Radiotherapy in the management of PDAC, from past to present

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal forms of cancer, with a dismal survival rate. Therapeutic options are restricted in surgery for patients with resectable disease and in chemotherapy for those with unresectable disease. The potential benefits of radiotherapy (RT) or chemoradiotherapy (CRT) have been extensively investigated in both neoadjuvant and adjuvant settings in the management of patients with PDAC. Nevertheless, a substantial number of clinical trials have yielded conflicting findings, thereby rendering the impact of RT on patient survival and margin-negative (R0) resection inconclusive. A comprehensive examination of the historical evolution of RT in PDAC, encompassing the identification of both constraints and opportunities for advancement, is essential to establish RT as a promising therapeutic avenue for patients with PDAC. The aim of this review is to provide a synthesis of past clinical trials and future studies to elucidate the evolving role of RT in the management of PDAC as adjuvant and neoadjuvant CRT across different stages of the disease.