N. R. Suss1, M. S. Talamonti1,2, D. S. Bryan2, C. Wang1, K. M. Kuchta1, S. J. Stocker1, D. J. Bentrem3, K. K. Roggin2, D. J. Winchester1,2, R. Marsh1,2, R. A. Prinz1,2, M. S. Baker1,2 1NorthShore University HealthSystem,Department Of Surgery,Evanston, IL, USA 2University Of Chicago,Department Of Surgery,Chicago, IL, USA 3Feinberg School Of Medicine,Department Of Surgery,Chicago, IL, USA
Introduction: The benefit of adding radiation to adjuvant systemic chemotherapy in patients that have undergone a margin positive resection for early stage pancreatic cancer (PDAC) has not been well established.
Methods: We queried the National Cancer Database (NCDB) for 2004 through 2012 to identify patients with pathologic stage I-II PDAC of the pancreatic head who underwent pancreaticoduodenectomy and had a microscopic positive margin on final pathology (R1 resection). Kaplan-Meier, multivariable and cox regression modeling were employed to identify factors associated with radiation use and compare overall survival for patients receiving adjuvant chemotherapy with radiation (CRT) to those receiving adjuvant chemotherapy alone (ACT). Patients receiving neoadjuvant therapy and those who did not receive adjuvant chemotherapy were excluded.
Results: 1,310 patients met inclusion criteria. 255 (19.5%) were lymph node negative (Stages IA, IB, IIA) and 1,055 (80.5%) were node positive (Stage IIB). 897 (68.5%) patients received CRT, while 413 (31.5%) received ACT. Multivariable stepwise logistic regression identified younger age (OR 2.310, 95% CI [1.515, 3.521]), treatment in New England (OR 7.915, 95% CI [3.369,18.595]), and negative nodal status (OR 1.797, 95% CI [1.286, 2.511]) as independently associated with use of CRT. Cox modeling adjusting for age, sex, race, comorbid disease state, socioeconomic status (SES), insurance status, facility type and volume, surgery type, vascular abutment, pathological T stage, and nodal status, identified High SES (HR 0.717, 95% CI [0.609, 0.846]) and use of CRT (HR 0.828 95% CI [0.726, 0.944]) as independently associated with improved overall survival. Charlson score of one (HR 1.226 95% CI [1.069-1.406]) and node positivity (HR 1.547 95% CI [1.317, 1.817]) were independently associated with higher risk of mortality. Cox modeling stratified by stage demonstrated the benefit of radiation to be statistically significant in node positive patients only. Node positive patients undergoing CRT demonstrated a median survival of 17.1 months vs. 14.8 months for node positive patients undergoing ACT (p=0.001). In patients who were lymph node negative, there was no difference in overall survival with radiation (21.9 vs. 23.3 months, p=0.457) [Figure 1].
Conclusion: Addition of radiation to adjuvant chemotherapy confers a limited survival benefit over treatment with chemotherapy alone in patients having an R1 resection for lymph node positive pancreatic head cancer. Radiation offers no benefit for patients undergoing an R1 resection for disease that is node negative. Randomized trials are needed to better identify subgroups of PDAC patients for whom benefits of radiation justify the known risks.
