Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain; Upper Gastrointestinal Cancer Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain.
Oncology Data Science (ODysSey) Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain.
Eur J Cancer. 2023 Nov;194:113338. doi: 10.1016/j.ejca.2023.113338. Epub 2023 Sep 9.
The incidence of early-onset pancreatic cancer (EOPC) has risen dramatically in recent years. We aimed to characterise the clinical and genomic features of EOPC and evaluate their therapeutic implications.
We performed a comparative, single-centre, retrospective analysis of clinical, germline, and genomic features in EOPC (≤50 years) patients and compared them with a control group of average-onset pancreatic cancer patients (AOPC, ≥70 years). Key molecular findings were compared with an external, publicly available cohort.
We reviewed 336 patients who met all inclusion criteria (EOPC N = 139, AOPC N = 197). EOPC was associated with smoking status, lower prevalence of diabetes, better performance status, higher CA19.9 levels, and higher albumin levels at diagnosis. After adjustment for baseline covariates, we observed no differences in overall survival (OS). Age was associated with an increase in the incidence of KRAS both in our cohort and the validation cohort. EOPC were enriched in potentially actionable alterations according to ESCAT tiers I-IIIA when compared with AOPC in discovery and validation cohorts (19% versus 14% and 14% versus 8%, respectively). In the first-line metastatic setting, EOPC had a longer progression-free survival (hazard ratio [HR] 0.61, 95% confidence interval (CI) 0.43-0.87) and OS (HR 0.65, 95% CI 0.45-0.95), although there were no differences in response rate. After adjusting for the number of treatment lines, EOPC patients who did receive targeted therapies exhibited longer OS compared with EOPC who did not (HR 0.34, 95% CI 0.12-0.93).
EOPC patients have improved outcomes in the metastatic setting when compared to AOPC and are enriched for targetable alterations that open opportunities for precision oncology-based approaches.
近年来，早发性胰腺癌（EOPC）的发病率急剧上升。我们旨在描述 EOPC 的临床和基因组特征，并评估其治疗意义。
我们对 EOPC（≤50 岁）患者的临床、种系和基因组特征进行了对比、单中心、回顾性分析，并将其与平均发病年龄的胰腺癌患者（AOPC，≥70 岁）的对照组进行了比较。关键分子发现与外部公开队列进行了比较。
我们回顾了符合所有纳入标准的 336 名患者（EOPC N=139，AOPC N=197）。EOPC 与吸烟状况、糖尿病患病率较低、更好的体能状态、CA19.9 水平较高和白蛋白水平较高有关。在调整基线协变量后，我们观察到总生存期（OS）没有差异。年龄与我们的队列和验证队列中 KRAS 发生率的增加有关。EOPC 在发现和验证队列中根据 ESCAT 分层 I-IIIA 比 AOPC 更丰富，具有潜在的可操作改变（分别为 19%比 14%和 14%比 8%）。在一线转移性环境中，EOPC 的无进展生存期（HR 0.61，95%置信区间[CI]0.43-0.87）和 OS（HR 0.65，95%CI0.45-0.95）更长，尽管反应率没有差异。在调整治疗线数后，接受靶向治疗的 EOPC 患者的 OS 明显长于未接受靶向治疗的 EOPC 患者（HR 0.34，95%CI0.12-0.93）。
与 AOPC 相比，EOPC 患者在转移性环境中具有更好的结局，并且具有丰富的可靶向改变，为基于精准肿瘤学的方法提供了机会。
