Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors

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‐ca...

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Main Authors: 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, Robert Tanner Hagelstrom, Maxim Brevnov, Matthew Rabinowitz, Solomon Moshkevich, Bernhard G. Zimmermann, Minetta C. Liu, Alexey Aleshin
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Molecular Oncology
Subjects:
Online Access:https://doi.org/10.1002/1878-0261.13557
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author 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
Robert Tanner Hagelstrom
Maxim Brevnov
Matthew Rabinowitz
Solomon Moshkevich
Bernhard G. Zimmermann
Minetta C. Liu
Alexey Aleshin
author_facet 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
Robert Tanner Hagelstrom
Maxim Brevnov
Matthew Rabinowitz
Solomon Moshkevich
Bernhard G. Zimmermann
Minetta C. Liu
Alexey Aleshin
author_sort Ekaterina Kalashnikova
collection DOAJ
description 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.
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spelling doaj-art-8b2bcff23d824c9a904d5bfa7e01ecb72024-11-08T18:26:20ZengWileyMolecular Oncology1574-78911878-02612024-11-0118112649265710.1002/1878-0261.13557Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumorsEkaterina Kalashnikova0Vasily N. Aushev1Allyson Koyen Malashevich2Antony Tin3Shifra Krinshpun4Raheleh Salari5Carly Bess Scalise6Rosalyn Ram7Meenakshi Malhotra8Harini Ravi9Himanshu Sethi10Stephanie Sanchez11Robert Tanner Hagelstrom12Maxim Brevnov13Matthew Rabinowitz14Solomon Moshkevich15Bernhard G. Zimmermann16Minetta C. Liu17Alexey Aleshin18Natera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USANatera, Inc. Austin TX USASeveral 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.https://doi.org/10.1002/1878-0261.13557biomarkerscirculating tumor DNAmean tumor moleculesvariant allele frequency
spellingShingle 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
Robert Tanner Hagelstrom
Maxim Brevnov
Matthew Rabinowitz
Solomon Moshkevich
Bernhard G. Zimmermann
Minetta C. Liu
Alexey Aleshin
Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors
Molecular Oncology
biomarkers
circulating tumor DNA
mean tumor molecules
variant allele frequency
title Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors
title_full Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors
title_fullStr Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors
title_full_unstemmed Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors
title_short Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors
title_sort correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors
topic biomarkers
circulating tumor DNA
mean tumor molecules
variant allele frequency
url https://doi.org/10.1002/1878-0261.13557
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