Abstract 323P
Background
Tumor mutation burden (TMB) may predict immune checkpoint inhibitor (ICI) response. TMB calculation included all nonsynonymous somatic mutations, but not all mutations were favorable and the efficient of TMB is attenuated by including adverse mutations. Moreover, no universal cutoff value of high TMB hindered its application in practice.
Methods
Tumor mutation score (TMS), defined as number of genes with nonsynonymous somatic mutations, was compared with TMB in 10,336 cancer patients from MSK-IMPACT cohort. TMS55, TMS of 55 favorable prognosis genes and TMB were calculated and compared in 1,661 advanced cancer patients treated with ICI and 3,840 matching non-ICI patients of ten major cancer types.
Results
TMS55 was significantly associated with TMB. In 1,661 ICI patients, high TMS55 (TMS55>5) was more robust than high TMB (highest 20% in each histology) in predicting better overall survival. Separately, TMS55 was significantly associated with improved survival in more tumor types than TMB with smaller hazard ratio values, especially in non-small cell lung cancer, melanoma, bladder cancer and colorectal cancer. Conversely, high TMS55 and TMB predicted worse overall survival in 3,840 non-ICI patients.
Conclusions
Novel TMS55 might be better than TMB as biomarker for patients treated with ICI and customized TMS might substitute non-selective TMB as mutation-based biomarker. Easy calculation and universal cutoff value of TMS will not be affected across platforms and is more feasible in clinical, which may greatly promote its application in clinical with further validations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
97P - The role of adjuvant chemotherapy according to the status of surgical margin in rectal cancer
Presenter: Jong Hoon Lee
Session: Poster display session
Resources:
Abstract
98P - Influence of DPYD*9, DPYD*6 and GSTP1 ile105val genetic polymorphisms on capecitabine and oxaliplatin (CAPOX) associated toxicities in colorectal cancer patients
Presenter: Ashok Varma
Session: Poster display session
Resources:
Abstract
99P - Patient-derived tumour model by new culture method leading to the precision medicine
Presenter: Norikatsu Miyoshi
Session: Poster display session
Resources:
Abstract
100P - Clinical impact and carcinogenic mechanism of NCAPG overexpression in colon cancer
Presenter: Kai-Yuan Lin
Session: Poster display session
Resources:
Abstract
101P - Combined cellular immunotherapy and chemotherapy improves clinical outcome and displays safety in the treatment of patients with colorectal cancer
Presenter: Chang Wang
Session: Poster display session
Resources:
Abstract
102P - Clinical features of anorectal cancer in patients with Crohn’s disease: Japanese single center study
Presenter: Kazuhiro Watanabe
Session: Poster display session
Resources:
Abstract
103P - Contrast-enhanced CT-based textural parameters as potential prognostic factors of survival for colorectal cancer patients receiving targeted therapy
Presenter: Yanfei Yang
Session: Poster display session
Resources:
Abstract
104P - Prognostic significance of tumour location to the oncologic outcome of colon cancer
Presenter: Sare Hosseini
Session: Poster display session
Resources:
Abstract
105P - Detection and clinical significance of circulating tumour cells in patients with rectal cancer
Presenter: Shuohui Dong
Session: Poster display session
Resources:
Abstract
106P - The risk of malignization incidence in patients with polyps and polyposis of the colon and rectum
Presenter: Yakov Ten
Session: Poster display session
Resources:
Abstract