A Multi-Institutional Phase II Trial of Ablative 5-Fraction Stereotactic MR-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

Overview

abstract

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultra-hypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). METHODS: LAPC/BRPC patients were eligible for this multi-institutional single arm phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. 50 Gy in 5 fractions was prescribed on a 0.35 Tesla MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART. RESULTS: 136 patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and prior to SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 months and 8.8 months, respectively. The incidence of acute grade ≥ 3 GI toxicity possibly or probably attributed to SMART was 8.8%, including two postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥ 3 GI toxicity definitely related to SMART. 1-year overall survival from SMART was 65.0%. CONCLUSIONS: The primary endpoint of this study was met with no acute grade ≥ 3 GI toxicity definitely attributed to ablative 5-fraction SMART. While it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.