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IKCS 2019: Challenges of Using ctDNA in Renal Cell Carcinoma

By: Lauren Harrison, MS
Posted: Tuesday, December 17, 2019

A large cohort analysis of patients with renal cell carcinoma matched genomic data from both primary tumor DNA and circulating tumor DNA (ctDNA) to establish comparable mutational profiles for renal cell carcinoma–specific alterations. This work was presented at the 2019 International Kidney Cancer Symposium (IKCS) in Miami by Ritesh Kotecha, MD, of Memorial Sloan Kettering Cancer Center, New York. Dr. Kotecha noted that despite the group’s results, there are still a number of challenges in developing a liquid biopsy for renal cell cancer.

A total of 110 patients with metastatic clear cell carcinoma who had prior tissue mutational profiles on nephrectomy or metastatic tissue generated via next-generation sequencing were included in the study. Patients underwent a single-time point plasma collection for ctDNA extraction. Bidirectional cross genotyping was performed on the ctDNA and tumor DNA, after which liberal (1–2 reads) and stringent (3 reads) were applied.

Most of the patients included in the study (96%) had undergone nephrectomy prior to ctDNA collection and were heavily pretreated, with an average of three systemic therapies. The median time between diagnosis of disease and ctDNA collection was 22.1 months, and the median time between primary tissue (nephrectomy or metastatic tissue) and ctDNA collection was 23.8 months.

Within the identified cohort, a total of 587 mutations were identified, 58% from primary kidney tumors and 42% from metastatic sites. Each patient had a median of five genetic alterations. When applying the “liberal” criteria to samples, 72 patients were found to have at least 1 mutation in their ctDNA, comprising a total of 182 alterations. Using the “stringent” criteria, 24 patients were identified with at least 1 alteration in ctDNA across the cohort, for a total of 43 total alterations. Mutations in the Von Hippel-Lindau gene were seen in the primary tissue and in ctDNA (both liberal and stringent criteria), with totals of 102, 31, and 13 alterations, respectively.

“Further efforts that integrate algorithm-based approaches to improve the fidelity of ctDNA and integrate clinical parameters for timepoint selection may help address some of these limitations…,” the study authors concluded.

Disclosure: The full disclosures of the study authors can be found at https://www.kidneycancer.org/.



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