NEOADJUVANT RADIOTHERAPY IS ASSOCIATED WITH IMPROVED PATHOLOGIC OUTCOMES AND SURVIVAL IN RESECTED STAGE II-III PANCREATIC ADENOCARCINOMA TREATED WITH MULTI-AGENT NEOADJUVANT CHEMOTHERAPY IN THE MODERN ERA
Jonathan J. Hue2, Kavin Sugumar2, Jeffrey Hardacre2, John Ammori2, Luke Rothermel2, Jennifer Dorth2, Joel Saltzman2, Amr Mohamed2, J. Eva Selfridge2, David Bajor2, Jordan M. Winter2, Lee M. Ocuin*1
1Surgery, Atrium Health, Concord, NC; 2University Hospitals, Cleveland, OH
Introduction: Neoadjuvant chemotherapy (CT) is being utilized more frequently in patients diagnosed with localized pancreatic adenocarcinoma. The role of neoadjuvant radiotherapy (RT) remains undefined. We explored outcomes associated with neoadjuvant RT in combination with systemic CT in the modern era.
Methods: The National Cancer Database (2010-2016) was queried for patients with clinical stage II-III pancreatic adenocarcinoma who received multi-agent systemic neoadjuvant CT + RT prior to surgery. Demographics, pathologic outcomes, postoperative outcomes, and overall survival were compared by univariable and multivariable analysis.
Results: A total of 3,854 patients were included, of whom 2,236 received CT alone and 1,618 received CT + RT. On multivariable analysis, treatment at academic facilities (OR 1.22, 95%CI 1.03-1.43) and clinical T4 tumors (OR 1.85, 95%CI 1.38-2.48) were associated with a higher frequency of neoadjuvant RT, whereas pancreatic head lesions (OR 0.80, 95%CI 0.67-0.96) were associated with a lower frequency of neoadjuvant RT. The majority of patients (83.1%) treated with neoadjuvant RT received external beam radiotherapy (EBRT), and the remainder (16.9%) received stereotactic beam radiotherapy (SBRT). Overall, the median dose of RT was 4,500 cGy. Patients treated with CT + RT had a higher frequency of ypT0-T2 tumors (30.9% vs 19.1%), a lower rate of ypT3 tumors (58.1% vs 73.3%; all p<0.001), a lower rate of node-positive disease (33.4% vs 57.2%, p<0.001), and a lower rate of margin-positive resection (14.1% vs 21.2%, p<0.001). Patients treated with CT + RT had slightly higher rates of 90-day postoperative mortality (5.7% vs 3.5%, p=0.005). In the overall cohort, treatment with neoadjuvant CT + RT was associated with longer overall survival (30.0 vs 27.3 months, p=0.044), and remained associated with survival on multivariable analysis (HR 0.91, 95%CI 0.82-0.99). In the subset of patients treated with EBRT, patients with clinical T4 tumors had improved overall survival compared to CT alone when 90-day mortality was excluded (30.9 vs 27.3 months, p=0.026). In the subgroup of patients treated with SBRT, patients with clinical T3 tumors treated had improved overall survival compared to CT alone (35.0 vs 27.4 months, p=0.029), and improved to >10 months when 90-day mortality was excluded (38.6 vs 28.3 months, p=0.037).
Conclusions: In patients with stage II-III pancreatic adenocarcinoma, the addition of neoadjuvant radiotherapy to multi-agent neoadjuvant chemotherapy is associated with increased rates of node-negative and margin-negative resection as well as improved overall survival in patients who undergo surgery. This association appears to be driven by improved survival in patients with clinical stage T4 tumors treated with EBRT, and clinical T3 tumors treated with SBRT.
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