ReviewJournal for immunotherapy of cancer2021
Assessing tumor heterogeneity: integrating tissue and circulating tumor DNA (ctDNA) analysis in the era of immuno-oncology - blood TMB is not the same as tissue TMB.
Review in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Evaluating Tumour Mutational Burden as a Key Biomarker in Personalized Cancer Immunotherapy: A Pan-Cancer Systematic Review.Cancers · 2025Pooled it
- Toripalimab plus chemotherapy for first line treatment of advanced non-small cell lung cancer (CHOICE-01): final OS and biomarker exploration of a randomized, double-blind, phase 3 trial.Signal transduction and targeted therapy · 2024Trial
- Necessity for Development and Validation of Comprehensive Circulating Tumor DNA Profiling Panels.Annals of laboratory medicine · 2026Article
- Prognostic Impact of Blood Tumor Mutational Burden in pMMR/MSS Metastatic Colorectal Cancer Assessed by FoundationOneCancers · 2026Article
- Evolving non-invasive biomarkers in NSCLC immunotherapy: integrating liquid biopsy and multi-omics profiling for precision oncology.Frontiers in immunology · 2026Review
- Prognostic value of ctDNA-derived maximum somatic allele frequency in patients with metastatic gastric cancer.Therapeutic advances in medical oncology · 2026Article
- Immune biomarkers for head and neck cancer.Cancer immunology, immunotherapy : CII · 2025Review
- The role of neoantigens and tumor mutational burden in cancer immunotherapy: advances, mechanisms, and perspectives.Journal of hematology & oncology · 2025Review
- Tissue-agnostic biomarkers in solid tumors: current approvals and emerging candidates.Cancer metastasis reviews · 2025Review
- Review
- Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols.Journal for immunotherapy of cancer · 2025Article
- Review
- Differential impact of intratumor heterogeneity (ITH) on survival outcomes in early-stage lung squamous and adenocarcinoma based on tumor mutational burden (TMB).Translational lung cancer research · 2024Article
- Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP.Cancer research and treatment · 2024Review
- Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP.Journal of pathology and translational medicine · 2024Review
- Implication of Pre- and Post-radiotherapy ctDNA Dynamics in Patients with Residual Triple-Negative Breast Cancer at Surgery after Neoadjuvant Chemotherapy: Findings from a Prospective Observational Study.Cancer research and treatment · 2024Observational
- Modeling the Effect of Spatial Structure on Solid Tumor Evolution and Circulating Tumor DNA Composition.Cancers · 2024Article
- Challenges and Future Directions in the Management of Tumor Mutational Burden-High (TMB-H) Advanced Solid Malignancies.Cancers · 2023Review
- Modeling the effect of spatial structure on solid tumor evolution and ctDNA composition.bioRxiv : the preprint server for biology · 2023Article
- Biomarkers for Immune Checkpoint Inhibitors in Renal Cell Carcinoma.Journal of clinical medicine · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue tumor mutational burden (tTMB) is calculated to aid in cancer treatment selection. High tTMB predicts a favorable response to immunotherapy in patients with non-small cell lung cancer. Blood TMB (bTMB) from circulating tumor DNA is reported to have similar predictive power and has been proposed as an alternative to tTMB. Across many studies not only are tTMB and bTMB not concordant but also as reported previously by our group predict conflicting outcomes. This implies that bTMB is not a substitute for tTMB, but rather a composite index that may encompass tumor heterogeneity. Here, we provide a thorough overview of the predictive power of TMB, discuss the use of tumor heterogeneity alongside TMB to predict treatment response and review several methods of tumor heterogeneity assessment. Furthermore, we propose a hypothetical method of estimating tumor heterogeneity and touch on its clinical implications.
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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.