Simple SummaryThe very poor prognosis and the absence of radical treatment options in cases of unresectable “locally advanced pancreatic cancer (LAPC)” focus its management on palliation. An “overall survival (OS)” benefit has been shown with new systemic therapy agents; however, not all patients are good candidates for systemic treatments at diagnosis, and LAPC is often associated with a high symptom burden that greatly impacts patients’ quality of life. Studying dose optimization of radiation as an option for local progression cessation is therefore necessary. Research in this setting as opposed to other treatment sites is under-represented in the literature and the guidelines are based on very scarce data. We aim to present the outcomes of “stereotactic body radiotherapy (SBRT)” (ablative radiotherapy) vs. non-ablative radiotherapy through our patient population and the available data in the literature.AbstractWe studied the dose–local control (LC) relationship in ablative vs. non-ablative radiotherapy in a non-radical treatment setting of “locally advanced pancreatic cancer (LAPC)” by comparing our patients (n = 89) treated with SBRT on the CyberKnife unit vs. conventional radiation between January 2005 and January 2021, and by reviewing the literature. A systematic search was performed leveraging Medline for references on SBRT use in pancreatic cancer without date terms or language restrictions. A total of 3702 references were identified and the search was then repeated in Embase and the Cochrane database. Ultimately, 12 studies were eligible for inclusion, which either compared SBRT to conventional radiation, or SBRT use in dose escalation for primary LAPC in a non-neoadjuvant setting. Our cohort’s median overall survival was 152 days (CI 95%, 118–185); including 371 days (CI 95%, 230–511) vs. 126 days (CI 95%, 90–161) favoring SBRT,p= 0.004. The median time to local progression was 170 days (48–923) for SBRT vs. 107 days (27–489) for the non-ablative group. In our SBRT patients, no local progressions were seen with BED10> 60 Gy. Even when palliating LAPC, SBRT should be considered as an alternative to conventional radiation, especially in patients with a low disease burden. BED10≥ 60–70 Gy offers better local control without increasing toxicity rates. Less local progression may provide a better quality of life to those patients who already have a short life expectancy.