Definitive Radiotherapy for Locally Advanced Unresectable Pancreatic Cancer: Historical Review, Current State and Future Directions.

Based on available Level 1 evidence, standard dose conventional chemoradiation does not improve survival in patients with locally advanced pancreas cancer (LAPC), thus chemotherapy remains the only widely accepted therapy. Yet prognosis remains poor, and despite the negative trial outcomes, most would contend that the addition of radiotherapy does confer benefit in a subset of patients with LAPC. This work reviews the published data, then discusses several key considerations for designing radiotherapy trials in LAPC including choosing clinically meaningful patient-centered endpoints, optimizing patient selection and standardizing target volume delineation. Lastly, we review several promising single arm studies on dose-escalated radiotherapy in LAPC which have paved the way for upcoming Phase III randomized trials assessing this strategy.