Abstract 1803P
Background
Tumor mutational burden (TMB) has been reported to be a predictive biomarker for immune checkpoint inhibitor (ICI). However, most studies adopted a universal TMB for a cohort of cancers. Therefore, we test whether TMB vary across cancer types. Moreover, we compared TMB in cancers of the same type while of different pathology. And we explore whether the predictive effect of TMB for ICI vary according to tumor types or whether the predictive value of TMB might be pathology-dependent even in the same tumor type.
Methods
The genomic (based on MSK-IMPACT sequencing) and survival information of enrolled patients with various types of cancer were collected. cBioPortal was adopted to analyze these data. We have compared the TMB score in a cohort of cancers. We further investigated the optimal TMB cutoff values for different tumor types and tumors of different histology within the same tumor type using the X-tile model.
Results
We found a wide range of the median TMB value in different cancer types, ranging from 4.25 Mut/Mb in renal cell carcinoma to 26.67 Mut/Mb in colorectal cancer. Despite of the same cancer type, tumors of different pathologies were found to have different median TMB. The optimal TMB cutoff value affecting survival was lowest in renal cell carcinoma, and highest in NSCLC, with others in between. For patients with NSCLC, melanoma, bladder cancer, renal cell carcinoma, head and neck cancer, esophagogastric cancer and colorectal cancer, high TMB was associated with relatively better survival. However, for glioma, high TMB is linked with relatively worse survival with ICI treatment. We demonstrated a marked difference in TMB cutoff between LUAD and LUSC. Moreover, higher TMB is linked with better prognosis with ICI in LUAD while predicts worse survival in LUSC subject to ICI. Similarly, the optimal TMB cutoff to predict survival is discrepant in tumors with different pathological types.
Conclusions
Our results reveal that TMB is cancer type and pathology specific. We recommend that tumor type and pathological type should not be neglected when distinguishing tumor mutational burden scores. Our findings allow a more robust and precise assessment rather than arbitrary judgment of TMB, which affects our decision-making regarding ICI adoption.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Haiyong Wang.
Funding
Special funds for Taishan Scholars Project (Grant no. tsqn201812149); Academic promotion programme of Shandong First Medical University (2019RC004).
Disclosure
All authors have declared no conflicts of interest.