Initial Dosimetric Outcomes and Treatment Related Toxicities Using Stereotactic MRI-Guided Radiation Therapy (SMART) for Unresectable Pancreatic Cancer at a Single Institution

Abstract

High dose stereotactic body radiotherapy (SBRT) may offer improved disease outcomes for locally advanced pancreatic cancer but treatment delivery remains a challenge due to tumor proximity to organs-at-risk (OAR) and daily, anatomic variability. Stereotactic MRI-guided adaptive radiation therapy (SMART) with real-time tumor tracking allows for improved dose delivery to disease targets and OAR sparing by accounting for anatomic changes with each treatment. This study reports initial dosimetric outcomes and treatment related toxicities in unresectable pancreatic cancer patients treated using SMART. Ten patients with unresectable, locally advanced pancreatic cancer were treated on a MR-guided linear accelerator using real-time tumor tracking and motion management. A plan was generated for each patient after initial CT and MR-simulation. At each treatment, MR imaging was obtained for the daily anatomy and the initial (unadapted) plan was compared to obtain a predicted dose coverage of tumor volumes and OAR constraints using a prescribed dose of 50 Gy in 5 fractions. If OAR constraints were not met or PTV coverage was inadequate, an adaptive plan was generated based on the anatomy imaged on the day of treatment. Goal PTV coverage was 95% of the volume at 100% of prescription dose, however, this was subject to hard OAR constraints and plans were optimized for best PTV coverage within an acceptable OAR dose. For each adaptive plan generated, the delivered dose for that fraction was compared to the predicted dose from the initial plan. Only toxicities grade 3 or higher were considered for inclusion. At time of analysis, from June 2018 to February 2019, a total of 46 fractions were delivered to ten patients. Of the 46 treatments, 5 were with the initial, unadapted plan and 41 were adaptive. Due to intra-fraction adjustments that occurred during 6 treatments, only 35 adaptive plans were included for analysis. When comparing the performance of the initial plan on the daily updated MR anatomy, adaptive planning led to improved coverage of both PTV (86.36% vs. 73.15% at 100% of prescribed dose) and CTV (95.97% vs 89.59% at 95% of prescribed dose). Unadapted plans were much more likely to exceed OAR constraints, with 27 of 35 (77%) unadapted fractions predicted to violate prescribed duodenal, stomach, or small bowel constraints compared to 2 of 35 (6%) of adapted fractions. Moreover, 16/35 (46%) of unadapted fractions violated constraints for 2 of 3 abdominal OARs and 5/35 (14%) violated constraints for all 3 compared to none for adapted fractions. No grade 3 toxicities were reported in any of the treated patients. Stereotactic adaptive MRI-guided radiotherapy led to improved tumor volume coverage and reduced dose to abdominal OARs in patients with locally advanced pancreatic cancer with no grade 3 or higher toxicities. Prospective studies examining disease outcomes and treatment related toxicities are ongoing.