Dataset Information

BITH, a blood-based metric of intratumor heterogeneity, is associated with clinical response to immune checkpoint blockade in non-small cell lung cancer.

ABSTRACT:

Background

Intratumor heterogeneity (ITH) has been associated with poor prognosis in advanced non-small cell cancer (NSCLC) patients receiving immune checkpoint blockade (ICB) therapies. However, there is currently no evidence supporting an ITH metric as a predictor of clinical benefit from ICB. The unique advantages of blood make it a promising material for ITH estimation and relevant applications. This study aims to develop and validate a blood-based ITH index for predicting ICB response.

Methods

NSCLC patients from the OAK and POPLAR clinical trials were used as the training cohorts for algorithm development. Survival analyses with overall survival (OS) and progression-free survival (PFS) as endpoints were performed to assess clinical response. The predictive value of bITH was subsequently validated with an independent cohort of 42 NSCLC patients treated with PD-1 blockade.

Findings

bITH was significantly associated with the differential OS and PFS elicited by atezolizumab vs. docetaxel in both univariable and multivariable analyses in the OAK patients, suggesting bITH as an independent predictor for response to ICB. Moreover, compared with blood tumor mutation burden (bTMB), bITH enabled greater OS segregation and comparable PFS segregation, and obtained a predictive role regardless of bTMB status. Moreover, the association between bITH and PFS was validated with an independent cohort.

Interpretation

Patients with low blood-based ITH metric manifest significant OS and PFS benefit from immunotherapy versus chemotherapy. Future research is awaited to corroborate our findings and to enrich the clinical utility of ITH.

Funding

This study was supported by the National Natural Science Foundation of China (Nos. 81972718 and 81572321), the Natural Scientific Foundation of Zhejiang Province, China (No. LY19H160007), the Science and Technology Program for Health and Medicine in Zhejiang Province, China (No. 2021KY541), the Scientific Research Project, Science and Technology Department of Sichuan Province (No. 21YYJC1616), the Scientific Research Project, Sichuan Medical Association (No. S20002), Wu Jieping Medical Foundation (No. 320.6750), and 2018 Entrepreneurial Leading Talent of Guangzhou Huangpu District and Guangzhou Development District (No. 2022-L023).

SUBMITTER: Fan Y

PROVIDER: S-EPMC10149223 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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bITH, a blood-based metric of intratumor heterogeneity, is associated with clinical response to immune checkpoint blockade in non-small cell lung cancer.

Fan Yun Y Liu Yang Y Liu Yang Y Wang Liuchun L Cai Yiran Y Cao Wen W Sun Wenjie W Zou Xiao X Li Bing B Zhang Zhou Z Cai Shangli S Chuai Shannon S Han Yusheng Y Pan Xiaojie X Huang Dingzhi D

EBioMedicine 20230423

<h4>Background</h4>Intratumor heterogeneity (ITH) has been associated with poor prognosis in advanced non-small cell cancer (NSCLC) patients receiving immune checkpoint blockade (ICB) therapies. However, there is currently no evidence supporting an ITH metric as a predictor of clinical benefit from ICB. The unique advantages of blood make it a promising material for ITH estimation and relevant applications. This study aims to develop and validate a blood-based ITH index for predicting ICB respon ...[more]

PMID: 37094467

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