Role of neoadjuvant radiation in downstaging patients with localized pancreatic cancer – analysis of the ncdb database

Background: Although the acceptance of neoadjuvant therapy for patients with localized pancreatic cancer is growing, there is not an accepted standard therapy. The use of neoadjuvant radiation therapy remains controversial. We sought to examine the role of neoadjuvant radiation on pathologic outcomes. Methods: Patients with stage I-II PC who received neoadjuvant therapy were identified from the National Cancer Database. Patients were classified by type of neoadjuvant therapy received: chemotherapy (nChemo) or chemotherapy and radiation (nC+XRT). Pathologic nodal status was classified as negative (ypN0) or positive (ypN1/N2). Margin status was classified as negative (ypR0) or positive (ypR1/2). Chi squared test was used to compare categorical variables and median test was used to compare continuous variables. The log rank test was used to compare survival and cox proportional hazards regression was used to model survival time. Results: Of the 2,132 patients identified, 1,071 (50%) received nChemo and 1,061 (50%) received nC+XRT. Demographic characteristics are summarized in Table 1. Neoadjuvant radiation was associated with a significant decrease in ypN1/N2 pathology (393/1061 patients (37%) vs. 624/1071 patients (58%), p < 0.001) and ypR1/2 (138/1061 patients (13%) vs. 188/1071 patients (18%), p = 0.004). Adjuvant therapy was administered to 487 (45%) of 1,071 patients who received nChemo and 326 (31%) of 1,061 patients who received nC+XRT (p < 0.001). The median overall survival (mOS) was 26 months, 32 vs. 23 months in ypN0 and ypN1/N2 patients, respectively (p < 0.001). The mOS for patients with ypR0 disease was 29 months, and 19 months for patients with ypR1/R2 disease (p < 0.001). In an adjusted proportional hazards model, ypN1/N2 disease and ypR1/2 disease was associated with a 1.36-fold (95%CI: 1.21-1.52, p < 0.001), and 1.68 (95%CI: 1.40-2.02, p < 0.001) increased risk of death, respectively. Conclusion: Patients treated with nC+XRT had higher rates of ypN0 disease and ypR0 margin status than patients treated with nChemo. Since both nodal disease burden and margin status are important prognostic factors, radiation therapy should be incorporated in neoadjuvant treatment regimens.