ArticleCancer research communications2025
Methylation-Based ctDNA Tumor Fraction Changes Predict Long-Term Clinical Benefit From Immune Checkpoint Inhibitors in RADIOHEAD, a Real-World Pan-Cancer Study.
Article in Cancer research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Disease: Primary Aggregated Analysis of All Baskets from the Phase II Randomized EXTEND Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Trial
- Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026Review
- Longitudinal methylated ctDNA increases predict immunotherapy progression across solid tumors.The journal of liquid biopsy · 2026Article
- Circulating Tumor Function: A Systems Biology Framework for Liquid Biopsy in Genitourinary Cancers.Genes · 2026Review
- Impact of baseline medications on real-world overall survival in immune checkpoint inhibitor-treated patients with cancer in the RADIOHEAD cohort.Med (New York, N.Y.) · 2026Article
- Methylation-based ctDNA monitoring in metastatic breast cancer during CDK4/6 inhibitor therapy.Nature communications · 2026Article
- Longitudinal evaluation of serial ctDNA kinetics using joint modeling in patients with metastatic breast cancer.NPJ precision oncology · 2026Article
- Methylated circulating tumor DNA: technical challenges and clinical applications in non-small cell lung cancer patients-a narrative review.Translational lung cancer research · 2026Review
- Camonsertib, an ATRi, in Combination with Low-Dose Gemcitabine in Solid Tumors with DNA Damage Response Aberrations: Preclinical and Phase Ib Results.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Clinical validation of a tissue-agnostic genome-wide methylome enrichment assay to monitor response to pembrolizumab.NPJ precision oncology · 2026Article
- Liquid biopsies for detection, characterization, and interception of therapy resistance in thoracic malignancies.Frontiers in oncology · 2026Review
- Chemotherapy response monitoring with DNA methylation-based ctDNA tumor fraction: Evidence from a real-world cohort of patients with advanced common solid malignancies.The journal of liquid biopsy · 2025Article
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Authors and funding
13 authors.
Funding
Abstract
Current response evaluation methods have accuracy limitations. Monitoring with a ctDNA methylation-based tumor fraction (TF) may provide a more accurate assessment of tumor burden across solid tumors. In this study, we evaluate a tissue-free, methylation-based TF and explore the association with treatment outcomes in RADIOHEAD, a cohort of 1,070 patients with solid tumors receiving standard-of-care immune checkpoint inhibition (ICI) regimens, with blood samples collected prospectively for retrospective analysis. A total of 1,997 baseline and serial on-treatment plasma samples from 627 patients with stage IV cancer were analyzed with an analytically validated next-generation sequencing methylation-based ctDNA assay (Guardant Reveal). The primary outcome measure was real-world progression-free survival (rwPFS). Secondary outcomes included real-world overall survival (rwOS) and the lead time between nonmolecular response (nMR) to rwPFS event. Patients with any decrease in TF while receiving ICI had superior outcomes. Patients with ≥80% decrease in TF at two timepoints or TF below the limit of quantification had longer rwPFS and rwOS than those with <80% decrease [nMR; rwPFS HR, 0.24 (95% confidence interval, 0.19-0.32) P < 0.005; rwOS HR, 0.28 (95% confidence interval, 0.21-0.38) P < 0.005]. nMR was detected prior to clinical progression in 209 patients with a median lead time of 3.03 months. Among 627 patients with stage IV cancer receiving standard-of-care ICI, monitoring with methylation-based TF identified patients who have significantly longer rwPFS and rwOS. Changes in TF on ICI can provide additional response data earlier than imaging alone and support the potential of serial monitoring to inform treatment decisions. SIGNIFICANCE: This study found that early decreases in tumor DNA levels in the blood are linked to longer survival in patients with cancer treated with immunotherapy. These findings support the use of blood-based monitoring to help predict treatment response and improve decision-making in real-world cancer care.
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