Borderline Resectable Pancreatic Cancer: Impact on Neoadjuvant Response Post Integration of MRI Guided Adaptive Radiation Therapy

The optimal neoadjuvant therapy regimen for patients with borderline resectable pancreas cancer (BRPC) remains to be defined, with a recent ALLIANCE study reporting that chemotherapy alone prior to resection is an acceptable standard of care. However, pathologic differences in response between patients receiving chemotherapy alone and chemotherapy with radiation with stereotactic technique is not clear. In this study, we sought to compare differences in pathologic outcomes between patients undergoing surgery in 2018 compared with 2021 at our comprehensive cancer center, after the new data of chemotherapy alone had been reported and after our center integrated stereotactic MRI guided online adaptive radiotherapy (SMART).Newly diagnosed BRPC patients were included on this IRB approved study if they were treated on our institutional clinical pathway with initial chemotherapy (FOLFIRINOX or Gemcitabine based) followed by 5 fraction stereotactic body radiation therapy (SBRT) with the intention of primary tumor resection. After surgical resection, tumor response was classified by the Tumor Regression Grading (TRG) System of the College of American Pathology on a scale from 0 (complete response) to 3 (poor response).In 2018 when patients were treated on a conventional Linac, the median SBRT dose was 40.5 Gy compared with 46.1 Gy in 2021 after SMART integration. In 2018, 54 BRPC patients were treated and 52% were explored. Of those, 72% were resected with a 95% (19/20) rate of R0 resection. In 2021, 66 BRPC patients were treated and 45% were explored. Of those, 74% were resected with a 100% (22/22) rate of R0 resection. In 2018, pathological results showed that 55% (11/20) had lymphovascular invasion (LVI) and 90% (18/20) had perineural invasion (PNI) with a median tumor size of 2.5 cm. The average lymph node ratio in 2018 was 0.06 in 2018 and 0.05 in 2021. In 2021, pathological results showed that 36% (8/22) had LVI and 64% (14/22) had PNI with a median tumor size of 2.2 cm. In 2018, 43% of surgeries required portal vein (PV) resection compared with 27% in 2021. In 2018, of those patients who underwent surgery, 65% (13/20) received both chemotherapy and SBRT compared to 10% (2/20) with chemotherapy alone. In 2021, 73% (16/22) received chemotherapy and SBRT prior to surgery compared with 27% (6/22) who received chemotherapy only. Patients who received chemotherapy only (n = 8) had an average TRG of 2.1 compared to the patients receiving combination therapy (29) with an average TRG of 1.8.This data suggests that higher ablative dose delivery with SMART following systemic therapy may be associated with improved pathologic outcomes, with less LVI, PNI, portal vein resection and improved TRG scores. Further prospective study is needed to confirm improved pathologic outcomes with SMART and to optimize patient selection regarding which patients benefit the most from the combination of chemotherapy and SBRT.