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

<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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, <i>p</i> = 0.0035) and duodenum V40 Gy ≤ 0.03 cc (37 vs. 52.5 Gy, <i>p</i> = 0.0006) constraints. Stomach V40 Gy trended towards significance favoring SMART (37 vs. 40.3 Gy, <i>p</i> = 0.057) while no significant differences were seen. <b>Conclusions:</b> 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.