Association of tumor mutational burden with age in solid tumors.

Abstract

e13590 Background: Immunotherapy is becoming one of the promising treatments for cancer administration, and several studies indicated a better outcome was received in patients with high tumor mutation burden (TMB). The distribution of TMB is still unknown and this study aimed to analysis the association between TMB and age especially in East Asian populations. Methods: In our study, TMB value was measured as the numbers of synonymous, nonsynonymous mutations and InDels by next generation sequencing with 539 genes panel in tumor tissue. TMB-H was defined as highest mutation load quintile (top 20%) in each cancer type. The association between TMB and age in 874 patients was investigated including 174 patients with liver cancer, 32 patients with bile duct cancer, 54 patients with gastric cancer, 119 patients with colorectal cancer, 27 patients with pancreatic cancer, 32 patients with melanoma, 25 patients with glioma and 411 patients with lung cancer cases, respectively. Spearman rank correlation analysis, Mann-Whitney U-test and Fisher’s exact test were used for statistical analysis. Results: A significant correlation between TMB and ages was observed in patients with solid tumors (r = 0.204, p = 1.263×10−9). The median age of included patients was 60 years-old. Based on nonparametric test, the value of TMB in patients with liver cancer ( p = 2.310×10−4), gastric cancer ( p = 0.029) and lung cancer ( p = 0.001) aged ≥ 60 years-old was significantly higher than the corresponding patients aged < 60 years-old. No significant differences of TMB values were found between patients < 60 and ≥ 60 years-old in bile duct cancer ( p = 0.419), colorectal cancer ( p = 0.075), pancreatic cancer ( p = 1), melanoma ( p = 0.952) and glioma ( p = 0.720). The TMB-H ratio in patients with liver ( p = 0.049) and gastric ( p = 0.015) cancer aged < 60 years old was significantly lower than patients aged ≥ 60 years-old. Conclusions: Our study indicated the TMB value and TMB-H ratio were relatively higher with ages ≥ 60 years old in specific tumors, which might provide useful information to guide precisely the the application of PD-1 or PD-L1 inhibitors. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.