Magnetic resonance (MR) image guidance holds promise for enhancing the safety of high-dose, short-course radiation therapy for pancreatic cancer that cannot be surgically removed. This study investigated the safety of Stereotactic MR-Guided On-table Adaptive Radiation Therapy (SMART), delivered in 5 fractions, for patients with locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC).
This phase 2, multi-center trial enrolled patients with LAPC or BRPC who had received at least 3 months of chemotherapy without their cancer spreading to distant sites. Treatment was delivered using a 0.35T MR-guided radiation system, with a prescribed dose of 50 Gray in 5 fractions. The primary goal was to assess the occurrence of severe acute gastrointestinal (GI) side effects (grade ≥3) directly caused by SMART.
A total of 136 patients, with a mean age of 65.7 years (ranging from 36 to 85), participated in the study between January 2019 and January 2022. The majority had tumors in the head of the pancreas (66.9%). The most common initial chemotherapy regimens were (modified)FOLFIRINOX (65.4%) and gemcitabine/nab-paclitaxel (16.9%). The average CA19-9 level, a tumor marker, before SMART treatment was 71.7 U/mL (ranging from 0 to 468). Notably, adaptive replanning, where the treatment plan is adjusted based on the daily anatomy visible on the MR images just before treatment, was performed in 93.1% of all treatment sessions. Patients were followed for a median of 16.4 months from diagnosis and 8.8 months from SMART. Acute severe GI toxicity possibly or probably related to SMART occurred in 8.8% of patients, including two post-operative deaths potentially linked to SMART in patients who underwent surgery. Critically, there were no cases of acute severe GI toxicity definitively attributed to SMART. The one-year overall survival rate from the time of SMART was 65.0%.
In conclusion, this study successfully met its primary safety endpoint. Ablative 5-fraction SMART, guided on high-precision MR imaging, did not result in any definitively attributable acute severe GI toxicity. However, while the role of SMART in post-operative complications remains unclear, caution is advised when considering surgery, particularly vascular resection, following SMART. Ongoing follow-up is essential to fully evaluate long-term side effects, quality of life, and the lasting effectiveness of this treatment approach.
