Role of ctDNA Tumor Fraction in Selecting Immunotherapy Based Regimens in Advanced Non-small Cell Lung Cancer.

Authors

Filippo G Dall'Olio, Wael Zrafi, Damien Vasseur, Camilo Garcia, Kristi Beshiri, Arianna Marinello, Marco Tagliamento, David Planchard, Nathalie Lassau, Damien Drubay, Aaron Mamann, Lama Dawi, Littisha Lawrance, Ludovic Lacroix, Fabrice Barlesi, Daniel Gautheret, Etienne Rouleau, Desirée de Andreis, Amaya Gasco, Lincoln W Pasquina, Antoine Italiano, Geoffrey R Oxnard, Russell W Madison, Benjamin Besse

Published in

Clinical cancer research : an official journal of the American Association for Cancer Research. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

Immune checkpoint blockers (ICBs) 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.
Liquid biopsy (LBx) assessment was performed using hybrid capture-based next-generation sequencing of plasma cell-free DNA. LBx data, molecular profile, and clinico-pathological data were collected. The predictive and prognostic values of tumor fraction (TF) were assessed using a de-identified nationwide (US-based) NSCLC clinicogenomic database (CGDB). An independent cohort with aNSCLC from Gustave Roussy was used to validate the findings and to study the correlation of ctDNA tumor fraction and total metabolic tumor volume (tMTV) and its molecular correlates.
In 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.
ctDNA TF integrates disease burden and biology. Patients with high ctDNA TF derive greater benefit from chemo-immunotherapy, supporting its use as a biomarker to guide treatment intensification.

PMID:
42440365
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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