PO.CL02.01 · 临床研究

分子分型预测接受新辅助治疗后手术的胰腺癌患者的首个复发部位

Molecular profiling to predict the first site of recurrence in pancreatic cancer patients receiving neoadjuvant therapy followed by surgery

编号 6446 展板 13 时间 4/21 02:00–05:00 区域 Section 40 主讲 Luigi Liguori, MD

分会场 Biostatistics in Clinical Trials / Surgical Oncology

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作者与单位 Authors & Affiliations

Luigi Liguori¹, Marco Ventin¹, Liti Zhang¹, Erica Daniels¹, Giulia Cattaneo¹, Chiara Camillo¹, Maoyang Qi¹, Enrica Quattrocchi¹, Eduardo Tejeda-polanco¹, Arsen Osipov¹, Alexandra Gangi¹, Andrew Hendifar¹, Nicholas Nissen¹, Kambiz Kosari¹, Francesco Sabbatino², Cristina R. Ferrone¹

¹Cedars Sinai Medical Center, Los Angeles, CA,²University of Salerno, Baronissi, Italy

摘要 Abstract

中文摘要

胰腺导管腺癌（PDAC）仍是最致命的癌症之一，五年生存率仅为13%。尽管新辅助化疗和放疗改善了可切除性和生存结局，但大多数患者最终会经历疾病复发。因此，识别能够对复发模式进行分层的生物标志物对于优化患者选择和定制术后管理至关重要。我们回顾性分析了2013年5月至2024年11月期间在Cedars Sinai医学中心接受新辅助治疗后手术的PDAC患者的数据。使用包括临床病理变量和基于NGS的分子特征的单变量和多变量二元逻辑回归来预测首个复发部位。在244名接受PDAC新辅助治疗的患者中，138名具有完整的临床病理和基于NGS的分子数据。最常见的突变基因包括TP53（69.6%）、KRAS G12D（43.5%）、KRAS G12V（31.2%）、CDKN2A（24.6%）、SMAD4（20.3%）、KRAS G12R（12.3%）、CDKN2B（10.1%）、KRAS Q61X（7.2%）、ATM（5.1%）和BRCA2（4.3%）。首个复发部位模式为局部区域（25.5%）、肝脏（32.6%）、肺（21.0%）、腹膜（14.5%）和骨（7.2%）。分子特征独立且显著地预测了首个复发部位。具体而言，KRAS Q61X突变与局部区域复发风险增加相关（OR 5.6，95% CI 1.4-22.4，p=0.01），CDKN2B突变与肝复发相关（OR 4.4，95% CI 1.2-16.2，p=0.02），ATM突变与肺复发（OR 7.7，95% CI 1.3-44.9，p=0.02）和腹膜复发（OR 5.0，95% CI 1.0-24.4，p=0.04）均相关，BRCA2突变与骨复发相关（OR 7.7，95% CI 1.2-48.9，p=0.03）。我们的研究表明，分子分型可以预测接受新辅助治疗后手术的PDAC患者的首个复发部位。虽然需要在更大队列中进行前瞻性验证，但这项工作为在PDAC中开发风险适应性术后监测策略奠定了基础。

查看英文原文 English abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, with a five-year survival rate of only 13%. Although neoadjuvant chemotherapy and radiotherapy have improved resectability and survival outcomes, most patients ultimately experience disease recurrence. Identifying biomarkers that can stratify recurrence patterns is therefore critical for optimizing patient selection and tailoring postoperative management. We retrospectively analyzed data from PDAC patients who underwent neoadjuvant therapy followed by surgery at Cedars Sinai Medical Center between May 2013 and November 2024. Uni- and multivariable binary logistic regression including clinicopathologic variables and NGS-based molecular features was used to predict the first site of recurrence. Among 244 patients receiving neoadjuvant therapy for PDAC, 138 had complete clinicopathologic and NGS-based molecular data. Most common mutated genes included TP53 (69.6%), KRAS G12D (43.5%), KRAS G12V (31.2%), CDKN2A (24.6%), SMAD4 (20.3%), KRAS G12R (12.3%), CDKN2B (10.1%), KRAS Q61X (7.2%), ATM (5.1%), and BRCA2 (4.3%). First-site recurrence patterns were locoregional (25.5%), liver (32.6%), lung (21.0%), peritoneum (14.5%), and bone (7.2%). Molecular features independently and significantly predicted the first site of recurrence. Specifically, KRAS Q61X mutation was associated with increased risk of locoregional recurrence (OR, 5.6, 95% CI 1.4-22.4, p=0.01), CDKN2B mutations with liver recurrence (OR, 4.4, 95% CI 1.2-16.2, p=0.02), ATM mutations with both lung (OR, 7.7, 95% CI 1.3-44.9, p=0.02) and peritoneal recurrence (OR, 5.0, 95% CI 1.0-24.4, p=0.04), and BRCA2 mutations with bone recurrence (OR, 7.7, 95% CI 1.2-48.9, p=0.03). Our study demonstrates that molecular profiling can predict the first site of recurrence in PDAC patients who have undergone neoadjuvant therapy followed by surgery. While prospective validation in larger cohorts is warranted, this work provides a foundation for developing risk-adapted postoperative surveillance strategies in PDAC.

利益披露 Disclosure

L. Liguori, None.. M. Ventin, None.. L. Zhang, None.. E. Daniels, None.. G. Cattaneo, None.. C. Camillo, None.. M. Qi, None.. E. Quattrocchi, None.. E. Tejeda-polanco, None.. A. Osipov, None.. A. Gangi, None.. A. Hendifar, None.. N. Nissen, None.. K. Kosari, None.. F. Sabbatino, None.. C. Ferrone, None.

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