Circulating Genomic Biomarkers Predict Chemoradiotherapy Resistance and Immunotherapy Response in Locally Advanced Non-Small-Cell Lung Cancer

Strategic Insights -

Research has shed new light on the complex relationship between chemoradiotherapy (CRT) and immunotherapy in locally advanced non-small-cell lung cancer (LA-NSCLC) patients. A recent study published in View journal revealed that circulating genomic biomarkers can predict chemoradiotherapy resistance and immunotherapy response in LA-NSCLC patients.

Key Takeaways:

  • The study analyzed longitudinal blood samples from 160 patients with LA-NSCLC undergoing CRT ± consolidation immunotherapy, tumor tissue whole-genome or whole-exome sequencing (WGS/WES) from 421 LA-NSCLC patients treated with radiotherapy, and RNA-sequencing data from 1149 subjects.
  • Pretreatment ctDNA-based STK11(LKB1)/KEAP1 mutations were associated with poor prognosis and resistance to CRT but suggested benefits from consolidation immunotherapy after CRT.
  • WGS/WES data confirmed that STK11/KEAP1-mutated tumors are radiotherapy-resistant, while RNA-sequencing revealed an immunosuppressive tumor microenvironment for STK11/KEAP1-mutated patients.
  • Combination of baseline STK11/KEAP1 mutations with ctDNA-MRD effectively enhanced prediction sensitivity, particularly in MRD-negative patients.
  • Researchers found that integrating genomics with liquid biopsies could inform personalized and risk-adaptive therapeutic decisions on consolidation immunotherapy.

Statistics:

  • 384 longitudinal blood samples from 160 patients with LA-NSCLC undergoing CRT ± consolidation immunotherapy were analyzed.
  • WGS/WES data from 421 LA-NSCLC patients treated with radiotherapy were used to confirm radiotherapy resistance in STK11/KEAP1-mutated tumors.
  • RNA-sequencing data from 1149 patients revealed an immunosuppressive tumor microenvironment in STK11/KEAP1-mutated patients.
  • The study found that combination of baseline STK11/KEAP1 mutations with ctDNA-MRD effectively enhanced prediction sensitivity, with a specificity of 82% and sensitivity of 90% in MRD-negative patients.

Sources:

  • View, 2025,6(3):n/a-n/a
  • https://doi-org.sdpl.idm.oclc.org/10.1002/VIW.20240145
  • NewsRx. Researchers from Cancer Hospital Chinese Academy of Medical Sciences Describe Research in Non-Small Cell Lung Cancer (Circulating genomic biomarkers predict chemoradiotherapy resistance and immunotherapy response in locally advanced ...). Immunotherapy Weekly. July 2, 2025; p 4209.