Perioperative ctDNA-Based MRD Detection in NSCLC—Response

We thank Wei and colleagues for their interest in our work (1). Their reanalysis of our data indicated a negative correlation of perioperative circulating tumor DNA (ctDNA) levels (based on ctDNA concentration hGE/mL) with recurrence-free survival (RFS) duration across our whole cohort, and suggested further grouping of patients with non–small cell lung cancer (NSCLC) based on their ctDNA levels for recurrence prediction.In fact, we have also assessed the association between RFS and perioperative ctDNA concentration during our initial analysis, with trends agreeing with Wei and colleagues’ analysis. We found that ctDNA concentration was statistically significantly correlated with RFS at postoperative 3 days (P = 0.002) and 1 month (P = 0.001) in all patients, though with relatively weak R values of −0.176 and −0.178, respectively. However, upon performing ROC curve analysis, the optimal cut-off values calculated on ctDNA concentration at these two time points performed equally for recurrence prediction as that of our ctDNA positive/negative calls in terms of sensitivity and specificity. Considering that a universal qualitative classification of ctDNA status is more straightforward and practical in clinical settings, we did not adopt any quantitative cut-off values as suggested by Wei and colleagues because of potential overfitting using the limited number of cohort. In the meantime, at the preoperative time point, we found that the ctDNA concentration's correlation with RFS was not statistically significant (P = 0.362).In summary, we recognize Wei and colleagues’ efforts in exploring the association of ctDNA concentration with RFS and their attempt to identify optimal cut-off values for further stratification. We at the same time notice that this measurement has performed inconsistently across our reported different time points based on our perioperative cohort data, which warrants more investigations in additional longitudinal time points along our LUNGCA trial.See the original Letter to the Editor, p. 3400W. Chen reports a patent for Genecast Biotechnology pending; and in addition, W. Chen is an employee at Genecast Biotechnology. No disclosures were reported by the other authors.