Mahmood Umair, Lynch Joanna, Sandhu Simran Kaur, Amin Zahir, Bridgewater John, Hochhauser Daniel, Shiu Kai-Keen, Miller Paul, Smyth Elizabeth C, Khan Khurum
Department of Gastrointestinal Oncology, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK.
Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK.
Cancers (Basel). 2025 Jun 5;17(11):1896. doi: 10.3390/cancers17111896.
We reviewed outcomes of short and long-term chemotherapy with or without breaks in pancreatic ductal adenocarcinoma (PDAC) patients. PDAC patients receiving ≥3 chemotherapy cycles between 2019 and 2024 at three institutions were included. Progression-free survival after first-line chemotherapy (PFS1), overall survival (OS) and best overall response (BOR) to chemotherapy were assessed using the Wilcoxon test, Kaplan-Meier test, and univariate and multivariate Cox regression models. We screened 237 patients, and 135 patients met the study criteria. Among these patients, 25 had resectable disease, and 110 had unresectable/metastatic disease (13% borderline resectable (BRPC), 20% locally advanced (LAPC), 10% localised developing metastases, 57% de novo metastatic). Ten patients (7%) underwent genetic profiling; aberrations (N = 4), actionable mutations (N = 3), alteration (N = 1). Two patients were managed with PARP inhibitors after receiving multiple lines of chemotherapy. Median PFS1 and OS were concordant with the published literature, but select patient groups achieved prolonged survival outcomes. Among the 36 BRPC/LAPC patients, we observed >1-year PFS1 in 9 (25%) patients and >2-year OS in 3 (8%) patients. Among the 63 de novo metastatic patients, we observed >1-year PFS1 and >2-year OS in 6 (10%) patients. Among patients with localised disease, smoking history was a poor prognostic factor with respect to OS ( = 0.03). Improved PFS1 and OS was associated with ≥6 cycles of first-line chemotherapy, its duration of ≥3.66 months, and local treatment after first chemotherapy ( < 0.05 for all). Stereotactic body radiotherapy following first-line chemotherapy was delivered in N = 6 (27%) and N = 1 (7%) of patients with LAPC and BRPC, respectively. Chemotherapy interruption duration, but not number, was associated with PFS1 and OS only in the localised cohort ( < 0.05). In patients with de novo metastatic disease, prevalence of type 2 diabetes was adversely associated with OS ( = 0.03). Improved PFS and OS was associated with ≥6 cycles of first-line chemotherapy, its duration of ≥4.37 months, and BOR to it (only in this cohort) ( < 0.05 for all). A favourable OS was associated with >1 line of chemotherapy ( = 0.003). Despite challenges, extended chemotherapy and multiple treatment lines may improve survival, with localised treatments benefiting select patients.
我们回顾了胰腺导管腺癌（PDAC）患者接受短期和长期化疗（有或无化疗中断）的治疗结果。纳入了2019年至2024年在三家机构接受≥3个化疗周期的PDAC患者。使用Wilcoxon检验、Kaplan-Meier检验以及单因素和多因素Cox回归模型评估一线化疗后的无进展生存期（PFS1）、总生存期（OS）和化疗的最佳总体缓解（BOR）。我们筛查了237例患者，135例患者符合研究标准。在这些患者中，25例患有可切除疾病，110例患有不可切除/转移性疾病（13%为临界可切除（BRPC），20%为局部晚期（LAPC），10%为局部进展性转移，57%为初发性转移）。10例患者（7%）进行了基因检测；检测到畸变（N = 4）、可操作突变（N = 3）、改变（N = 1）。2例患者在接受多线化疗后接受了PARP抑制剂治疗。PFS1和OS的中位数与已发表的文献一致，但部分患者组实现了更长的生存结果。在36例BRPC/LAPC患者中，我们观察到9例（25%）患者的PFS1>1年，3例（8%）患者的OS>2年。在63例初发性转移患者中，我们观察到6例（10%）患者的PFS1>1年，OS>2年。在局限性疾病患者中，吸烟史是OS的不良预后因素（P = 0.03）。PFS1和OS的改善与一线化疗≥6个周期、其持续时间≥3.66个月以及首次化疗后的局部治疗相关（所有P均<0.05）。一线化疗后分别有6例（27%）LAPC患者和1例（7%）BRPC患者接受了立体定向体部放疗。仅在局限性队列中，化疗中断持续时间而非次数与PFS1和OS相关（P<0.05）。在初发性转移疾病患者中，2型糖尿病的患病率与OS呈负相关（P = 0.03）。PFS和OS的改善与一线化疗≥6个周期、其持续时间≥4.37个月以及化疗的BOR（仅在该队列中）相关（所有P均<0.05）。良好的OS与>1线化疗相关（P = 0.003）。尽管存在挑战，但延长化疗和多线治疗可能改善生存，局部治疗使部分患者受益。
