R. Bonate1, M. J. Awan2, M. E. Shukla2, S. Tarima3, H. A. Himburg2, J. Zenga4, and E. S. Paulson2; 1Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, 2Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, 3Medical College of Wisconsin, Milwaukee, WI, 4Department of Surgery, Medical College of Wisconsin, Milwaukee, WI
Purpose/Objective(s): Recently, we demonstrated the utility of daily quantitative MRI (qMRI) obtained during MR-guided radiotherapy (MRgRT) in detecting differential responses to radiotherapy (RT) in head and neck squamous cell cancer (HNSCC) patients. We investigate here whether biologically relevant tumor subregions, such as the tumor core, demonstrate differential responses on daily qMRI.Materials/
Methods: Seventeen HNSCC patients treated with hypo-fractionated MRgRT at 50-60 Gy in 15 fractions were included in the study (DEHART, NCT04477759). Five patients were treated with concurrent atezolizumab and twelve patients were treated with RT alone. Daily intravoxel incoherent motion (IVIM), variable flip angle SPGR, and CPMG sequences were acquired on a 1.5T MR-Linac in the idle time during adaptive plan generation. Median ADC, T1, T2, f, and Dslow (derived from b-values 150 and 550 s/mm2) values were extracted from core and shell contours derived as discrete percentage and fixed margin erosions of the physician-defined primary GTV (GTVp). Percent-volume core and corresponding shell contours of the GTVp were obtained via eroding the GTVp spherical diameter by 7.2%, 15.7%, 26.3%, and 41.5% and reconstituting the core and shell subregions. The fixed margin core and shell contours were generated by progressively eroding the GTVp contour by 3-12 mm at discrete 3mm margins. A manually defined posterior paraspinal muscle contour served as control. Mixed effects modeling was performed for each qMRI parameter with contour and treatment effects. The analysis was run on the full patient cohort. Results: ADC, Dslow, f, and T2 increased over the course of treatment with significant differences in each parameter detected in the GTVp between weeks 1 and 3 for all patients studied (max p=0.0179). Percent-volume based subregions demonstrated less consistency than fixed margins subregions. Dslow response was found to be statistically significant for a range of fixed margin cores between weeks 1 and 3 (p<0.0001 for 3mm, 6mm, 9mm, and 12mm erosions, hereon labeled E3, E6, E9, and E12 respectively). ADC response varied across fixed margin cores, with differences between most subregions normalizing over the length of treatment except for the very core of the tumor (E3-E9 p=0.0179 at week 1 and p=0.4458 at week 3; E3-E15 p=0.9798 at week 1 and p=0.0105 at week 3). Response in T2 varied between subregions, with outer shells of the tumor demonstrating significant response between weeks 1 and 3 (E3, E6 max p=0.0004) and inner subregions demonstrating no between weeks 1 and 3 (E12 p=0.5846, E15 p=0.6910). Conclusion: Discrete segmentation of the GTVp in HNSCC may reveal additional treatment response information when combined with daily qMRI. Responses in Dslow, f, and ADC suggest a microstructural response in all subregions of the tumor, with perfusion-related changes occurring in the tumor periphery. T2 differences across tumor subregions may reflect edema or inflammatory change in the tumor periphery.
