Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Patients With Non-Small Cell Lung Cancer With Use of a Next-Generation Sequencing Cancer Gene Panel

JAMA Oncology
Zhijie WangJie Wang

Abstract

Tumor mutational burden (TMB), as measured by whole-exome sequencing (WES) or a cancer gene panel (CGP), is associated with immunotherapy responses. However, whether TMB estimated by circulating tumor DNA in blood (bTMB) is associated with clinical outcomes of immunotherapy remains to be explored. To explore the optimal gene panel size and algorithm to design a CGP for TMB estimation, evaluate the panel reliability, and further validate the feasibility of bTMB as a clinical actionable biomarker for immunotherapy. In this cohort study, a CGP named NCC-GP150 was designed and virtually validated using The Cancer Genome Atlas database. The correlation between bTMB estimated by NCC-GP150 and tissue TMB (tTMB) measured by WES was evaluated in matched blood and tissue samples from 48 patients with advanced NSCLC. An independent cohort of 50 patients with advanced NSCLC was used to identify the utility of bTMB estimated by NCC-GP150 in distinguishing patients who would benefit from anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1) therapy. The study was performed from July 19, 2016, to April 20, 2018. Assessment of the Spearman correlation coefficient between bTMB estimated by NCC-GP150 and t...Continue Reading

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Citations

Mar 16, 2019·Nature Reviews. Clinical Oncology·David Killock
Aug 31, 2019·Expert Review of Molecular Diagnostics·Ernest Y Lee, Rajan P Kulkarni
Jul 17, 2019·Journal for Immunotherapy of Cancer·Laura FancelloLuca Mazzarella
Nov 5, 2019·Expert Review of Molecular Diagnostics·Arutha KulasingheChamindie Punyadeera
Dec 22, 2019·Cancers·Erika RijavecFrancesco Grossi
Dec 8, 2019·Clinical Chemistry·Shana O Kelley, Klaus Pantel
Oct 15, 2019·Expert Review of Molecular Diagnostics·Alessandro RussoChristian Rolfo
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Software Mentioned

R
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GraphPad Prism
GraphPad
PlasmaSELECT
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