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PURPOSE This study was designed to assess the ability of perioperative circulating tumor DNA (ctDNA) to predict surgical outcome and recurrence following neoadjuvant chemoradiation for locally advanced rectal cancer (LARC). MATERIALS AND METHODS Twenty-nine patients with newly diagnosed LARC treated between January 2014 and February 2018 were enrolled. Patients received long-course neoadjuvant chemoradiation prior to surgery. Plasma ctDNA was collected at baseline, preoperatively, and postoperatively. Next-generation sequencing was used to identify mutations in the primary tumor, and mutation-specific droplet digital polymerase chain reaction was used to assess mutation fraction in ctDNA. RESULTS The median age was 54 years. The overall margin-negative, node-negative resection rate was 73% and was significantly higher among patients with undetectable preoperative ctDNA (n = 17, 88%) versus patients with detectable preoperative ctDNA (n = 9, 44%; P = .028). Undetectable ctDNA was also associated with more favorable neoadjuvant rectal scores (univariate linear regression, P = .029). Recurrence-free survival (RFS) was calculated for the subset (n = 19) who both underwent surgery and had postoperative ctDNA available. At a median follow-up of 20 months, patients with detectable postoperative ctDNA experienced poorer RFS (hazard ratio, 11.56; P = .007). All patients (4 of 4) with detectable postoperative ctDNA recurred (positive predictive value = 100%), whereas only 2 of 15 patients with undetectable ctDNA recurred (negative predictive value = 87%). CONCLUSION Among patients treated with neoadjuvant chemoradiation for LARC, patients with undetectable preoperative ctDNA were more likely to have a favorable surgical outcome as measured by the rate of margin-negative, node-negative resections and neoadjuvant rectal score. Furthermore, we have confirmed prior reports indicating that detectable postoperative ctDNA is associated with worse RFS. Future prospective study is needed to assess the potential for ctDNA to assist with personalizing treatment for LARC.

562 Background: This study was designed to assess the capability of perioperative ctDNA analysis to predict surgical outcome and recurrence following neoadjuvant CRT for LARC. Methods: Thirty-one patients (pts) with newly diagnosed LARC ( n = 29) or locally recurrent (non-metastatic) rectal cancer ( n= 3) were treated between 7/2013 - 7/2017. Pts received long-course neoadjuvant CRT prior to surgical resection: 50.4 Gy/28 fractions. Serum ctDNA was typically measured at baseline, weekly during CRT, pre-operatively, and post-operatively. Next-generation sequencing was used to identify mutations in the primary tumor, and mutation-specific droplet digital PCR was used to detect mutation fraction in ctDNA. Results: The median age of the cohort was 53 years (IQR 46.5-65.3 y). The overall R0-node negative (R0-NN) resection rate was 66.7%. The rate of R0-NN resection was significantly higher among pts with undetectable preoperative ctDNA ( n = 17, 88%) compared to pts with a detectable preoperative ctDNA ( n = 10, 30%, Fisher’s exact p = 0.036). The overall pathologic complete response (pCR) rate was 18.5%. The pCR rate among pts with undetectable preoperative ctDNA was 23.5% vs 10% among pts with detectable preoperative ctDNA ( ns). For patients with a positive assay at baseline and weekly draws available, those who went on to have an R0NN resection were observed to exhibit ctDNA clearance by the second week of chemoradiation. Recurrence free survival (RFS) was calculated for the subset ( n= 22) who were able to undergo surgery and had post-operative ctDNA available. Pts with detectable postoperative ctDNA experienced poorer RFS than those with undetectable ctDNA, HR 8.0, p < 0.001. Conclusions: Undetectable preoperative ctDNA is associated with R0-NN surgical outcome, and detectable postoperative ctDNA is associated with worse RFS in a cohort of pts treated with neoadjuvant CRT for LARC. Validation is ongoing in a larger cohort of 39 pts.