Background: Chemotherapy is required to improve the overall survival (OS) of patients with resectable pancreatic ductal adenocarcinoma (PDAC). Assessing the impact of chemotherapy dose density (DD) on survival is difficult as a result of confounding. The objective of this study was to determine the impact of chemotherapy DD on OS in patients with resectable PDAC.
Methods: This was a secondary analysis of SWOG 1505, a randomized phase 2 trial of perioperative chemotherapy in resectable PDAC. DD was defined as the percentage of chemotherapy dose received of the total planned. Two landmark time points for OS were used: after surgery and at 40 weeks (which encompassed the entire treatment period).
Results: Of the 102 eligible patients enrolled, 73 (71%) underwent surgery, and median preoperative chemotherapy DD was 89%. Patients with ≥85% DD had higher OS compared to those with <85% DD (median, 38.1 vs. 17.2 months; p = .039). Of the 82 patients who survived to 40 weeks postrandomization, 67 underwent surgery, and median DD for all perioperative chemotherapy was 67%. In this cohort, DD ≥70% was associated with better OS (median, 32.2 vs. 14.0 months; p = .017). Perioperative DD was not significantly associated with pathologic response, margin status, or lymph node negativity.
Conclusions: This is the first study to identify a prognostic association of chemotherapy DD with OS in patients undergoing perioperative chemotherapy and surgery for resectable PDAC. Patients who received ≥85% DD preoperatively and/or ≥70% DD perioperatively survived longer than those receiving a smaller proportion of protocol therapy.
Keywords: chemotherapy; dose density; pancreatic adenocarcinoma; surgery.
© 2025 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.