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Review
. 2019 Nov 12;10(61):6604-6622.
doi: 10.18632/oncotarget.27287.

Tumor mutational burden in lung cancer: a systematic literature review

Connor Willis  1 , Michelle Fiander  1 , Dao Tran  2 , Beata Korytowsky  3 , John-Michael Thomas  3 , Florencio Calderon  3 , Teresa M Zyczynski  3 , Diana Brixner  1 , David D Stenehjem  1   2
Affiliations
Review

Tumor mutational burden in lung cancer: a systematic literature review

Connor Willis et al. Oncotarget. .

Abstract

Purpose: To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy for lung cancer. Results: In total, 4,303 publications were identified; 81 publications were included. The majority of publications assessing clinical efficacy of immunotherapy reported an association with high TMB, particularly when assessing progression-free survival and objective response rate. High TMB was consistently associated with TP53 alterations, and negatively associated with EGFR mutations. High TMB was also associated with smoking, squamous cell non-small cell lung carcinoma, and being male. Methods: A systematic literature review based upon an a priori protocol was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane methodologies. Searches were conducted in EMBASE, SCOPUS, Ovid MEDLINE®, and Emcare (from January 2012 until April 2018) and in two clinical trial registries. Conference abstracts were identified in EMBASE, and in targeted searches of recent major conference proceedings (from January 2016 until April 2018). Publications reporting data in patients receiving therapy for lung cancer that reported TMB and its association with clinical efficacy, or with other biomarkers or patient/disease characteristics, were included. Results are presented descriptively. Conclusion: This systematic literature review identified several clinical outcomes, biomarkers, and patient/disease characteristics associated with high TMB, and highlights the need for standardized definitions and testing practices. Further studies using standardized methodology are required to inform treatment decisions.

Keywords: PD-L1; biomarkers; chemotherapy; immunotherapy; lung cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST Beata Korytowsky, John-Michael Thomas, Florencio Calderon and Teresa M. Zyczynski are employees of, and hold stock in, Bristol-Myers Squibb Company.

Figures

Figure 1
Figure 1. PRISMA flow diagram of publication identification process.
TMB, tumor mutational burden. ‘Presented’ categories are not mutually exclusive.
See this image and copyright information in PMC

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