
  • Correlation of UGT1A1 Gene Polymorphisms or Prior Irinotecan Treatment and Treatment Outcomes of Nanoliposomal-Irinotecan plus 5-Fluorouracil/Leucovorin for Pancreatic Ductal Adenocarcinoma: A Multicenter, Retrospective Cohort Study (HGCSG2101).
    Kazuaki Harada, Takahiro Yamamura, Osamu Muto, Michio Nakamura, Susumu Sogabe, Kentaro Sawada, Shintaro Nakano, Masataka Yagisawa, Tetsuhito Muranaka, Masayoshi Dazai, Miki Tateyama, Yoshimitsu Kobayashi, Sosuke Kato, Kazuteru Hatanaka, Yasuyuki Kawamoto, Satoshi Yuki, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
    Journal of clinical medicine, 12, 4, 2023年02月17日, [国際誌]
    英語, 研究論文(学術雑誌), The effects of UGT1A1 gene polymorphisms or prior irinotecan treatment on treatment outcomes of nanoliposomal-irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) are not established. This multicenter, retrospective cohort study compared treatment outcomes in patients with UGT1A1*1/*1 and those with UGT1A1*1/*6 or *1/*28 genotypes. We also analyzed the impact of prior irinotecan treatment on survival outcomes in 54 patients treated with nal-IRI+5-FU/LV. Comparable effectiveness was found regardless of the UGT1A1 genotypes. While no significant differences were found, grade ≥3 neutropenia and febrile neutropenia were more frequent in patients with UGT1A1*1/*6 or *1/*28 than in those with UGT1A1*1/*1 genotypes (grade ≥3 neutropenia, 50.0% vs. 30.8%, p = 0.24; febrile neutropenia, 9.1% vs. 0.0%, p = 0.20, respectively). No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between irinotecan-naïve-patients and other patients. However, irinotecan-resistant patients showed significantly shorter PFS (hazard ratio (HR) 2.83, p = 0.017) and OS (HR 2.58, p = 0.033) than other patients. Our study indicated that patients with UGT1A1*1/*6 or *1/*28 may be prone to neutropenia, though further study is needed. The survival benefit of nal-IRI+5-FU/LV could be maintained in patients without disease progression after irinotecan therapy.
  • Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial
    Nakachi, K., Ikeda, M., Konishi, M., Nomura, S., Katayama, H., Kataoka, T., Todaka, A., Yanagimoto, H., Morinaga, S., Kobayashi, S., Shimada, K., Takahashi, Y., Nakagohri, T., Gotoh, K., Kamata, K., Shimizu, Y., Ueno, M., Ishii, H., Okusaka, T., Furuse, J., Okamura, K., Kawamoto, Y., Katanuma, A., Unno, M., Shirakawa, H., Yamaguchi, H., Takahashi, A., Yanagibashi, H., Kato, N., Sakamoto, Y., Kojima, Y., Higuchi, R., Sasahira, N., Sano, K., Sunakawa, Y., Kumamoto, Y., Sugimori, K., Nomura, T., Shibuya, K., Makino, I., Yamazaki, K., Mizuno, N., Wada, H., Sekimoto, M., Ajiki, T., Nakamura, I., Miki, I., Nagano, H., Ohta, K., Okabayashi, T., Furukawa, M., Fujimori, N.
    The Lancet, 401, 10372, 2023年
    研究論文(学術雑誌)
  • Anti-epidermal growth factor receptor treatment for patients with NeoRAS wild-type metastatic colorectal cancer: a case report of two cases.
    Kazuaki Harada, Satoshi Yuki, Yasuyuki Kawamoto, Takeaki Nakamura, Shiho Kaneko, Koichi Ishida, Naoya Sakamoto, Yoshito Komatsu
    Therapeutic advances in medical oncology, 15, 17588359231216090, 17588359231216090, 2023年, [国際誌]
    英語, The NeoRAS phenomenon is defined as the conversion of tumor RAS status from mutant-type (MT) to wild-type (WT) after systemic chemotherapy in metastatic colorectal cancer (mCRC). Cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody, is effective in patients with RAS WT mCRC but ineffective in those with RAS MT mCRC; however, its outcome in patients with NeoRAS WT mCRC is unclear. Herein, we report two cases of NeoRAS WT mCRC that responded clinically to anti-EGFR treatment. The first was a 40-year-old man with synchronous peritoneal metastatic rectosigmoid cancer. The first RAS testing on tumor tissue revealed a KRAS G12C mutation, which was converted to RAS WT after two lines of chemotherapy, as assessed by liquid biopsy. After initiating irinotecan plus cetuximab treatment, a computed tomography (CT) scan revealed that malignant ascites had resolved. The treatment was discontinued after 4 months because of disease progression. The second was a 68-year-old male patient with synchronous liver metastasis from sigmoid colon cancer. The KRAS G12D mutation, initially detected in tumor tissue, was not detected by liquid biopsy after six lines of chemotherapy. Cetuximab monotherapy was initiated, and the liver metastases shrank significantly. The patient continued cetuximab monotherapy for 8 months without disease progression. Our cases demonstrate the efficacy of anti-EGFR therapy for NeoRAS WT mCRC and highlight the importance of capturing the gene mutation profile throughout the clinical course for optimal treatment selection.
  • Feasibility of edoxaban for asymptomatic cancer-associated thrombosis in Japanese patients with gastrointestinal cancer: ExCAVE study.
    Michio Nakamura, Atsushi Ishiguro, Masayoshi Dazai, Yasuyuki Kawamoto, Satoshi Yuki, Susumu Sogabe, Ayumu Hosokawa, Kentaro Sawada, Osamu Muto, Naoki Izawa, Koji Nakashima, Yoshiki Horie, Masataka Yagisawa, Shinya Kajiura, Takayuki Ando, Yosuke Mitsuhashi, Yu Sunakawa, Yasuka Kikuchi, Yoshito Komatsu
    BMC cancer, 22, 1, 1322, 1322, 2022年12月16日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Although initial therapy with a parenteral anticoagulant is required before edoxaban, this strategy is frequently avoided in actual clinical practice because of its complexity. This study assessed the feasibility of edoxaban without initial heparin usage for asymptomatic cancer-associated thrombosis (CAT) in Japanese patients with gastrointestinal cancer (GIC) at high risk of bleeding. METHODS: In this multicenter prospective feasibility study conducted at 10 Japanese institutions, patients with active GIC who developed accidental asymptomatic CAT during chemotherapy were recruited. Edoxaban was orally administered once daily without initial parenteral anticoagulant therapy within 3 days after detecting asymptomatic CAT. The primary outcome was the incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) during the first 3 months of edoxaban administration. RESULTS: Of the 54 patients enrolled from October 2017 to September 2020, one was excluded because of a misdiagnosis of CAT. In the remaining 53 patients, the primary outcome occurred in six patients (11.3%). MB occurred in four patients (7.5%), including gastrointestinal bleeding in three patients and intracranial hemorrhage in one patient. CRNMB occurred in two patients (3.8%), including bleeding from the stoma site and genital bleeding in one patient each. There were no deaths attributable to bleeding, and all patients who experienced MB or CRNMB recovered. CONCLUSIONS: The risk of bleeding after edoxaban without heparin pretreatment was acceptable, demonstrating new treatment options for asymptomatic CAT in patients with GIC.
  • Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis.
    Yukio Yoshida, Satoshi Kobayashi, Makoto Ueno, Chigusa Morizane, Kunihiro Tsuji, Yuta Maruki, Keita Mori, Kazuo Watanabe, Akihiro Ohba, Mitsuhiro Furuta, Akiko Todaka, Akiko Tsujimoto, Masato Ozaka, Naohiro Okano, Kei Yane, Kumiko Umemoto, Yasuyuki Kawamoto, Takeshi Terashima, Hidetaka Tsumura, Keitaro Doi, Kazuhiko Shioji, Akinori Asagi, Yasushi Kojima, Eiichiro Suzuki, Reishi Toshiyama, Masayuki Furukawa, Atsushi Naganuma, Rei Suzuki, Haruo Miwa, Masafumi Ikeda, Junji Furuse
    Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 22, 8, 1159, 1166, 2022年09月08日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND/OBJECTIVES: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC. METHODS: We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions. RESULTS: Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively. CONCLUSIONS: This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.
  • 内科・外科による消化器病共同診療の現況と展望 局所進行直腸癌における術前FOLFOX療法の有効性の検討(RNAC01試験)の解釈とその発展               
    藤好 直, 本間 重紀, 市川 伸樹, 結城 敏志, 川本 泰之, 原田 一顕, 吉田 雅, 柴田 賢吾, 松井 博紀, 小松 嘉人, 坂本 直哉, 武冨 紹信
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 131回・125回, 26, 26, 日本消化器病学会-北海道支部, 2022年09月
    日本語
  • 内科・外科による消化器病共同診療の現況と展望 当科における切除可能境界膵癌に対する術前治療の現状               
    原田 一顕, 中村 赳晶, 渡辺 亮介, 山村 貴洋, 川本 泰之, 結城 敏志, 桑谷 将城, 田口 大志, 加藤 徳雄, 浅野 賢道, 中村 透, 平野 聡, 小松 嘉人, 坂本 直哉
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 131回・125回, 28, 28, 日本消化器病学会-北海道支部, 2022年09月
    日本語
  • Usefulness of ultrasonography and elastography in diagnosing oxaliplatin-induced sinusoidal obstruction syndrome.
    Rika Saito, Yasuyuki Kawamoto, Mutsumi Nishida, Takahito Iwai, Yasuka Kikuchi, Isao Yokota, Ryo Takagi, Takahiro Yamamura, Ken Ito, Kazuaki Harada, Satoshi Yuki, Yoshito Komatsu, Naoya Sakamoto
    International journal of clinical oncology, 27, 11, 1780, 1790, 2022年08月30日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early. METHODS: In this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT. RESULTS: Of the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase  ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32-0.41). The change in rate of LSM by SWE was correlated with an SV increase  ≥ 30% (r = 0.40). CONCLUSIONS: The usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS.
  • An open-label, crossover study to compare different formulations and evaluate effect of food on pharmacokinetics of pimitespib in patients with advanced solid tumors.
    Yoshito Komatsu, Tsuneo Shimokawa, Kohei Akiyoshi, Masato Karayama, Akihiko Shimomura, Yasuyuki Kawamoto, Satoshi Yuki, Yuichi Tambo, Kazuo Kasahara
    Investigational new drugs, 40, 5, 1011, 1020, 2022年08月06日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), This study compared the bioavailability of two pimitespib formulations (Formulations A and B), evaluated the food effect on Formulation A, and evaluated the safety and efficacy of multiple pimitespib doses in patients with solid tumors. This clinical, pharmacological multicenter study had two cohorts and periods. A single dose of Formulation A or B was administered in a crossover design to compare the pharmacokinetics in Cohort 1. In Cohort 2, the effects of fed vs fasting conditions were evaluated among those receiving Formulation A. Subsequently, multiple Formulation A doses were administered to all patients for safety and efficacy assessments. In Cohorts 1 and 2, 12 and 16 patients, respectively, were analyzed for pharmacokinetics. Thirty patients were analyzed for safety and efficacy. Maximum concentration (Cmax), area under the curve (AUC)last, and AUCinf geometric mean ratios for Formulations A and B (90% confidence interval [CI]) were 0.8078 (0.6569-0.9933), 0.7973 (0.6672-0.9529), and 0.8094 (0.6697-0.9782), respectively; 90% CIs were not within the bioequivalence range (0.80-1.25). In Cohort 2, mean Cmax, AUClast, and AUCinf were higher in fed vs fasting conditions. No safety concerns emerged with single or multiple administration. Overall response rate, disease control rate, and median progression-free survival were 0%, 33%, and 1.5 months, respectively. Four patients had stable disease ≥ 5 months. Bioequivalence of the two formulations was unconfirmed. Systemic exposure of Formulation A was approximately 20% less than Formulation B. A high-fat/calorie meal increased the relative pharmacokinetics and bioavailability of a single 160-mg dose. Trial Registration: JapicCTI-184191 (Japan Pharmaceutical Information Center) registered on November 5, 2018.
  • Phase II Study of Ramucirumab Plus Irinotecan Combination Therapy as Second-Line Treatment in Patients with Advanced Gastric Cancer: HGCSG1603.
    Yasuyuki Kawamoto, Satoshi Yuki, Kentaro Sawada, Michio Nakamura, Osamu Muto, Susumu Sogabe, Yoshiaki Shindo, Atsushi Ishiguro, Atsushi Sato, Yasushi Tsuji, Masayoshi Dazai, Hiroyuki Okuda, Takashi Meguro, Kazuaki Harada, Mari Sekiguchi, Kazufumi Okada, Yoichi M Ito, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
    The oncologist, 27, 8, e642-e649, 2022年08月05日, [査読有り], [筆頭著者], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Ramucirumab is a human IgG1 monoclonal vascular endothelial growth factor receptor-2 antibody that inhibits tumor cell growth and affects the tumor cell microenvironment. We assessed the efficacy and safety of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with previously treated advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric cancer refractory or intolerant to primary chemotherapy were included. Ramucirumab 8 mg/kg plus irinotecan 150 mg/m2 combination therapy was administered every 2 weeks. The primary endpoint was progression-free survival rate at 6 months and secondary endpoints were overall survival, progression-free survival, response rate, safety, and dose intensity for each drug. RESULTS: Thirty-five patients were enrolled between January 2018 and September 2019. The progression-free survival rate at 6 months was 26.5% [95%CI, 13.2%-41.8%, P = .1353)]. Median progression-free and overall survivals were 4.2 months (95%CI, 2.5-5.4 months) and 9.6 months (95%CI, 6.4-16.6 months), respectively. The overall response rate was 25.9% (95%CI, 11.1-36.3%) and disease control rate was 85.2% (95%CI, 66.3-95.8%). Grade ≥3 adverse events that occurred in >10% of patients included neutropenia, leucopenia, anemia, anorexia, and febrile neutropenia. No death or new safety signals with a causal relation to the study treatment were observed. CONCLUSION: Although the primary endpoint was not achieved statistically, combination therapy of ramucirumab plus irinotecan showed anticancer activity and a manageable safety profile for second-line treatment of patients with advanced gastric cancer.
  • Analysis of the Pancreatic Cancer Microbiome Using Endoscopic Ultrasound–Guided Fine-Needle Aspiration–Derived Samples
    Shintaro Nakano, Yasuyuki Kawamoto, Yoshito Komatsu, Rika Saito, Ken Ito, Takahiro Yamamura, Kazuaki Harada, Satoshi Yuki, Kazumichi Kawakubo, Ryo Sugiura, Shin Kato, Koji Hirata, Hajime Hirata, Masahito Nakajima, Ryutaro Furukawa, Yunosuke Takishin, Kousuke Nagai, Isao Yokota, Keisuke H. Ota, Shinji Nakaoka, Masaki Kuwatani, Naoya Sakamoto
    Pancreas, Publish Ahead of Print, 4, 351, 357, Ovid Technologies (Wolters Kluwer Health), 2022年06月13日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), OBJECTIVES: Most previous studies have analyzed bacteria in tumors using resected pancreatic cancer (PC) tissues, because it is difficult to obtain tissue samples from unresectable advanced PC. We aimed to determine whether minimal tissue obtained by endoscopic ultrasound-guided fine-needle aspiration is useful for microbiome analysis. METHODS: Thirty PC and matched duodenal and stomach tissues (N = 90) were prospectively collected from 30 patients who underwent endoscopic ultrasound-guided fine-needle aspiration. Bacterial DNA was extracted, and 16S rRNA sequencing was performed. The primary outcome was the success rate of bacterial detection in tumors. Bacterial diversity and structure were investigated. RESULTS: The bacterial detection rates were 80%, 100%, and 97% in PC, gastric, and duodenal samples, respectively. Pancreatic cancer tissues showed a lower α-diversity and a significantly different microbial structure than stomach and duodenal tissues. Proteobacteria were more abundant, whereas Firmicutes, Bacteroidetes, and Fusobacteria were less abundant in PC tissues than in stomach and duodenal tissues. Acinetobacter was more abundant in PC tissues than in stomach and duodenal tissues, and Delftia was more frequently detected in resectable PC. CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration samples were valuable for PC microbiome analysis, revealing that the bacterial composition of PC is different from that of the stomach and duodenum.
  • Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing unresectable or recurrent biliary tract cancer (BTC): An investigator-initiated multicenter phase 2 study (HERB trial).
    Akihiro Ohba, Chigusa Morizane, Yasuyuki Kawamoto, Yoshito Komatsu, Makoto Ueno, Satoshi Kobayashi, Masafumi Ikeda, Mitsuhito Sasaki, Junji Furuse, Naohiro Okano, Nobuyoshi Hiraoka, Hiroshi Yoshida, Aya Kuchiba, Ryo Sadachi, Kenichi Nakamura, Naoko Matsui, Yoshiaki Nakamura, Wataru Okamoto, Takayuki Yoshino, Takuji Okusaka
    Journal of Clinical Oncology, 40, 16_suppl, 4006, 4006, American Society of Clinical Oncology (ASCO), 2022年06月01日
    研究論文(学術雑誌), 4006

    Background: BTCs have an aggressive tumor biology with limited treatment options. With a HER2-positivity rate of 5–20% in BTCs, case series and small clinical trials have shown signs of activity for HER2 blockade in these pts. T-DXd is an antibody-drug conjugate composed of a humanized monoclonal anti-HER2 antibody, a cleavable linker, and a topoisomerase I inhibitor. The HERB trial is an investigator-initiated, multicenter, single-arm phase 2 trial of T-DXd in pts with HER2-expressing BTCs. Methods: Centrally confirmed HER2-expressing (HER2-positive: IHC3+ or IHC2+/ISH+, and HER2-low-expressing [HER2-low]: IHC/ISH status of 0/+, 1+/-, 1+/+, or 2+/-) pts with BTCs who were refractory or intolerant to gemcitabine containing regimen received 5.4 mg/kg of T-DXd every 3 weeks. The primary endpoint was the confirmed objective response rate (ORR) in HER2-positive pts by independent central review. The sample size of 22 had 80% power with one-sided alpha error of 5%; threshold ORR, 15%; and expected ORR, 40%. The ORR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS) in HER2-positive/-low pts, and incidence of treatment-emergent adverse events (TEAEs) were assessed as secondary endpoints. Results: A total of 32 pts, 24 with HER2-positive and 8 with HER2-low BTCs, received T-DXd. Twenty-two pts with HER2-positive, excluding 2 ineligible pts, were identified for primary efficacy analysis. Among the 22 pts, IHC3+ and IHC2+/ISH+ were 45.5% and 54.5%, primary sites: gallbladder/extrahepatic/intrahepatic/Vater were 11/6/3/2, median number of prior regimens was 2 (range, 1–4). The confirmed ORR in HER2-positive pts was 36.4% (8/22; 2 CR and 6 PR; 90% CI, 19.6–56.1), indicating statistically significant improvement in ORR (P = 0.01). The DCR, median (m) PFS, mOS were 81.8% (95% CI, 59.7–94.8), 4.4 months (mo) (95% CI, 2.8–8.3), 7.1 mo (95% CI, 4.7–14.6), respectively. In addition, encouraging efficacy were seen even in HER2-low pts; ORR, DCR, mPFS, and mOS were 12.5% (1/8; 1 PR; 95% CI, 0.3–52.7), 75.0% (95% CI, 34.9–96.8), 4.2 mo (95% CI, 1.3–6.2), and 8.9 mo (95% CI, 3.0–12.8), respectively. In the safety analysis set (n = 32), TEAEs of > = grade (G) 3 occurred in 81.3% (26/32); the common TEAEs were anemia (53.1%), neutropenia (31.3%), and leukopenia (31.3%). TEAEs leading to drug discontinuation occurred in 8 pts (25.0%). Eight pts (25.0%) had interstitial lung disease (ILD; G1/G2/G3/G5 were 3/1/2/2) not adjudicated by an independent committee. Conclusions: T-DXd showed promising activity in pts with HER2-expressing BTCs. Although the safety profile was generally consistent with other T-DXd studies, ILD, an important identified risk of T-DXd, requires more careful monitoring and intervention. These results support further exploration of T-DXd in this patient population. Clinical trial information: JMA-IIA00423.
  • Multicenter, prospective, observational study of chemotherapy-induced dysgeusia in gastrointestinal cancer.
    Ken Ito, Satoshi Yuki, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Kazuaki Harada, Shintaro Nakano, Rika Saito, Takayuki Ando, Kentaro Sawada, Masataka Yagisawa, Atsushi Ishiguro, Masayoshi Dazai, Ichiro Iwanaga, Kazuteru Hatanaka, Atsushi Sato, Ryusuke Matsumoto, Yoshiaki Shindo, Miki Tateyama, Tetsuhito Muranaka, Masaki Katagiri, Isao Yokota, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 30, 6, 5351, 5359, 2022年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Dysgeusia is an adverse event caused by chemotherapy. Although retrospective studies have shown zinc administration improves dysgeusia, there have been no prospective studies. The present study examined effects of zinc therapy on dysgeusia in patients with gastrointestinal cancer. METHODS: This multicenter, prospective, observational study enrolled patients with dysgeusia during chemotherapy treatment. Patients received no intervention (control), polaprezinc p.o., or zinc acetate hydrate p.o., and serum zinc levels were measured at 0 (baseline), 6, and 12 weeks. Dysgeusia was assessed using CTCAE v5.0 and subjective total taste acuity (STTA) criteria using questionnaires at baseline and 12 weeks. RESULTS: From February 2020 to June 2021, 180 patients were enrolled from 17 institutes. There were no differences in mean baseline serum zinc levels among the groups (67.3, 66.6, and 67.5 μg/dL in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. P = 0.846). The changes in mean serum zinc levels after 12 weeks were - 3.8, + 14.3, and + 46.6 μg/dL, and the efficacy rates of dysgeusia were 33.3%, 36.8%, and 34.6% using CTCAE and 33.3%, 52.6%, 32.7% using STTA in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. The STTA scores improved in all groups, with significant improvement observed in the polaprezinc group compared with the no intervention group (P = 0.045). CONCLUSION: There was no significant correlation between the degree of serum zinc elevation and improvement in dysgeusia, suggesting that polaprezinc, but not zinc acetate hydrate, was effective in improving chemotherapy-induced dysgeusia. TRIAL REGISTRATION: UMIN000039653. Date of registration: March 2, 2020.
  • Study protocol of the HGCSG1803: a phase II multicentre, non-randomised, single-arm, prospective trial of combination chemotherapy with oxaliplatin, irinotecan and S-1 (OX-IRIS) as first-line treatment for metastatic or relapsed pancreatic cancer.
    Shintaro Nakano, Yasuyuki Kawamoto, Satoshi Yuki, Kazuaki Harada, Takuto Miyagishima, Susumu Sogabe, Masayoshi Dazai, Atsushi Sato, Atsushi Ishiguro, Michio Nakamura, Shinya Kajiura, Yasuo Takahashi, Miki Tateyama, Kazuteru Hatanaka, Yasushi Tsuji, Takahide Sasaki, Yoshiaki Shindo, Tomoe Kobayashi, Isao Yokota, Naoya Sakamoto, Yuh Sakata, Yoshito Komatsu
    BMJ open, 12, 5, e048833, 2022年05月09日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), INTRODUCTION: Combination chemotherapy with oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) has become one of the standard treatments for metastatic pancreatic cancer. However, the use of FOLFIRINOX requires prolonged infusion. Therefore, we planned to develop a new combination chemotherapy regimen with oxaliplatin, irinotecan and S-1 (OX-IRIS) for advanced pancreatic cancer. In the phase Ⅰ study that was conducted previously, the safety and recommended dose of OX-IRIS were assessed. In this study, we will evaluate the efficacy and safety of OX-IRIS. METHODS AND ANALYSIS: The HGCSG1803 study started as a multicentre, non-randomised, single-arm, prospective, phase II study in December 2019. Eligible subjects were patients with untreated metastatic or relapsed pancreatic cancer. OX-IRIS is administered as follows: 30 min infusion of antiemetic; 2-hour infusion of oxaliplatin (65 mg/m2); 1.5-hour infusion of irinotecan (100 mg/m2) on day 1 and 15 of each 4-week cycle; and oral S-1 (40 mg/m2) twice daily from after dinner on day one to after breakfast on day 15, followed by a 14-day rest, to be repeated every 2 weeks until disease progression, unacceptable toxicity or patient refusal. The primary endpoint is response rate. The secondary endpoints are overall and progression-free survival, safety and dose for each drug. Using a binomial test, a sample size of 40 patients was set with a threshold value of 10% and expected value of 30%. Registration of 40 cases is planned from 18 institutions in Japan. ETHICS AND DISSEMINATION: All the procedures will be conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki of 1964 and its later versions. All the patients will receive written information about the trial and will provide informed consent before enrolment. This trial was approved by the Hokkaido University Certified Review Board (approval No: 018-037). TRIAL REGISTRATION NUMBER: jRCTs011190008.
  • Phase II Study of Continued Trastuzumab Plus Irinotecan in Patients with HER2-positive Gastric Cancer Previously Treated with Trastuzumab (HGCSG 1201).
    Yasuyuki Kawamoto, Satoshi Yuki, Takashi Meguro, Kazuteru Hatanaka, Minoru Uebayashi, Michio Nakamura, Hiroyuki Okuda, Ichiro Iwanaga, Takashi Kato, Shintaro Nakano, Atsushi Sato, Kazuaki Harada, Koji Oba, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
    The oncologist, 27, 5, 340-e374, 2022年05月06日, [査読有り], [筆頭著者], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: The efficacy of irinotecan plus continuous trastuzumab beyond progression in patients with gastric cancer previously treated with trastuzumab plus standard first-line chemotherapy has not been reported. METHODS: Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer who were previously treated with trastuzumab received trastuzumab every 3 weeks and irinotecan every 2 weeks. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), 6-month survival rates, safety, and subgroup analysis by HER2 status. RESULTS: Sixteen patients were enrolled in a 3-year pre-planned registration period. This study was prematurely closed due to poor patient accrual. The ORR and disease control rate were 6.7% (95% CI, 0.2-32.0) and 53.3% (95% CI, 26.6-78.7). The median PFS and overall survival (OS) were 2.4 months (95% CI, 0.0-5.2) and 9.7 months (95% CI, 8.2-11.2), respectively. The most frequently reported grades 3-4 adverse events were neutropenia (40%), anemia (27%), anorexia (33%), and fatigue (33%). CONCLUSION: With only 16 patients enrolled, the present study has very low power to detect any clinical benefit of trastuzumab plus irinotecan beyond disease progression in patients with HER2-positive advanced gastric cancer who previously received trastuzumab.Trial Identifier: UMIN000007636.
  • Multicenter phase II trial of trastuzumab deruxtecan for HER2-positive unresectable or recurrent biliary tract cancer: HERB trial.
    Akihiro Ohba, Chigusa Morizane, Makoto Ueno, Satoshi Kobayashi, Yasuyuki Kawamoto, Yoshito Komatsu, Masafumi Ikeda, Mitsuhito Sasaki, Naohiro Okano, Junji Furuse, Nobuyoshi Hiraoka, Hiroshi Yoshida, Aya Kuchiba, Ryo Sadachi, Kenichi Nakamura, Naoko Matsui, Yoshiaki Nakamura, Wataru Okamoto, Takayuki Yoshino, Takuji Okusaka
    Future oncology (London, England), 18, 19, 2351, 2360, 2022年05月05日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of a humanized monoclonal anti-HER2 antibody, a cleavable tetrapeptide-based linker and a potent topoisomerase I inhibitor. The drug's efficacy has been proven in HER2-positive breast and gastric cancers. The rate of HER2 positivity in biliary tract cancer (BTC) has been reported to be 5-20%, and case reports and clinical trials have suggested that HER2 inhibitors might be active in HER2-positive BTC. Here we describe the rationale and design of the phase II HERB trial that will evaluate the efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing unresectable or recurrent BTC. The primary end point will be the centrally assessed objective response rate in HER2-positive patients.
  • 個別化医療を見据えた消化器診療の現状 超音波内視鏡下穿刺吸引法で得られた検体を用いた膵腫瘍内細菌叢の検討               
    中野 真太郎, 川本 泰之, 小松 嘉人, 伊藤 憲, 原田 一顕, 結城 敏志, 川久保 和道, 杉浦 諒, 加藤 新, 平田 幸司, 平田 甫, 中島 正人, 古川 龍太郎, 滝新 悠之介, 永井 孝輔, 横田 勲, 太田 圭祐, 中岡 慎治, 桑谷 将城, 坂本 直哉
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 130回・124回, 36, 36, 日本消化器病学会-北海道支部, 2022年03月
    日本語
  • The survival benefit of increasing the number of active drugs for metastatic colorectal cancer: A multicenter retrospective study
    Takeshi Kawakami, Toshiki Masuishi, Yasuyuki Kawamoto, Hirofumi Go, Kyoko Kato, Ryosuke Kumanishi, Kentaro Sawada, Satoshi Yuki, Kouji Yamamoto, Yoshito Komatsu, Kei Muro, Kunihiro Fushiki, Hiromichi Shirasu, Kentaro Yamazaki
    Cancer Medicine, 11, 11, 2184, 2192, Wiley, 2022年02月19日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: The development of chemotherapy and treatment strategies for metastatic colorectal cancer (mCRC) have provided patients with significant survival benefits. Currently, molecular targeting agents and late-line treatment with regorafenib and trifluridine/tipiracil (FTD/TPI) are available. However, the impact of this increase in drug availability on overall survival (OS) in mCRC remains a clinical question. METHODS: We retrospectively collected data on consecutive mCRC patients who were treated at three institutions in Japan. We divided the patients into three cohorts: patients who initiated first-line treatment from Jan 2005 to Dec 2006 (cohort A: only cytotoxic drugs available), Jan 2007 to Dec 2011 (cohort B: molecular targeting drugs available), and Jan 2012 to Sep 2016 (cohort C: late-line treatment available). RESULTS: A total of 1409 consecutive patients were analyzed. The median survival time (MST) in cohorts A, B, and C was 18.6, 25.4, and 26.4 months, respectively. The hazard ratio (HR) for cohort B versus A was 0.81 (95% CI 0.68-0.97), for cohort C versus A was 0.74 (95% CI 0.61-0.89), and for cohort C versus B was 0.92 (0.81-1.03). The median number of administered drugs (range) was 3 (1-5) in cohort A, 4 (1-7) in cohort B, and 4 (1-7) in cohort C. The increase in drug availability extended the MST from 15.5 months in patients treated with ≤3 drugs to 36.0-37.3 months in patients treated with six to seven drugs. CONCLUSION: The development of chemotherapy including late-line treatments could improve the prognosis of mCRC patients.
  • Endoscopic duodenal stent placement versus gastrojejunostomy for unresectable pancreatic cancer patients with duodenal stenosis before introduction of initial chemotherapy (GASPACHO study): a multicenter retrospective study.
    Nobuaki Azemoto, Makoto Ueno, Hiroaki Yanagimoto, Nobumasa Mizuno, Yasuyuki Kawamoto, Yuta Maruki, Kazuo Watanabe, Rei Suzuki, Junichi Kaneko, Yuya Hisada, Hiroki Sato, Satoshi Kobayashi, Hideki Miyata, Masayuki Furukawa, Takuro Mizukami, Haruo Miwa, Yoshinori Ohno, Kunihiro Tsuji, Akiko Tsujimoto, Hiroaki Nagano, Hiroyuki Okuyama, Akinori Asagi, Naohiro Okano, Hiroshi Ishii, Chigusa Morizane, Masafumi Ikeda, Junji Furuse
    Japanese journal of clinical oncology, 52, 2, 134, 142, 2022年02月05日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Endoscopic duodenal stent placement is an alternative technique to gastrojejunostomy for gastric outlet obstruction due to pancreatic cancer. We compared the efficacy of endoscopic duodenal stent placement with that of gastrojejunostomy for treating patients with pancreatic cancer who are candidates for intensive combination chemotherapies as the first line of treatment. METHODS: This retrospective observational study included 100 patients from 18 institutions in Japan. Inclusion criteria were as follows: (1) cytologically or histologically confirmed adenocarcinoma of the pancreas, (2) good performance status, (3) gastric outlet obstruction scoring system score of 0-1 and (4) no history of treatment for pancreatic cancer. RESULTS: There was no significant difference in the background characteristics of patients in the endoscopic duodenal stent placement (n = 57) and gastrojejunostomy (n = 43) groups. The median overall survival in the endoscopic duodenal stent placement and gastrojejunostomy groups was 5.9 and 6.0 months, respectively. Clinical success was achieved in 93 cases; the median time to food intake resumption was significantly shorter in the endoscopic duodenal stent placement group (median: 3 days, n = 54) than in the gastrojejunostomy group (median: 5 days, n = 43). Chemotherapy was introduced in 63% of the patients in both groups after endoscopic duodenal stent placement or gastrojejunostomy. Chemotherapy was started earlier in the endoscopic duodenal stent placement group (median: 14 days) than in the gastrojejunostomy (median: 32 days) group. CONCLUSIONS: Endoscopic duodenal stent placement showed similar or better clinical outcomes than gastrojejunostomy. Thus, it might be a promising option in patients with good performance status.
  • S-1併用陽子線治療後conversion surgeryを行った切除不能局所進行膵癌の1例               
    小泉 富基, 加藤 徳雄, 打浪 雄介, 田口 大志, 青山 英史, 清水 伸一, 中村 透, 川本 泰之, 高尾 聖心, 田村 昌也, 松浦 妙子, 清水 伸一
    Japanese Journal of Radiology, 40, Suppl., 3, 3, (公社)日本医学放射線学会, 2022年02月
    日本語
  • The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: an exploratory analysis of JCOG1113.
    Ikuhiro Yamada, Chigusa Morizane, Takuji Okusaka, Junki Mizusawa, Tomoko Kataoka, Makoto Ueno, Masafumi Ikeda, Naohiro Okano, Akiko Todaka, Satoshi Shimizu, Nobumasa Mizuno, Mitsugu Sekimoto, Kazutoshi Tobimatsu, Hironori Yamaguchi, Tomohiro Nishina, Hirofumi Shirakawa, Yasushi Kojima, Takamasa Oono, Yasuyuki Kawamoto, Masayuki Furukawa, Tomohisa Iwai, Kentaro Sudo, Keiya Okamura, Tatsuya Yamashita, Naoya Kato, Kazuhiko Shioji, Kyouko Shimizu, Toshio Nakagohri, Ken Kamata, Hiroshi Ishii, Junji Furuse
    Scientific reports, 12, 1, 987, 987, 2022年01月19日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), In the FUGA-BT trial (JCOG1113), gemcitabine plus S-1 (GS) showed non-inferiority to gemcitabine plus cisplatin (GC) in overall survival (OS) with good tolerance for patients with advanced biliary tract cancer (BTC). We performed a subgroup analysis focused on the elderly cohort of this trial. All 354 enrolled patients in JCOG1113 were classify into two groups; < 75 (non-elderly) and ≥ 75 years (elderly) group. We investigated the influence of age on the safety analysis, including the incidence of chemotherapeutic adverse events and the efficacy analysis, including OS. There were no remarkable differences in OS between the elderly (n = 60) and the non-elderly groups (n = 294). In the elderly group, median OS was 12.7 and 17.7 months for those who received GC (n = 20) and GS (n = 40), respectively. The prevalence of all-grade adverse events was similar between the elderly and the non-elderly groups. However, among the elderly group, Grade ≥ 3 hematological adverse events were more frequently observed in the GC arm than in the GS arm. The clinical outcomes of combination chemotherapy in elderly patients with advanced BTC were comparable to non-elderly patients. GS may be the more favorable treatment for elderly patients with advanced BTC.
  • がん治療医・緩和ケアスタッフを対象としたターミナルケア態度尺度を用いた意識調査
    熊井 正貴, 加藤 信太郎, 小柳 遼, 敦賀 健吉, 伊藤 陽一, 山田 武宏, 武隈 洋, 菅原 満, 川本 泰之, 小松 嘉人
    Palliative Care Research, 17, 2, 51, 58, (NPO)日本緩和医療学会, 2022年
    日本語
  • Study protocol for HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer refractory to anti-EGFR antibodies.
    Hiroshi Nakatsumi, Yoshito Komatsu, Tetsuhito Muranaka, Satoshi Yuki, Yasuyuki Kawamoto, Kazuaki Harada, Masayoshi Dazai, Miki Tateyama, Yusuke Sasaki, Takuto Miyagishima, Yasushi Tsuji, Masaki Katagiri, Michio Nakamura, Susumu Sogabe, Kazuteru Hatanaka, Takashi Meguro, Tomoe Kobayashi, Atsushi Ishiguro, Osamu Muto, Yoshiaki Shindo, Masahito Kotaka, Takayuki Ando, Ryo Takagi, Naoya Sakamoto, Yu Sakata
    Frontiers in oncology, 12, 939425, 939425, 2022年, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: The first-line chemotherapy for patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies. METHODS: FOLFIRI (irinotecan 180 mg/m2, l-leucovorin 200 mg/m2, bolus 5-FU 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi. DISCUSSION: There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs011190006.
  • がん治療医・緩和ケアスタッフを対象としたターミナルケア態度尺度を用いた意識調査               
    熊井 正貴, 加藤 信太郎, 小柳 遼, 敦賀 健吉, 伊藤 陽一, 山田 武宏, 武隈 洋, 菅原 満, 川本 泰之, 小松 嘉人
    Palliative Care Research, 17, 2, 51, 58, (NPO)日本緩和医療学会, 2022年, [査読有り]
    日本語
  • Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study.
    Kohichi Takada, Tomohiro Kubo, Junko Kikuchi, Makoto Yoshida, Ayako Murota, Yohei Arihara, Hajime Nakamura, Hiroyuki Nagashima, Hiroki Tanabe, Shintaro Sugita, Yumi Tanaka, Ayana Miura, Yoshihito Ohhara, Atsushi Ishiguro, Hiroshi Yokouchi, Yasuyuki Kawamoto, Yusuke Mizukami, Hirofumi Ohnishi, Ichiro Kinoshita, Akihiro Sakurai
    Frontiers in oncology, 12, 988527, 988527, 2022年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.
  • Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113
    Makoto Ueno, Chigusa Morizane, Takuji Okusaka, Junki Mizusawa, Tomoko Kataoka, Masafumi Ikeda, Masato Ozaka, Naohiro Okano, Kazuya Sugimori, Akiko Todaka, Satoshi Shimizu, Nobumasa Mizuno, Tomohisa Yamamoto, Keiji Sano, Kazutoshi Tobimatsu, Akio Katanuma, Atsushi Miyamoto, Hironori Yamaguchi, Tomohiro Nishina, Hirofumi Shirakawa, Yasushi Kojima, Takamasa Oono, Yasuyuki Kawamoto, Masayuki Furukawa, Tomohisa Iwai, Kentaro Sudo, Hiroyuki Miyakawa, Tatsuya Yamashita, Ichirou Yasuda, Hidenori Takahashi, Naoya Kato, Kazuhiko Shioji, Kyoko Shimizu, Toshio Nakagohri, Ken Kamata, Hiroshi Ishii, Junji Furuse
    Scientific Reports, 11, 1, 12885, 12885, Springer Science and Business Media LLC, 2021年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), AbstractJCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504–0.937) in the low CCr group. Although the total number of incidences of all Grade 3–4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.
  • 再発胆道癌に対する積極的外科切除の成績               
    野路 武寛, 松井 あや, 田中 公貴, 中西 喜嗣, 渡邉 祐介, 浅野 賢道, 海老原 裕磨, 倉島 庸, 中村 透, 村上 壮一, 土川 貴裕, 岡村 圭佑, 七戸 俊明, 川本 泰之, 桑谷 将城, 平野 聡
    日本消化器外科学会雑誌, 54, Suppl.2, 155, 155, (一社)日本消化器外科学会, 2021年11月
    日本語
  • 再発胆道癌に対する積極的外科切除の成績               
    野路 武寛, 松井 あや, 田中 公貴, 中西 喜嗣, 渡邉 祐介, 浅野 賢道, 海老原 裕磨, 倉島 庸, 中村 透, 村上 壮一, 土川 貴裕, 岡村 圭佑, 七戸 俊明, 川本 泰之, 桑谷 将城, 平野 聡
    日本消化器外科学会雑誌, 54, Suppl.2, 155, 155, (一社)日本消化器外科学会, 2021年11月
    日本語
  • がん治療医・緩和ケアスタッフを対象としたターミナルケア態度尺度を用いた意識調査               
    熊井 正貴, 加藤 信太郎, 小柳 遼, 敦賀 健吉, 伊藤 陽一, 山田 武宏, 川本 泰之, 武隈 洋, 菅原 満, 小松 嘉人
    Palliative Care Research, 16, Suppl._Hokkaido, S492, S492, (NPO)日本緩和医療学会, 2021年10月
    日本語
  • がん治療医・緩和ケアスタッフを対象としたターミナルケア態度尺度を用いた意識調査               
    熊井 正貴, 加藤 信太郎, 小柳 遼, 敦賀 健吉, 伊藤 陽一, 山田 武宏, 川本 泰之, 武隈 洋, 菅原 満, 小松 嘉人
    Palliative Care Research, 16, Suppl._Hokkaido, S492, S492, (NPO)日本緩和医療学会, 2021年10月
    日本語
  • HGCSG2101 実臨床における進行膵癌に対するnal/IRI+5-FU/LVの治療成績               
    山村 貴洋, 原田 一顕, 曽我部 進, 澤田 憲太郎, 八木澤 允貴, 中野 真太郎, 太宰 昌佳, 舘山 美樹, 伊藤 憲, 斎藤 里佳, 川本 泰之, 結城 敏志, 坂本 直哉, 坂田 優, 小松 嘉人
    日本癌治療学会学術集会抄録集, 59回, O43, 2, (一社)日本癌治療学会, 2021年10月
    英語
  • HGCSG1901 切除不能結腸直腸癌におけるIRIS/Bevの後方視的研究 抗EGFR抗体後の検討               
    斎藤 絢介, 伊藤 憲, 結城 敏志, 川本 泰之, 八木澤 允貴, 澤田 憲太郎, 佐藤 温, 辻 靖, 安藤 孝将, 中野 真太郎, 若林 俊樹, 小高 雅人, 高橋 康雄, 坂田 優, 小松 嘉人
    日本癌治療学会学術集会抄録集, 59回, O56, 4, (一社)日本癌治療学会, 2021年10月
    英語
  • A Phase I Trial of Oxaliplatin, Irinotecan, and S‐1 Combination Therapy ( OX‐IRIS ) as Chemotherapy for Unresectable Pancreatic Cancer ( HGCSG 1403)
    Yasuyuki Kawamoto, Hiroshi Nakatsumi, Kazuaki Harada, Tetsuhito Muranaka, Atsushi Ishiguro, Yoshimitsu Kobayashi, Hideyuki Hayashi, Satoshi Yuki, Kentaro Sawada, Masataka Yagisawa, Shintaro Nakano, Naoya Sakamoto, Yoshito Komatsu
    The Oncologist, 26, 10, e1675-e1682, Wiley, 2021年10月, [査読有り], [筆頭著者], [国際誌]
    英語, 研究論文(学術雑誌), LESSONS LEARNED: Because S-1 is orally administered, OX-IRIS does not necessitate the continuous infusion of 5-FU and is more convenient. The recommended dose of OX-IRIS was determined to be level -1 (oxaliplatin, 65 mg/m2 ; irinotecan, 100 mg/m2 ; S-1, 80 mg/m2 ), which has manageable safety and promising anticancer activities. BACKGROUND: OX-IRIS is a new combination therapy of oxaliplatin, irinotecan, and S-1 for unresectable pancreatic ductal adenocarcinoma (PDAC), which may be beneficial because S-1 is administered orally and continuous infusion of 5-fluorouracil (5-FU) is not needed. METHODS: Patients who had not received prior therapy for unresectable PDAC were enrolled. Adenocarcinoma or adenosquamous histology was required. Oxaliplatin and irinotecan were administered on days 1 and 15; S-1 was administered orally twice a day on days 1-14, followed by 14 days of rest (one cycle). Primary endpoints were dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). Secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: In level 0 (oxaliplatin, 85 mg/m2 ; irinotecan, 100 mg/m2 ; S-1, 80 mg/m2 ), two of five patients experienced DLT. In level -1 (oxaliplatin, 65 mg/m2 ; irinotecan, 100 mg/m2 ; S-1, 80 mg/m2 ), DLT could not be evaluated in two of eight patients because one cycle was not completed; one of the remaining six patients experienced DLT. Anemia, thrombocytopenia, fatigue, nausea, anorexia, diarrhea, and peripheral sensory neuropathy were seen frequently in levels 0 and -1. ORR was 30% in levels 0 and -1. Median progression-free survival and median overall survival were 4.1 months (95% confidence interval [CI], 0.0-8.9 months) and 13.7 months (95% CI, 4.8-22.6 months), respectively. CONCLUSION: MTD of OX-IRIS therapy was estimated to be level 0, and the recommended dose (RD) for future trial was level -1.
  • The Prognostic Impact of KRAS G12C Mutation in Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Observational Study
    Keigo Chida, Daisuke Kotani, Toshiki Masuishi, Takeshi Kawakami, Yasuyuki Kawamoto, Kyoko Kato, Kunihiro Fushiki, Kentaro Sawada, Ryosuke Kumanishi, Hiromichi Shirasu, Yuki Matsubara, Satoshi Yuki, Yoshito Komatsu, Kentaro Yamazaki, Takayuki Yoshino
    The Oncologist, 26, 10, 845, 853, Wiley, 2021年10月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: KRAS is one of the most frequently mutated oncogenes in colorectal cancer (CRC). Recently, a novel therapy targeting KRAS G12C mutation has demonstrated promising activities for corresponding advanced solid tumors, including metastatic CRC (mCRC). However, the prognostic impact of the KRAS G12C mutation remains unclear in patients with mCRC. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with mCRC who received first-line chemotherapy between January 2005 and December 2017 at four large oncology facilities in Japan. Survival outcomes were compared between patients with KRAS G12C and those with non-G12C mutations. RESULTS: Among 2,457 patients with mCRC, 1,632 met selection criteria, and of these, 696 had KRAS exon 2 mutations, including 45 with KRAS G12C mutation tumors. Patient characteristics were not significantly different between the KRAS G12C and non-G12C groups. At a median follow-up of 64.8 months, patients with the KRAS G12C mutation showed significantly shorter first-line progression-free survival (PFS; median, 9.4 vs. 10.8 months; p = .015) and overall survival (OS; median, 21.1 vs. 27.3 months; p = .015) than those with non-G12C mutations. Multivariate analysis also showed that KRAS G12C mutation was significantly associated with shorter PFS (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.04-1.96, p = .030) and OS (HR, 1.42; 95% CI, 1.01-2.00; p = .044). CONCLUSION: We demonstrate that, compared with non-G12C mutations, KRAS G12C mutation is significantly correlated with shorter first-line PFS and OS. These findings indicate the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC. IMPLICATIONS FOR PRACTICE: Among patients with KRAS exon 2 mutated metastatic colorectal cancer (mCRC), median progression-free survival (PFS) and overall survival (OS) were 9.4 and 21.1 months, respectively, for G12C mutation and 10.8 and 27.3 months, respectively, for patients with non-G12C mutations, indicating significantly shorter PFS (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08-2.01; p = .015) and OS (HR, 1.50; 95% CI, 1.08-2.08; p = .015) in patients with G12C mutation than in those with non-G12C mutations. Furthermore, multivariate analysis showed that KRAS G12C mutation was independently associated with shorter first-line PFS and OS. Thus, these findings underscore the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC.
  • Impact of tumor growth rate during preceding treatment on tumor response to nivolumab or irinotecan in advanced gastric cancer
    Kato, K., Masuishi, T., Fushiki, K., Nakano, S., Kawamoto, Y., Narita, Y., Tsushima, T., Harada, K., Kadowaki, S., Todaka, A., Yuki, S., Tajika, M., Machida, N., Komatsu, Y., Yasui, H., Muro, K., Kawakami, T.
    ESMO Open, 6, 4, 100179, 100179, Elsevier BV, 2021年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • P4-10 The impact of neutrophil/lymphocyte ratio (NLR) on overall survival for patients with metastatic colorectal cancer
    Kazuaki Harada, Takeshi Kawakami, Toshiki Masuishi, Yasuyuki Kawamoto, Hirohumi Go, Kyoko Kato, Ryosuke Kumanishi, Satoshi Yuki, Kouji Yamamoto, Hirofumi Yasui, Yoshito Komatsu, Kei Muro, Takeharu Yamanaka, Kentaro Yamazaki
    Annals of Oncology, 32, S332, S332, Elsevier BV, 2021年07月
    研究論文(学術雑誌)
  • RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment With Anti-EGFR Antibodies in Patients With Metastatic Colorectal Cancer.
    Yu Sunakawa, Masato Nakamura, Masahiro Ishizaki, Masato Kataoka, Hironaga Satake, Masaki Kitazono, Hideyuki Yanagisawa, Yasuyuki Kawamoto, Hidekazu Kuramochi, Hisatsugu Ohori, Michio Nakamura, Fumiyo Maeda, Chihiro Komeno, Tomoko Sonezaki, Masahiro Takeuchi, Masashi Fujii, Takayuki Yoshino, Akihito Tsuji, Wataru Ichikawa
    JCO precision oncology, 4, 898, 911, 2020年11月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Several trials have evaluated the efficacy of rechallenge treatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with metastatic colorectal cancer (mCRC). A recent trial indicated that RAS status in circulating tumor DNA (ctDNA) may potentially predict patients with RAS wild-type mCRC resistant to anti-EGFR mAb who would benefit from rechallenge treatment, and the findings should be further investigated. MATERIAL AND METHODS: We enrolled patients whose plasma samples were collected in prospective phase II trials, the JACCRO CC-08 (n = 36) and CC-09 (n = 25), which evaluated rechallenge chemotherapy with anti-EGFR mAb for KRAS wild-type mCRC. RAS in ctDNA was analyzed at the time points of baseline, 8 weeks, and progression using OncoBEAM RAS CRC kit. RESULTS: Sixteen patients were enrolled in this study, with a response rate of 0% and a disease control rate (DCR) of 62.5%. RAS mutations were found at baseline in six patients. The DCR was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation at baseline. Patients with RAS mutation at baseline had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without RAS mutation (median PFS, 2.3 v 4.7 months; hazard ratio [HR], 6.2; P = .013; median OS, 3.8 v 16.0 months; HR, 12.4; P = .0028). Six of 10 patients without RAS mutation at baseline acquired RAS mutations at progression. Postprogression survival after rechallenge treatment was numerically shorter in patients with RAS mutation at progression. CONCLUSION: RAS status in ctDNA was significantly associated with clinical outcomes in patients with mCRC receiving rechallenge treatment with anti-EGFR mAb. These findings could support the clinical utility of OncoBEAM RAS CRC kits for anti-EGFR mAb rechallenge in RAS wild-type mCRC.
  • Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies.
    Yoshiaki Nakamura, Hiroya Taniguchi, Masafumi Ikeda, Hideaki Bando, Ken Kato, Chigusa Morizane, Taito Esaki, Yoshito Komatsu, Yasuyuki Kawamoto, Naoki Takahashi, Makoto Ueno, Yoshinori Kagawa, Tomohiro Nishina, Takeshi Kato, Yoshiyuki Yamamoto, Junji Furuse, Tadamichi Denda, Hisato Kawakami, Eiji Oki, Takako Nakajima, Naohiro Nishida, Kensei Yamaguchi, Hisateru Yasui, Masahiro Goto, Nobuhisa Matsuhashi, Koushiro Ohtsubo, Kentaro Yamazaki, Akihito Tsuji, Wataru Okamoto, Katsuya Tsuchihara, Takeharu Yamanaka, Izumi Miki, Yasutoshi Sakamoto, Hiroko Ichiki, Masayuki Hata, Riu Yamashita, Atsushi Ohtsu, Justin I Odegaard, Takayuki Yoshino
    Nature medicine, 26, 12, 1859, 1864, 2020年10月05日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Comprehensive genomic profiling enables genomic biomarker detection in advanced solid tumors. Here, to evaluate the utility of circulating tumor DNA (ctDNA) genotyping, we compare trial enrollment using ctDNA sequencing in 1,687 patients with advanced gastrointestinal (GI) cancer in SCRUM-Japan GOZILA (no. UMIN000016343), an observational ctDNA-based screening study, to enrollment using tumor tissue sequencing in the same centers and network (GI-SCREEN, 5,621 patients). ctDNA genotyping significantly shortened the screening duration (11 versus 33 days, P < 0.0001) and improved the trial enrollment rate (9.5 versus 4.1%, P < 0.0001) without compromising treatment efficacy compared to tissue genotyping. We also describe the clonal architecture of ctDNA profiles in ~2,000 patients with advanced GI cancer, which reinforces the relevance of many targetable oncogenic drivers and highlights multiple new drivers as candidates for clinical development. ctDNA genotyping has the potential to accelerate innovation in precision medicine and its delivery to individual patients.
  • Oxaliplatinによる類洞閉塞症候群の診断における腹部超音波検査の有用性の検討               
    斎藤 里佳, 西田 睦, 岩井 孝仁, 菊池 穏香, 吉野 裕紀, 横田 勲, 高木 諒, 川本 泰之, 山村 貴洋, 伊藤 憲, 中野 真太郎, 原田 一顕, 結城 敏志, 小松 嘉人, 坂本 直哉
    日本癌治療学会学術集会抄録集, 58回, P, 178, (一社)日本癌治療学会, 2020年10月
    英語
  • 消化管間質腫瘍(GIST)におけるレゴラフェニブ治療と骨格筋量の変化に関する検討               
    伊藤 憲, 原田 一顕, 川本 泰之, 中積 宏之, 中野 真太郎, 斎藤 里佳, 山村 貴洋, 結城 敏志, 小松 嘉人, 坂本 直哉
    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 127回・121回, 62, 62, 日本消化器病学会-北海道支部, 2020年10月
    日本語
  • IRIS/Bev療法時の下痢に対する半夏瀉心湯予防投与の第二相試験 生存期間の解析               
    原田 一顕, 中積 宏之, 川本 泰之, 結城 敏志, 石黒 敦, 舘山 美樹, 宮城島 拓人, 中村 路夫, 太宰 昌佳, 奥田 博介, 畑中 一映, 天野 虎次, 小松 嘉人
    日本癌治療学会学術集会抄録集, 58回, P, 122, (一社)日本癌治療学会, 2020年10月
    英語
  • 膵癌に対するS-1併用術前化学放射線療法(S-1併用NACRT)の治療成績               
    小泉 富基, 加藤 徳雄, 中村 透, 川本 泰之, 田口 大志, 打浪 雄介, 清水 伸一, 青山 英史
    日本医学放射線学会秋季臨床大会抄録集, 56回, S103, S103, (公社)日本医学放射線学会, 2020年10月
    日本語
  • 切除不能大腸癌における一次化学療法開始からの生存期間に対する後方治療の影響               
    加藤 恭子, 川上 武志, 舛石 俊樹, 川本 泰之, 郷 洋文, 熊西 亮介, 澤田 憲太郎, 結城 敏志, 山本 紘司, 安井 博史, 小松 嘉人, 室 圭, 山中 竹春, 山崎 健太郎
    日本癌治療学会学術集会抄録集, 58回, O25, 3, (一社)日本癌治療学会, 2020年10月
    英語
  • Impact of single-heterozygous UGT1A1 on the clinical outcomes of irinotecan monotherapy after fluoropyrimidine and platinum-based combination therapy for gastric cancer: a multicenter retrospective study.
    Shintaro Nakano, Satoshi Yuki, Yasuyuki Kawamoto, Hiroshi Nakatsumi, Takayuki Ando, Shinya Kajiura, Ayumu Yoshikawa, Kazuaki Harada, Kazuteru Hatanaka, Aya Tanimoto, Atsushi Ishiguro, Takuya Honda, Masayoshi Dazai, Takahide Sasaki, Naoya Sakamoto, Yoshito Komatsu
    International journal of clinical oncology, 25, 10, 1800, 1806, 2020年10月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌), BACKGROUND: It is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and toxicity of irinotecan monotherapy in advanced gastric cancer (AGC). We investigated the association between clinical outcomes (efficacy and safety) and UGT1A1 status in patients who received irinotecan monotherapy. METHODS: We evaluated AGC patients who received irinotecan monotherapy between January 2011 and December 2017. Efficacy was assessed according to overall survival (OS) and progression-free survival (PFS). Toxicity was graded using the Common Toxicity Criteria for Adverse Events (version 4.0). RESULTS: A total of 100 patients were evaluated (62 and 38 patients with UGT1A1 WT and SH, respectively). In the WT and SH groups, the irinotecan dose was reduced in 19 (30.6%) and 18 (47.2%) patients (p = 0.135), respectively; treatment was delayed due to adverse events (AEs) in 19 (30.6%) and 13 (34.2%) patients (p = 0.826), respectively; the median PFS was 3.15 and 3.25 months (HR, 0.734; 95% CI 0.465-1.158; p = 0.184), respectively; and the median OS was 10.4 and 7.26 months (HR, 1.137; 95% CI 0.752-1.721; p = 0.543), respectively. Severe hematological AEs (Grade ≥ 3) were significantly more frequent in the SH group than in the WT group (63% vs. 36%; p = 0.008), while severe non-hematological AEs was not significantly different (16.0% vs. 6.5%; p = 0.173). CONCLUSION: There was no significant difference in the efficacy of irinotecan monotherapy between UGT1A1 WT and UGT1A1 SH, but UGT1A1 SH was associated with a high frequency of severe hematological toxicity.
  • Clinical outcomes of chemotherapy in patients with undifferentiated carcinoma of the pancreas: a retrospective multicenter cohort study.
    Hiroshi Imaoka, Masafumi Ikeda, Kosuke Maehara, Kumiko Umemoto, Masato Ozaka, Satoshi Kobayashi, Takeshi Terashima, Hiroto Inoue, Chihiro Sakaguchi, Kunihiro Tsuji, Kazuhiko Shioji, Keiya Okamura, Yasuyuki Kawamoto, Rei Suzuki, Hirofumi Shirakawa, Hiroaki Nagano, Makoto Ueno, Chigusa Morizane, Junji Furuse
    BMC cancer, 20, 1, 946, 946, 2020年10月01日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer. Although UC has been considered a highly aggressive malignancy, no clinical studies have addressed the efficacy of chemotherapy for unresectable UC. Therefore, we conducted multicenter retrospective study to investigate the efficacy of chemotherapy in patients with UC of the pancreas. METHODS: This multicenter retrospective cohort study was conducted at 17 institutions in Japan between January 2007 and December 2017. A total of 50 patients treated with chemotherapy were analyzed. RESULTS: The median overall survival (OS) in UC patients treated with chemotherapy was 4.08 months. The details of first-line chemotherapy were as follows: gemcitabine (n = 24), S-1 (n = 12), gemcitabine plus nab-paclitaxel (n = 6), and other treatment (n = 8). The median progression-free survival (PFS) was 1.61 months in the gemcitabine group, 2.96 months in the S-1 group, and 4.60 months in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel significantly improved PFS compared with gemcitabine (p = 0.014). The objective response rate (ORR) was 4.2% in the gemcitabine group, 0.0% in the S-1 group, and 33.3% in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel also showed a significantly higher ORR compared with both gemcitabine and S-1 (gemcitabine plus nab-paclitaxel vs. gemcitabine: p = 0.033; gemcitabine plus nab-paclitaxel vs. S-1: p = 0.034). A paclitaxel-containing first-line regimen significantly improved OS compared with a non-paclitaxel-containing regimen (6.94 months vs. 3.75 months, respectively; p = 0.041). After adjustment, use of a paclitaxel-containing regimen in any line was still an independent predictor of OS (hazard ratio for OS, 0.221; 95% confidence interval, 0.076-0.647; p = 0.006) in multiple imputation by chained equation. CONCLUSIONS: The results of the present study indicate that a paclitaxel-containing regimen would offer relatively longer survival, and it is considered a reasonable option for treating patients with unresectable UC.
  • Association between the use of antibiotics and efficacy of gemcitabine plus nab-paclitaxel in advanced pancreatic cancer.
    Shintaro Nakano, Yoshito Komatsu, Yasuyuki Kawamoto, Rika Saito, Ken Ito, Hiroshi Nakatsumi, Satoshi Yuki, Naoya Sakamoto
    Medicine, 99, 39, e22250, 2020年09月25日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), It is unclear whether the use of antibiotics is related to the efficacy of gemcitabine plus nab-paclitaxel (GnP). Therefore, we investigated the association between the use of antibiotics and efficacy of GnP.We conducted a retrospective single center study from January 2014 to December 2018 in Hokkaido University Hospital.Ninety-nine patients were eligible for the study. Thirty-seven used antibiotics (U) and 62 did not use antibiotics (NU) during GnP therapy. In the U group, 15 patients used β-lactam antibiotics, 21 used new quinolones, and 1 used carbapenem. The median progression-free survival was 5.8 and 2.7 months (hazards ratio [HR] .602, 95% confidence interval [CI] .391-.928, P = .022) and the median overall survival was 11.0 and 8.4 months (HR .768, 95% CI .491-1.202, P = .248) in the U and not use antibiotics groups, respectively. Antibiotic use (HR .489, 95% CI .287-.832, P = .008) and locally advanced pancreatic cancer (HR 1.808, 95% CI 1.051-3.112, P = .032) were independent prognostic factors for progression-free survival.Antibiotic use was associated with a higher efficacy of GnP, and therefore, it may be employed as a novel treatment strategy.
  • 進行消化器がんを対象としたGOZILA studyにおけるcirculating tumor DNA(ctDNA)解析による二次的所見(SF)に関する調査
    平岡 弓枝, 中村 能章, 田辺 記子, 平田 真, 川本 泰之, 池田 公史, 坂東 英明, 江崎 泰斗, 上野 誠, 洞澤 智至, 三木 いずみ, 谷口 浩也, 森実 千種, 吉野 孝之, 桑田 健
    日本遺伝カウンセリング学会誌, 41, 2, 78, 78, 日本遺伝カウンセリング学会, 2020年06月
    日本語
  • 【消化管がん】下部消化管がん治療 state-of-the-art
    川本 泰之, 結城 敏志
    腫瘍内科, 25, 6, 613, 621, (有)科学評論社, 2020年06月, [招待有り], [筆頭著者]
    日本語
  • Conversion surgery for initially unresectable biliary malignancies: a multicenter retrospective cohort study.
    Takehiro Noji, Minoru Nagayama, Koji Imai, Yasuyuki Kawamoto, Masaki Kuwatani, Masafumi Imamura, Keikuke Okamura, Yastoshi Kimura, Satoshi Hirano
    Surgery today, 50, 11, 1409, 1417, 2020年05月28日, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌), PURPOSE: Few studies have focused on conversion surgery for biliary malignancy; thus, it is not clear if this treatment modality can extend the survival of patients with unresectable biliary malignancy. We conducted a multicenter retrospective cohort study to evaluate the surgical outcomes of conversion surgery in this setting and analyze long-term survival. METHODS: We collected clinical data retrospectively on patients who underwent conversion surgery for biliary malignancy. RESULTS: Twenty-four patients met our inclusion criteria. Preoperative chemotherapy regimens or chemoradiation therapy regimens were administered based on the institutional criteria, and surgical procedures were chosen based on tumor location. Morbidity occurred in 16 patients (66.7%), and 1 patient died of liver failure after surgery. The overall 5-year survival rate following initial therapy was 43.2%, and the median survival time was 57.4 months. The corresponding values following surgery were 38.2% and 34.3 months, respectively. The 5-year survival rate of the 24 patients who received both chemotherapy and surgery was significantly better than that of 110 patients treated with chemotherapy only (p < 0.001). CONCLUSION: Conversion surgery for initially unresectable biliary malignancies may be feasible and achieve long-term survival for selected patients.
  • ペムブロリズマブが奏効した高頻度マイクロサテライト不安定性の肝内胆管癌の1例               
    斎藤 里佳, 伊藤 憲, 中野 真太郎, 川本 泰之, 中積 宏之, 結城 敏志, 小松 嘉人, 坂本 直哉
    日本消化器病学会北海道支部例会プログラム・抄録集, 126回, 41, 41, 日本消化器病学会-北海道支部, 2020年03月
    日本語
  • 進行膵癌における化学療法施行例の予後因子解析               
    中野 真太郎, 小松 嘉人, 斉藤 里佳, 伊藤 憲, 川本 泰之, 中積 宏之, 結城 敏志, 坂本 直哉
    日本消化器病学会北海道支部例会プログラム・抄録集, 126回, 58, 58, 日本消化器病学会-北海道支部, 2020年03月
    日本語
  • 【肝・胆・膵がんの薬物療法】胆道がん 進行胆道がんに対する分子標的治療薬と免疫チェックポイント阻害薬
    川本 泰之, 小松 嘉人
    腫瘍内科, 25, 2, 159, 166, (有)科学評論社, 2020年02月, [招待有り], [筆頭著者, 責任著者]
    日本語
  • S-1またはカペシタビンを含む標準治療に不応・不耐の胃癌に対するbolus 5-FU/I-LV療法の多施設共同第II相試験 前治療別の解析               
    村中 徹人, 小松 嘉人, 結城 敏志, 中野 真太郎, 澤田 憲太郎, 川本 泰之, 中積 宏之, 原田 一顕, 宮城島 拓人, 畑中 一映, 太宰 昌佳, 植田 亮, 笹木 祐介, 辻 靖, 西本 尚樹, 坂田 優, 坂本 直哉
    日本消化管学会雑誌, 4, Suppl., 262, 262, (一社)日本消化管学会, 2020年01月
    日本語
  • Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: The FUGA-BT (JCOG1113) randomized phase III clinical trial
    Morizane, C., Okusaka, T., Mizusawa, J., Katayama, H., Ueno, M., Ikeda, M., Ozaka, M., Okano, N., Sugimori, K., Fukutomi, A., Hara, H., Mizuno, N., Yanagimoto, H., Wada, K., Tobimatsu, K., Yane, K., Nakamori, S., Yamaguchi, H., Asagi, A., Yukisawa, S., Kojima, Y., Kawabe, K., Kawamoto, Y., Sugimoto, R., Iwai, T., Nakamura, K., Miyakawa, H., Yamashita, T., Hosokawa, A., Ioka, T., Kato, N., Shioji, K., Shimizu, K., Nakagohri, T., Kamata, K., Ishii, H., Furuse, J.
    Annals of Oncology, 30, 12, 1950, 1958, Elsevier BV, 2019年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • 胸部食道扁平上皮癌に対する術前補助化学療法・根治切除術および根治的化学放射線療法についての後方視的検討
    中積 宏之, 村中 徹人, 川本 泰之, 小松 嘉人, 結城 敏志, 中野 真太郎, 澤田 憲太郎, 坂本 直哉, 打浪 雄介, 田口 大志, 白土 博樹, 海老原 裕磨, 七戸 俊明, 平野 聡
    北海道医学雑誌, 94, 2, 120, 121, 北海道医学会, 2019年11月
    日本語
  • Impact of tumour growth rate during preceding treatment on tumour response to regorafenib or trifluridine/tipiracil in refractory metastatic colorectal cancer.
    Toshiki Masuishi, Hiroya Taniguchi, Takeshi Kawakami, Yasuyuki Kawamoto, Shigenori Kadowaki, Yusuke Onozawa, Tetsuhito Muranaka, Masahiro Tajika, Hirofumi Yasui, Hiroshi Nakatsumi, Satoshi Yuki, Kei Muro, Katsuhiro Omae, Yoshito Komatsu, Kentaro Yamazaki
    ESMO open, 4, 6, 2019年11月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Although regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) have been recognised as standard treatments in metastatic colorectal cancer (mCRC), the best option remains unclear. Pretreatment tumour growth rate (TGR) is associated with radiotherapeutic efficacy in laryngeal cancer. However, no reports are available on the association between TGR during preceding treatment and the efficacy of REG or FTD/TPI. PATIENTS AND METHODS: We retrospectively analysed the data of consecutive mCRC patients treated with REG or FTD/TPI and classified them into slow-growing or rapid-growing (SG or RG) groups according to TGR and emergence of new lesion (NL+) or their absence (NL-) during preceding treatment period [SG: NL- with low TGR (<0.33%/day); RG: NL+ or high TGR (≥0.33%/day)]. RESULTS: A total of 244 patients (RG/SG, 133/111; REG/FTD/TPI, 132/112) were eligible. The RG proportion with a long duration from first-line chemotherapy and the SG proportion with elevated alkaline phosphatase were higher in REG, whereas the SG proportion with performance status 2 was higher in FTD/TPI. The disease control rates (DCRs) were similar between REG and FTD/TPI (24%/30%; OR: 0.74; p=0.44; adjusted OR: 0.73; p=0.47) in the RG, whereas the DCR was significantly higher for FTD/TPI than for REG (47%/26%; OR: 2.56; p=0.029; adjusted OR: 3.38; p=0.01) in the SG. CONCLUSIONS: TGR and NL during preceding treatment may be helpful for drug selection in refractory mCRC patients to be treated with REG or FTD/TPI. However, further studies are needed to confirm the value of TGR for drug selection.
  • 進行大腸がんにおけるctDNA中のRAS変異と抗EGFR抗体薬リチャレンジ治療の効果               
    辻 晃仁, 砂川 優, 中村 将人, 石崎 雅浩, 片岡 政人, 佐竹 悠良, 北薗 正樹, 柳澤 秀之, 川本 泰之, 倉持 英和, 大堀 久詔, 中村 路夫, 竹内 正弘, 藤井 雅志, 市川 度
    日本癌治療学会学術集会抄録集, 57回, O63, 5, (一社)日本癌治療学会, 2019年10月
    英語
  • The impact of late-line treatment on overall survival (OS) from the initiation of first-line chemotherapy (CT) for patients (pts) with metastatic colorectal cancer (mCRC)
    T. Kawakami, T. Masuishi, Y. Kawamoto, H. Go, H. Shirasu, K. Kato, R. Kumanishi, K. Sawada, K. Yamamoto, S. Yuki, Y. Komatsu, H. Yasui, K. Muro, T. Yamanaka, K. Yamazaki
    Annals of Oncology, 30, v222, v222, Elsevier BV, 2019年10月
    研究論文(学術雑誌)
  • 経口フッ化ピリミジン不応の胃がんに対するRPMI療法(HGCSG1502試験)OS・QOL解析結果               
    太宰 昌佳, 村中 徹人, 川本 泰之, 中積 宏之, 原田 一顕, 宮城島 拓人, 畑中 一映, 植田 亮, 加藤 総介, 笹木 有佑, 結城 敏志, 坂本 直哉, 西本 尚樹, 坂田 優, 小松 嘉人
    日本癌治療学会学術集会抄録集, 57回, P69, 1, (一社)日本癌治療学会, 2019年10月
    英語
  • 転移を有する膵癌に対する化学療法薬剤使用歴と治療成績の関係の検討               
    川本 泰之, 斎藤 里佳, 伊藤 憲, 中野 真太郎, 中積 宏之, 結城 敏志, 小松 嘉人, 坂本 直哉
    日本癌治療学会学術集会抄録集, 57回, P86, 7, (一社)日本癌治療学会, 2019年10月
    英語
  • 局所進行膵癌における化学療法および化学放射線療法の検討               
    中野 真太郎, 小松 嘉人, 川本 泰之, 斎藤 里佳, 伊藤 憲, 中積 宏之, 結城 敏志, 坂本 直哉
    日本消化器病学会北海道支部例会プログラム・抄録集, 125回, 55, 55, 日本消化器病学会-北海道支部, 2019年09月
    日本語
  • mFOLFIRINOX療法にて完全奏効が得られた進行膵癌の2例               
    伊藤 憲, 小松 嘉人, 結城 敏志, 中積 宏之, 川本 泰之, 中野 真太郎, 齋藤 里佳
    日本消化器病学会北海道支部例会プログラム・抄録集, 125回, 55, 55, 日本消化器病学会-北海道支部, 2019年09月
    日本語
  • 大腸癌におけるリキッドバイオプシーの有用性 大腸がんにおけるリキッドバイオプシー研究 JACCROバイオマーカー研究のまとめ               
    砂川 優, 辻 晃仁, 佐竹 悠良, 中村 将人, 片岡 政人, 宮本 裕士, 石崎 雅浩, 塩澤 学, 北薗 正樹, 高金 明典, 柳澤 秀之, 寺沢 哲志, 川本 泰之, 渡邉 貴紀, 倉持 英和, 石榑 清, 藤井 雅志, 市川 度
    日本大腸肛門病学会雑誌, 72, 9, A76, A76, (一社)日本大腸肛門病学会, 2019年09月
    日本語
  • 【消化管がん】下部消化管がん治療 state-of-the-art
    川本 泰之, 結城 敏志
    腫瘍内科, 23, 6, 546, 553, (有)科学評論社, 2019年06月, [招待有り], [筆頭著者, 責任著者]
    日本語
  • Synchronous multiple pancreatic cancers developed long after severe postendoscopic retrograde cholangiopancreatography pancreatitis.
    Sugiura R, Kuwatani M, Hirata K, Kato S, Kawamoto Y, Kawakubo K, Mitsuhashi T, Asano T, Hirano S, Sakamoto N
    Endoscopic ultrasound, 8, 3, 213, 214, 2019年05月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Comparative sequence analysis of patient-matched primary colorectal cancer, metastatic, and recurrent metastatic tumors after adjuvant FOLFOX chemotherapy.
    Kazuaki Harada, Wataru Okamoto, Sachiyo Mimaki, Yasuyuki Kawamoto, Hideaki Bando, Riu Yamashita, Satoshi Yuki, Takayuki Yoshino, Yoshito Komatsu, Atsushi Ohtsu, Naoya Sakamoto, Katsuya Tsuchihara
    BMC cancer, 19, 1, 255, 255, 2019年03月21日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: In the era of genome-guided personalized cancer treatment, we must understand chemotherapy-induced genomic changes in tumors. This study evaluated whether adjuvant FOLFOX chemotherapy modifies the mutational profile of recurrent colorectal cancer (CRC). METHODS: Whole exome sequencing was performed on samples from primary CRC tumors, untreated metastatic tumors, and recurrent tumors following adjuvant FOLFOX chemotherapy. The samples were resected from four patients. RESULTS: The number of mutations or the mutation spectrum in individual patients was nearly identical. Copy number variants persisted regardless of FOLFOX therapy administration. The genomic signature of oxaliplatin exposure (G > T/C > A, T > A/A > T) was not enriched after FOLFOX chemotherapy. Overlapping single nucleotide variants (SNVs) and indels remained in 26-65% of the patient-matched tumor samples. One patient harbored an AKT1 E17K mutation in the recurrent tumor, whereas PIK3CA E542K and E88Q mutations were detected in the primary and untreated metastatic tumor samples. Genes related to intracellular Ca2+ homeostasis were enriched among the genes uniquely mutated after FOLFOX chemotherapy. CONCLUSIONS: We found that the mutation rates, mutation spectrum, and copy number variants were nearly identical regardless of the administration of FOLFOX therapy in the four CRC cases. The mutational discordance between the patient-matched tumor samples is likely caused by tumor heterogeneity and chemotherapy-induced clonal selection. These findings might be useful as pilot data for larger studies to clarify the changes in the mutational landscape induced by adjuvant FOLFOX chemotherapy.
  • The Effect of Everolimus on Refractory Hypoglycemia in a Patient with Inoperable Metastatic Insulinoma Evaluated by Continuous Glucose Monitoring.
    Shingo Yanagiya, Kyu Yong Cho, Akinobu Nakamura, Hiroshi Nomoto, Yasuyuki Kawamoto, Kazumichi Kawakubo, Yoshito Komatsu, Tomoko Mitsuhashi, Hideaki Miyoshi, Tatsuya Atsumi
    Internal medicine (Tokyo, Japan), 57, 17, 2527, 2531, 2018年09月01日, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌), An 84-year-old Japanese woman with metastatic insulinoma suffered from frequent hypoglycemic events. Continuous glucose monitoring (CGM) confirmed severe and frequent symptomatic/asymptomatic hypoglycemia. After the initiation of everolimus treatment, the hypoglycemic events were rapidly eliminated. CGM revealed that her blood glucose levels were maintained without hypoglycemia throughout the day. Furthermore, everolimus reduced the duration of time above the upper limit (>180 mg/dL) along with the standard deviation and mean amplitude of glycemic excursions. This case shows the potential effects of everolimus on hypoglycemia and glycemic control in a patient with inoperable metastatic insulinoma evaluated by CGM.
  • Study protocol of HGCSG1404 SNOW study: a phase I/II trial of combined chemotherapy of S-1, nab-paclitaxel and oxaliplatin administered biweekly to patients with advanced gastric cancer.
    Yasuyuki Kawamoto, Yoshito Komatsu, Satoshi Yuki, Kentaro Sawada, Tetsuhito Muranaka, Kazuaki Harada, Hiroshi Nakatsumi, Hiraku Fukushima, Atsushi Ishiguro, Masayoshi Dazai, Kazuteru Hatanaka, Michio Nakamura, Ichiro Iwanaga, Minoru Uebayashi, Susumu Sogabe, Yoshimitsu Kobayashi, Takuto Miyagishima, Kota Ono, Naoya Sakamoto, Yuh Sakata
    BMC cancer, 17, 1, 837, 837, 2017年12月08日, [査読有り], [筆頭著者], [国際誌]
    英語, 研究論文(学術雑誌)
  • 前治療における腫瘍増殖速度がレゴラフェニブとTAS-102の抗腫瘍効果に与える影響               
    舛石 俊樹, 谷口 浩也, 川上 武志, 川本 泰之, 門脇 重憲, 小野澤 祐輔, 村中 徹人, 田近 正洋, 安井 博史, 中積 宏之, 結城 敏志, 室 圭, 大前 勝弘, 小松 嘉人, 山崎 健太郎
    日本癌治療学会学術集会抄録集, 55回, O31, 6, (一社)日本癌治療学会, 2017年10月
    日本語
  • 【がん分子標的薬の効果と副作用-期待される効果と評価-】抗体薬 抗VEGF抗体薬・抗VEGFR抗体薬
    川本 泰之
    日本臨床, 75, 9, 1353, 1358, (株)日本臨床社, 2017年09月
    日本語
  • 【消化管がん】 切除不能・再発進行大腸がんの治療戦略state-of-art
    川本 泰之, 結城 敏志
    腫瘍内科, 20, 1, 2, 7, (有)科学評論社, 2017年07月, [筆頭著者, 責任著者]
    日本語
  • Comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine with nab-paclitaxel in unresectable pancreatic cancer.
    Tetsuhito Muranaka, Masaki Kuwatani, Yoshito Komatsu, Kentaro Sawada, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Satoshi Yuki, Yoshimasa Kubota, Kimitoshi Kubo, Shuhei Kawahata, Kazumichi Kawakubo, Hiroshi Kawakami, Naoya Sakamoto
    Journal of gastrointestinal oncology, 8, 3, 566, 571, AME Publishing Company, 2017年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • HGCSG 1201: Phase II study of trastuzumab with irinotecan in HER2-positive metastatic or advanced gastric cancer patients previously treated with trastuzumab
    Sasaki Takahide, Kawamoto Yasuyuki, Yuki Satoshi, Meguro Takashi, Hatanaka Kazuteru, Uebayashi Minoru, Iwanaga Ichiro, Nakamura Michio, Eto Kazunori, Okuda Hiroyuki, Abe Masakazu, Oba Ayane, Abe Nobuhiko, Sato Atsushi, Nakatsumi Hiroshi, Harada Kazuaki, Muranaka Tetsuhito, Yagisawa Masataka, Oba Koji, Sakata Yuh, Komatsu Yoshito
    ANNALS OF ONCOLOGY, 28, 2017年06月
    英語
  • Efficacy and Safety of Bolus 5-Fluorouracil and L-Leucovorin as Salvage Chemotherapy for Oral Fluoropyrimidine-Resistant Unresectable or Recurrent Gastric Cancer: A Single Center Experience.
    Tetsuhito Muranaka, Satoshi Yuki, Yoshito Komatsu, Kentaro Sawada, Kazuaki Harada, Yasuyuki Kawamoto, Hiroshi Nakatsumi, Naoya Sakamoto
    Journal of gastric cancer, 16, 3, 177, 181, 2016年09月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • 生涯教育シリーズ 消化器疾患診療の最前線 大腸癌に対する化学療法の最前線               
    川本 泰之
    北海道医報, 1176, 8, 10, 北海道医師会, 2016年09月
    日本語
  • Eccentric Abscess Due to Bile Duct Microperforation Caused by Self-expandable Metal Stent and Neoadjuvant Chemoradiation.
    Masaki Kuwatani, Yasuyuki Kawamoto, Toru Nakamura
    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 14, 5, A29-30, XXX, 2016年05月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.
    Yoshito Komatsu, Kenji Okita, Satoshi Yuki, Tomohisa Furuhata, Hiraku Fukushima, Hiroyuki Masuko, Yasuyuki Kawamoto, Hiroshi Isobe, Takuto Miyagishima, Kazuaki Sasaki, Michio Nakamura, Yoshinobu Ohsaki, Junta Nakajima, Miki Tateyama, Kazunori Eto, Shinya Minami, Ryoji Yokoyama, Ichiro Iwanaga, Hitoshi Shibuya, Mineo Kudo, Koji Oba, Yasuo Takahashi
    Cancer science, 106, 7, 891, 5, 2015年07月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.
  • Successful treatment of advanced sigmoid colon cancer with liver metastases with cetuximab monotherapy as first-line treatment - A case report
    Kazuaki Harada, Kazuteru Hatanaka, Kenji Kinoshita, Yasuyuki Kawamoto, Hiroaki Yamato, Koji Ogawa, Yoshiya Yamamoto, Hirohito Naruse
    Japanese Journal of Cancer and Chemotherapy, 41, 7, 897, 900, Japanese Journal of Cancer and Chemotherapy Publishers Inc., 2014年07月01日, [査読有り], [国内誌]
    日本語, 研究論文(学術雑誌)
  • 一次治療としてCetuximab単剤投与が奏効した黄疸を伴うS状結腸癌多発肝転移の1例
    原田 一顕, 畑中 一映, 木下 賢治, 川本 泰之, 大和 弘明, 小川 浩司, 山本 義也, 成瀬 宏仁
    癌と化学療法, 41, 7, 897, 900, (株)癌と化学療法社, 2014年07月
    日本語
  • 当院におけるc-Stage2/3食道癌に対する治療の検討               
    畑中 一映, 川本 泰之, 木下 賢二, 原田 一顕, 大和 弘明, 小川 浩司, 山本 義也, 成瀬 宏仁, 遠山 茂, 喜多村 圭, 下山 則彦, 工藤 和洋
    日本消化器病学会雑誌, 110, 臨増総会, A306, A306, (一財)日本消化器病学会, 2013年02月
    日本語
  • 超音波内視鏡下、総胆管・十二指腸内瘻術を施行した1例               
    成瀬 宏仁, 木下 賢治, 原田 一顕, 川本 泰之, 大和 弘明, 小川 浩司, 畑中 一映, 山本 義也, 工藤 和洋, 下山 則彦
    道南医学会大会並びに総会プログラム・抄録集, 65回, 43, 43, 道南医学会, 2012年11月
    日本語
  • 当院におけるc-Stage II/III食道癌に対する治療の検討               
    畑中 一映, 川本 泰之, 木下 賢治, 原田 一顕, 大和 弘明, 小川 浩司, 山本 義也, 成瀬 宏仁, 遠山 茂, 喜多村 圭, 下山 則彦, 工藤 和洋
    道南医学会大会並びに総会プログラム・抄録集, 65回, 44, 44, 道南医学会, 2012年11月
    日本語
  • 虫垂粘液嚢腫により腸重積をきたした1例               
    東出 侑子, 木下 賢治, 原田 一顕, 川本 泰之, 大和 弘明, 小川 浩司, 畑中 一映, 山本 義也, 成瀬 宏仁, 工藤 和洋, 下山 則彦
    道南医学会大会並びに総会プログラム・抄録集, 65回, 47, 47, 道南医学会, 2012年11月
    日本語
  • 粘膜下腫瘍の形態を呈した直腸粘液癌の1例               
    中村 晃久, 木下 賢治, 原田 一顕, 川本 泰之, 大和 弘明, 小川 浩司, 畑中 一映, 山本 義也, 成瀬 宏仁, 工藤 和洋, 下山 則彦
    道南医学会大会並びに総会プログラム・抄録集, 65回, 48, 48, 道南医学会, 2012年11月
    日本語
  • KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer
    Y. Kawamoto, K. Tsuchihara, T. Yoshino, N. Ogasawara, M. Kojima, M. Takahashi, A. Ochiai, H. Bando, N. Fuse, M. Tahara, T. Doi, H. Esumi, Y. Komatsu, A. Ohtsu
    BRITISH JOURNAL OF CANCER, 107, 2, 340, 344, 2012年07月, [査読有り], [筆頭著者]
    英語, 研究論文(学術雑誌)
  • Retrospective cohort study on the risk factors of admission due to serious adverse events during S-1 (tegaful, gimeracil, oteracil potassium) containing chemotherapy for gastric cancer.
    Kawamoto Yasuyuki, Yuki Satoshi, Kobayashi Yoshimitsu, Oba Koji, Hayashi Hideyuki, Nakatsumi Hiroshi, Komatsu Yoshito
    JOURNAL OF CLINICAL ONCOLOGY, 30, 4, 2012年02月01日
  • QOLを考えた支持療法のすべて インフュージョン・リアクションに対して
    川本 泰之
    臨床腫瘍プラクティス, 7, 3, 314, 318, (株)ヴァンメディカル, 2011年08月
    日本語
  • [Clinical significance and the handling of KRAS testing on metastatic colorectal cancer].
    Kawamoto, Y., Yoshino, T.
    Nihon rinsho. Japanese journal of clinical medicine, 69 Suppl 3, 346, 350, 2011年04月, [査読有り]
    研究論文(学術雑誌)
  • 【大腸癌 最新の研究動向】大腸癌の検査・診断 大腸癌の分子生物学的検査 KRAS遺伝子変異検査の意義と実際(各種方法について)
    川本 泰之, 吉野 孝之
    日本臨床, 69, 増刊3 大腸癌, 346, 350, (株)日本臨床社, 2011年04月, [国内誌]
    日本語, 研究論文(学術雑誌)
  • Feasibility and robustness of amplification refractory mutation system (ARMS)-based KRAS testing using clinically available formalin-fixed, paraffin-embedded samples of colorectal cancers.
    Naomi Ogasawara, Hideaki Bando, Yasuyuki Kawamoto, Takayuki Yoshino, Katsuya Tsuchihara, Atsushi Ohtsu, Hiroyasu Esumi
    Japanese journal of clinical oncology, 41, 1, 52, 6, 2011年01月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • A case of sigmoid colon cancer with temporary dysarthria associated with irinotecan
    Susumu Sogabe, Satoshi Yuki, Hironobu Takano, Yoshimitsu Kobayashi, Hiroshi Nakatsumi, Takahide Sasaki, Yasuyuki Kawamoto, Hiraku Fukushima, Ichiro Iwanaga, Yasuko Uehata, Yoshito Komatsu, Masahiro Asaka
    Japanese Journal of Cancer and Chemotherapy, 38, 8, 1375, 1377, Japanese Journal of Cancer and Chemotherapy Publishers Inc., 2011年, [査読有り], [国内誌]
    日本語, 研究論文(学術雑誌)
  • 【がんの分子標的治療】消化管がんに対する分子標的薬               
    久保田 祐太郎, 川本 泰之, 吉野 孝之
    BIO Clinica, 25, 11, 934, 939, (株)北隆館, 2010年10月
    日本語
  • 【分子標的治療薬で変わるがん治療】体細胞変異検査の動向               
    川本 泰之, 吉野 孝之
    医薬ジャーナル, 46, 10, 2477, 2483, (株)医薬ジャーナル社, 2010年10月
    日本語
  • 検査ONE POINT 大腸癌のKRAS遺伝子検査               
    川本 泰之, 吉野 孝之
    SRL宝函, 31, 3, 43, 46, (株)エスアールエル, 2010年10月
    日本語
  • 【大腸癌研究の最新知見】大腸癌分子標的治療 分子標的薬治療効果予測マーカーの現状 ras変異は治療効果判定の指標となるか?
    佐竹 悠良, 川本 泰之, 吉野 孝之
    大腸癌Frontier, 3, 3, 227, 233, (株)メディカルレビュー社, 2010年09月
    日本語
  • 【POPを中心としたトランスレーショナルリサーチの進歩】KRAS/BRAF
    川本 泰之, 吉野 孝之
    腫瘍内科, 6, 1, 9, 18, (有)科学評論社, 2010年07月
    日本語
  • 【GIST 診断・治療の進歩】イマチニブ耐性GISTの新規治療薬               
    朝山 雅子, 川本 泰之, 土井 俊彦
    臨床消化器内科, 25, 6, 719, 730, (株)日本メディカルセンター, 2010年05月
    日本語
  • Pharmacogenomics For Cancer Therapy VEGF阻害剤のバイオマーカーとpharmacogenomics
    川本 泰之, 吉野 孝之
    がん分子標的治療, 8, 2, 128, 136, (株)メディカルレビュー社, 2010年04月
    日本語
  • A case of sigmoid colon cancer with lymphangitis carcinomatosa successfully treated with chemotherapies including molecular targeting drugs
    Susumu Sogabe, Satoshi Yuki, Tomofumi Takagi, Takuji Miyazaki, Hironobu Takano, Yasuyuki Kawamoto, Hiroshi Nakatsumi, Takahide Sasaki, Ichiro Iwanaga, Yasuko Uehata, Masahiro Asaka, Yoshito Komatsu
    Japanese Journal of Cancer and Chemotherapy, 37, 3, 535, 538, Japanese Journal of Cancer and Chemotherapy Publishers Inc., 2010年03月06日, [査読有り], [国内誌]
    日本語, 研究論文(学術雑誌)
  • 【消化器がん化学療法看護完全マスターBOOK 分子標的薬と従来型抗がん剤のケア 副作用 治療のしくみがやさしくわかる!】分子標的薬の必須情報と副作用対策 分子標的薬をもっと知ろう! 消化器がんで使われている&使われる可能性がある薬 抗VEGFモノクローナル抗体 ベバシズマブ               
    川本 泰之, 吉野 孝之
    消化器外科Nursing, 2010臨時増刊, 160,179, 161,179, (株)メディカ出版, 2010年02月
    日本語
  • 【消化器がん化学療法看護完全マスターBOOK 分子標的薬と従来型抗がん剤のケア 副作用 治療のしくみがやさしくわかる!】分子標的薬の必須情報と副作用対策 分子標的薬をもっと知ろう! 消化器がんで使われている&使われる可能性がある薬 抗EGFRモノクローナル抗体 セツキシマブ、パニツムマブ               
    川本 泰之, 吉野 孝之
    消化器外科Nursing, 2010臨時増刊, 162,179, 163,179, (株)メディカ出版, 2010年02月
    日本語
  • 【癌治療の現状と展望 分子標的薬剤とバイオマーカー、有害事象管理】標準治療と連携でのポイント 大腸癌 K-rasとB-raf               
    川本 泰之, 吉野 孝之
    カレントテラピー, 27, 12, 1100, 1106, (株)ライフメディコム, 2009年12月
    日本語
  • 抗悪性腫瘍薬 Cetuximab
    川本 泰之, 福島 拓, 吉野 孝之
    腫瘍内科, 4, 2, 183, 191, (有)科学評論社, 2009年08月
    日本語
  • Second-line chemotherapy for colorectal cancer
    Yoshito Komatsu, Susumu Sogabe, Yasuyuki Kawamoto, Ichiro Iwanaga, Yasuko Uehata, Satoshi Yuki, Masahiro Asaka
    Japanese Journal of Cancer and Chemotherapy, 36, 5, 721, 725, Japanese Journal of Cancer and Chemotherapy Publishers Inc., 2009年, [査読有り], [国内誌]
    日本語, 研究論文(学術雑誌)
  • 急性心筋梗塞後肺炎を呈し死亡した1症例
    川本 泰之, 岸 杏子, 工藤 和洋, 下山 則彦
    函館医学誌, 30, 1, 81, 84, 市立函館病院, 2006年09月
    日本語

その他活動・業績

共同研究・競争的資金等の研究課題

  • 膵癌における腫瘍内細菌叢と腫瘍免疫逃避機構の解明
    科学研究費助成事業
    2024年04月01日 - 2027年03月31日
    結城 敏志, 川久保 和道, 川本 泰之, 桑谷 将城
    日本学術振興会, 基盤研究(C), 北海道大学, 24K10445
  • SCRUM-Japanの基盤を活用した血液循環腫瘍DNAゲノムスクリーニングに基づくBRCA変異を有する胆道がんに対する医師主導治験               
    臨床研究・治験推進研究事業
    2020年04月 - 2024年03月
    国立研究開発法人日本医療研究開発機構, 国立大学法人北海道大学 北海道大学病院, 研究代表者
  • 超音波内視鏡下針生検による膵臓癌腫瘍内細菌叢の検出可能性の研究
    科学研究費助成事業 若手研究
    2019年04月01日 - 2021年03月31日
    川本 泰之
    2019年5月から2020年3月の間に30症例から膵癌腫瘍検体を収集した。腫瘍内細菌の由来を検討するため、超音波内視鏡下針生検(EUS-FNA)検体採取時に、胃粘膜・十二指腸粘膜も同時に収集し、合計90検体が収集された。
    検体解析成功率は、膵癌EUS-FNA:80%、胃粘膜:100%、十二指腸粘膜:97%であった。
    膵癌FNA検体におけるα多様性は胃・十二指腸粘膜よりも低く、β多様性は膵癌FNA検体と十二指腸粘膜では組成が異なることが示された。これらの結果からそれぞれの採取部位における細菌叢の分布は異なることが示された。また、膵内の原発巣部位や制酸剤の使用による多様性の偏りは認めなかった。
    日本学術振興会, 若手研究, 北海道大学, 19K17479