Estimation of Cumulative Organ Maximum Dose and Confidence Intervals for MRI-Guided Adaptive Radiotherapy of Abdominal Cancer

Abstract

<h3>Purpose/Objective(s)</h3> The maximum dose (Dmax), e.g., D0.03cc (dose to 0.03cc volume), of adjacent organs at risk (OARs) is a primary dose-limiting constraint in MRI-guided adaptive radiotherapy (MRgART) of abdominal cancer. We utilized inverse consistency error (ICE) maps to estimate voxel-wise uncertainties in deformable image registration (DIR) based dose accumulation (DDA) and confidence intervals in cumulative OARs Dmax during MRgART for pancreatic cancer. <h3>Materials/Methods</h3> Motion-average reference (first fraction) and subsequent daily MRIs, collected in MRgART for five pancreatic cancer patients treated with 33 Gy in 5 fractions on a 1.5T MR-Linac, were registered using a free-form DIR algorithm based on feature similarity scoring metrics and were used to accumulate daily doses. Forward and reverse DIRs were performed, and ICE maps were calculated in the reference image. The correlation between ICE and actual registration error (RE) was assessed by identifying anatomical landmarks (63) in a reference-daily image pair and measuring the landmark REs (after forward-DIR) and ICEs (after forward and reverse DIRs). To account for the deformation vector field spatial uncertainty affecting the DDA, for each voxel in the reference image we associated a cloud of dose grid points centered at the voxel landing coordinates in the daily image with a radius proportional to the ICE length. We considered that the cloud would encompass the "true" registration point with a high likelihood. The uncertainty in the dose mapped to each voxel from each fraction was determined as the standard deviation of the grid point doses within the cloud. The maxima and minima of the dose distributions were computed from the cumulative uncertainties, and confidence intervals for Dmax were determined. <h3>Results</h3> The measured REs and ICEs for landmarks indicated a positive correlation between these errors (Pearson's correlation coefficient r=0.795, p-value=7.04 × 10⁻¹⁵), RE being about twice ICE. The ICEs averaged 1.5 mm and 2.5 mm in the duodenum and stomach. For the duodenum, cumulative D0.03cc and D1cc at the end of treatment ranged from 85.7% to 100.4% of the plan constraint value (confidence intervals included). The uncertainty intervals were between 1.1% and 2.2% in four cases and approximately 7% for the fifth case. Cumulative D0.03cc in the stomach varied from 89.4% to 102.8%, with uncertainty intervals that extended from 2.5% to 6.4%. All Dmax lower limits were below 100%. <h3>Conclusion</h3> Voxel-wise uncertainties in DIR-based dose accumulation during MRgART of abdominal cancer can be estimated using an ICE-based technique. The derived confidence intervals for cumulative Dmax (D1cc or D0.03cc) of OARs (the duodenum and stomach) can be utilized to guide daily dose adaptation throughout MRgART.