domingo, 22 de julio de 2018

Urinary measurement of circulating tumor DNA for treatment monitoring and prognosis of metastatic colorectal cancer patients. - PubMed - NCBI

2018 Jul 17. pii: /j/cclm.ahead-of-print/cclm-2017-0675/cclm-2017-0675.xml. doi: 10.1515/cclm-2017-0675. [Epub ahead of print]

Urinary measurement of circulating tumor DNA for treatment monitoring and prognosis of metastatic colorectal cancer patients.

Song T1, Mao F2, Shi L1, Xu X1, Wu Z1, Zhou J1, Xiao M3.

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Abstract

Background Solid tumor tissue testing is the gold standard for molecular-based assays for metastatic colorectal cancer (mCRC). This poses challenges during treatment monitoring. Total DNA derived from urine specimens offers clear advantages to track the disease dynamics. Our study aims to evaluate the sensitivity for total DNA recovered from urine and its clinical relevance to mCRC. Methods KRAS mutations in urine specimens were examined in 150 mCRC patients. Baseline concordance was established to determined clinical relevance. The total DNA quantities were also prospectively examined in serial samplings during treatment. Results Analysis of the genetic mutations showed good agreement for baseline samples. Matched tumor and urine specimens' molecular profiles were observed to have 90% concordance. Comparing with healthy volunteers, we established a cutoff of 8.15 ng that demonstrated elevated total DNA levels was associated with mCRC patients (sensitivity: 90.7%; specificity: 82.0%). For patients treated with chemotherapy or anti-epidermal growth factor receptor inhibitors, DNA quantity mirrored early treatment response. Survival analysis showed that patients with sustained elevated quantities of KRAS mutations had poorer outcome. Conclusions Total urine DNA offers a viable complement for mutation profiling in mCRC patients, given the good agreement with matched tumor samples. Our study also established that this is specific based on the results from healthy individuals. Serial monitoring of total DNA levels allowed early prediction to treatment response and was effective to identify high risk patients. This is potentially useful to complement current disease management.