Patterns of Locoregional Failure After Ablative 5-Fraction Stereotactic MR-Guided on-Table Adaptive Radiation Therapy for Pancreatic Cancer

SBRT for pancreatic ductal adenocarcinoma (PDAC) is routinely delivered with non-ablative dose to only gross disease resulting in locoregional failure (LRF) rates of >50%, most commonly near the celiac artery (CA) and/or superior mesenteric artery (SMA). It is unclear whether an alternative approach of prescribing ablative dose to gross disease plus elective coverage prevents and/or delays LRF. The study objective was to describe the incidence and anatomic distribution of LRF using this treatment approach.A single institution retrospective analysis was performed of non-metastatic PDAC patients who received ablative stereotactic MR-guided on-table adaptive radiation therapy (A-SMART) on a 0.35T MR-Linac from 2018-2022. Median prescribed dose was 50 Gy/5 fractions. Elective coverage (EC), including a margin around the primary tumor, CA, and SMA, to 33-35 Gy/5 fractions became routine in 2019 using a simultaneous integrated boost; the porta hepatis was not routinely covered. LRFs were contoured and defined as out-of-field (OOF), marginal (M), or in-field (IF) if >80%, 20-80%, or <20% of it was outside of the most peripheral prescription isodose line.One hundred four patients were evaluated (87% head tumors). 94% had induction chemotherapy (median 4 months), usually FOLFIRINOX (66%) or gemcitabine/nab-paclitaxel (27%). 88% received EC. Median GTV, CTV, PTVgrosstumor, and PTVelective volumes were 29 cc, 90 cc, 64 cc, and 127 cc, respectively. 16 patients (15%) had LRF after a median of 17 months (range: 2.4-30.8) from A-SMART; 13 had scans available for delineating LRF. Median follow-up from A-SMART for the entire cohort vs. LRF was 12 vs. 24 months. LRF involved the primary tumor (31%), retroperitoneal lymph nodes (25%), SMA (19%), porta hepatis (19%), and CA (6%). LRF was OOF, M, or IF in 30.8% (n = 4), 61.5% (n = 8), and 7.7% (n = 1). Distance from the 3 SMA failures to SMA origin was 10 cm (EC used), 9.3 cm (EC used), and 3 cm (no EC). The 1 CA failure involved the CA origin (no EC). Median mean, maximum, and minimum dose of the contoured LRF region on the original plan was 33.3 Gy (range: 9.7-50.3 Gy), 56 Gy (range: 44.2-71.4 Gy), and 11.4 Gy (range: 1.2-22.7 Gy), respectively. Median V20, V25, V30, V35, and V40 of the contoured LRF was 84.3% (range: 16.1-100%), 69.2% (range: 12.5-99.7%), 57.5% (range: 9.3-95.5%), 41.2% (range: 6.8-84.0%), and 32.7% (range: 4.8-71.8%).This study represents the first patterns of LRF analysis after ablative 5-fraction SBRT for PDAC. Although EC is not currently endorsed by published pancreas SBRT guidelines, our low LRF incidence especially involving the CA/SMA demonstrates that EC should be considered, even when delivering ablative dose. Furthermore, given that nearly all LRF were M or OOF we have considered expanding our institutional elective volumes. While the optimal EC dose is uncertain, 33-35 Gy appears effective in limiting IF LRF and therefore has been standardized within ongoing ablative SBRT trials for PDAC at our institution.