Value Of Serial Multi-Parametric Functional Mri And Fdg-Pet During Radiation Therapy In Predicting Clinical Outcomes In Patients With Head And Neck Squamous Cell Carcinoma

To assess the utility of mid-treatment FDG-PET, DWI and R2*-MR functional imaging in predicting clinical response in patients receiving definitive radiotherapy (RT) for mucosal head and neck squamous cell carcinoma (HNSCC). Patients undergoing definitive radiotherapy with/without systemic therapy were recruited in a prospective imaging biomarker study. FDG-PET/CT was performed at baseline, during (week 3) and post RT (3 months). Diffusion-weighted imaging (DWI) and susceptibility-weighted MRI were performed using 3T scanner at baseline and during RT (week 2, 3, 5 and 6). The mean apparent diffusion coefficient (ADCmean) from DWI, mean R2* values derived from T2*-MRI and PET metabolic parameters including maximum standardized uptake (SUVmax), mean standardized uptake (SUVmean), metabolic tumor volume (MTV) and total lesional glycolysis (TLG) were measured for the primary tumor. Absolute and relative percentage change (%Δ) in serial PET and MR parameters were correlated to local and distant recurrence and survival using the Mann-Whitney U test. Poor imaging response was dichotomized in relation to; 1) mean values of ADCmean and; 2) 50% reduction in PET parameters for Kaplan-Meier survival analysis. Pre-treatment scans were performed in 33 patients and analyzable mid-treatment scans were available for 21 patients. Median follow-up was 43 months and 2-year local recurrence-free survival (LRFS), distant metastatic relapse-free survival (DMFS) and overall survival (OS) rates were 81%, 90% and 62%, respectively. Patients with local recurrence (LR) had a significantly lower %Δ in SUVmax (p=0.05), SUVmean (p=0.04) and TLG (p=0.05) at week 3 compared to baseline. There was trend towards higher pre-treatment ADCmean in patients with LR (1.09 vs 1.27 x 10-3mm2s-1) without reaching statistical significance potentially due to sample size. A significant rise in ADCmean was found during the first half (p < 0.001) of RT but not in the second half of the treatment. Patients with poor week 2 %Δ ADCmean rise during RT had worse LRFS (100% vs 63%, p<0.04). %Δ ADCmean at subsequent weeks were not associated with LRFS, DMFS, or OS. No absolute or %Δ R2* values were associated with clinical outcomes. Using combination of poor week 2 %Δ ADCmean and SUVmax response at week 3 was associated with improved LRFS (100% vs 43%, p=0.005). Early changes in FDG-PET and ADC can potentially predict clinical response to radiotherapy in HNSCC and aid in future risk-adaptation studies. Combination of functional imaging parameters show a promising avenue to enhance prediction of response. Based on our results week 2 appears to be a promising time period for mid-treatment DWI assessment of tumor response.