Effect of prior therapy on tumor mutational burden in NSCLC
| Autor: | Kelsey Poorman, John Y. Hu, Sushma Jonna, Stephen V. Liu, Xinyu von Buttlar, Ari M. Vanderwalde, Jorge Nieva, Michelle Saul |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Chemotherapy medicine.medical_specialty business.industry medicine.medical_treatment non-small cell lung cancer (NSCLC) Single-nucleotide polymorphism medicine.disease Frameshift mutation Radiation therapy 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Prior Therapy 030220 oncology & carcinogenesis Internal medicine medicine Original Article business Lung cancer Prior Radiation Therapy |
| Zdroj: | Transl Lung Cancer Res |
| ISSN: | 2226-4477 2218-6751 |
| DOI: | 10.21037/tlcr-20-1076 |
| Popis: | Background Higher tumor mutation burden (TMB) in advanced non-small cell lung cancer (NSCLC) is associated with superior outcomes with checkpoint inhibitor therapy. Tissue samples subject to TMB analysis may be acquired after DNA-damaging therapies such as chemotherapy or radiation. The impact of these therapies on TMB results is unclear. This retrospective analysis explored differences in TMB among treatment-naive samples and treatment-experienced samples. Methods NSCLC samples that underwent molecular profiling at a CLIA-certified genomics laboratory (Caris Life Sciences, Phoenix, AZ) and had available treatment and clinical history were identified. TMB was estimated by counting all coding variants (missense, nonsense, frameshift, in-frame InDels) identified by next-generation sequencing. Exceptions were synonymous mutations and any single nucleotide polymorphisms described as germline. History was reviewed under an IRB approved protocol to determine whether patients had received cytotoxic chemotherapy or radiation therapy in the year prior to collection of the tissue subject to TMB analysis. TMB values were compared between cohorts using the Wilcoxon test. Smoking adjusted P values were calculated using the chi-squared test of deviance. Results TMB was calculated for 970 annotated tumor specimens. Of these, 155 patients received chemotherapy and/or radiation prior to tissue collection. The median TMB was 8 mut/Mb in both the treatment-naive and treatment-experienced cohorts. After adjusting for smoking, there was no significant difference in TMB between these cohorts (P=0.22). When analyzed separately, neither prior chemotherapy nor prior radiation therapy influenced TMB. TMB was higher when the specimen source was collected from a metastatic site compared to the primary site. Conclusions Prior exposure to chemotherapy or radiation therapy was not associated with a significant difference in TMB. |
| Databáze: | OpenAIRE |
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