Long-term outcomes by response to neoadjuvant chemotherapy or chemoradiation in patients with resected pancreatic adenocarcinoma

Ahmed Khattab, Sunita Patruni, Stephen Abel, Shaakir Hasan, Ethan B. Ludmir, Gene Finley, Dulabh Monga, Rodney E. Wegner, Vivek Verma


Background: Response of pancreatic adenocarcinoma to neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) may be associated with prognosis, but long-term outcomes based on response to neoadjuvant therapy have not been well evaluated to date.
Methods: The National Cancer Database was queried for patients with pancreatic adenocarcinoma receiving nCT/nCRT. To evaluate response to nCT/nCRT, comparisons were made from cT and cN stage to the respective post-neoadjuvant therapy ypT and ypN stages. Based on these comparisons, patients were classified as responders, progressors, or non-responders. Statistical analyses included estimation of survival using Kaplan-Meier analysis, as well as multivariable Cox proportional hazards modeling.
Results: Of 2,028 patients, 30% had a response, 32% progressed, and 38% had no response; 1% of patients experienced pathologic complete response (pCR). Responders were more likely to have received multi-agent chemotherapy (P=0.0001) as well as radiotherapy (RT) (P=0.02) in the neoadjuvant setting. Response to nCT/nCRT was also associated with a higher R0 resection rate (P=0.02). At a median follow-up of 49 months, median overall survival (OS) was higher in responders than non-responders or progressors (29.9 vs. 24.3 vs. 22.2 months, P<0.001). The mean OS for patients experiencing pCR was 55.5 months. On multivariable analysis, treatment response was independently associated with OS (P=0.02).
Conclusions: Response to nCT/nCRT independently predicts long-term outcomes following resection of pancreatic adenocarcinoma; higher rates of treatment response were observed for patients receiving neoadjuvant RT as well as neoadjuvant multi-agent chemotherapy. These results may have implications on strategies to improve response rates.