# TOTEM: a multi-cancer detection and localization approach using circulating tumor DNA methylation markers

Source: https://onco.cc/key-papers/paper-totem-genecast-bmc-cancer-2024/  
OnCo record `paper-totem-genecast-bmc-cancer-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Genecast's methylation blood test for seven cancers found about two in three cancers in a laboratory set at 98 to 100% specificity, and about half of early-stage cancers.

## Summary

Xiong and colleagues (Kunming Medical University with Genecast Biotechnology, Wuxi) ran enzymatic-conversion targeted methylation sequencing of plasma from 500 healthy controls and 733 patients with breast, colorectal, oesophageal, gastric, liver, lung or pancreatic cancer, plus an independent cohort of 143 controls and 179 liver or stomach cancer patients. The model used 57 diagnostic markers and 873 origin markers. Specificity was 100% in testing and 98.6% in independent validation; overall sensitivity was 67.3% and 55.9%; early-stage (I and II) sensitivity was 45.7% in testing. Among correctly detected cancers the top predicted origin was right in 77.7% (testing) and 76.0% (independent validation). The authors state that real-world performance needs a much larger prospective cohort.

## Fields

- Kind: Key paper
- Last checked: 2026-11-03
- Journal: BMC Cancer
- Year: 2024
- DOI: 10.1186/s12885-024-12626-7
- Authors: Xiong D, Han T, Li Y, Hong Y, et al.
- Findings: Testing cohort: 67.3% sensitivity at 100% specificity; independent validation: 55.9% at 98.6%.; Stage I and II sensitivity 45.7% in testing.; Top predicted origin correct in 76 to 78% of detected cancers.
- What it means: A company development study with known cancers; the authors themselves say it has to be tested prospectively.
- Caveats: Case-control; independent validation covered only liver and stomach cancer.; Genecast affiliation among authors.

## Sources

- BMC Cancer 2024: TOTEM: https://doi.org/10.1186/s12885-024-12626-7
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39009999/

## 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: [TOTEM (Genecast)](https://onco.cc/drugs/totem-genecast/)
- companies: [Genecast Biotechnology](https://onco.cc/companies/genecast/)
- journals: [BMC cancer](https://onco.cc/journals/bmc-cancer/)

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