# Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies

Source: https://onco.cc/key-papers/paper-gao-thunder-ann-oncol-2023/  
OnCo record `paper-gao-thunder-ann-oncol-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The Chinese validation study behind Burning Rock's OverC test: in an independent set of 1,010 people it found about seven in ten of six cancers with about one false positive in a hundred.

## Summary

THUNDER (NCT04820868) evaluated enhanced linear-splinter amplification sequencing of cell-free DNA methylation over a panel of 161,984 CpG sites for six cancers (colorectum, oesophagus, liver, lung, ovary and pancreas). Two models were trained on 1,693 retrospective samples and validated in a prospective, independent, age-matched cohort of 1,010 people (505 with cancer). MCDBT-1 had 69.1% sensitivity (64.8 to 73.3), 98.9% specificity (97.6 to 99.7) and 83.2% tissue-origin accuracy; sensitivity for stages I to III was 59.8%. MCDBT-2, at 95.1% specificity, had 75.1% sensitivity. A simulation using Chinese incidence projected reductions in late-stage incidence; that is a model, not an observed outcome.

## Fields

- Kind: Key paper
- Last checked: 2026-10-29
- Journal: Annals of Oncology
- Year: 2023
- DOI: 10.1016/j.annonc.2023.02.010
- Authors: Gao Q, Lin YP, Li BS, et al.
- Findings: MCDBT-1: sensitivity 69.1%, specificity 98.9%, tissue-origin accuracy 83.2% in independent validation.; Stage I to III sensitivity 59.8%; no stage I figure in the abstract.
- What it means: The strongest published evidence for OverC, still from people already diagnosed with cancer rather than a screening population.
- Caveats: Case-control validation, half the set had cancer.; Late-stage reductions are simulated, not observed.; Burning Rock collaborated.

## Sources

- Annals of Oncology 2023: THUNDER: https://doi.org/10.1016/j.annonc.2023.02.010
- PubMed: https://pubmed.ncbi.nlm.nih.gov/36849097/
- ClinicalTrials.gov NCT04820868: https://clinicaltrials.gov/study/NCT04820868

## Connected records

- fronts: [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- technologies: [Cell-free DNA methylation tests](https://onco.cc/technologies/cfdna-methylation-testing/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/)
- drugs: [OverC Multi-Cancer Detection Blood Test](https://onco.cc/drugs/overc-mcdbt/)
- companies: [Burning Rock Biotech](https://onco.cc/companies/burning-rock/)
- trials: [THUNDER (blinded validation of Burning Rock's methylation test)](https://onco.cc/trials/thunder-overc/)
- journals: [Annals of Oncology](https://onco.cc/journals/annals-of-oncology/)

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