Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study.
Jeanne Tie, Joshua D Cohen, Yuxuan Wang, Lu Li, Michael Christie, Koen Simons, Hany Elsaleh, Suzanne Kosmider, Rachel Wong, Desmond Yip, Margaret Lee, Ben Tran, David Rangiah, Matthew Burge, David Goldstein, Madhu Singh, Iain Skinner, Ian Faragher, Matthew Croxford, Carolyn Bampton, Andrew Haydon, Ian T Jones, Christos S Karapetis, Timothy Price, Mary J Schaefer, Jeanne Ptak, Lisa Dobbyn, Natallie Silliman, Isaac Kinde, Cristian Tomasetti, Nickolas Papadopoulos, Kenneth Kinzler, Bert Volgestein, Peter Gibbs,
Gut, November 30, -0001
For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC. We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4-10 weeks after surgery. Somatic mutations in individual patient’s tumour were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. We then designed personalised assays to quantify ctDNA in plasma samples. Patients received adjuvant therapy at clinician discretion, blinded to the ctDNA results. We analysed 462 serial plasma samples from 159 patients. ctDNA was detectable in 77%, 8.3% and 12% of pretreatment, postchemoradiotherapy and postsurgery plasma samples. Significantly worse recurrence-free survival was seen if ctDNA was detectable after chemoradiotherapy (HR 6.6; P
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Pubmed Link: 29420226