Background:We reviewed outcomes of short and long-term chemotherapy with or without breaks in pancreatic ductal adenocarcinoma (PDAC) patients.Methods: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.Results: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;KRASaberrations (N = 4), actionablePLAB2/BRCA2/FGFR2mutations (N = 3),ATM/BRIP1alteration (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 (p= 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 (p< 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 (p< 0.05). In patients with de novo metastatic disease, prevalence of type 2 diabetes was adversely associated with OS (p= 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) (p< 0.05 for all). A favourable OS was associated with >1 line of chemotherapy (p= 0.003).Conclusion:Despite challenges, extended chemotherapy and multiple treatment lines may improve survival, with localised treatments benefiting select patients.
背景：本研究回顾了胰腺导管腺癌（PDAC）患者接受短期与长期化疗（含或不含间歇期）的疗效结果。 方法：纳入2019至2024年间在三个医疗中心接受≥3周期化疗的PDAC患者。采用Wilcoxon检验、Kaplan-Meier法以及单因素与多因素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）及化疗最佳总体缓解率（BOR）。 结果：共筛查237例患者，其中135例符合研究标准。患者中25例为可切除疾病，110例为不可切除/转移性疾病（13%为临界可切除[BRPC]，20%为局部晚期[LAPC]，10%为局部进展后发生转移，57%为新发转移）。10例（7%）患者接受基因检测：KRAS变异（4例）、可干预的PLAB2/BRCA2/FGFR2突变（3例）、ATM/BRIP1改变（1例）。2例患者在多线化疗后接受PARP抑制剂治疗。中位PFS1与OS与已发表文献一致，但特定患者亚组获得长期生存获益。在36例BRPC/LAPC患者中，9例（25%）PFS1超过1年，3例（8%）OS超过2年。在63例新发转移患者中，6例（10%）PFS1超过1年且OS超过2年。在局部疾病患者中，吸烟史是OS的不良预后因素（p=0.03）。更长的PFS1与OS与以下因素相关：一线化疗≥6周期、持续时间≥3.66个月以及化疗后接受局部治疗（均p<0.05）。LAPC与BRPC患者中分别有6例（27%）和1例（7%）在一线化疗后接受立体定向放疗。仅在局部疾病队列中，化疗中断时长（而非中断次数）与PFS1和OS相关（p<0.05）。在新发转移患者中，2型糖尿病的存在与OS呈负相关（p=0.03）。更长的PFS与OS与以下因素相关：一线化疗≥6周期、持续时间≥4.37个月以及BOR（仅在该队列中）（均p<0.05）。接受>1线化疗与更优OS相关（p=0.003）。 结论：尽管面临挑战，延长化疗周期与多线治疗可能改善生存，局部治疗可为特定患者带来获益。
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