Chemotherapy in resected pancreatic adenocarcinoma: impact of duration and treatment strategy

Keywords

adenocarcinoma - pancreatic - resected - chemotherapy - treatment

Background: Pancreatic adenocarcinoma (PDAC) treatment remains a challenging problem. Although adjuvant chemotherapy is the gold standard in resectable disease, neoadjuvant has been investigated in recent trials. Also, it is known that 6-months of treatment is used in most adjuvant trials. However, it is a debate concerning the best strategy. This study aimed to assess the association of chemotherapy duration, treatment strategy (neoadjuvant vs adjuvant) in resected PDAC patients.

Methods: This was a retrospective chart review of non-metastatic PDAC patients that were treated with surgery and received chemotherapy (neoadjuvant or adjuvant) from January 1, 2019 through December 31, 2023 at AC Camargo Cancer Center. We analyzed the treatment duration (≤3 vs >3 months), treatment strategy (neo vs adjuvant) and others clinical-treatment features (ECOG, resectability classification, initial Ca19-9 levels). The primary endpoint was overall survival (OS). Cox regression multivariable analysis for OS was performed to adjust for prognostic variables in PDAC.

Results: We included 86 patients in the study, in which 77.9% were classified as resectable, 24.1% had Ca19-9 levels>500 and 33.8% were ECOG 1/2. Chemotherapy duration ≤3 months occurred in 15.1%, FOLFIRINOXm was used in 74.4%. Concerning treatment strategy, patients received neoadjuvant (47.8%), adjuvant (37.5%) and perioperative (14.7%). Median follow-up time was 32.5 months. Overall survival was 39 months (95% CI: 31.9-46.1). Patients who received less than 3 months of chemotherapy had inferior survival (29.0 vs 48.0 months, p = 0.01) compared to >3 months. Regarding FOLFIRINOX chemotherapy, patients who received neoadjuvant treatment had inferior prognosis compared to adjuvant FOLFIRINOX (37.0 vs 65.0, p = 0.02). Neoadjuvant therapy was not associated with positive margins or post-operative complications. In Cox multivariate analysis (adjusted for ECOG, resectability classification, Ca19-9 levels), adjuvant FOLFIRINOX compared to neoadjuvant FOLFIRINOX was associated with 69% reduction in risk of death (95% CI: 0.09-0.95); regarding chemotherapy duration, patients who performed > 3 months had 88% reduction in risk of death (95% CI: 0.08-0.73).

Conclusions: In this retrospective unicentric analysis in non-metastatic PDAC patients who were submitted to surgery the duration of total chemotherapy ≤3 months and neoadjuvant FOLFIRINOX were associated with worst survival.

Corresponding author: Italo Barradas e Silva Borges (e-mail: [e-mail]).