Neoadjuvant stereotactic body vs conventionally fractionated radiation therapy for borderline resectable and locally advanced pancreatic cancer: a propensity score–matched analysis

Background Stereotactic body radiation therapy (SBRT) is increasingly used in neoadjuvant chemoradiotherapy (NCRT) for borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PC), but head-to-head data on SBRT vs conventionally fractionated radiation therapy (CFRT) remain limited. We compared clinical and pathological outcomes of SBRT vs CFRT in BR/LA PC. Methods We retrospectively analyzed 312 patients with BR/LA PC who received NCRT followed by margin-negative (R0)/margin-positive surgery at 3 high-volume academic centers (2011–2021). To reduce selection bias, 1:1 propensity score matching (PSM) was applied based on baseline clinical variables. The primary outcome was overall survival (OS), and the secondary outcome was clinical and pathological response to NCRT. Results Of 312 patients, 177 (56.7%) received SBRT and 135 (43.3%) received CFRT. Before PSM, significant differences were observed in patient age, neoadjuvant chemotherapy regimen, and duration of the preoperative interval. After PSM, 180 patients were matched, with no significant differences in pretreatment variables between groups. Clinical and pathological outcomes were similar between the matched cohorts, including complete/near-complete pathological response rates (36.7% vs 45.6%; P =.56), node-positive disease (32.2% vs 36.7%; P =.53), and R0 resection rates (80.0% vs 82.2%; P =.70). The median OS was not significantly different (27.2 vs 40.6 months; P =.70). Patients in the SBRT cohort were more likely to receive adjuvant therapy than those in the CFRT cohort (60.0% vs 38.9%; P =.007). In subgroup analyses restricted to patients treated with neoadjuvant FOLFIRINOX (FFX), SBRT was associated with a significantly longer OS among those presenting with markedly elevated pretreatment carbohydrate antigen 19-9 (CA19-9) levels (≥1500 U/mL) (29.8 vs 12.1 months; P =.02). Conclusion Neoadjuvant SBRT achieves oncologic outcomes comparable with CFRT in BR/LA PC and is associated with greater adjuvant therapy use. A potential survival signal for SBRT in patients receiving FFX with CA19-9 of ≥1500 U/mL is hypothesis generating and warrants validation and formal interaction testing.