Utility of circulating tumor DNA in genomic profiling of colorectal cancer with peritoneal metastasis.

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e16057 Background: Patients (pts) with peritoneal metastatic (PM) colorectal cancer (CRC) have significantly poorer prognosis than those with other metastases. In this study, we aim to investigate genomic profiles of PM-CRC and metastatic CRC without peritoneal involvement (non-PM-CRC) and PM-CRC with other organ involvement (PM-CRC+) using circulating tumor DNA (ctDNA)-based sequencing. Methods: A total of 169 pts with metastatic CRC were enrolled irrespective of treatment history, including 53 pts with non-PM-CRC, 47 pts with PM-CRC, and 69 pts with PM-CRC+. Matched tumor-normal next-generation sequencing of 1021 cancer-related genes was performed on ctDNA and white blood cells derived from plasma samples. The differences of mutation number were examined with student t test, and the differences of mutation detection rate were examined with two tailed Fisher’s exact test. p≤0.05 was considered statistically significant. Results: Somatic mutations were identified in 96% of pts with non-PM-CRC, 77% of pts with PM-CRC, and 97% of pts with PM-CRC+. The number of somatic mutations observed in the PM-CRC cohort was significantly lower than that in the other cohorts with the median value of 2 in the PM-CRC cohort, 9 in the non-PM-CRC cohort, and 7 in the PM-CRC+ cohort (p = 0.0002 and p < 0.0001, respectively). The most frequently mutated genes in these cohorts was listed in Table. The detection rate of APC and TP53 mutations in the PM-CRC cohort was significantly lower than the other cohorts. Significant differences were also observed when comparing TCF7L2 mutations in the non-PM-CRC and the other cohorts, LRP1B mutations in the PM-CRC cohort and PM-CRC+ cohort, and NOTCH4 and PCK1 mutations in the non-PM-CRC and PM-CRC+ cohorts. In addition, BRAF mutations were more commonly observed in the PM-CRC cohort (13%) than the other cohorts (8% for non-PM-CRC cohort, 4% for PM-CRC+ cohort) (p = 0.51 and 0.16, respectively). Conclusions: Pts with PM-CRC exhibit a distinct molecular profile compared with non-PM-CRC and PM-CRC+, which may be helpful to explain their relatively poor prognosis and potentially be used in the early diagnosis of PM. [Table: see text]