2021 Targeted Therapies of Lung Cancer (TTLC) Meeting - Posters-P03. Comparison of Tumor Mutational Burden in Paired Primary Versus Lung Cancer Brain Metastasis

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Researchers at Massachusetts General Hospital and the University of Washington School of Medicine conducted a study to compare the tumor mutational burden (TMB) in paired primary and brain metastasis samples of non-small cell lung cancer (NSCLC) patients. The study aimed to explore the relationship between TMB and tissue sampling site in NSCLC.<br /><br />The cohort consisted of 66 patients with metastatic lung adenocarcinoma who had paired primary and brain metastasis samples obtained between 1996 and 2014. Whole exome sequencing was used to estimate TMB, which was defined as non-synonymous mutations per coding region.<br /><br />The results showed that 53% of primary specimens and 50% of brain metastasis specimens had a TMB of 10 mut/Mb or greater. There was no clinically meaningful difference in TMB estimates between primary and brain metastasis sites when analyzing paired primary-brain metastasis specimens. However, a statistically significant difference in median TMB was observed between primary and brain metastasis specimens among metachronous (occurring at different times) specimens.<br /><br />The study concluded that lung adenocarcinoma brain metastases frequently contain high TMB. Analysis of paired primary-brain metastasis specimens showed no significant differences in TMB estimates between sites. However, TMB was significantly higher in brain metastasis specimens diagnosed in the metachronous setting compared to synchronous (occurring at the same time) specimens. This suggests that a diagnosis of metachronous brain metastasis may be associated with CNS disease harboring a higher TMB compared to primary disease. The study also suggested that resected synchronous brain metastasis samples can be reliable surrogates for TMB estimation.<br /><br />Further research in larger cohorts is needed to validate these findings. TMB could potentially be used as a biomarker to predict the efficacy of immune checkpoint inhibitors in NSCLC patients with brain metastases.

Asset Subtitle

Matthew Strickland

Meta Tag

Speaker Matthew Strickland

Topic Immunotherapy - IO & other Novel Combinations

Keywords

tumor mutational burden

non-small cell lung cancer

NSCLC

brain metastasis

lung adenocarcinoma

primary specimens

metastasis specimens

metachronous specimens

synchronous specimens

immune checkpoint inhibitors