Development and validation of a preoperative noninvasive predictive model based on circular tumor DNA for lymph node metastasis in resectable non-small cell lung cancer

BACKGROUND: Clinical lymph node staging in resectable non-small cell lung cancer (NSCLC) patients not only indicates prognosis, but also determines primary treatment strategy. The demand of noninvasive tool for preoperative lymph node metastasis prediction remains significant. This study aimed to develop and externally validate a preoperative noninvasive predictive model based on circular tumor DNA (ctDNA) for the lymph node metastasis in resectable NSCLC patients. METHODS: Resectable NSCLC patients in TRACERx cohort were included as training group. Potential preoperative noninvasively accessible predictors were incorporated into the development of a nomogram via multivariate logistic regression. The predictive model was externally validated by a similar cohort from our hospital. RESULTS: Overall, 58 patients from TRACERx cohort were included as training group and 37 patients from our hospital were included as external validation group. Variant allele frequency (VAF) level of ctDNA was significantly associated with lymph node metastasis (OR: 4.89, 95% CI: 1.22–19.54, P=0.03). The predictive model incorporating age, tumor size and VAF demonstrated satisfactory discrimination and calibration in both training group (AUC =0.77, 95% CI: 0.65–0.90, P=0.001) and external validation group (AUC =0.84, 95% CI: 0.70–0.99, P=0.005). CONCLUSIONS: High VAF level in preoperative ctDNA may indicate lymph node metastasis of resectable NSCLC. And a preoperative noninvasive predictive model based on ctDNA for the lymph node metastasis in resectable NSCLC patients was developed and externally validated with satisfactory discrimination and calibration.