慶應義塾研究者情報データベース

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• Study protocol of a randomized controlled phase II trial comparing nivolumab, ipilimumab plus radiotherapy versus nivolumab plus ipilimumab for advanced or recurrent esophageal cancer: Japan Clinical Oncology Group study JCOG2311 (ART NOUVEAU)

  Sakanaka K., Sasaki K., Tsushima T., Machida R., Hamai Y., Watanabe A., Kawabata K., Matsuda S., Kato K., Fukuda H., Takeuchi H.

  BMC Cancer 26 （ 1 ）  2026年12月

  　概要を見る

  Background: The immunogenic cell death induced by radiotherapy (RT) has been demonstrated to enhance the systemic antitumor effect of immune checkpoint inhibitors (ICIs). The incorporation of RT into ICIs has the potential to mitigate the occurrence of early treatment failure, particularly with dual ICI combination, in patients with advanced or recurrent esophageal cancer. Methods: This randomized phase II trial, initiated in November 2024, aims to explore the superiority of the combination of RT with nivolumab plus ipilimumab over nivolumab plus ipilimumab alone in patients with advanced or recurrent esophageal squamous cell carcinoma. The primary endpoint is progression-free survival, while the secondary endpoints include overall survival, response rate, duration of response, and adverse events. We assumed a 6-month PFS of 35% in the nivolumab plus ipilimumab alone arm and expected a 15% increase in the 6-month PFS for the RT with nivolumab plus ipilimumab arm (HR, 0.66). The total required sample size was calculated to be 70 (35 per arm) to achieve a desired power of 80% with an overall one-sided alpha of 20%, an accrual period of 2.5 years, and a follow-up period of 1 year. A total of 74 patients will be enrolled from 41 institutions in Japan. An ancillary study analyzes cytokine profiles and phenotypic characteristics in peripheral blood mononuclear cells during treatment with the protocol. Discussion: The objective of this trial is to assess the safety and efficacy of RT in combination with dual ICIs in reducing early treatment failure and improving outcomes with translational research. Findings from this trial will inform a future phase III trial in this patient population. Trial registration: This trial has been registered on November 5th, 2024, in the Japan Registry of Clinical Trials as jRCT1031240461 (https://jrct.mhlw.go.jp/en-latest-detail/jRCT1031240461).

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• Additional treatment for esophageal cancer patients with incomplete resection due to the surrounding organ invasion: a nationwide survey of 45 Japanese centers

  Okamura A., Watanabe M., Okui J., Matsuda S., Hamai Y., Takahashi N., Sato S., Abe T., Ishida H., Goto H., Bamba T., Kakishita T., Booka E., Kitagami H., Kuwabara S., Kimura Y., Kosumi K., Matsumoto S., Nakajima M., Inoue S., Kitagawa H., Shibasaki S., Sadanaga N., Takebayashi K., Shichinohe T., Kawakubo H., Kakeji Y., Kono K., Kitagawa Y., Takeuchi H.

  Esophagus 23 （ 1 ） 88 - 98 2026年01月

  ISSN  16129059

  　概要を見る

  Background: We occasionally experience incomplete resection of esophageal cancer due to the surrounding organ invasion. The efficacy of additional treatment in these cases is unknown. Methods: We studied 445 patients with esophageal squamous cell carcinoma who were unable to undergo curative esophagectomy due to cancer invasion to the surrounding organs at 45 esophageal centers in Japan. Survival outcomes were compared based on the additional treatment modalities. Results: Postoperatively, 175 (40.0%) received no additional treatment, while 59 (13.5%), 153 (35.0%), and 50 (11.4%) received additional chemotherapy, chemoradiotherapy, or radiotherapy, respectively. The three-year disease progression and overall survival rates were 90.6% (95% confidence interval 87.2–93.1%) and 15.4% (95% confidence interval 12.2–19.3%), respectively. Multivariable analysis revealed that chemotherapy, chemoradiotherapy, and radiotherapy were all independently associated with reduced disease progression (hazard ratios [95% confidence intervals]: 0.57 [0.40–0.81], 0.52 [0.39–0.69], and 0.48 [0.33–0.72], respectively). Meanwhile, additional treatment with chemotherapeutic agents (chemotherapy and chemoradiotherapy) was independently associated with better overall survival (hazard ratios [95% confidence intervals]: 0.51 [0.35–0.73] and 0.59 [0.44–0.79], respectively); however, radiotherapy alone had a limited impact (hazard ratio [95% confidence interval]: 0.74 [0.50–1.10]). Conclusions: Any additional treatment could suppress disease progression after incomplete resection, but radiotherapy alone has a limited effect. Additional systemic chemotherapeutics may increase patient survival.

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• Impact of prophylactic drain placement on intra-abdominal infections after gastrectomy: nationwide inpatient database study in Japan

  Kouzu K., Aso S., Hirano Y., Matsui H., Fushimi K., Kitagawa H., Kato T., Yamane N., Hagiwara O., Miyoshi N., Matsuda S., Maruyama H., Morikane K., Sasaki J., Yasunaga H., Kitagawa Y., Tsujimoto H.

  Gastric Cancer 29 （ 1 ） 230 - 237 2026年01月

  ISSN  14363291

  　概要を見る

  Objective: This study aimed to evaluate the impact of drain placement on the incidence of postoperative complications in patients undergoing gastrectomy. Background: The effectiveness of prophylactic abdominal drain placement in gastrectomy remains unclear. Nevertheless, they are still commonly used following gastrectomy. Methods: We conducted a retrospective cohort study using a nationwide inpatient database in Japan. Patients who underwent gastrectomy for gastric cancer between January 2014 and March 2022 were included. We applied overlap weighting based on propensity scores to adjust for baseline characteristics. The primary outcome was the incidence of intra-abdominal infections. Secondary outcomes included postoperative percutaneous drainage, in-hospital death, length of hospital stay, and total hospitalization costs. Results: A total of 217,750 patients met the inclusion criteria, and 196,660 (90.3%) received prophylactic abdominal drains. After overlap weighting, the drain group had a significantly lower incidence of intra-abdominal infections compared to the no-drain group (6.3% vs. 7.6%; 95% confidence interval [CI] − 1.7 to − 1.0). The prophylactic drains were also associated with reduced in-hospital postoperative mortality (0.6% vs. 0.8%; 95% CI − 0.3 to − 0.1). No significant differences were observed between the two groups in postoperative percutaneous drainage or hospital stay duration. Conclusion: This study suggests that prophylactic abdominal drainage was associated with a reduced incidence of intra-abdominal infections after gastrectomy without increasing hospitalization duration or medical costs.

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• Plasma Fibrinogen Predicts Response to Immune Checkpoint Inhibitor by Inflammatory Tumor Microenvironment in Esophageal Cancer

  Ho K., Matsuda S., Booka E., Soneda W., Okui J., Hoshino S., Takeuchi M., Fukuda K., Horie S., Saito Y., Kogure Y., Kawakubo H., Hara K., Okita H., Kataoka K., Sekine S., Takeuchi H., Kitagawa Y.

  Cancer Medicine 15 （ 1 ）  2026年01月

  　概要を見る

  Background: Plasma fibrinogen (FNG) is a prognostic marker in esophageal squamous cell carcinoma (ESCC). However, its predictive value for immune checkpoint inhibitor (ICI) efficacy and the underlying mechanisms remain unclear. This study aimed to evaluate the clinical significance of plasma FNG levels in ICI-treated ESCC patients and investigate its association with tumor-associated neutrophils (TANs) and genomic alterations. Methods: A retrospective, multicenter analysis of 167 ESCC patients treated with ICIs was performed. TANs were quantified via immunohistochemistry using CD11b and CD66b staining, and PD-L1 expression was assessed using the tumor proportion score (TPS). Whole-exome and RNA sequencing were conducted to analyze genomic and transcriptomic profiles. Results: Elevated plasma FNG levels correlated with lower ICI response rates and decreased survival. In first-line treatment, chemo-ICI therapy demonstrated superior efficacy compared to dual-ICI therapy in high-FNG patients, while the reverse trend was observed in low-FNG patients. High-FNG tumors showed increased TAN infiltration, independent of PD-L1 expression. RNA sequencing revealed enrichment of neutrophil activation and extravasation pathways in high-FNG tumors. Conclusions: Elevated plasma FNG levels predict poor prognosis and reduced ICI efficacy in ESCC. They may be potential biomarkers for first-line ICI-based therapy and correlate with TAN infiltration. Further validation and mechanistic investigations are warranted.

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• Safety and efficacy of conversion therapy for metastatic esophageal cancer: exploratory analysis of JCOG1314

  Matsuda S., Tsushima T., Kawakubo H., Hironaka S., Tsubosa Y., Sakanaka K., Oguma J., Kadowaki S., Tsunoda S., Hara H., Koyanagi K., Yamaguchi T., Harada K., Takahashi M., Minashi K., Baba E., Sasaki K., Machida R., Takeuchi H.

  Esophagus 23 （ 1 ） 111 - 119 2026年01月

  ISSN  16129059

  　概要を見る

  Background: Recent advances in multimodal treatments indicate that conversion therapy (CT) is a viable option for metastatic esophageal cancer (EC). JCOG1314 was a randomized phase III trial to confirm the survival benefit of docetaxel plus cisplatin plus 5-fluorouracil (DCF) versus cisplatin plus 5-fluorouracil (CF) for metastatic EC. The purpose of this analysis was to evaluate the safety and survival of CT in patients enrolled in JCOG1314. Methods: CT was defined as surgery or chemoradiotherapy (CRT) aimed at cure following initial treatment for tumors that were initially unresectable because of distant metastasis. Clinicopathological factors, surgical outcomes, toxicities during CRT, and survival were compared between the CT and non-CT groups. Results: Of 240 patients enrolled in JCOG1314, excluding patients with recurrent disease, 154 with initially unresectable EC because of distant metastasis were selected. Of these patients, 21 received CT, which included conversion surgery (n = 5) and conversion CRT (n = 16). There was no significant difference in the number of metastatic organs or chemotherapy regimen between the CT and non-CT groups. The most common M1 factor in the CT group was the thoracic lymph node. The 3-year overall survival (OS) for the CT and non-CT groups was 52.4 and 14.3%, respectively. Multivariable analysis revealed that CT patients showed significantly better OS compared with the non-CT group (HR 0.36, 95% CI 0.19–0.67, p < 0.01). Conclusion: CT may be safely performed with a favorable prognosis in EC. A prospective study is warranted to determine whether CT improves survival in metastatic EC.

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• 食道癌における手術回避を目指した腫瘍と宿主の双方向性モニタリング手法確立

  松田, 諭

  科学研究費補助金研究成果報告書 2023年

• 食道癌マルチオミックスデータを用いた術前化学療法耐性機序の解明

  松田, 諭

  科学研究費補助金研究成果報告書 2022年

• 臨床・ゲノムデータを含む多層データの臨床応用基盤構築と有用性の検証

  松田, 諭

  科学研究費補助金研究成果報告書 2022年

• 食道癌におけるリキッドバイオプシーを用いた手術回避を目指した治療開発

  松田, 諭

  科学研究費補助金研究成果報告書 2021年

• 食道癌におけるリキッドバイオプシーを用いた手術回避戦略の確立

  松田, 諭

  学事振興資金研究成果実績報告書 （慶應義塾大学）  2020年

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• Reply to: “Critical Insights on the Clinical and Technical Limitations of AI-Assisted RLN Recognition in Esophageal Surgery”

  Takeuchi M., Furube T., Matsuda S., Kawakubo H., Kitagawa Y.

  Annals of Surgical Oncology 32 （ 3 ） 1696 - 1697 2025年03月

  ISSN  10689265

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• ASO Author Reflections: Can Conversion Therapy be an Option for Advanced Esophageal Cancer with Distant Metastases?

  Tsuji T., Matsuda S., Sato Y., Tanaka K., Sasaki K., Watanabe M., Hamai Y., Nasu M., Saze Z., Nakashima Y., Nomura M., Yamamoto S., Booka E., Ishiyama K., Bamba T., Sakanaka K., Tsushima T., Takeuchi H., Kato K., Kawakubo H.

  Annals of Surgical Oncology 32 （ 1 ） 325 - 326 2025年01月

  ISSN  10689265

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• ASO Author Reflections: Preoperative Prediction of Pathological Complete Response Using Deep Neural Network After Neoadjuvant Chemotherapy in Esophageal Cancer Patients

  Matsuda S., Irino T., Okamura A., Mayanagi S., Booka E., Takeuchi M., Kawakubo H., Takeuchi H., Watanabe M., Kitagawa Y.

  Annals of Surgical Oncology 30 （ 12 ） 7509 - 7510 2023年11月

  ISSN  10689265

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• Author response to: Comment on: Early postoperative non-steroidal anti-inflammatory drugs and anastomotic leakage after oesophagectomy

  Hirano Y., Konishi T., Kaneko H., Matsuda S., Kawakubo H., Daiko H., Itano O., Yasunaga H., Kitagawa Y.

  British Journal of Surgery 110 （ 9 ）  2023年09月

  ISSN  00071323

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• ASO Author Reflections: Can Circulating Tumor DNA Guide Individualized Treatment for Patients with Esophageal Squamous Cell Carcinoma?

  Morimoto Y., Matsuda S., Kawakubo H., Nakamura K., Kobayashi R., Hisaoka K., Okui J., Takeuchi M., Aimono E., Fukuda K., Nakamura R., Saya H., Nishihara H., Kitagawa Y.

  Annals of Surgical Oncology 30 （ 6 ） 3757 - 3758 2023年06月

  ISSN  10689265

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• リキッドバイオプシーとAI画像診断による多角的腫瘍モニタリング手法確立

  2024年04月

  -

  2027年03月

  松田 諭, 基盤研究(C), 補助金,  研究代表者

• 食道癌における手術回避を目指した腫瘍と宿主の双方向性モニタリング手法確立

  2022年04月

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  2024年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 松田 諭, 若手研究, 補助金,  研究代表者

• 食道癌におけるリキッドバイオプシーを用いた手術回避を目指した治療開発

  2020年04月

  -

  2022年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 松田 諭, 若手研究, 補助金,  研究代表者

• 腫瘍微小環境における細胞老化を介した食道癌に対する集学的治療抵抗性機序の解明

  2019年08月

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  2021年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 松田 諭, 研究活動スタート支援, 補助金,  研究代表者