Serial circulating tumor DNA (ctDNA) and recurrence risk in patients (pts) with resectable colorectal liver metastasis (CLM).

Abstract

e15131 Background: In pts with metastatic colorectal cancer (mCRC), the resection of isolated CLM is potentially curative. Previous studies have shown that ctDNA can be detected in a high proportion of pts with mCRC. ctDNA detection after resection of CLM may be a marker of residual micrometastatic disease. If so, serial analysis of ctDNA after CLM resection could inform adjuvant chemotherapy decision making and pt follow-up. Methods: We prospectively collected serial (pre-op, post-op and 3 to 6 monthly during adjuvant chemotherapy and follow-up) plasma in pts with resectable CLM. Chemotherapy use was at clinician discretion, blinded to ctDNA result. With targeted sequencing of 15 genes commonly mutated in CRC, we identified somatic mutations in each pt’s tumor, and then designed a personalised assay to quantify a selected mutant DNA in plasma samples (ctDNA) using the Safe-SeqS digital genomic assay. Results: From July 2011 to March 2014, 37 pts were recruited, 25 male, median age 64 years (range 31-82). 19 had a single liver metastasis, 11 had 2-3, and seven had ≥ 4 lesions. Available plasma samples were analyzed. Prior to any treatment, ctDNA was positive in 31/35 (89%) pts. 36 pts (97%) underwent R0 resection, 26 pts (70%) received chemotherapy after surgery. At a median follow-up of 27 months, 14 of 37 pts (38%) have recurred. Ten of 10 pts (100%) with positive post-treatment (surgery and chemotherapy) ctDNA experienced recurrence vs 4 of 27 (15%) with negative post-treatment ctDNA (HR 13.16, p < 0.0001). Of 9 pts with positive ctDNA after surgery, one had negative ctDNA after adjuvant chemotherapy and remains disease free. All 6 pts where ctDNA remained positive after chemotherapy and all 2 who did not have chemotherapy have recurred. At recurrence, ctDNA was positive in 12/13 (92%), while 6/13 (46%) had an elevated CEA (p = 0.03). ctDNA was detectable at a median of 3 months (range 0 - 14) prior to clinical recurrence. Conclusions: ctDNA is detectable in the majority of pts with CLM. In our series, all pts where ctDNA remained positive following treatment experienced recurrence. Serial ctDNA after chemotherapy and during follow-up may be a marker of adjuvant chemotherapy impact and an early marker of recurrence. Clinical trial information: ACTRN12612000345886.