Neoadjuvant Stereotactic Ablative Radiotherapy for Pancreatic Ductal Adenocarcinoma

Pancreatic cancer (PC) is expected to be the third leading cause of cancer death in Canada in 2019 \[1\]. Localized pancreatic cancer may be classified as resectable, borderline resectable, or locally advanced. To date, radical surgical resection and adjuvant treatment provide the greatest chance of long-term disease control and overall survival \[2,3\]. Despite this favourable group, the five-year survival rates are approximately 20% \[4\]. Neoadjuvant therapy (NAT) for resectable pancreatic cancer (RPC) has been widely accepted for the management of borderline resectable PC (BRPC) to increase the likelihood of achieving R0 resection \[4-7\]. However, to date, NAT for RPC is still an area of debate due to the lack of large prospective randomized controlled trials that compare this technique to surgery plus adjuvant therapy. Stereotactic ablative radiation therapy (SABR) uses modern radiotherapy planning and targeting technologies to precisely deliver larger, ablative doses of radiotherapy in 1-8 fractions. The role of SABR in RPC has yet to be fully established. The typical goal of radiation therapy in the neoadjuvant setting is to improve local control and increase R0 resection rates. However, there are still concerns about the timing of surgery after SABR and any implementation should be evaluated for safety. Treatments inherently changes the tumour and can cause immunomodulatory effects. SABR has anti-neoplastic effects both directly on the tumour and by its interactions with the immune system. In addition to the direct DNA damage, it is felt that SABR also increases T-cell priming, antigen production and presentation. Pancreatic cancer's dense, collagen rich stroma has prevented patients from receiving the same benefits of checkpoint inhibition that have been achieved in other cancer sites.