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Poster display session

1270 - A Novel Circulating Cell Free DNA-Based Assay Can Predict Tumor Response to Systematic Chemotherapy

Date

11 Sep 2017

Session

Poster display session

Presenters

Toshiaki Toshima

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

T. Toshima1, T. Nagasaka1, Y. Mori1, T. Kawai1, K. YASUI1, T. Fuji1, F. Taniguchi1, K. Kimura1, H. Kishimoto1, Y. Umeda1, A. Goel2, T. Fujiwara1

Author affiliations

  • 1 Gastroenterological Surgery, Okayama University Hospital, 700-8558 - Okayama/JP
  • 2 Center For Gastrointestinal Research Center For Translational Genomics And Oncology, CeBaylor Scott & White Research Institutenter for Translational Genomics and Oncology, 75246 - Texas/US
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Resources

Abstract 1270

Background

Although circulating cell-free DNA (cfDNA) in blood is being touted as a frontier noninvasive approaches, its clinical utility still remains questionable. The purpose of this study was to compare the efficacy of cfDNA by comparing with blood CEA levels and radiological evaluation in patients with unresectable metastatic colorectal cancer (mCRC) during treatment of systemic chemotherapy.

Methods

In this study, 12 patients with mCRC who were intended to receiving systemic chemotherapy were enrolled. Methylation status of CpG sites, considered as cancer-specific alteration, and concentration of cfDNA were evaluated from blood plasma obtained before administration of systemic chemotherapy in each treatment cycle. To analyze aberrant cancer-specific methylation, we modified the highly sensitive assay for bisulfite DNA (Hi-SA) followed by fluorescence-based PCR, as reported previously (JNCI 2009). Our modified methodology can detect 8 loci of target promoters, therefore methylation score (MS) could be ranged from 0 to 8 at a given time.

Results

Of the 12 patients enrolled, 10 patients experienced radiological progressive disease (PD). Plasma MS was significantly increased before radiological PD in 8 of 10 patients with PD. Thus MS had the median lead time of 73 days (range: 0-231 days) before documentation of radiological PD. In contrast, serum CEA level could predict PD only in the 2 patients before documentation of their radiological PD. Consequently, plasma MS could predict radiological PD with the median lead time of 9 days (range: 0-21 days) compared with serum CEA. We also examined whether cfDNA concentration level in plasma was associated with radiological PD. Of the 12 patients, only 3 patients increased cfDNA concentration level before radiological PD with the median lead time of 88 days (range; 21-140 days).

Conclusions

Our circulating cell free DNA-based assay is a robust methodology for capturing DNA methylation in circulating cell-free DNA in plasma, and is useful for the early identification of CRC patients that are at risk of developing PD prior to radiographic documentation.

Clinical trial identification

Legal entity responsible for the study

Takeshi Nagasaka

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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