Prognostic Value of Serum NPY Hypermethylation in Neoadjuvant Chemoradiotherapy for Rectal Cancer
| Autor: | Rikke F. Andersen, Anders Jakobsen, Jan Lindebjerg, Ane L Appelt |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Multivariate analysis Colorectal cancer business.industry Proportional hazards model Hazard ratio medicine.disease Confidence interval law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law 030220 oncology & carcinogenesis Internal medicine medicine 030212 general & internal medicine Prospective cohort study business Survival rate |
| Zdroj: | Appelt, A L, Andersen, R F, Lindebjerg, J & Jakobsen, A 2020, ' Prognostic Value of Serum NPY Hypermethylation in Neoadjuvant Chemoradiotherapy for Rectal Cancer : Secondary Analysis of a Randomized Trial ', American Journal of Clinical Oncology, vol. 43, no. 1, pp. 9-13 . https://doi.org/10.1097/COC.0000000000000609 |
| ISSN: | 0277-3732 |
| DOI: | 10.1097/coc.0000000000000609 |
| Popis: | Objectives: Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial. Materials and Methods: Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer. Positivity for and fractional abundance of meth-ctDNA in baseline samples were estimated. Overall survival (OS) and the rate of distant metastases were compared between meth-ctDNA positive and negative patients; other prognostic factors were controlled for in multivariate Cox regression. Importance of quantitative load was examined by considering the fractional abundance of meth-ctDNA relative to total circulating DNA. Results: Baseline serum samples were available for 146 patients. In total, 30 patients had presence of meth-ctDNA, with no correlation with cT (P=0.8) or cN (P=0.6) stages. Median follow-up was 10.6 years for OS and 5.1 years for freedom from distant metastases. Patients with meth-ctDNA had significantly worse 5-year OS (47% vs. 69%), even when controlling for other prognostic factors (hazard ratio=2.08; 95% confidence interval, 1.23-1.51). This seemed mainly driven by disparity in the rate of distant metastases (55% vs. 72% at 5 y, P=0.01); hazard ratio=2.20 (95% confidence interval, 1.19-4.07, P=0.01) in multivariate analysis. Increased quantitative load was highly significant for worse outcomes. Conclusions: Meth-ctDNA could be a potential prognostic marker in the neoadjuvant setting and may, if validated, identify patients at increased risk of distant metastases. |
| Databáze: | OpenAIRE |
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