Genomics

Illustration of Temporal Evolution in Patients with mRCC Using Both ctDNA and Tissue-Based Genomic Data


(UroToday.com) Temporal and spatial heterogeneity have been consistently identified as contributing to perceived discordance between circulating tumor DNA and tissue-based assays. At the 2020 European Society of Medical Oncology Annual Congress, Zengin et al. previously demonstrated the feasibility of circulating tumor DNA assessment in metastatic renal cell carcinoma (mRCC) and preliminarily showed agreement between circulating tumor DNA and tissue-based genomic findings. This data suggested that the degree of agreement is dependent upon the temporal separation of blood and tissue samples. At the 2021 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, Dr. Zeynep Zengin and colleagues presented results of their study further exploring this temporal impact in a separate validation cohort.

In this study, patients with mRCC who underwent circulating tumor DNA genomic profiling were identified. Circulating tumor DNA analysis was performed using a CLIA-certified 73-74 gene panel (Guardant360), and from this cohort, Dr. Zengin identified a subset of patients who also underwent tissue-based genomic profiling using either a whole-exome sequencing platform (GEM ExTra®, TGen, Phoenix, Arizona) or a targeted next-generation sequencing platform (Foundation Medicine, Cambridge, Massachusetts or Tempus, Chicago, Illinois). Only alterations covered by both assays were included for the current analysis. The difference in the proportion of alterations detected on tissue and circulating tumor DNA was compared between these cohorts and at a six-month landmark using the χ2 test.

In total, circulating tumor DNA and tissue-based genomic profiling was assessed in 112 patients (81 males, 31 females), with the most common histology being clear cell (85.7%). The median time between circulating tumor DNA and tissue assessments was 9.8 months (IQR 1.15-23.7). When examining paired samples in which >1 circulating tumor DNA alteration was detected, 32% (43/133) of alterations detected on tissue were also detected in circulating tumor DNA. This proportion increased to 43% (29/67) when samples collected within 6 months of each other and was 51% (28/55) in samples collected within 3 months of each other:

circulating tumor DNA and tissue based genomic profiling samples

The percentage of alterations detected on tissue and also detected on the circulating tumor DNA panel were assessed at different time points and cohorts. This frequency was statistically different when samples were collected within 6 months compared to >6 months in all cohorts. When the two cohorts were compared, the overall shared alteration frequency in both was different (46% versus 25%):

percentage of alterations detected on tissue also detected on ctdna

Dr. Zengin concluded that this study confirms that circulating tumor DNA and tissue-based genomic profiling continue to provide consistently high levels of agreement. Notably, the percentage of samples with ≥1 circulating tumor DNA alteration detected was significantly lower in both cohorts compared to previous studies in RCC. More shared alterations were found on circulating tumor DNA when both circulating tumor DNA and tissue-based assessment were obtained at closer intervals.

Presented by: Zeynep B. Zengin, MD, Posdoctoral Fellow, City of Hope Comprehensive Cancer Center, Duarte, California

Written by: Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021



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