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Integrated multi-omic profiling enables recurrence risk stratification beyond pathological stage in resected EGFR-mutant lung adenocarcinoma
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Integrated multi-omic profiling enables recurrence risk stratification beyond pathological stage in resected EGFR-mutant lung adenocarcinoma

Journal of Thoracic Oncology·September 16Open Access
Respiratory SystemPractice changingEGFR-Mutant Non-Small Cell Lung CancerLung AdenocarcinomaRetrospective Cohort StudyEGFR Tyrosine Kinase InhibitorMulti-Omic ProfilingAdultTagrissoOsimertinib

Summary

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What was studied

Integrated clinical, genomic, and transcriptomic profiling of 400 resected stage IA–IIIA EGFR-mutant lung adenocarcinoma (LUAD) patients to develop and validate multi-omic recurrence risk models across one internal and three external cohorts.

Key findings

A multi-omic model achieved a median concordance index of 75.4% across four independent validation cohorts, outperforming clinical or genomic variables alone, and successfully stratified recurrence risk within individual pathological stages—including stage I—while identifying patients most likely to benefit from adjuvant EGFR TKI therapy.

Study limitations

Retrospective design requiring prospective validation in larger cohorts; real-world data show up to 40% of patients remain disease-free at five years without adjuvant osimertinib, suggesting the baseline comparator population is heterogeneous; external cohort characteristics and follow-up durations are not fully described in the abstract.

Clinical implications

Multi-omic profiling (combining genomic and transcriptomic data) can stratify recurrence risk beyond pathological stage in resected EGFR-mutant LUAD and may help identify which stage IB–IIIA patients are most likely to benefit from adjuvant osimertinib—though prospective validation is still needed before routine clinical use.

Caveats

  • The concordance index of 75.4% is a median across validation cohorts—performance in individual cohorts may vary and cohort-level details are not fully reported
  • The study is retrospective; prospective validation in larger, diverse cohorts is explicitly required before clinical implementation
  • Up to 40% of patients in real-world data remain disease-free without adjuvant osimertinib, meaning some patients may currently be overtreated—this model's ability to safely de-escalate therapy has not yet been prospectively confirmed

Related Questions

Explore related topics

Which patients with resected EGFR-mutant lung adenocarcinoma benefit most from adjuvant osimertinib after surgery?How do TP53 co-mutations and APOBEC signatures affect recurrence risk in early-stage EGFR-mutant NSCLC?What biomarkers beyond pathological stage predict recurrence in resected stage I lung adenocarcinoma?

Publication Details

Year
2026
Journal
Journal of Thoracic Oncology
Sample Size
n=400
Source
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