Establishing the Aortic Maximum Tolerated Dose (MTD) for Ablative 5-Fraction Stereotactic MR-Guided Adaptive Radiation Therapy (SMART)

Abstract

Stereotactic MR-guided adaptive radiotherapy (SMART) can facilitate the safe delivery of ablative dose (BED > 100 Gy10) for inoperable pancreas cancer while sparing gastrointestinal (GI) OARs. Initially restricted to small volume pancreatic targets, SMART has now been expanded to provide ablative elective nodal irradiation (ENI). With this evolution, the proximity of the aorta to the ENI region becomes a concern. Given that the aortic maximum tolerated dose (MTD) for an ultra-hypofractioned course is poorly understood, our working hypothesis is that the MTD for aortic toxicities within the first year after a 5 fraction SMART course is > 52.5 Gy (Dmax). We tested this on our in-house clinical datasets.Twenty-nine inoperable pancreatic cancer patients were treated with 50 Gy in 5 fractions daily (QD) SMART course from April 2019 to March 2020. All patients underwent adaptive radiotherapy in which the dose was minimized to GI OARs, but no intentional aortic sparing was undertaken. For this study, the cumulative dose from all 5 SMART fractions was summed onto a TRUFI MR fractional scan (i.e., fraction 1). To this end, a rigid transformation was performed from each fractional scan (fraction 2-5) to fraction 1 frame of reference (FOR) based on alignment of aorta adjacent to the PTV. Fractional dose was transformed to fraction 1 FOR followed by summation. A contouring ring (2 cm in SI, 3 cm in AP/LR from PTV) was delineated. The aorta was segmented within the contouring ring. The aortic wall (AW) was delineated based on reported variable thickness of 1-2.5 mm in the literature on TRUFI MR sequence, and denoted as AW#mm.The median follow-up of patients was 17.4 months from SMART. 90% of patients (27 of 29) received ENI, typically including a 5-10 mm margin around celiac axis and superior mesenteric artery. Using the following maximum aortic dose parameter (Dmax/D0.03cc/D0.05cc/D1cc), the respective mean ± SD values in Gy were 56.7 ± 6.1/55.1 ± 6.6/49.3 ± 7.5/44.2 ± 8.3 (AW1mm), 56.7 ± 6.1/55.2 ± 6.6/51.1 ± 7.6/48.0 ± 8.0 (AW1.63mm), 56.9 ± 6.0/55.5 ± 6.4/51.8 ± 7.3/49.2 ± 7.6 (AW2mm), 56.8 ± 6.2/55.4 ± 6.6/51.8 ± 7.5/49.6 ± 7.8 (AW2.5mm). For D5cc/D10cc the respective mean ± SD dose in Gy was 13.5 ± 8.1/3.1 ± NA (AW1mm), 28.0 ± 8.0/8.1 ± 7.0 (AW1.63mm), 33.0 ± 8.6/14.4 ± 10.2 (AW2mm), 35.9 ± 9.3/21.3 ± 9.6 (AW2.5mm). No grade 3 or higher toxicities were observed during this follow-up period. 83% of patients (24 of 29) had Dmax > 52.5 Gy; 48% of patients (14 of 29) had D1cc > 47.5 Gy; 48% of patients (14 of 29) had D0.5cc > 50.4 Gy for all AW thicknesses. 72% (21 of 29), 59% (17 of 30) and 28% (8 of 29) of patients had aorta Dmax greater than 53.5 Gy, 55 Gy, and 60 Gy, respectively.An aorta Dmax of 53.5 Gy in 5 fractions was found to be safe for pancreatic cancer patients receiving daily SMART (n = 21 patients)-an increase from the RTOG 0813 MTD limit (i.e., 52.5 Gy). For ablative stereotactic pancreatic patients with inclusion of ENI, aorta dose should be tracked for further understanding of the aortic MTD.K.E. Mittauer: Research Grant; ViewRay Inc. Honoraria; ViewRay Inc. Travel Expenses; ViewRay Inc. Partnership; MR Guidance LLC.R. Herera: None. T. Romaguera: None. D. Alvarez: None. M.P. Mehta: None. A. Gutierrez: None. M.D. Chuong: Research Grant; ViewRay, AstraZeneca. Honoraria; ViewRay, Sirtex, Accuray. Speaker's Bureau; ViewRay, Sirtex, Accuray. Advisory Board; ViewRay, Advanced Accelerator Applications. Travel Expenses; ViewRay, AstraZeneca, Accuray; Particle Therapy Cooperative Group. Manages the operations and activities within the proton center; Miami Cancer.