Investigation of Isotoxic Dose Escalation and Plan Quality with TDABC Analysis on a 0.35 T MR-Linac (MRL) System in Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided Radiation Therapy (MRgRT) for Primary Pancreatic Cancer

Abstract

This study investigates plan quality generated by an MR-Linac (MRL) treatment planning system (TPS) for 5-fraction stereotactic body radiation therapy (SBRT) of primary pancreatic cancer (PCa). In addition, an isotoxic dose escalation was investigated with the MRL TPS based on stereotactic MR-guided adaptive radiation therapy (SMART) trial constraints. A clinical workflow was developed for adaptive and non-adaptive treatments with the MRL, on which a time-driven activity-based costing (TDABC) analysis was performed to quantify clinical efficacy. Fifteen PCa patients previously treated with a conventional Linac were retrospectively re-planned for this study. Three plans were generated for each patient using the original prescription dose (PD) and organ at risk (OAR) constraints (Plan 1), following SMART trial's OAR constraints but with the original PD (Plan 2), starting with Plan 2, following an isotoxic dose escalation strategy where the dose was escalated until any one of the SMART trial's OAR constraints reached its limit (Plan 3). Conformity index (CI) and the ratio of the 50% isodose volume to PTV (R50%) conformity metrics were calculated for all 45 MRL plans, in addition to standard dose-volume indices. Forty-five MRL plans were created which met their respective dosimetric criteria described above. For Plan 1, the MRL TPS successfully achieved equivalent or lower OAR doses while maintaining the prescribed PTV coverage for the 15 plans. A maximum dose to the small bowel was reduced on average by 4.97 Gy (range: 1.11-10.58 Gy). For Plan 2, the MRL TPS successfully met all SMART trial OAR constraints while maintaining equivalent PTV coverage. For Plan 3, the MRL TPS was able to escalate the prescription dose from the original 25-33 Gy by, on average, 36 Gy (range: 15-70 Gy), and dose to the PTV was successfully escalated to at least 50 Gy for all 15 plans. These achievements were made possible, in part, due to the omission of the ITV afforded by the MRL's real-time target tracking technology and sharper dose penumbra due to its unique dual-focus MLC design. The 0.35T MRL TPS can generate plans that are equivalent to conventional Linac-based plans for SBRT of PCa. Through analyzing Plan 2 and 3 strategies, and due to the real-time target localization capabilities of the MRL system, increased OAR sparing and/or target dose escalation are possible.

Keywords: MR-Linac; MRgRT; dose escalation; pancreatic cancer.

Figure 1

Depicts a sample patient picked from the group for Plan 1 (A,D), Plan 2 (B,E), and Plan 3 (C,F). Note that for this sample, Plan 3 escalation dose was 77 Gy to 95% of PTV_High.

Figure 2

Depicts process map for MRgRT simulation. The times depicted are approximated from data gathered by VCU health staff.

Figure 3

Depicts process map for MRgRT non-adaptive treatment. The times depicted are approximated from data gathered by VCU health staff.

Figure 4

Depicts a process map for adaptive MRgRT. The times depicted are approximated from data gathered by VCU health staff.