Abstract B038: Long-term outcomes following surgical resection in a three-center subset of a randomized phase II trial of dose-escalated radiotherapy for borderline resectable and locally advanced pancreatic cancer
Todd A . Aguilera, Parag Parikh, Jessica M. Frakes, Sal Almutar, Celina Chiodo, Neha Barrows, Sarah HoffeAbstract
Background:
Surgical resection following neoadjuvant therapy is associated with prolonged survival in borderline resectable and locally advanced pancreatic cancer (BRPC/LAPC), yet whether this reflects improved local disease control alone or identifies patients with intrinsically favorable disease biology remains uncertain. We evaluated the prognostic significance of successful conversion to surgical resection among patients treated on GRECO-2, a randomized phase II trial of dose-escalated stereotactic ablative radiotherapy (SAbR) with or without the superoxide dismutase mimetic rucosopasem.
Methods:
This retrospective subset analysis included patients treated at three participating GRECO-2 institutions. Overall survival (OS) and progression-free survival (PFS), the primary and key secondary trial endpoints, were estimated from randomization using Kaplan-Meier methods. Local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were evaluated as exploratory endpoints to characterize patterns of failure. To account for the time-dependent nature of surgery, outcomes were evaluated using Kaplan-Meier, landmark, and time-dependent Cox proportional hazards analyses adjusted for randomized treatment arm and baseline disease stage.
Results:
Among 77 randomized patients, 22 (29%) underwent surgical resection. All but two resections occurred within two months of randomization, whereas only 8 of 55 unresected patients (15%) experienced documented disease progression during the same interval, indicating that failure to proceed to surgery was not primarily explained by early metastatic progression. Compared with unresected patients, resection was associated with significantly improved OS and PFS (both P<0.001). In adjusted time-dependent Cox models, resection remained independently associated with improved OS (HR 0.29, 95% CI 0.14–0.59; P<0.001) and PFS (HR 0.33, 95% CI 0.18–0.63; P<0.001), with consistent findings in both 6- and 9-month landmark analyses. Exploratory analyses also demonstrated significantly improved LRFS and DMFS (both P<0.001). Despite these improvements, distant metastasis remained the predominant first site of failure irrespective of resection status, suggesting that resection delays rather than fundamentally alters recurrence patterns. Among resected patients, postoperative OS did not differ between randomized treatment arms.
Conclusions:
Successful conversion to surgical resection identifies a subgroup of patients with exceptional long-term outcomes following contemporary multimodality therapy for BRPC/LAPC. The persistence of improved survival after accounting for surgery timing, together with parallel improvements in local and distant disease control and the absence of differential postoperative survival by randomized treatment arm, suggests that successful surgical conversion is a clinical surrogate of favorable disease biology rather than simply a consequence of treatment timing or study-drug effect. AI was used in analysis of data and writing.
Citation Format:
Todd A . Aguilera, Parag Parikh, Jessica M. Frakes, Sal Almutar, Celina Chiodo, Neha Barrows, Sarah Hoffe. Long-term outcomes following surgical resection in a three-center subset of a randomized phase II trial of dose-escalated radiotherapy for borderline resectable and locally advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr B038.