Role of Circulating Tumor DNA in Evaluating Clinical Tumor Burden and Predicting Survival in Chinese Metastatic Colorectal Cancer Patients

Abstract

Background:The aim of this study was to further explore the utility of ctDNA in the evaluation of clinical tumor burden and survival in Chinese metastatic CRC (mCRC) patients and to preliminarily summarize some metastatic characteristics associated with mutations in ctDNA. Patients and Methods:A four-gene mutation testing panel covering a total 197 mutation hotspots of KRAS, NRAS, BRAF and PIK3CA was used to evaluate their mutant status via next-generation sequencing of plasma from patients with mCRC. Clinical markers including CEA, CA199, CA125,NSE and LDH in serum and the sum of all tumor diameters on CT or PET/CT were collected to indicate clinical tumor burden. The correlations between cfDNA levels and clinical tumor burden were analyzed using Pearson correlation and linear regression models. The median PFS and 1-year OS rates were calculated by Kaplan–Meier (K–M) survival analysis. Results：The study enrolled 126 mCRC patients for ctDNA testing. Wild-type patients accounted for 54.8% (69/126) of the total patients, and mutated patients accounted for 45.2% (57/126) of the total patients. Mutations in KRAS, NRAS, BRAF and PIK3CA were detected in 37.3% (47/126), 1.6% (2/126), 3.2% (4/126) and 13.5% (17/126) of patients, respectively. The overall concordance rate of gene status between ctDNA and matched tissues was 78.6% (99/126). The concentration of cfDNA was significantly correlated with the levels of clinical markers, especially CEA (P<0.0001, Pearson r = 0.81), LDH (P<0.0001, Pearson r = 0.84) and the sum of tumor diameters (P<0.0001, Pearson r = 0.80). The median PFS (11.7 versus 6.6 months, P<0.0001) and 1-year OS rates (94% versus 56%, P<0.0001) were significantly different between patients with a low cfDNA concentration (≤17.91 ng/ml) and those with a high cfDNA concentration (>17.91 ng/ml). The most common metastatic site was liver (77.8%), followed by lymph nodes (62.7%), lung (40.5%), peritoneum (14.3%) and bone (10.3%), in all patients. There was no significant difference in metastasis regardless of gene status. Conclusion:These results suggested that the level of cfDNA could be a quantitative biomarker of tumor burden and could predict survival in Chinese patients with mCRC. Patients with gene mutations had a similar metastatic pattern to those with wild-type genes.