Correlation of ctDNA and radiographic imaging features derived from ¹⁸F-FDG PET/CT for patients with metastatic melanoma treated with immunotherapy.

3057 Background: 18 F-FDG PET/CT scans are used to assess tumor response for patients undergoing immunotherapy for metastatic melanoma (MM). Evaluating the relationship between features derived from quantitative medical image analysis and markers in blood samples such as circulating tumor DNA (ctDNA) may present an opportunity to discover imaging and blood biomarkers that can influence future patient care. This study evaluates the correlation of ctDNA and radiographic imaging features derived from FDG PET/CT. Methods: Whole-body FDG PET/CT scans from MM patients between 2014-2020 were retrospectively collected under IRB-approved protocol. Patients received pembrolizumab (n=20), ipilimumab (n=4), nivolumab (n=7), or a combination of ipilimumab and nivolumab (n=19). TRAQinform IQ software (AIQ Solutions) identified and quantified regions of interest suspicious of cancer (lesion-ROI), enabling extraction of imaging features including SUV max , SUV mean , and SUV total in baseline ( BL ) and follow-up ( FU ) images and change. Plasma ctDNA concentration (copies/ml) and frequency abundance (FA) were evaluated for the first sample ( 1 ) after immunotherapy had started (between baseline and first on-treatment scan), and the next available sample ( 2 ). Patients were further grouped by ctDNA mutation for analysis. Correlation between imaging features and ctDNA features was assessed using Spearman coefficient (ρ). Results: The patient cohort included 32 males and 19 females with average age of 62 years (range 23-83). For all 51 patients, moderate correlation was observed in SUV max,BL with ctDNA copies/ml 1 (ρ = 0.48, p<< 0.001) and ctDNA FA 1 (ρ = 0.49, p << 0.001) and in SUV total,BL with ctDNA FA 1 (ρ= 0.41, p < 0.001). In BRAF mutation patients (N=32), moderate correlations existed between SUV max,BL with ctDNA copies/ml 1 (ρ = 0.49, p = 0.0041 and ctDNA FA 1 (ρ = 0.05, p = 0.0035), and SUV total,BL with ctDNA copies/ml 2 (ρ = 0.42, p = 0.017), ctDNA FA 1 (ρ = 0.40, p = 0.023), and ctDNA FA 2 (ρ = 0.43, p = 0.012). All the other combinations displayed weak correlations (ρ < 0.39, p > 0.05). Conclusions: This study shows that in patients with MM receiving immunotherapy, quantitative features from blood biomarkers such as ctDNA correlate with FDG PET/CT imaging features. Combining blood biomarkers with imaging features that are spatially localizable may strengthen prognostication in this patient group. Further analysis is being performed with more types of ctDNA mutations.