Background: Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Toxicities during NT are common, often leading to the inability to undergo surgical resection, yet risk factors for attrition are poorly understood. Therefore, we sought to evaluate the impact of baseline frailty on outcomes of patients with PDAC undergoing NT.Methods: All patients with potentially resectable (PR) or borderline resectable (BR) PDAC who initiated neoadjuvant chemotherapy and/or chemoradiation between 2019 and 2025 at a single institution were assessed retrospectively in an intention-to-treat fashion. The association between frailty as defined by the modified 11-item frailty index (mFI-11) and receipt of surgical resection as well as other secondary endpoints was assessed. Comprehensive functional frailty assessments were prospectively obtained in a subset of patients.Results: Among 252 eligible patients, the median age was 67 years, 56.7% were male, 90.9% were White, 49.6% had PR disease, and 5.2% were frail according to mFI-11. After a median 3.6 months of NT, 62.7% underwent surgical resection. Frail individuals had worse performance status and increased comorbidities compared with non-frail patients. On multivariable analysis, male sex, BR anatomic staging, initial use of Gemcitabine + nab-paclitaxel, and frailty (OR 0.09; 95%CI 0.02–0.44) were associated with reduced odds of undergoing resection. Along with increased baseline CA 19-9 levels, frailty was independently associated with worse overall survival (HR 3.00; 95%CI 1.46–6.20). Among 39 patients who underwent formal functional frailty assessment, only abnormal posture was associated with lower odds of surgical resection following NT (OR, 0.22; 95% CI, 0.05–0.92), and no aspects of functional frailty were associated with overall survival.Conclusions: Among patients with localized PDAC initiating NT, frailty as assessed by mFI-11 was associated with reduced odds of undergoing surgical resection and worse overall survival. Future research should focus on efforts to improve functional status during NT.
背景：新辅助治疗（NT）在局限性胰腺导管腺癌（PDAC）患者中的应用日益广泛。NT期间的毒性反应较为常见，常导致患者无法接受手术切除，但导致治疗中断的风险因素尚不明确。因此，本研究旨在评估基线衰弱状态对接受NT的PDAC患者预后的影响。 方法：本研究回顾性分析了2019年至2025年间在一家机构启动新辅助化疗和/或放化疗的所有潜在可切除（PR）或临界可切除（BR）PDAC患者，采用意向性治疗原则进行分析。评估了基于改良11项衰弱指数（mFI-11）定义的衰弱状态与接受手术切除及其他次要终点之间的关联。在一部分患者中前瞻性地进行了全面的功能性衰弱评估。 结果：在252例符合条件的患者中，中位年龄为67岁，56.7%为男性，90.9%为白人，49.6%为PR疾病，根据mFI-11，5.2%的患者存在衰弱。经过中位3.6个月的NT后，62.7%的患者接受了手术切除。与非衰弱患者相比，衰弱患者的功能状态更差，合并症更多。多变量分析显示，男性、BR解剖分期、初始使用吉西他滨+白蛋白结合型紫杉醇以及衰弱状态（OR 0.09；95%CI 0.02–0.44）与接受手术切除的几率降低相关。此外，衰弱状态与升高的基线CA 19-9水平一样，是总生存期较差（HR 3.00；95%CI 1.46–6.20）的独立相关因素。在39例接受正式功能性衰弱评估的患者中，仅有姿势异常与NT后手术切除几率降低相关（OR, 0.22; 95% CI, 0.05–0.92），而功能性衰弱的其他方面均与总生存期无关。 结论：在启动NT的局限性PDAC患者中，通过mFI-11评估的衰弱状态与手术切除几率降低和总生存期较差相关。未来的研究应侧重于改善NT期间患者功能状态的策略。
Impact of Frailty on the Outcomes of Patients with Pancreatic Cancer Undergoing Neoadjuvant Therapy
肿瘤(癌症)患者之家