Predictors and survival for pathologic tumor response grade (TRG) in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy (SBRT).

Abstract

453 Background: Neoadjuvant therapy response correlates with survival in several gastrointestinal malignancies. Thus, we intensified our neoadjuvant approach to pancreas adenocarcinoma in part to induce greater response. Here we analyzed whether pre- and post- therapy CA19-9 or SUVmax correlated with College of American Pathology TRG at pancreatectomy and whether TRG associated with survival. Methods: After IRB approval, we identified BRPC and LAPC patients treated in our standardized pathway who underwent surgical resection with reported TRG (n = 81, median follow-up 30.8 months). Patients had baseline CA19-9, CT, endoscopic ultrasound, and FDG PET/CT then underwent multi-agent chemotherapy (79% with planned 3 cycles of GTX) followed by 5 fraction SBRT. They then underwent restaging CT, PET/CT, and CA19-9 prior to resection. Overall (OS) and progression free survival (PFS) were estimated and compared by Kaplan-Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, re-staging, and change in CA19-9 (16% with missing values or CA19-9 < 5 excluded) and SUVmax (14% with missing values or no hypermetabolism excluded). Results: Decrease in CA19-9 before and after neoadjuvant therapy correlated with improved TRG (p = 0.02) as did re-staging SUVmax (p < 0.01), though not decrease in SUVmax (p = 0.08). The TRG groupings had similar OS and PFS except the TRG 0 (complete response) group. Compared to TRG 1-3 patients (median OS 38.4 months, median PFS 17.8 months), the 6 patients with TRG 0 had no deaths (p = 0.05) and only 1 failure (p = 0.03). A group of 10 TRG 1 patients with only isolated tumor cells remaining had similar outcomes to the other TRG 1-3 patients. Conclusions: Pre-operative PET-CT and CA19-9 response correlate with neoadjuvant therapy response by TRG. Patients with complete pathologic response have superior outcomes. This provides rationale for further intensification of neoadjuvant therapy in BRPC and LAPC. Further work seeks to identify techniques to better select which BRPC and LAPC patients should undergo tumor resection.