Academic Journal
Unraveling the potential clinical utility of circulating tumor DNA detection in colorectal cancer—evaluation in a nationwide Danish cohort
| العنوان: | Unraveling the potential clinical utility of circulating tumor DNA detection in colorectal cancer—evaluation in a nationwide Danish cohort |
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| المؤلفون: | Henriksen, T. V., Demuth, C., Frydendahl, A., Nors, J., Nesic, M., Rasmussen, M. H., Reinert, T., Larsen, O. H., Jaensch, C., Løve, U. S., Andersen, P. V., Kolbro, T., Thorlacius-Ussing, O., Monti, A., Gögenur, M., Kildsig, J., Bondeven, P., Schlesinger, N. H., Iversen, L. H., Gotschalck, K. A., Andersen, C. L. |
| المصدر: | Henriksen , T V , Demuth , C , Frydendahl , A , Nors , J , Nesic , M , Rasmussen , M H , Reinert , T , Larsen , O H , Jaensch , C , Løve , U S , Andersen , P V , Kolbro , T , Thorlacius-Ussing , O , Monti , A , Gögenur , M , Kildsig , J , Bondeven , P , Schlesinger , N H , Iversen , L H , Gotschalck , K A & Andersen , C L 2024 , ' Unraveling the potential clinical .... |
| سنة النشر: | 2024 |
| المجموعة: | University of Southern Denmark: Research Output / Syddansk Universitet |
| مصطلحات موضوعية: | cell-free DNA, circulating tumor DNA, colorectal cancer, minimal residual disease, recurrence surveillance, Circulating Tumor DNA/genetics, Humans, Neoplasm Recurrence, Local, Biomarkers, Tumor/genetics, Colorectal Neoplasms/diagnosis, DNA, Neoplasm/genetics, Algorithms, Denmark |
| الوصف: | Background: Increasingly, circulating tumor DNA (ctDNA) is proposed as a tool for minimal residual disease (MRD) assessment. Digital PCR (dPCR) offers low analysis costs and turnaround times of less than a day, making it ripe for clinical implementation. Here, we used tumor-informed dPCR for ctDNA detection in a large colorectal cancer (CRC) cohort to evaluate the potential for post-operative risk assessment and serial monitoring, and how the metastatic site may impact ctDNA detection. Additionally, we assessed how altering the ctDNA-calling algorithm could customize performance for different clinical settings. Patients and methods: Stage II-III CRC patients (N = 851) treated with a curative intent were recruited. Based on whole-exome sequencing on matched tumor and germline DNA, a mutational target was selected for dPCR analysis. Plasma samples (8 ml) were collected within 60 days after operation and—for a patient subset (n = 246)—every 3-4 months for up to 36 months. Single-target dPCR was used for ctDNA detection. Results: Both post-operative and serial ctDNA detection were prognostic of recurrence [hazard ratio (HR) = 11.3, 95% confidence interval (CI) 7.8-16.4, P < 0.001; HR = 30.7, 95% CI 20.2-46.7, P < 0.001], with a cumulative ctDNA detection rate of 87% at the end of sample collection in recurrence patients. The ctDNA growth rate was prognostic of survival (HR = 2.6, 95% CI 1.5-4.4, P = 0.001). In recurrence patients, post-operative ctDNA detection was challenging for lung metastases (4/21 detected) and peritoneal metastases (2/10 detected). By modifying the cut-off for calling a sample ctDNA positive, we were able to adjust the sensitivity and specificity of our test for different clinical contexts. Conclusions: The presented results from 851 stage II-III CRC patients demonstrate that our personalized dPCR approach effectively detects MRD after operation and shows promise for serial ctDNA detection for recurrence surveillance. The ability to adjust sensitivity and specificity shows exciting ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1016/j.annonc.2023.11.009 |
| الاتاحة: | https://portal.findresearcher.sdu.dk/da/publications/7c3bfce4-b4f4-47a8-a5f7-06c156f563ef https://doi.org/10.1016/j.annonc.2023.11.009 https://findresearcher.sdu.dk/ws/files/255744575/1-s2.0-S0923753423050731-main.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.83A4DCF7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.annonc.2023.11.009 |
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