Chemotherapy plus radiation, radiation dose and fractionation, and overall survival in patients with nonmetastatic pancreatic adenocarcinoma managed without surgery

Introduction The role of chemotherapy plus radiation and the optimal radiation therapy (RT) dose in the overall survival (OS) of patients diagnosed with pancreatic adenocarcinoma (PA) who did not undergo surgery is not well known. Our study aimed to assess the association of chemotherapy plus RT, total radiation dose (TD), and fractionation with the OS of these patients. Materials and methods We used the National Cancer Database and included patients diagnosed with non-metastatic pancreatic cancer between 2004 and 2023. Multivariable Cox analysis was used to assess the association of various factors with the OS of patients. Results Among the 63, 261 patients, 45, 838 received chemotherapy (CT), and 17, 423 received chemotherapy plus RT. Chemotherapy plus RT was associated with improved OS compared with CT alone (HR 0.71, 95% CI 0.69–0.72; p<0.001). The extended Cox model showed that the association between RT and mortality varied over follow-up with the apparent benefit attenuating at later time points. In the propensity score-matched analysis, chemotherapy plus RT was still associated with improved OS compared to chemotherapy alone (HR: 0.71, 95% CI: 0.69- 0.72; p<0.001). A 5-fraction stereotactic body radiation therapy (SBRT) with a total dose (TD) between 50 and 80 Gy was associated with improved OS compared with a 5-fraction SBRT with a TD between 30 and 49 Gy (HR 0.86, 95% CI: 0.76–0.97; p=0.01). The OS benefit of chemotherapy plus RT vs. CT was greater in patients diagnosed between 2014 and 2023 vs. 2004 and 2013 (HR: 0.65, 95% CI:0.63-0.67; p<0.001 vs. HR: 0.77, 95% CI: 0.75-0.79; p<0.001). The biologically effective dose (BED 10 ) categories of 100–151 and 90–99 Gy were associated with a better OS compared with the BED 10 category of 53.1–89 Gy (HR: 0.77, 95% CI: 0.70-0.86; p<0.001 and HR: 0.78, 95% CI: 0.67-0.91; p=0.006). Conclusions Chemotherapy plus RT was associated with improved overall survival compared to CT alone. However, the association varied over follow-up. A 5-fraction SBRT with a TD between 50 and 80 Gy was associated with improved overall survival. A higher BED 10 was associated with better OS than a lower BED 10 only in the modern chemotherapy era.