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食管癌淋巴结清扫数量对生存预后的影响——按新辅助策略分层的多中心欧洲队列研究

The Prognostic Impact of Lymph Node Yield Upon Survival in Esophageal Cancer Broken Down by Neoadjuvant Strategy: A Multicenter European Cohort Study.

期刊
Annals of Surgery
PMID
42533309
原文
PubMed ↗
发布日期

作者

  • Nadia Guidozzi — Nuffield Department of Surgical Sciences, Surgical Intervention Trials Unit, University of Oxford, Oxford, UK.
  • Wing K Chou — Nuffield Department of Surgical Sciences, Surgical Intervention Trials Unit, University of Oxford, Oxford, UK.
  • Lorenzo Giorgi — Nuffield Department of Surgical Sciences, Surgical Intervention Trials Unit, University of Oxford, Oxford, UK.
  • Riadh Salem — Nuffield Department of Surgical Sciences, Surgical Intervention Trials Unit, University of Oxford, Oxford, UK.
  • Stijn Vanstraelen — Department of Thoracic Surgery, University Hospital Leuven, Leuven, Belgium.
  • Helena Gielen — Department of Thoracic Surgery, University Hospital Leuven, Leuven, Belgium.
  • Johnny Moons — Department of Thoracic Surgery, University Hospital Leuven, Leuven, Belgium.
  • Philippe Nafteux — Department of Thoracic Surgery, University Hospital Leuven, Leuven, Belgium.
  • Femke E Lammes — Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Jelle P Ruurda — Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Richard van Hillegersberg — Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Alban Todesco — Department of Thoracic Surgery, North Hospital, Aix-Marseille University, Marseille, France.
  • Xavier B D'Journo — Department of Thoracic Surgery, North Hospital, Aix-Marseille University, Marseille, France.
  • Alice Collizzolli — General and Upper Gastrointestinal Surgery, Verona University, Verona, Italy.
  • Barbara Ajazi — General and Upper Gastrointestinal Surgery, Verona University, Verona, Italy.
  • Simone Giacopuzzi — General and Upper Gastrointestinal Surgery, Verona University, Verona, Italy.
  • Maria Bencivenga — General and Upper Gastrointestinal Surgery, Verona University, Verona, Italy.
  • Sam Alhayo — Department of Upper Gastrointestinal Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Ella Seabourne — Department of Upper Gastrointestinal Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Ewen A Griffiths — Department of Upper Gastrointestinal Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Aram Abu Hejleh — Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Cologne, Cologne, Germany.
  • Lars M Schiffmann — Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Cologne, Cologne, Germany.
  • Christiane J Bruns — Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Cologne, Cologne, Germany.
  • Giovanni M Garbarino — Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • Andrea Pansa — Upper Gastrointestinal Surgery Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
  • Silvia Basato — Upper Gastrointestinal Surgery Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
  • Ophélie Bacoeur-Ouzillou — Department of Visceral Surgery, Oesogastric Unit, Bordeaux University Hospital, Bordeaux, France.
  • Caroline Gronnier — Department of Visceral Surgery, Oesogastric Unit, Bordeaux University Hospital, Bordeaux, France.
  • Sofie P G Henckens — Department of Surgery, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
  • Suzanne S Gisbertz — Department of Surgery, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
  • Rakesh Ahmed — The National Centre for Advanced Medical Imaging (CAMI), Trinity College Dublin, Dublin, Ireland.
  • Nithiesh Loganathan — Department of Surgery, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Dublin, Ireland.
  • Jessie A Elliott — Department of Surgery, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Dublin, Ireland.
  • Kirsty Cole — Department of Surgery, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Dublin, Ireland.
  • Youssef Ibrahim — Department of Surgery, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Dublin, Ireland.
  • Chanakya Anand — Department of Surgery, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Dublin, Ireland.
  • Philip H Pucher — Department of Surgery, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Dublin, Ireland.
  • Martin Skogar — Department of General Surgery, Portsmouth University Hospitals, NHS Trust, Portsmouth, UK.
  • Jakob Hedberg — Department of General Surgery, Portsmouth University Hospitals, NHS Trust, Portsmouth, UK.
  • Eloise Bonnin — Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  • Julie Veziant — Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  • Guillaume Piessen — Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  • Agnese Carresi — Department of Digestive and Oncological Surgery, CHU Lille, France.
  • Silvia Battaglia — Department of Digestive and Oncological Surgery, CHU Lille, France.
  • Francesco Puccetti — Department of Digestive and Oncological Surgery, CHU Lille, France.
  • Riccardo Rosati — Department of Digestive and Oncological Surgery, CHU Lille, France.
  • Fahad Murad — Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Surgery and Oncology, Karolinska Institutet, Stockholm, Sweden.
  • Fredrik Klevebro — Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Surgery and Oncology, Karolinska Institutet, Stockholm, Sweden.
  • Magnus Nilsson — Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Surgery and Oncology, Karolinska Institutet, Stockholm, Sweden.
  • Grard A P Nieuwenhuijzen — Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.
  • Lars van de Sanden — Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.
  • Misha D P Luyer — Department of Electrical Engineering, University of Technology, Eindhoven, The Netherlands.
  • Rita Alfieri — Upper Gastrointestinal Surgery Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
  • Carlo Castoro — Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • Mark I van Berge Henegouwen — Department of Surgery, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
  • Sheraz R Markar — Nuffield Department of Surgical Sciences, Surgical Intervention Trials Unit, University of Oxford, Oxford, UK.

作者单位

  • Nuffield Department of Surgical Sciences, Surgical Intervention Trials Unit, University of Oxford, Oxford, UK.
  • Department of Thoracic Surgery, University Hospital Leuven, Leuven, Belgium.
  • Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Department of Thoracic Surgery, North Hospital, Aix-Marseille University, Marseille, France.
  • General and Upper Gastrointestinal Surgery, Verona University, Verona, Italy.
  • Department of Upper Gastrointestinal Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Cologne, Cologne, Germany.
  • Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • Upper Gastrointestinal Surgery Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
  • Department of Visceral Surgery, Oesogastric Unit, Bordeaux University Hospital, Bordeaux, France.
  • Department of Surgery, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
  • The National Centre for Advanced Medical Imaging (CAMI), Trinity College Dublin, Dublin, Ireland.
  • Department of Surgery, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Dublin, Ireland.
  • Department of General Surgery, Portsmouth University Hospitals, NHS Trust, Portsmouth, UK.
  • Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  • Department of Digestive and Oncological Surgery, CHU Lille, France.
  • Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Surgery and Oncology, Karolinska Institutet, Stockholm, Sweden.
  • Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.
  • Department of Electrical Engineering, University of Technology, Eindhoven, The Netherlands.

摘要

中文

本研究旨在确定食管腺癌患者在新辅助治疗后接受食管切除术时，与总生存期（OS）和无病生存期（DFS）改善相关的淋巴结清扫数量（LNY）变化点。次要终点包括复发模式和基于病理分期的生存情况。LNY 与食管癌预后改善相关；新辅助治疗后淋巴结清扫的最佳范围仍不明确。这项多中心欧洲研究纳入了 2018 年至 2023 年间接受化疗（CT）或放化疗（CRT）后行食管切除术的患者。RA-CUSUM 分析确定了 LNY 与生存之间的变化点；自举重采样确定最佳 LNY；多变量 Cox 比例风险模型将 LNY 作为连续变量和分类变量进行分析。在 CT 患者中进行了事后探索性亚组分析，比较达到最佳 LNY 的 CT 组与不考虑 LNY 的 CRT 组。使用 Fisher 精确检验评估复发模式。共纳入 2069 例患者：CT 组 957 例，CRT 组 1112 例，中位 LNY 为 32。CT 数据集：确定最佳阈值为 25 个淋巴结（95% CI：20–39）；使用 ≥25 个淋巴结的分类分析显示死亡率降低 29%（HR：0.714，P=0.0017）。CRT 数据集：任何终点均未显示显著的 LNY 相关性；连续 LNY 呈无效效应（P=0.633），分类分析未见获益（P=0.66）。在校正潜在混杂变量后，CT 联合 ≥25 个 LNY 较 CRT 的死亡率降低约 44%（HR=0.563，P<0.001）。每个阳性淋巴结使 CT 组和 CRT 组的死亡风险分别增加 7.3% 和 11.2%。CT 组疾病复发率 32.7%，CRT 组 38.3%（P=0.001）。基于上述数据，在接受 CT 的患者中，实施根治性淋巴结清扫并至少清扫 25 个淋巴结具有明确的生存与复发获益。

English

To establish a lymph node yield (LNY) change-point associated with improvements in overall survival (OS) and disease-free survival (DFS) in patients undergoing esophagectomy following neoadjuvant treatment for esophageal adenocarcinoma. Secondary endpoints include recurrence patterns and survival based on pathological staging. LNY has been associated with improved outcomes in esophageal cancer. The extent of lymphadenectomy following neoadjuvant treatment remains unclear. This multicenter European study included patients undergoing chemotherapy (CT) or chemoradiotherapy (CRT) followed by esophagectomy between 2018 and 2023. RA-CUSUM analysis identified change points between LNY and survival. Bootstrap resampling determined the optimal LNY, and multivariable Cox proportional hazards models analyzed LNY as continuous and categorical variables. A post hoc exploratory subgroup analysis was conducted in CT patients with optimal LNY compared with CRT irrespective of LNY. Recurrence patterns were assessed using the Fisher exact test. A total of 2069 patients were included: 957 CT versus 1112 CRT. Median LNY was 32. CT data set: an optimal threshold of 25 nodes was identified (95% CI: 20-39). Categorical analysis using ≥25 nodes demonstrated 29% mortality reduction (HR: 0.714, P=0.0017). CRT data set: no significant LNY association across any endpoint. Continuous LNY showed a null effect (P=0.633), and categorical analysis showed no benefit (P=0.66). CT with ≥25 LNY had ∼44% lower mortality compared with CRT after adjustment for potential confounding variables (HR=0.563, P<0.001). Each positive LN increased the hazard for death by 7.3% in CT and 11.2% in CRT. Disease recurrence occurred in 32.7% of CT versus 38.3% of CRT (P=0.001). On the basis of this data, there is a clear survival and recurrence benefit to performing a radical lymphadenectomy with a lymph node harvest of at least 25 nodes in patients who have received CT.

分类与指标

研究类型
临床研究
病种
食管癌
JCR 分区
Q1
影响因子
7.4
新锐分区
1区