Value of tumor mutational burden as a prognostic factor in patients with non-small cell lung carcinoma.

Abstract

e20043 Background: Recently, the use of next generation sequencing (NGS) has increased drastically in the treatment of non-small cell lung cancer (NSCLC), especially with the rise of targeted therapies. NGS provides detailed mutation analysis, and patients’ tumor mutational burden (TMB), which is a measurement of the number of somatic mutations per megabase of sequenced genetic material. Previous studies show that TMB in patients with lung cancer is higher than other solid tumors, thought to be a direct result of cigarette smoke mutagens. High TMB has also proved to be an effective predictive marker in treatment with immunotherapy. The aim of this study was to determine the utility of TMB as prognostic factor in the treatment of NSCLC patients treated with a combination of chemotherapy, radiation, and immunotherapy through a retrospective study. Methods: Data concerning NGS biopsy results, stage at diagnosis, incidence of progression, and survival was extracted from the electronic medical record of 218 patients with NSCLC treated between 2016 and 2024.Patients without all data points documented were excluded. TMB data was gathered from biopsy reports. TMB greater than 10 mut/Mb was reported as high tumor burden, per industry guidelines. Multivariate correlation and regression analysis was conducted to determine if an independent association existed between patients with high TMB versus low TMB in regards to stage at diagnosis, progression free survival, and incidence of early progression, defined as progression at fourth cycle scans. Results: Total of 64 patients were analyzed, after accounting for missing data. A statistically significant association was found between high TMB and advanced stage at diagnosis (p=0.021). Low TMB was associated with a significantly higher occurrence of progression in general (p=0.045), and early progression (p=0.025). High TMB was also associated with significantly longer progression free survival than patients with a low TMB (HR= 0.402 [0.2138, 0.7559] p=0.005). Conclusions: Based on the results from this study, a higher TMB offers a favorable prognosis, compared to a lower TMB. Patients with a higher TMB had longer progression free survival and less instances of early progression. Since immunotherapy is the mainstay of treatment in early and late stage, and higher TMB correlates with immunotherapy response, that may account for improved progression free survival. Further research is needed to determine specific therapies and their efficacy with varying TMB statuses. Outcomes by TMB value. Stage at Diagnosis (p=0.02108) High TMB (>10 mut/Mb) Low TMB (<10 mut/Mb) I or II 2 (25%) 6 (75%) III or IV 39 (69.6%) 17 (30.4%) Progression (p=0.04486)  Y 25 (55.6%) 20 (44.4%)  N 16 (84.2%) 3 (15.8%) Early Progression* (p=0.02475)  Y 5 (35.7%) 9 (64.3%)  N 36 (72%) 14 (28%) Average Progression Free Survival (days) (HR= 0.402 [0.2138, 0.7559] p=0.005) 488 164 *Evidence of progression at 4th cycle scan.