Extended Data Fig. 9: Comparison of ctDNA status with mRECIST response.

(a) Per patient differential ctDNA detectable status (yellow circles indicate detectable ctDNA, blue circles denote undetectable ctDNA) and kinetics (blue connecting lines indicate ≥95% cfDNA TF reduction at pre-surgery or undetectable ctDNA across neoadjuvant timepoints, orange connecting lines indicate <95% cfDNA TF reduction pre-surgery, while gray denotes unevaluable cases. Patients are grouped based on radiographic imaging response by mRECIST. Patients with a radiographic partial response by mRECIST (n = 2) had undetectable ctDNA throughout their neoadjuvant treatment, while significant heterogeneity with respect to ctDNA status and kinetics was noted for patients with mRECIST stable disease (n = 11) or progressive disease (n = 11). (b) Waterfall plot showing quantitative comparison between mRECIST kinetics (estimated by the change in sum of longest diameters [SLD] from baseline to three days before surgery [D-3]) and ctDNA dynamics (as percentage cfDNA TF change from C1D1 to pre-surgery). Patients in Arm A are ordered on the left and patients in Arm B are ordered on the right. Changes in cfDNA TF did not mirror changes in mRECIST SLD. Abbreviations: PR, partial response; SD, stable disease; PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumors; mRECIST, modified Response Evaluation Criteria in Solid Tumors; cfDNA, cell-free DNA; ctDNA, circulating tumor DNA; TF, tumor fraction; UD, undetectable; C1D1, cycle 1 day 1; C2D1, cycle 2 day 1; C3D1, cycle 3 day 1; SLD, sum of longest diameters.