胰腺癌（PDAC）是一种主要的健康负担，可能成为发达国家第二大癌症死亡原因。早发性胰腺癌（EOPC，定义为诊断年龄<50岁）的发病率正在增加。在这里，我们对我们机构跟踪的所有 PDAC 患者进行了一项研究。患者被分类为 EOPC 或非早发型 (nEOPC，>50)。共纳入 878 名患者，其中 113 名 EOPC，表现出相当的体能状态。 EOPC 更常见于转移期（70.0% vs 58.3%），肝转移在诊断时更为常见（60.2% vs. 43.9%）。诊断后的中位总生存期 (OS) 为 18.1 个月，EOPC 和 nEOPC 相似。在接受手术的患者中，各年龄组的无复发生存率相似。在转移性患者中，一线患者的无进展生存期相似，但 EOPC 接受了更多的治疗线（72.3% vs. 58.1% 接受≥2 线）。关于分子改变，EOPC 的平均肿瘤突变负荷 (TMB) 较低（1.42 与 2.95 mut/Mb）。 KRAS 和 BRCA1/2 突变的发生率相似，但 EOPC 在 CNKN2A/B 中显示较少的改变。 58 名患者 (18.6%) 发生了可操作的改变 (ESCAT I-III)，其中 31 名接受了分子匹配治疗。在转录组水平上，尽管 EOPC 具有临床侵袭性，但它不太可能表现出类似基底的表型。总而言之，EOPC 在转移阶段更容易被诊断出来。 OS 和第一线 PFS 与 nEOPC 相似。 EOPC 显示出特定的分子特征，例如较低的 TMB 和 CDKN2A/B 中较少的改变。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Pancreatic adenocarcinoma (PDAC) is a major health burden and may become the second cause of death by cancer in developed countries. The incidence of early-onset pancreatic cancer (EOPC, defined by an age at diagnosis <50 years old) is increasing. Here, we conducted a study of all PDAC patients followed at our institution. Patients were classified as EOPC or non-early onset (nEOPC, >50). Eight hundred and seventy eight patients were included, of which 113 EOPC, exhibiting a comparable performance status. EOPC were more often diagnosed at the metastatic stage (70.0% vs 58.3%) and liver metastases were more prevalent at diagnosis (60.2% vs. 43.9%). The median overall survival (OS) from diagnosis was 18.1 months, similar between EOPC and nEOPC. Among patients who underwent surgery, recurrence-free survival was similar between age groups. Among metastatic patients, first line progression free survival was similar but EOPC received more treatment lines (72.3% vs. 58.1% received ≥2 lines). Regarding molecular alterations, the mean tumor mutational burden (TMB) was lower in EOPC (1.42 vs. 2.95 mut/Mb). The prevalence of KRAS and BRCA1/2 mutations was similar, but EOPC displayed fewer alterations in CNKN2A/B. Fifty eight patients (18.6%) had actionable alterations (ESCAT I-III) and 31 of them received molecularly matched treatments. On the transcriptomic level, despite its clinical aggressiveness, EOPC was less likely to display a basal-like phenotype. To conclude, EOPC were diagnosed more frequently at the metastatic stage. OS and 1st line PFS were similar to nEOPC. EOPC displayed specific molecular features, such as a lower TMB and fewer alterations in CDKN2A/B.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.