ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026
Role of ctDNA Tumor Fraction in Selecting Immunotherapy-Based Regimens in Advanced Non-Small Cell Lung Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Circulating tumor DNA tumor fraction as a biomarker in refractory metastatic colorectal cancer: findings from the CAVE-2 GOIM trial.The journal of liquid biopsy · 2026Article
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24 authors.
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Abstract
purposeImmune checkpoint blockers (ICB) have transformed advanced non-small cell lung cancer (aNSCLC) treatment, but identifying patients who benefit from adding chemotherapy remains challenging, especially in PD-L1 ≥ 50%. PD-L1 is an imperfect biomarker, highlighting the need for better selection tools. EXPERIMENTAL
designLiquid biopsy (LBx) assessment was performed using hybrid capture-based next-generation sequencing of plasma cell-free DNA. LBx data, molecular profile, and clinicopathologic data were collected. The predictive and prognostic values of tumor fraction (TF) were assessed using a deidentified nationwide (US-based) NSCLC clinicogenomic database [Clinico-Genomic Database (CGDB)]. An independent cohort with aNSCLC from Gustave Roussy was used to validate the findings and to study the correlation of circulating tumor DNA (ctDNA) TF and total metabolic tumor volume and its molecular correlates.
resultsIn the CGDB database (n = 965), elevated ctDNA TF was prognostic for worse outcomes on ICBs and, when ≥5%, predictive of benefit from ICB + chemotherapy [HR for real-world progression-free survival 0.58 (0.41-0.82); P = 0.002]. The 5% cutoff for TF was validated in an independent cohort from Gustave Roussy. In 283 patients with paired PET scans, ctDNA TF correlated with metabolic tumor volume (rho = 0.46; P < 0.001) and was influenced by TP53/RB1 mutations.
conclusionsctDNA TF integrates disease burden and biology. Patients with high ctDNA TF derive greater benefit from chemoimmunotherapy, supporting its use as a biomarker to guide treatment intensification.
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