ArticleMolecular diagnosis & therapy2019
Bioinformatic Methods and Bridging of Assay Results for Reliable Tumor Mutational Burden Assessment in Non-Small-Cell Lung Cancer.
Article in Molecular diagnosis & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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
36 citing papers in PubMed.
- Inflammation and mutational burden differentially associated with nivolumab or ipilimumab combination efficacy in colorectal cancer.Nature communications · 2025Trial
- Adjuvant nivolumab in muscle-invasive urothelial carcinoma: exploratory biomarker analysis of the randomized phase 3 CheckMate 274 trial.Nature medicine · 2025Trial
- Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial.Nature medicine · 2025Trial
- Randomized, open-label, phase 2 study of nivolumab plus ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden.Journal for immunotherapy of cancer · 2024Trial
- Nivolumab with or without ipilimumab in pediatric patients with high-grade CNS malignancies: Safety, efficacy, biomarker, and pharmacokinetics-CheckMate 908.Neuro-oncology · 2023Trial
- TMB and Inflammatory Gene Expression Associated with Clinical Outcomes following Immunotherapy in Advanced Melanoma.Cancer immunology research · 2021Trial
- Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Randomized Phase II Trial and Tumor Mutational Spectrum Analysis from Cabozantinib versus Chemotherapy in Metastatic Uveal Melanoma (Alliance A091201).Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Expert consensus on the detection and clinical application of tumor mutational burden.Cancer biology & medicine · 2026Article
- TMB as a predictive biomarker for ICI response in TNBC: current evidence and future directions for augmented anti-tumor responses.Clinical and experimental medicine · 2025Review
- Tumour mutational burden: clinical utility, challenges and emerging improvements.Nature reviews. Clinical oncology · 2024Review
- KRAS and TP53 co-mutation predicts benefit of immune checkpoint blockade in lung adenocarcinoma.British journal of cancer · 2024Article
- Understanding the Impact of Population and Cancer Type on Tumor Mutation Burden Scores: A Comprehensive Whole-Exome Study in Cancer Patients From India.JCO global oncology · 2023Article
- Preclinical investigation of patient-derived cervical cancer organoids for precision medicine.Journal of gynecologic oncology · 2023Article
- Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing.Cancer research communications · 2023Article
- Evaluating Multiple Next-Generation Sequencing-Derived Tumor Features to Accurately Predict DNA Mismatch Repair Status.The Journal of molecular diagnostics : JMD · 2023Article
- Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit.JCO precision oncology · 2022Article
- Article
- Homologous recombination deficiency is inversely correlated with microsatellite instability and identifies immunologically cold tumors in most cancer types.The journal of pathology. Clinical research · 2022Article
- Open the Technical Black Box of Tumor Mutational Burden (TMB): Factors Affecting Harmonization and Standardization of Panel-Based TMB.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTumor mutational burden (TMB) has emerged as a clinically relevant biomarker that may be associated with immune checkpoint inhibitor efficacy. Standardization of TMB measurement is essential for implementing diagnostic tools to guide treatment.
objectiveHere we describe the in-depth evaluation of bioinformatic TMB analysis by whole exome sequencing (WES) in formalin-fixed, paraffin-embedded samples from a phase III clinical trial.
methodsIn the CheckMate 026 clinical trial, TMB was retrospectively assessed in 312 patients with non-small-cell lung cancer (58% of the intent-to-treat population) who received first-line nivolumab treatment or standard-of-care chemotherapy. We examined the sensitivity of TMB assessment to bioinformatic filtering methods and assessed concordance between TMB data derived by WES and the FoundationOne
resultsTMB scores comprising synonymous, indel, frameshift, and nonsense mutations (all mutations) were 3.1-fold higher than data including missense mutations only, but values were highly correlated (Spearman's r = 0.99). Scores from CheckMate 026 samples including missense mutations only were similar to those generated from data in The Cancer Genome Atlas, but those including all mutations were generally higher. Using databases for germline subtraction (instead of matched controls) showed a trend for race-dependent increases in TMB scores. WES and FoundationOne CDx outputs were highly correlated (Spearman's r = 0.90).
conclusionsParameter variation can impact TMB calculations, highlighting the need for standardization. Encouragingly, differences between assays could be accounted for by empirical calibration, suggesting that reliable TMB assessment across assays, platforms, and centers is achievable.
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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 Socratic graph.