ArticleJournal for immunotherapy of cancer2022
Biological and technical factors in the assessment of blood-based tumor mutational burden (bTMB) in patients with NSCLC.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02894853 (Lung Cancer Early Molecular Assessment Trial), which is not on this map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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.
Lung Cancer Early Molecular Assessment Trial
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Role of tumor mutational burden in patients with urothelial carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Evaluation of tissue- and plasma-derived tumor mutational burden (TMB) and genomic alterations of interest in CheckMate 848, a study of nivolumab combined with ipilimumab and nivolumab alone in patients with advanced or metastatic solid tumors with high TMB.Journal for immunotherapy of cancer · 2023Trial
- Expert consensus on the detection and clinical application of tumor mutational burden.Cancer biology & medicine · 2026Article
- Synthetic Lethal Co-Mutations in DNA Damage Response Pathways Predict Response to Immunotherapy in Pan-Cancer.JCO precision oncology · 2025Article
- Effectiveness and mechanisms of lymphocytes at different time points in predicting consolidation immunotherapy following adaptive chemoradiotherapy in locally advanced non-small cell lung cancer.Frontiers in oncology · 2025Article
- Machine learning-driven estimation of mutational burden highlights DNAH5 as a prognostic marker in colorectal cancer.Biology direct · 2024Article
- Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review.Cancers · 2024Review
- Two nomograms constructed for predicting the efficacy and prognosis of advanced non‑small cell lung cancer patients treated with anti‑PD‑1 inhibitors based on the absolute counts of lymphocyte subsets.Cancer immunology, immunotherapy : CII · 2024Article
- Clinical application of ctDNA in early diagnosis, treatment and prognosis of patients with non-small cell lung cancer.Future oncology (London, England) · 2024Review
- The potential clinical utility of cell-free DNA for gastric cancer patients treated with nivolumab monotherapy.Scientific reports · 2023Article
- Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application.Molecular cancer · 2023Review
- Prognostic Utility of the Modified Glasgow Prognostic Score in Urothelial Carcinoma: Outcomes from a Pooled Analysis.Journal of clinical medicine · 2022Article
- Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II-IIIA NSCLC patients.Molecular oncology · 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
- Erratum issued
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients treated with immunotherapy are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Tumor mutational burden (TMB) has emerged as a promising predictive biomarker but requires tumor tissue which is not always available. Blood-based TMB (bTMB) may provide a minimally invasive assessment of mutational load. However, because of the required sequencing depth, bTMB analysis is costly and prone to false negative results. This study attempted to design a minimally sized bTMB panel, examined a counting-based method for bTMB in patients with stage I to IV non-small cell lung cancer (NSCLC) and evaluated both technical factors such as bTMB and tissue-based TMB (tTMB) cut-off, as well as sample-related factors such as cell-free DNA input mass which influence the correlation between bTMB and tTMB.
methodsTissue, plasma, and whole blood samples collected as part of the LEMA trial (NCT02894853) were used in this study. Samples of 185 treatment naïve patients with stage I to IV NSCLC were sequenced at the Roche Sequencing Solutions with a custom panel designed for TMB, using reagents and workflows derived from the AVENIO Tumor Tissue and circulating tumor DNA Analysis Kits.
resultsA TMB panel of 1.1 Mb demonstrated highly accurate TMB high calls with a positive predictive value of 95% when using a tTMB cut-off of 16 mut/Mb, corresponding with 42 mut/Mb for bTMB. The positive per cent agreement (PPA) of bTMB was relatively low at 32%. In stage IV samples with at least 20 ng of cfDNA input, PPA of bTMB improved to 63% and minimizing the panel to a subset of 577 kb was possible while maintaining 63% PPA.
conclusionPlasma samples with high bTMB values are highly correspondent with tTMB, whereas bTMB low results may also be the result of low tumor burden at earlier stages of disease as well as poorly shedding tumors. For advanced stages of disease, PPA (sensitivity) of bTMB is satisfactory in comparison to tTMB, even when using a panel of less than 600 kb, warranting consideration of bTMB as a predictive biomarker for patients with NSCLC eligible for immunotherapy in the future.
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