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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Unseld, M; Belic, J; Pierer, K; Zhou, Q; Moser, T; Bauer, R; Piringer, G; Gerger, A; Siebenhüner, A; Speicher, M; Heitzer, E; Prager, GW.
A higher ctDNA fraction decreases survival in regorafenib-treated metastatic colorectal cancer patients. Results from the regorafenib's liquid biopsy translational biomarker phase II pilot study.
Int J Cancer. 2021; 148(6):1452-1461 Doi: 10.1002/ijc.33303 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Führende Autor*innen der Med Uni Graz
Heitzer Ellen
Co-Autor*innen der Med Uni Graz
Bauer Raimund
Belic Jelena
Gerger Armin
Moser Tina
Pierer Kerstin
Speicher Michael
Zhou Qing

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The predictive effect of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) treatment is still highly discussed. The primary objective of our study was to investigate a possible prognostic/predictive value of ctDNA under regorafenib treatment. This prospective multicenter translational biomarker phase II pilot study enrolled 30 metastatic CRC patients (67% men, 33% women) treated with regorafenib. ctDNA was assessed in plasma before treatment start and at defined time points during administration. Measurement of tumor fraction as well as mutation and copy number analysis of CRC driver genes were performed by next-generation sequencing approaches. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and Eastern Cooperative Oncology Group. Disease control rate was 30%. Median tumor fraction at baseline was 18.5% (0-49.9). Mutations in CRC driver genes or genes involved in angiogenesis were identified in 25 patients (83.3%). KRAS mutations were detected in 13 of 14 KRAS-positive tumors; in three patients without KRAS mutation in the respective tumors, acquired mutations as a consequence of prior anti-EGFR treatment were detected. In a subset of patients, novel occurring mutations or focal amplifications were detected. A tumor fraction of 5% and higher at baseline was significantly associated with a decreased OS (P = .022; hazard ratio 3.110 (95% confidence interval: 1.2-8.2). ctDNA is detectable in a high proportion of mCRC patients. Higher ctDNA levels are associated with survival among regorafenib treatment. Moreover, our data highlight the benefit of a combined evaluation of mutations and somatic copy number alterations in advanced cancer patients.
Find related publications in this database (using NLM MeSH Indexing)
Adult - administration & dosage
Aged - administration & dosage
Biomarkers, Tumor - blood
Circulating Tumor DNA - blood
Colorectal Neoplasms - blood, drug therapy, genetics
Female - administration & dosage
Humans - administration & dosage
Liquid Biopsy - administration & dosage
Male - administration & dosage
Middle Aged - administration & dosage
Phenylurea Compounds - therapeutic use
Pilot Projects - administration & dosage
Prospective Studies - administration & dosage
Pyridines - therapeutic use
Treatment Outcome - administration & dosage

Find related publications in this database (Keywords)
circulating tumor DNA
metastatic colorectal cancer
prospective pilot study
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