Quantitate Image Responses in High Risk p16+ Oropharyngeal Cancer Patients Treated With Definitive ChemoRT and Concurrent Nivolumab Compared to ChemoRT Alone.

PURPOSE/OBJECTIVE(S) Biomarkers of immunotherapy response are increasingly important in oropharyngeal cancer with the rapid expansion of treatment in the R/M population and many ongoing upfront trials. CPS score is the most commonly used method to quantify immune infiltration and predict response to immunotherapy, although limited by its static nature and sampling error. Previous studies show that pre-RT to mid-treatment changes in MRI-derived blood volume (BV) and apparent diffusion coefficient (ADC) as well as FDG-PET derived metabolic tumor volume (MTV) and total lesion glycolysis (TLG) serve as imaging markers for pattern failure of HNC treated by CRT. The goal of this study is to evaluate changes in image metrics during concurrent immunotherapy and CRT compared to those from CRT. MATERIALS/METHODS MRI and FDG-PET scans were acquired pre- and mid-treatment (fx 10) from 75 patients with high risk p16+ OPSCC (AJCC stage 3 or "matted nodes") who were treated with definitive concurrent CRT on 2 prospective institutional trials. The patients included: 1) the first 15 patients treated with definitive CRT 70Gy/concurrent carboplatin/taxol and concurrent nivolumab (iCRT) and 2) 60 patients treated with 70-80Gy/concurrent weekly cisplatin/carboplatin (CRT). Changes in quantitative image metrics from pre- to mid-treatment of primary tumors and individual lymph nodes were evaluated: gross tumor volume (GTV), MTV at 50% max SUV, TLG, mean SUV, mean BV and ADC between the two treatment groups using unpaired t test. RESULTS Clinical characteristics and baseline quantitative image metrics were similar between CRT and iCRT groups, except the iCRT group had a lower BV value of primary tumors and a greater MTV of nodal tumors than CRT group (P = 0.05). However, at mid-treatment, iCRT patients had: 1) significantly greater increases in mean BV and ADC of primary tumors than CRT patients (49% vs. 23% and 21% vs. 12%, P < 0.007 and 0.03, respectively); but 2) less decreases in MTV, TLG and mean SUV of primary tumors than CRT patients, for which 11% of the TLG decrease was significantly different from 43% decrease of CRT group (P < 0.05); and 3) 12% decrease in mean SUV of nodal tumors that was significantly less than 25% in CRT group (P < 0.0001). With a mean follow-up of 11 months in the iCRT group, there has been only 1 DM in a patient with persistent low BV in the primary tumor, consistent with our previous findings in CRT patients. CONCLUSION This analysis suggests that high risk p16+ OPSCC patients treated with iCRT had larger increases in BV and ADC and a smaller decrease in TLG in primary tumors mid-treatment compared to CRT group. Increases in BV and ADC have been identified to be associated with improved tumor control by previous studies of CRT. The minimal reduction of FDG metrics of iCRT group may be due to inflammatory response to anti-PD1. These findings warrant further investigation as predictive biomarkers for iCRT response to treatment.