Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors
Ekaterina Kalashnikova, Vasily N. Aushev, Allyson Koyen Malashevich, Antony Tin, Shifra Krinshpun, Raheleh Salari, Carly Bess Scalise, Rosalyn Ram, Meenakshi Malhotra, Harini Ravi, Himanshu Sethi, Stephanie Sanchez, R. Tanner Hagelstrom, Maxim G. Brevnov, Matthew Rabinowitz, Solomon Moshkevich, Bernhard Zimmermann, Minetta C. Liu, Alexey Aleshin
Abstract
Several studies have demonstrated the prognostic value of circulating tumor DNA (ctDNA); however, the correlation of mean tumor molecules (MTM)/ml of plasma and mean variant allele frequency (mVAF; %) with clinical parameters is yet to be understood. In this study, we analyzed ctDNA data in a pan-cancer cohort of 23 543 patients who had ctDNA testing performed using a personalized, tumor-informed assay (Signatera™, mPCR-NGS assay). For ctDNA-positive patients, the correlation between MTM/ml and mVAF was examined. Two subanalyses were performed: (a) to establish the association of ctDNA with tumor volume and (b) to assess the correlation between ctDNA dynamics and patient outcomes. On a global cohort, a positive correlation between MTM/ml and mVAF was observed. Among 18 426 patients with longitudinal ctDNA measurements, 13.3% had discordant trajectories between MTM/ml and mVAF at subsequent time points. In metastatic patients receiving immunotherapy (N = 51), changes in ctDNA levels expressed both in MTM/ml and mVAF showed a statistically significant association with progression-free survival; however, the correlation with MTM/ml was numerically stronger.