ArticleCancer discovery2024
Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Plasma ctDNA kinetics as a predictor of systemic therapy response for advanced non-small cell lung cancer: a systematic review and meta-analysis.The oncologist · 2025Pooled it
- Trial
- Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026Review
- Circulating Cell-free DNA as a biomarker for radiation-induced injury: From mechanistic insights to clinical translation.Cancer metastasis reviews · 2026Review
- Circulating Cell-Free DNA Methylation Profiling Enables Detection, Distinction, and Estrogen Receptor Status Classification of Advanced Breast Cancer.Cancer research · 2026Article
- Advancing the applications of liquid biopsies in oncology.Nature reviews. Genetics · 2026Review
- Longitudinal methylated ctDNA increases predict immunotherapy progression across solid tumors.The journal of liquid biopsy · 2026Article
- Circulating tumor DNA-based minimal residual disease-guided adjuvant therapy in solid tumors: Current evidence, clinical trial frameworks, and future directions.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026Article
- Circulating cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) in oncology: from technological advances to clinical applications.NPJ precision oncology · 2026Review
- Circulating Tumour DNA and Extracellular Vesicle-Associated DNA as Biomarkers for Cancer Detection: A Systematic Review and Meta-Analysis.Journal of extracellular biology · 2026Article
- Review
- Investigating Early Kinetics in Plasma ctDNA and Peripheral T-cell Receptor Repertoire to Predict Treatment Outcomes to PD-1 Inhibitors in Head and Neck Squamous Cell Carcinoma.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
- A pan-cancer compendium of 1,294 plasma cell-free DNA methylomes and fragmentomes enabling multicancer detection.Nature cancer · 2026Article
- Prognostic value of tumor-informed ctDNA in HPV-independent head and neck squamous cell carcinoma.medRxiv : the preprint server for health sciences · 2026Article
- Emerging liquid biopsy markers in thyroid cancer: from isolation technologies to clinical translation.Frontiers in endocrinology · 2026Review
- A composite biomarker based on early dynamic changes in lactate dehydrogenase and PD-L1 expression enhances outcome prediction for immunochemotherapy in HER2-negative advanced gastric cancer.Frontiers in immunology · 2026Article
- Circulating tumour cells and circulating tumour DNA in head and neck cancer: from molecular insights to clinical impact.Cancer metastasis reviews · 2025Review
- Priming with DNMT Inhibitors Potentiates PD-1 Immunotherapy by Triggering Viral Mimicry in Relapsed/Refractory NK/T-cell Lymphoma.Cancer discovery · 2025Article
- Genomics and Epigenomics Approaches for the Quantification of Circulating Tumor DNA in Liquid Biopsy: Relevance of a Multimodal Strategy.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab but typically requires sequencing of matched tumor tissue or fixed gene panels. We analyzed genome-wide methylation and fragment-length profiles using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq) in 204 plasma samples from 87 patients before and during treatment with pembrolizumab from a pan-cancer phase II investigator-initiated trial (INSPIRE). We trained a pan-cancer methylation signature using independent methylation array data from The Cancer Genome Atlas to quantify cancer-specific methylation (CSM) and fragment-length score (FLS) for each sample. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. Early kinetics of CSM predict overall survival and progression-free survival, independently of tumor type, PD-L1, and tumor mutation burden. Early kinetics of FLS are associated with overall survival independently of CSM. Our tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab. SIGNIFICANCE: Analysis of methylation and fragment length in plasma using cfMeDIP-seq provides a tumor-naive approach to measure ctDNA with results comparable with a tumor-informed bespoke ctDNA. Early kinetics within the first weeks of treatment in methylation and fragment quantity can predict outcomes with pembrolizumab in patients with various advanced solid tumors. This article is featured in Selected Articles from This Issue, p. 897.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.