Extended Data Fig. 2

(a) Bar plot of number of ctDNA positive and negative samples at each time point in training. (b) Scatterplots showing correlation between mean variant allele frequencies versus mean tumor molecules per ml plasma in training. The baseline timepoint, in addition to having higher patient ctDNA tumor fractions due to occurring prior to treatment initiation, was sequenced with a 1.25Mb assay with reportable VAF range down to ~0.5%. On-treatment time points were sequenced with a 330kb assay with a reportable range down to ~0.01%, and restricted to only mutations detected at baseline. Pearson’s correlation coefficient is reported and its P value based on Pearson’s product moment correlation. (c) Boxplots showing association between baseline clinical features (6 panels, one for each feature) and ctDNA levels as measured by MTM (y axis) in training, where P values reported using a two-sided Wilcoxon rank sum test. The box plots depict the median at the middle line, with the lower and upper hinges at the first and third quartiles, respectively, the whiskers showing the minima to maxima no greater than 1.5× the interquartile range, and the remaining outlying data points plotted individually. Additionally, the mean and standard error are overlayed as red points. Sample sizes for the box plots from left to right are n = 99, 140; 133, 107; 98, 142; 45, 195; 120, 120; 102, 92, 46; 177, 63. (d) KM curve showing the prognostic value of baseline ctDNA MTM levels for PFS in training data. (e) Multivariable cox regression for PFS in training data. Two-sided Wald test P values are reported, and points and error bars indicate HR and 95% confidence interval, respectively. (f) Study schema showing when radiographic and plasma collections were performed in the treatment course. (g-h) Scatterplots showing association between radiographic assessment of tumor size by SLD measurement (x axis) versus ctDNA levels measure by MTM (y axis) for (g) baseline time point, (h) C3D1 time point, (i) change from BL to C3D1. Plots restrict to patients with ctDNA detected at baseline. Error band indicates 95% confidence interval. Pearson’s correlation coefficient is reported and its P value based on Pearson’s product moment correlation.