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Response to Neoadjuvant Therapy and Its Impact on Survival in Resected Pancreatic Cancer
Katelin A. Mirkin*, Erin K. Greenleaf, Christopher S. Hollenbeak, Joyce Wong
Department of Surgery, Hershey Penn State Medical Center, Hummelstown, PA

Background:
Surgical resection and systemic therapy offers the only hope for long-term survival in pancreatic cancer. Neoadjuvant therapy (NAT) has been increasingly employed to optimize outcomes; however, little is known about its impact on pathologic response. This study evaluates the response to NAT and its impact on survival in resected pancreatic cancer.

Methods:
The National Cancer Data Base (2003-2011) was retrospectively reviewed for patients with clinical stages 1-3 pancreatic carcinoma who underwent NAT and surgery vs. surgery alone. Response to NAT, determined by comparison of clinical with pathologic staging, was classified as downstaged, no change, or upstaged. Univariate, Kaplan-meier, and multivariate analyses using Weibull model were performed.

Results:
11,989 patients who underwent NAT and surgery and 6,338 patients who underwent surgery alone were included. With NAT, 362 (3%) were downstaged, 7,007 (58%) had no change, and 4,620 (39%) progressed to a higher stage. Patients who were downstaged tended to be younger, male, have less comorbidities, and higher clinical stage disease, as compared to those who had no change in stage, or progressed despite NAT. Of the NAT cohort, 9,328 (78%) had evaluable therapy information: 4,267 (46%) underwent neoadjuvant chemotherapy (NAC) and 5,061(54%) underwent neoadjuvant chemotherapy and radiation (NACR). Neoadjuvant chemotherapy and NACR seemed to afford similar median survival in clinical stage I and II disease. In clinical stage III disease, NACR extended median survival over NAC (16.4 vs. 11.9 months in those downstaged, 16.3 vs. 13.7 months in no change, and 14.4 vs. 11.1 months in those upstaged, respectively). On multivariate analysis, utilization of NAT was associated with a survival benefit (0.82 HR with NAC and 0.73 HR with NACR), as compared to surgical resection alone. Downstaging of disease afforded a 13% lower hazard of mortality up to 5 years, as compared to no change, while upstaging demonstrated a 22% higher hazard of mortality. Other factors contributing towards a worse prognosis included older age (>70 years), undergoing a whipple procedure, having positive margins and higher stage disease, p<0.05, all.

Conclusion:
The majority of patients treated with NAT do not experience a change in stage, despite therapy. However, those who respond to NAT or remain the same stage experience a survival benefit over those who experience disease progression. Neoadjuvant chemotherapy appears to confer similar survival benefits to neoadjuvant chemoradiation in early stage disease.


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