Longitudinal multi-gene panel assessment of circulating tumor DNA revealed tumor burden and molecular characteristics along treatment course of non-small cell lung cancer

Gloria Y.F. Ho, Tao Wang, Hoi Hin Kwok, Rehana Rasul, Rita Peila, Maria Guzman, Mary S.M. Ip, David C.L. Lam

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Most studies associating circulating tumor DNA (ctDNA) with outcome in lung cancer treatment were either cross-sectional or, if longitudinal, only analyzed a limited number of genes. This study evaluated the potential of utilizing ctDNA profiled by a panel of common cancer genes to monitor tumor burden and to reveal molecular characteristics of tumor along treatment course. Methods: Twenty Chinese non-small cell lung cancer (NSCLC) patients with serial plasma samples collected (I) before starting on either first- or second-line treatment, (II) at stable disease on treatment, and (III) upon disease progression, were analyzed for mutations in ctDNA using the PGDx 64-gene panel. Paired statistics compared mutation profiles between any two of the three time points. Results: Proportions with detectable ctDNA decreased from 65% at baseline to 35% at stable disease and rose to 80% at progression (P=0.012, between stable disease and progression); median ctDNA levels (mutated fragments per mL) were 7.8, 0, and 24.7 at the three time points, respectively (P=0.013 between baseline and progression; P=0.007 between stable disease and progression). Although plasma epidermal growth factor receptor (EGFR) mutations were commonly detected, 15% of patients had mutations other than EGFR detected during progression, such as various types of TP53 mutations. Conclusions: ctDNA profiling in serial blood samples reflected tumor burden over time, and a multi-gene panel was more sensitive in indicating lung cancer progression on treatment than a single gene approach. The detection of additional oncogenic mutations or their disappearance suggested evolution of tumor heterogeneity along treatment course.

Original languageEnglish (US)
Pages (from-to)1873-1884
Number of pages12
JournalTranslational Lung Cancer Research
Volume9
Issue number5
DOIs
StatePublished - Oct 2020

Keywords

  • Circulating tumor DNA (ctDNA)
  • Epidermal growth factor receptor (EGFR)
  • Longitudinal assessment
  • Lung cancer
  • Tumor burden

ASJC Scopus subject areas

  • Oncology

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