1. Longitudinal multi-gene panel assessment of circulating tumor DNA revealed tumor burden and molecular characteristics along treatment course of non-small cell lung cancer
- Author
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Tao Wang, David C.L. Lam, Gloria Y.F. Ho, Rehana Rasul, HH Kwok, Rita Peila, Maria Guzman, and Mary S.M. Ip
- Subjects
0301 basic medicine ,biology ,business.industry ,Tumor burden ,medicine.disease ,Disease course ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Stable Disease ,Oncology ,Circulating tumor DNA ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Medicine ,Original Article ,Non small cell ,Epidermal growth factor receptor ,business ,Lung cancer ,Gene - 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.
- Published
- 2020