Potential of circulating tumor DNA as a predictor of therapeutic responses to immune checkpoint blockades in metastatic renal cell carcinoma

Abstract

Abstract We evaluated the predictive role of circulating tumor DNA (ctDNA) detection by targeted deep sequencing in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint blockades (ICB). To determine the feasibility of ctDNA detection in our panel encompassing 40 genes, we collected 10 ml of blood from 20 patients at the time of radical nephrectomy. We analyzed somatic mutations in primary tumors and ctDNA samples from these patients. We finally collected 10 ml of blood before and after 1 month of treatment, respectively, from four patients with mRCC who received first-line ICB treatment. Variants were detected in primary tumors of 15 patients (75%) and ctDNA was detected in the plasma of 9 patients (45%). We examined the predictive role of ctDNA in four patients who received first-line ICB therapy. In two patients showing partial response, ctDNA levels decreased after 1 month of ICB treatment. However, in one patient who showed disease progression, ctDNA levels increased after 1 month of ICB treatment. Taken together, ctDNA detection in plasma by targeted deep sequencing was feasible in patients with RCC. Moreover, the levels of ctDNA could be an early predictor of treatment response in patients with mRCC who receive ICB therapy.