Abstract
cfDNA is a promising biomarker for early recurrence detection and disease monitoring in the NSCLC curative setting. However, less is known about cfDNA shedding characteristics and correlation with tumor burden in advanced NSCLC. We reviewed cfDNA results of NSCLC patients tested at our institution between November 2015 and December 2016 with Guardant 360, a comprehensive cfDNA assay that detects genomic alterations in 70-73 cancer genes. 141 cases with evaluable imaging were selected for this analysis, enriching for EGFR and KRAS mutated cases to facilitate comparisons of major genomic subtypes (Table 1). Tumor burden was approximated using the sum of longest diameters (SLD), per RECIST v1.1. There was a statistically significant correlation of moderate strength between cfDNA maximum variant allele frequency (VAF) detected and SLD (Spearman’s rho = 0.35, p <0.001). This correlation was strongest in KRAS mutant cases (rho = 0.52, p = 0.001) and weakest in EGFR mutated tumors (rho = 0.21, p <0.24). Multi-variate regression that included stage, histology, and mutation status confirmed the predictive value of cfDNA VAF for SLD (p = 0.03). TP53 mutants had higher cfDNA VAF (Wilcox p <0.001), even after accounting for SLD. Increased cfDNA VAF was also seen with EGFR mutants and patients with visceral metastasis, though possibly confounded by concomitant EGFR amplification and increased tumor burden, respectively. CNS metastasis was not associated with differential cfDNA shedding. In this primarily metastatic cohort, cfDNA VAF correlated with radiographic assessment of tumor burden by RECIST. This correlation was partially mediated by the presence of key driver mutations. TP53 and EGFR mutant tumors and the presence of visceral metastasis are associated with higher cfDNA VAF. These findings have potential implications for the use of cfDNA in advanced-stage NSCLC disease monitoring, where RECIST is more clinically applicable than formal volumetrics.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.