Harmonization of Tumor Mutational Burden Quantification and Association With Response to Immune Checkpoint Blockade in Non-Small-Cell Lung Cancer.

ABSTRACT: Heterogeneity in tumor mutational burden (TMB) quantification across sequencing platforms limits the application and further study of this potential biomarker of response to immune checkpoint inhibitors (ICI). We hypothesized that harmonization of TMB across platforms would enable integration of distinct clinical datasets to better characterize the association between TMB and ICI response. Cohorts of NSCLC patients sequenced by one of three targeted panels or by whole exome sequencing (WES) were compared (total n=7297). TMB was calculated uniformly and compared across cohorts. TMB distributions were harmonized by applying a normal transformation followed by standardization to z-scores. In sub-cohorts of patients treated with ICIs (DFCI n=272; MSKCC n=227), the association between TMB and o

SUBMITTER: Vokes NI 

PROVIDER: S-EPMC6907021 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature