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Tumor Mutation Burden as Prognostic Biomarker in Non–Small Cell Lung Cancer

By: Cordi Craig
Posted: Monday, January 28, 2019

“High synonymous tumor mutation burden represents a strong and favorable prognostic factor for outcomes in patients with resected non–small cell lung cancer [NSCLC],” according to findings from the LACE-Bio-II study, published in the Journal of Clinical Oncology. Siddhartha Devarakonda, MD, of Washington University School of Medicine in St. Louis, and colleagues suggest that tumor mutation burden may help to identify patients who may be less likely to benefit from adjuvant chemotherapy. However, future studies are necessary to confirm these results.

The investigators sequenced 908 unmatched resected lung cancer tumor specimens using a targeted panel of 1,538 genes. High nonsynonymous tumor mutation burden was defined as more than eight mutations per megabase, and low nonsynonymous tumor mutation burden was defined as a maximum of four mutations per megabase.

Of the 908 tumor samples, the authors identified nonsynonymous mutations in 1,515 genes. High nonsynonymous tumor mutation burden was associated with favorable outcomes in overall, disease-free, and lung cancer–specific survival. Patients with low nonsynonymous tumor mutation burden showed more pronounced disease–specific survival benefits to adjuvant chemotherapy.

Factors that did not significantly affect prognosis or predictions included the presence of mutations in DNA-repair pathways, tumor-infiltrating lymphocytes, TP53 alteration subtype, and intratumor heterogeneity. The investigators revealed that high false-discovery rates made it challenging to determine a statistically significant effect of mutations in individual genes.

Disclosure: The study authors’ disclosures can be found at ascopubs.org.



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