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Hepato-pancreato-biliary

E260: Impact of duration of neoadjuvant therapy on pathologic and clinical outcomes for pancreatic adenocarcinoma

Introduction: There has been an increase in the use of total neoadjuvant therapy (TNT, 6 months) for patients with pancreatic adenocarcinoma. Our aim was to evaluate if there is a survival benefit with TNT compared to perioperative (PERIOP, before/after surgery) or adjuvant therapy (ADJ) in pancreatic cancer.

Methods: This is a single-institution, retrospective study (2020-2023) of patients with resectable, borderline resectable, and locally advanced pancreatic adenocarcinoma that underwent surgical resection and chemotherapy with a total intended course of 6 months. We compared overall survival (OS), progression-free survival, and chemotherapy completion rates between the TNT, PERIOP, and ADJ groups in univariable and multivariable analyses.

Results: 75 patients were included (TNT=6, PERIOP=45, and ADJ=24). Patients in the ADJ group were more likely to have resectable disease (95.8%) than the TNT (33.3%) and PERIOP (44.4%, p< 0.01) groups. In the TNT group 33.3% of patients had locally advanced disease, while no patients in the PERIOP or ADJ group were locally advanced. There was no significant difference between groups regarding operative procedure, approach, or pathologic T stage. On final pathologic stage, positive lymph nodes were less likely in the TNT group, with 66.7% positive nodes in the ADJ group, 62.2% of the PERIOP group, and only 33.3% of the TNT group (P=0.03). Overall, 52% of the cohort received FOLFIRINOX and 30.7% received Gemcitabine/Abraxane as initial therapy. The TNT group was more likely to receive FOLFIRINOX (66.7%) as initial therapy than the ADJ (41.7%) or PERIOP (55.6%, p< 0.01) groups. By definition, the TNT group completed 6 months of chemotherapy while patients in the ADJ and PERIOP groups had significantly lower rates of completing 6 months of treatment (33.3 % vs. 37.8%, p=0.01). In all patients who completed 6 months of chemotherapy, the median OS was 18.3 months in those who did not complete chemotherapy compared to 35.7 months in those who completed treatment ([HR 4.48; 95% CI 1.93-10.42; p< 0.01]), and notably there was no significant difference in OS between groups.

Conclusions: Our results demonstrate that patients with pancreatic cancer who completed 6 months of chemotherapy have an improved OS, indicating that the completion of chemotherapy has a greater impact on survival than the timing of surgery. However, completion of full-course chemotherapy occurs in only a third of patients with PERIOP and ADJ approaches. This may support a TNT approach in more patients.

Learning Objectives:

  • infer that patients with pancreatic cancer who completed 6 months of chemotherapy have an improved OS; indicating that completing chemotherapy has a greater impact on survival than timing of surgery.
  • conclude that completion of full-course chemotherapy was significantly lower than in TNT group and occurs in only a third of patients with PERIOP and ADJ approaches.
  • compare institutional practices where in this study of pancreatic adenocarcinoma, TNT group was more likely to receive FOLFIRINOX as initial chemotherapy regimen compared to ADJ or PERIOP groups