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Metastatic Kidney Cancer Response Gauged With Digital Sequencing Approach Targeting Specific Mutations

In a pilot study appearing in JCO Precision Oncology, a team from the City of Hope Comprehensive Cancer Center, the Translational Genomics Research Institute, the University of Wisconsin-Madison, and the University of California, San Francisco explores the possibility of differentiating between metastatic renal cell carcinoma kidney cancer cases showing a partial response (PR) or complete response (CR) to immune checkpoint immunotherapy based on targeted digital sequencing (TARDIS) analyses on circulating tumor DNA (ctDNA) found in the blood. Based on tumor variant allele fractions found with TARDIS-based analyses on peripheral blood samples collected from 12 mRCC patients treated with the anti-PD-1 drug nivolumab alone or nivolumab in combination with the CTLA-4-targeting drug ipilimumab, the researchers saw enhanced ctDNA levels in half a dozen patients with treatment progression. In addition, they report, the variant allele frequencies for the 30 patient-specific mutations targeted with the approach were found at significantly different levels for patients with a CR relative to those showing a PR to treatment. "By employing a bespoke approach that uses WGS to identify an average of 30 patient-specific mutations, TARDIS was able to effectively differentiate patients who achieved a PR from those who achieved a CR with immunotherapy," the authors conclude. "These significant differences seen in ctDNA, if validated in larger series, imply that the assay may play a role in facilitating treatment discontinuation."