# Ablative Five-Fraction CT Versus MR-Guided Stereotactic Body Radiation Therapy for Pancreatic Cancer: In Silico Evaluation of Interfraction Anatomic Changes as a Rationale for Online Adaptive Replanning

## TL;DR

This study shows that using MRI-guided adaptive radiation therapy is better than CT-guided methods for reducing organ damage during high-dose pancreatic cancer treatment.

## Contribution

First study to quantify gastrointestinal organ constraint violations in ablative pancreatic SBRT with and without online adaptive replanning.

## Key findings

- 96% of fractions exceeded at least one gastrointestinal organ at risk constraint without online adaptive radiation therapy.
- SMART significantly reduced dose to the duodenum compared to non-adaptive CT-guided plans.
- No significant differences in target coverage between CT-guided and SMART plans.

## Abstract

Prospective data has now demonstrated superior outcomes for locally advanced pancreatic cancer patients treated with ablative rather than non-ablative stereotactic body radiation therapy (SBRT). MRI guided, online adaptive radiotherapy (oART) strategies have been employed to limit radiation doses and toxicity to organs at risk (OAR) during ablative SBRT. Given the paucity of cancer centers with oART capability, we compared non-adapted, CT-guided radiation plans with MR-guided plans using oART across all treatment fractions during ablative SBRT. Plan comparison was completed using pre-treatment MRI imaging and demonstrated significantly higher doses to organs at risk in the absence of oART. These results suggest the need to limit ablative SBRT to centers with oART capability.

Background/Objectives: Non-ablative stereotactic body radiation therapy (SBRT) is commonly employed for locally advanced pancreatic cancer (LAPC) using computed tomography-guided radiotherapy (CTgRT) without online adaptive radiation therapy (oART). The safe delivery of ablative SBRT has been demonstrated using stereotactic magnetic resonance-guided online adaptive radiation therapy (SMART). We performed an in silico comparison of non-adapted CTgRT versus SMART to better understand the potential benefit of oART for ablative pancreatic SBRT. Methods: We retrospectively evaluated original and daily adapted SMART plans that were previously delivered for 20 consecutive LAPC cases (120 total plans across all patients) treated on a 0.35 T MR-linac prescribed to 50 Gy (gross disease) and 33 Gy (elective sites) simultaneously in five fractions. Six comparative CTgRT plans for each patient (one original, five daily treatment) were retrospectively generated with the same prescribed dose and planning parameters as the SMART plans assuming no oART availability. The impact of daily anatomic changes on CTgRT and SMART plans without oART was evaluated across each treatment day MRI scan acquired for SMART. Results: Ninety percent of cases involved the pancreatic head. No statistically significant differences were seen between CTgRT and SMART with respect to target coverage. Nearly all (96%) fractions planned on either CT or MRI platforms exceeded at least one GI organ at risk (OAR) constraint without oART. Significant differences favoring SMART over non-adaptive CTgRT were observed for the duodenum V35 Gy ≤ 0.5 cc (34.2 vs. 41.9 Gy, p = 0.0035) and duodenum V40 Gy ≤ 0.03 cc (37 vs. 52.5 Gy, p = 0.0006) constraints. Stomach V40 Gy trended towards significance favoring SMART (37 vs. 40.3 Gy, p = 0.057) while no significant differences were seen. Conclusions: This is the first study that quantifies the frequency and extent of GI OAR constraint violations that would occur during ablative five-fraction SBRT using SMART vs. CTgRT. GI OAR constraint violations are expected for most fractions without oART whereas all constraints can be achieved with oART. As such, these data suggest that oART should be required for ablative five-fraction pancreatic SBRT.