e15066 Background: Circulating cell-free tumor-DNA (ctDNA) testing (‘liquid biopsy’) is increasingly being employed both in clinical trials as well as clinical practice. We aimed to contrast and compare the differences in the number of somatic mutations observed on ctDNA testing between mismatch repair deficient/microsatellite instability-high (dMMR/MSI-High) versus mismatch repair proficient/microsatellite stable (pMMR/MSS) colorectal cancers (CRC). Methods: We had 20 patients at Mayo Clinic Florida that were dMMR/MSI-High with testing through the commercially available platform (Guardant360) that uses a 73-gene panel. Median numbers of somatic mutations were compared between the 2 subset of CRC. Results: Patients with dMMR/MSI-High CRC had a median of 8 mutations (range: 2-15) versus a median of 4 mutations (range: 1-22) in pMMR/MSS patients, p-value of 0.001. Similarly, the mean number of somatic mutations were 7.47 (S.D. ± 4.15) versus 5.02 mutations (S.D. ± 3.83) in patients with dMMR/MSI-H and pMMR/MSS, tumors respectively. Though it is simplistic, we could still potentially identify patients who may be candidates for immunotherapy by gauging the mutational burden reported (Table). Furthermore, on serial testing, decline in mutational burden as early as few weeks into therapy was predictive of response later on imaging. Conclusions: Analysis of number of somatic mutations on ctDNA testing can be complementary to MMR/MSI-testing, especially in situations when tissue is not available or safe to obtain. This can also be of value in predicting and/or following response to immunotherapy. The utility of this may go beyond CRC in identifying patients who may benefit from immunotherapy. [Table: see text]
Mutational burden on circulating cell-free tumor-DNA testing as a surrogate marker of mismatch repair deficiency or microsatellite instability in patients with colorectal cancers