Bloedtest, uitgevoerd op in bloed circulerend DNA (ctDNA) op DNA mutaties afwijkingen, kan heel nauwkeurig nagenoeg alle vormen van kanker ontdekken.

4 juni 2023: zie ook dit artikel: https://kanker-actueel.nl/galleri-bloedtest-geeft-uitstekende-resultaten-via-ctdna-en-voorspelt-voor-85-procent-plaats-van-primaire-tumor-en-slechts-paar-procent-vals-positieve-uitslag.html

30 maart 2023: lees ook in gerelateerde artikelen

13 oktober 2022: lees ook dit artikel: https://kanker-actueel.nl/bloedtest-mced-spoort-kanker-op-nog-voor-de-eerste-symptomen-optreden-en-geeft-97-procent-zekerheid-blijkt-uit-pathfinderstudie.html

2 april 2020: Bron: Annals of oncology

Een bloedtest, uitgevoerd op in bloed circulerend DNA (ctDNA) op de zogenoemde methylatie afwijkingen, kan heel nauwkeurig nagenoeg alle vormen van kanker ontdekken. Ook ruim voordat mensen klachten / symptomen van kanker vertonen kwamen er resultaten naar voren die aantoonden dat die mensen ook al kanker hadden. Bovendien kunnen artsen via deze bloedtest redelijk goed inschatten waar een tumor zich bij de patiënt bevindt.

Wetenschappers van de Mayo Clinic in Rochester, Minnesota beoordeelden de prestaties van een doelgerichte methyleringsanalyse van in bloed circulerend DNA (ctDNA) onder 6.689 deelnemers (2.428 mensen met kanker [> 50 typen] en 4.207 mensen zonder kanker) die waren onderverdeeld in trainings- en validatiesets ( bevestigingsets).

Bij deze bloedtest zochten wetenschappers via een zogeheten machine learning-algoritme naar bekende kankersignalen in het DNA, die methylatiepatronen worden genoemd en waarvan bekend is dat die de genexpressie regelen. Abnormale methylatiepatronen en veranderingen in de genenexpressie kunnen tumorgroei stimuleren.

Uit de gevonden resultaten kwam naar voren dat de bloedtest met succes in feite alle vormen van kanker kon opsporen. De onderzoekers constateerden gelijkblijvende prestaties in zowel de trainings- als de validatiesets. Specificiteit was 99,3 procent in de validatieset.

In een vooraf gespecificeerde set gebruikt voor 12 kankertypes, die jaarlijks verantwoordelijk zijn voor ongeveer 63 procent van de Amerikaanse sterfgevallen door kanker, was de gevoeligheid van stadium I tot III 67,3 procent; gevoeligheid was 43,9 procent voor alle kankertypes. Naarmate het stadium van kanker toenam, nam ook de opsporing toe: bij de vooraf gespecificeerde kankersoorten was de gevoeligheid respectievelijk 39, 69, 83 en 92 procent in stadia I, II, III en IV. In 96 procent van de monsters met een methylatieafwijking en genexpressie die zou duiden op kanker werd de plaats van de primaire tumor voorspeld; lokalisatie van de primaire tumor was nauwkeurig in 93 procent.

En dat is voor een doelgerichte behandeling natuurlijk ontzettend belangrijk. Ook was het vals-positieve percentage slechts 0,7 procent, wat betekent dat minder dan 1 procent van de mensen ten onrechte de diagnose kanker kreeg. Dat is een zeer goed resultaat. Bedenkende dat met de op dit moment gebruikte standaardtesten 10 procent van de vrouwen een diagnose van borstkanker krijgen terwijl ze dat niet hebben.

Belangrijkste punten uit de studie onvertaald:

•: Targeted methylation analysis of cfDNA simultaneously detected and localized >50 cancer types, including high-mortality cancers that lack screening paradigms.
•: Cancers were detected across all stages (stage I–III sensitivity: 43.9%; stage I–IV sensitivity: 54.9%) at a specificity of >99% and a single false positive rate of <1%.
•: This targeted methylation approach localized the tissue of origin with >90% accuracy, which will be critical for directing follow-up care.
•: This supports the continued investigation of this test with the goal of population-scale early multi-cancer detection.

Het volledige studierapport: Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA is gratis in te zien.

Hier het abstract van de studie:

Under a Creative Commons license

open access

Highlights

•: Targeted methylation analysis of cfDNA simultaneously detected and localized >50 cancer types, including high-mortality cancers that lack screening paradigms.
•: Cancers were detected across all stages (stage I–III sensitivity: 43.9%; stage I–IV sensitivity: 54.9%) at a specificity of >99% and a single false positive rate of <1%.
•: This targeted methylation approach localized the tissue of origin with >90% accuracy, which will be critical for directing follow-up care.
•: This supports the continued investigation of this test with the goal of population-scale early multi-cancer detection.

Background

Early cancer detection could identify tumors when outcomes are superior at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity.

Participants and methods

The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization.

Results

Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage I–III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for ∼63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%.

Conclusions

cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.

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