Differential Response in Quantitative MRI Parameters Detected in Head and Neck Cancer Patients Treated with Concurrent Immunotherapy during Hypo-Fractionated MR-gRT

Abstract

Recently, multiple clinical trials have demonstrated success of PD-1/PD-L1-targeted immune checkpoint inhibition (ICI) in recurrent and metastatic head and neck cancer (HNC). However, three large clinical trials combining PD-1/PD-L1-targeted ICI with RT or chemo-RT (CRT) in the definitive management of HNC have shown no benefit of combination therapy with ICI over RT or CRT alone. Our overarching hypotheses are: i) hypo-fractionation may ultimately better synergize with ICI compared to conventional RT regimens, and ii) immunologic changes in the tumor microenvironment may be detectable using quantitative MRI (qMRI) parameters collected during RT. Seven patients treated with hypo-fractionated MR-guided RT of 50 Gy in 15 fractions (DEHART, NCT04477759) were included in the study. Four patients (Group 1) were treated with concurrent atezolizumab (a monoclonal antibody) and three patients (Group 2) were treated with RT alone. Daily DWI, T1 mapping, and T2 mapping sequences were acquired on a 1.5T MR-Linac in the idle time during adaptive plan generation. Median ADC, T1, T2, and Dslow (derived from b-values 150 and 550 s/mm2) values were extracted from physician-defined GTV and manually constructed posterior paraspinal muscle contours, the latter serving as a control. Wilcoxon signed rank tests were conducted using pre/post treatment data for each qMRI parameter. GTV ADC, Dslow, T2, and T1 increased for both patient groups over the course of treatment with significant differences in ADC, Dslow, and T2 detected between fractions 1 and 15 for all patients studied (p = 0.0156, p = 0.0156, and p = 0.0469, respectively). No significant differences were detected in control qMRI parameters pre/post treatment. No significant differences in ADC, Dslow, and T2 were detected between groups' fractions 1 and 15 in these small cohorts. However, interestingly, we observed a differential change in the increase of median GTV T2 and Dslow values during fractions 10-12 in Group 1 compared to Group 2, suggesting this time interval may prime the anti-tumor immune response. Combining hypo-fractionated RT with ICI leads to a differential response in quantitative MRI (qMRI) parameters in HNC patients. These results suggest that qMRI parameter changes ten days following the start of RT may reflect a critical juncture in the anti-tumoral immune response when ICI is combined with hypo-fractionated RT.