Zeynep Busra Zengin, MD, a postdoctoral fellow at the City of Hope, a comprehensive cancer center discusses the ASCO GU 2021 abstract – Illustration of temporal evolution in patients with metastatic renal cell carcinoma (mRCC) using both circulating tumor DNA (ctDNA) and tissue-based genomic data.
Link to Study –
https://meetinglibrary.asco.org/record/195147/abstract
Context:
We have previously shown the viability of mRCC ctDNA evaluation and have previously shown agreement between ctDNA and tissue-based genomic findings (Zengin et al ESMO 2020). Our data showed that the degree of agreement depended on the temporal separation of samples of blood and tissue. In a separate validation cohort, we sought to further explore this temporal effect.
In a separate validation cohort, we sought to further explore this temporal effect.
Methodology:
Patients (pts) with mRCC undergoing genomic ctDNA profiling have been reported. The ctDNA study was conducted using a 73-74 gene panel approved by CLIA (Guardant360). A subset of pts that also underwent tissue-based genomic profiling using either a full exome sequencing platform (GemExtra [TGen, Phoenix, AZ]) or a targeted next-generation sequencing platform was reported from this cohort (Foundation Medicine [Cambridge, MA] or Tempus [Chicago, IL]). For the current study, only alterations covered by both assays were used. The difference in the proportion of tissue and ctDNA alterations observed was compared between these cohorts and at the 6-mo point of reference using the χ2 test.
Outcomes:
Overall, 112 pts of ctDNA and tissue-based genomic profiling were evaluated (M:F, 81:31), with clear cell histology being the most common (85.7 percent ). A median period of 9.8 months between ctDNA and tissue evaluations was (IQR 1.15-23.7). 32 percent (43/133) of tissue alterations observed were also detected in ctDNA while analyzing paired samples in which >1 ctDNA alteration was detected. In samples collected within 6 months of each other, this proportion increased to 43 percent (29/67) and was 51 percent (28/55) in samples collected within 3 months of each other. There was no substantial difference between the cohorts in the frequency of shared mutations (P=0.09; Table).
Findings:
Our research confirms that ctDNA and genomic profiling based on tissues continue to have consistently high levels of agreement. Notably, relative to previous studies in RCC, the percentage of samples with ⇠1 ctDNA alteration detected was significantly lower in both cohorts. When both ctDNA and tissue-based evaluation were collected at closer intervals, more shared alterations were found on ctDNA.