Longitudinal diffusion and volumetric kinetics of head and neck cancer magnetic resonance on a 1.5T MR-Linear accelerator hybrid system: A prospective R-IDEAL Stage 2a imaging biomarker characterization/ pre-qualification study
Authors:   Joint Head and Neck Radiation Therapy-MRI Development Cooperative,   MR-Linac Consortium Head and Neck Tumor Site Group, El-Habashy Dina M , Wahid Kareem A , He Renjie , McDonald Brigid , Rigert Jillian , Mulder Samuel J. , Lim Tze Yee , Wang Xin , Yang Jinzhong , Ding Yao , Naser Mohamed A , Ng Sweet Ping , Bahig Houda , Salzillo Travis C , Preston Kathryn E , Abobakr Moamen , Shehata Mohamed A , Elkhouly Enas A , Alagizy Hagar A , Hegazy Amira H , Mohammadseid Mustefa , Terhaard Chris , Philippens Marielle , Rosenthal David I. , Wang Jihong , Lai Stephen Y. , Dresner Alex , Christodouleas John C. , Mohamed Abdallah Sherif Radwan , Fuller Clifton D 
Published: May 2023

ABSTRACTObjectivesWe aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort.MethodsThirty patients with pathologically confirmed HNSCC who received curative-intent RT at the University of Texas MD Anderson Cancer Center, were included in this prospective study. Baseline and weekly Magnetic resonance imaging (MRI) (weeks 1-6) were obtained, and various ADC parameters (mean, 5th, 10th, 20th, 30th, 40th, 50th, 60th, 70th, 80th, 90thand 95thpercentile) were extracted from the target regions of interest (ROIs). Baseline and weekly ADC parameters were correlated with response during RT, loco-regional control, and the development of recurrence using the Mann-Whitney U test. The Wilcoxon signed-rank test was used to compare the weekly ADC versus baseline values. Weekly volumetric changes (Δvolume) for each ROI were correlated with ΔADC using Spearman’s Rho test. Recursive partitioning analysis (RPA) was performed to identify the optimal ΔADC threshold associated with different oncologic outcomes.ResultsThere was an overall significant rise in all ADC parameters during different time points of RT compared to baseline values for both gross primary disease volume (GTV-P) and gross nodal disease volumes (GTV-N). The increased ADC values for GTV-P were statistically significant only for primary tumors achieving complete remission (CR) during RT. RPA identified GTV-P ΔADC 5thpercentile >13% at the 3rdweek of RT as the most significant parameter associated with CR for primary tumor during RT (p <0.001). Baseline ADC parameters for GTV-P and GTV-N didn’t significantly correlate with response to RT or other oncologic outcomes. There was a significant decrease in residual volume of both GTV-P & GTV-N throughout the course of RT. Additionally, a significant negative correlation between mean ΔADC and Δvolume for GTV-P at the 3rdand 4thweek of RT was detected (r = -0.39, p = 0.044 & r = -0.45, p = 0.019, respectively).ConclusionAssessment of ADC kinetics at regular intervals throughout RT seems to be correlated with RT response. Further studies with larger cohorts and multi-institutional data are needed for validation of ΔADC as a model for prediction of response to RT.