Abstract 1590: Personalized circulating tumor DNA analysis to monitor colorectal cancer
Authors: Reinert Thomas , Henriksen Tenna V. , Rasmussen Mads H. , Sethi Himanshu , Sharma Shruti , Wu Hsin-Ta , Hafez Dina , Natarajan Prashanthi , Dashner Scott , Balcioglu Mustafa , Nguyen Ann , Renner Derrick , Zimmermann Bernhard , Iversen Lene H- , Madsen Mogens R. , Lin Cheng-Ho Jimmy , Andersen Claus L. 
Published: August 2018

Early detection of disease recurrence has shown to improve survival in patients with early-stage colorectal cancer (CRC) (Pita-Fernandez et al., 2015). Detection of circulating tumor DNA (ctDNA) postoperatively in patients with stage II colon cancer provides direct evidence of residual disease and identifies patients at high risk of recurrence (Tie et al., 2016). Previous studies have performed ctDNA analysis to monitor tumor burden in early-stage CRC using small gene panel sequencing or digital droplet PCR (ddPCR) assays to detect specific variants (Tie et al., 2016, Reinert et al., 2016). Building upon these previous studies, here we use a personalized multiplex ctDNA technology measuring 16 mutations specific to each patient's tumor respectively to assess minimal residual disease postoperatively and to monitor treatment response in CRC. Our study includes 130 patients diagnosed with stage I-III CRC treated with intended curative surgery. Of the 130 patients, 80 received adjuvant chemotherapy for a duration of six months. For 119 patients, one pre-operative and one post-operative plasma sample were available. In addition, longitudinally-collected plasma samples were available from 78 of 130 patients for early detection of disease recurrence and to determine their relationship with imaging and carcinoembryonic antigen (CEA) during a 3-year post-operative surveillance period.

To identify patient-specific tumor mutation signatures, whole-exome sequencing of CRC tissue and germline DNA is used. Patient specific multiplex-PCR assay panels are designed to target 16 tumor-specific single-nucleotide variants (SNVs) in plasma. Targeted sequencing is then performed on plasma samples collected pre- and post-operative and during adjuvant therapy. We then correlate ctDNA status to the clinical outcome, including CEA and radiographic imaging, for each patient. Data collection is ongoing and results will be presented at the AACR 2018 meeting.

Conclusion. This study provides a novel methodology to detect minimal residual disease postoperatively and to monitor treatment efficacy in CRC using a personalized multiplex-PCR approach. The performance of this patient-specific ctDNA technology will be compared to the current standard of care for monitoring disease burden.

References:

S. Pita-Fernàndez, et al. Ann. Oncol. 26, 644–656 (2015).

Tie J, et al. Sci Transl Med. 2016 Jul 6;8(346):346ra92.

Reinert T. Gut. 2016 Apr;65(4):625-34.

Citation Format: Thomas Reinert, Tenna V. Henriksen, Mads H. Rasmussen, Himanshu Sethi, Shruti Sharma, Hsin-Ta Wu, Dina Hafez, Prashanthi Natarajan, Scott Dashner, Mustafa Balcioglu, Ann Nguyen, Derrick Renner, Bernhard Zimmermann, Lene H- Iversen, Mogens R. Madsen, Cheng-Ho Jimmy Lin, Claus L. Andersen. Personalized circulating tumor DNA analysis to monitor colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1590.