INTRODUCTION: Tumor mutation burden (TMB) is thought to be associated with the amount of neoantigen in the tumor and to have an important role in predicting the effect of immune checkpoint inhibitors. However, the relevance of TMB to prognosis is not yet fully understood. In this study, we investigated the clinical significance of TMB in patients with NSCLC and examined the relationship between TMB and prognosis. METHODS: We calculated TMB within individual tumors by whole-exome sequencing analysis using next-generation sequencing. We included that there were 90 patients with NSCLC who underwent surgery in the Hospital of Fukushima Medical University from 2013 to 2016. No patients received chemotherapy or immunotherapy before surgery. We assessed the correlation between TMB and prognosis. RESULTS: TMB greater than 62 was associated with worse overall survival (OS) of patients with NSCLC (hazard ratio [HR] = 6.633, p = 0.0003). Multivariate analysis showed poor prognosis with high TMB (HR = 12.31, p = 0.019). In patients with stage I NSCLC, higher TMB was associated with worse prognosis for both OS (HR = 7.582, p = 0.0018) and disease-free survival (HR = 6.07, p = 0.0072). CONCLUSIONS: High TMB in NSCLC is a poor prognostic factor. If high TMB is a predictor of the efficacy of immune checkpoint inhibitors, postoperative adjuvant therapy with immune checkpoint inhibitors may contribute to improvement of recurrence and OS.
INTRODUCTION:Tumor mutation burden (TMB) is thought to be associated with the amount of neoantigen in the tumor and to have an important role in predicting the effect of immune checkpoint inhibitors. However, the relevance of TMB to prognosis is not yet fully understood. In this study, we investigated the clinical significance of TMB in patients with NSCLC and examined the relationship between TMB and prognosis. METHODS: We calculated TMB within individual tumors by whole-exome sequencing analysis using next-generation sequencing. We included that there were 90 patients with NSCLC who underwent surgery in the Hospital of Fukushima Medical University from 2013 to 2016. No patients received chemotherapy or immunotherapy before surgery. We assessed the correlation between TMB and prognosis. RESULTS:TMB greater than 62 was associated with worse overall survival (OS) of patients with NSCLC (hazard ratio [HR] = 6.633, p = 0.0003). Multivariate analysis showed poor prognosis with high TMB (HR = 12.31, p = 0.019). In patients with stage I NSCLC, higher TMB was associated with worse prognosis for both OS (HR = 7.582, p = 0.0018) and disease-free survival (HR = 6.07, p = 0.0072). CONCLUSIONS: High TMB in NSCLC is a poor prognostic factor. If high TMB is a predictor of the efficacy of immune checkpoint inhibitors, postoperative adjuvant therapy with immune checkpoint inhibitors may contribute to improvement of recurrence and OS.
Authors: Jian Zhou; Francisco Sanchez-Vega; Raul Caso; Kay See Tan; Whitney S Brandt; Gregory D Jones; Shi Yan; Prasad S Adusumilli; Matthew Bott; James Huang; James M Isbell; Smita Sihag; Daniela Molena; Valerie W Rusch; Walid K Chatila; Natasha Rekhtman; Fan Yang; Marc Ladanyi; David B Solit; Michael F Berger; Nikolaus Schultz; David R Jones Journal: Clin Cancer Res Date: 2019-08-27 Impact factor: 12.531
Authors: William L Hwang; Rachel L Wolfson; Andrzej Niemierko; Karen J Marcus; Steven G DuBois; Daphne Haas-Kogan Journal: J Natl Cancer Inst Date: 2019-07-01 Impact factor: 13.506
Authors: Dana L Casey; Leonard H Wexler; Kenneth L Pitter; Robert M Samstein; Emily K Slotkin; Suzanne L Wolden Journal: Clin Cancer Res Date: 2019-11-07 Impact factor: 12.531
Authors: Katherine I Zhou; Bryan Peterson; Anthony Serritella; Joseph Thomas; Natalie Reizine; Stephanie Moya; Carol Tan; Yan Wang; Daniel V T Catenacci Journal: Clin Cancer Res Date: 2020-08-20 Impact factor: 12.531