PO.CL12.02 · 临床研究

极早发结直肠癌中独特的分子和临床侵袭性：30-39岁与40-49岁患者之间的生存和基因组差异

Distinct molecular and clinical aggressiveness in very early-onset colorectal cancer: Survival and genomic divergence between patients aged 30-39 vs 40-49 years

编号 7908 展板 13 时间 4/22 09:00–12:00 区域 Section 48 主讲 Andrea Pretta, MD

分会场 Translational Biomarkers and Emerging Molecular Approaches

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作者与单位 Authors & Affiliations

Andrea Pretta¹, Gaia Rebecchi², Giulia Maddalena³, Federica Marmorino⁴, Pina Ziranu⁵, Federica Manoni⁶, Maria Caterina De Grandis³, Martina Carullo⁴, Clelia Donisi⁵, Giovanni Randon⁶, Eleonora Perissinotto³, Ada Taravella⁴, Vincenzo Nasca⁶, Federica Buggin³, Paolo Ciracì⁴, Francesca Bergamo³, Chiara Cremolini⁷, Sara Lonardi³, Mario Scartozzi⁵, Filippo Pietrantonio⁶

¹Medical Oncology Unit, University and University Hospital of Cagliari, Cagliari, Italy,²IRCCS Istituto Nazionale dei Tumori, Milan, Italy,³Oncology Unit 1, Veneto Institute of Oncology IOV—IRCCS, Padua, Italy,⁴Unit of Oncology, University Hospital of Pisa, Pisa, Italy,⁵Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy,⁶Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy,⁷Polo Oncologico - AOUP, Pisa, Italy

摘要 Abstract

中文摘要

背景：早发结直肠癌（EO-CRC）在全球范围内呈上升趋势，并表现出临床异质性。40岁以下患者可能构成EO-CRC内一个生物学上独特的亚组。我们研究了“极早发”结直肠癌（VEO-CRC，30-39岁）与40-49岁患者相比是否表现出特定的临床和基因组特征，以及这些差异是否导致转移性诊断时的生存差异。方法：我们分析了来自一个多机构数据库的转移性EO-CRC患者，分为两个预先设定的年龄组：30-39岁（n=65）和40-49岁（n=199）。使用Kaplan-Meier方法估计自转移性诊断起的总生存期（OS），并用Cox回归计算风险比（HRs）。使用Foundation Medicine二代测序平台（FoundationOne® CDx / Heme；超过300个癌症相关基因）进行全面基因组分析。使用比值比（ORs）比较关键分子改变（KRAS、NRAS、BRAF、APC、PTEN、POLE），并采用预先设定的单侧检验判断方向性。基线临床病理特征采用χ²或Fisher精确检验评估。结果：30-39岁患者的中位OS明显短于40-49岁患者（30.0 vs 38.0个月；log-rank p = 0.0269；HR = 0.67，95% CI 0.48-0.96）。VEO-CRC呈现出独特的基因组特征，其特点是KRAS突变率更高（55.4% vs 42.0%；OR=1.71；95% CI 0.98-3.01；单侧p=0.041）和APC改变更低（69.2% vs 82.0%；OR=0.49；95% CI 0.26-0.94；单侧p=0.024）。NRAS、BRAF、PTEN和POLE改变在方向上与更具侵袭性的生物学一致，尽管事件计数有限。临床上，总体ECOG分布相似（χ² p=0.099），但ECOG 0在VEO-CRC中更常见（89.1% vs 76.8%；p=0.0468）。腹膜转移在30-39岁患者中发生频率显著更高（32.3% vs 19.6%；p=0.041）。在肝、肺或淋巴结受累方面未观察到差异。结论：30-39岁患者构成EO-CRC内一个生物学上独特的亚组，具有更短的生存期、更高的KRAS富集、更少的APC改变和更多的腹膜受累，尽管体能状态相似。这些发现支持了关于一种“超年轻”、基因组驱动的CRC亚型这一新兴观点，对疾病生物学、风险评估和治疗开发具有意义。

查看英文原文 English abstract

Background: Early-onset colorectal cancer (EO-CRC) is rising worldwide and exhibits clinical heterogeneity. Patients under 40 may constitute a biologically distinct subgroup within EO-CRC. We investigated whether “very early-onset” colorectal cancer (VEO-CRC, ages 30-39) exhibits specific clinical and genomic features compared with patients aged 40-49, and whether these differences lead to variations in survival at the point of metastatic diagnosis. Methods: We analysed metastatic EO-CRC patients from a multi-institutional database, divided into two predefined age groups: 30-39 years (n=65) and 40-49 years (n=199). Overall survival (OS) from metastatic diagnosis was estimated using Kaplan-Meier methods, and hazard ratios (HRS) were calculated with Cox regression. Comprehensive genomic profiling was carried out using the Foundation Medicine next-generation sequencing platform (FoundationOne® CDx / Heme; over 300 cancer-related genes). Key molecular alterations (KRAS, NRAS, BRAF, APC, PTEN, POLE) were compared using odds ratios (ORs), with prespecified one-sided tests for directionality. Baseline clinicopathologic characteristics were assessed with χ² or Fisher's exact tests. Results: Median OS was notably shorter in patients aged 30-39 years than in those aged 40-49 years (30.0 vs 38.0 months; log-rank p = 0.0269; HR = 0.67, 95% CI 0.48-0.96). A distinct genomic profile appeared in VEO-CRC, characterised by higher KRAS mutation rates (55.4% vs 42.0%; OR=1.71; 95% CI 0.98-3.01; one-sided p=0.041) and lower APC alterations (69.2% vs 82.0%; OR=0.49; 95% CI 0.26-0.94; one-sided p=0.024). NRAS, BRAF, PTEN, and POLE alterations were directionally consistent with a more aggressive biology, although event counts were limited. Clinically, overall ECOG distribution was similar (χ² p=0.099), but ECOG 0 was more common in VEO-CRC (89.1% vs 76.8%; p=0.0468). Peritoneal metastases occurred significantly more frequently in patients aged 30-39 (32.3% vs 19.6%; p=0.041). No differences were observed regarding liver, lung, or nodal involvement. Conclusions: Patients aged 30-39 years constitute a biologically distinct subgroup within EO-CRC, with shorter survival, greater KRAS enrichment, fewer APC alterations, and increased peritoneal involvement, despite similar performance status. These findings support the emerging idea of an “ultra-young,” genomically driven CRC subtype, with implications for disease biology, risk assessment, and treatment development.

利益披露 Disclosure

A. Pretta, Merck Other, speaker. Sanofi Other, Speaker. Servier Other, Speaker. Deciphera Other, Speaker. G. Rebecchi, None.. G. Maddalena, None.. F. Marmorino, None.. P. Ziranu, None.. F. Manoni, None.. M. De Grandis, None.. M. Carullo, None.. C. Donisi, None.. G. Randon, None.. E. Perissinotto, None.. A. Taravella, None.. V. Nasca, None.. F. Buggin, None.. P. Ciracì, None.. F. Bergamo, None.. S. Lonardi, None.. M. Scartozzi, None.. F. Pietrantonio, None.

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