Extended Data Fig. 4: Changes in genomic and transcriptomic features on therapy.

(a) Clonal evolution of somatic mutations on treatment. Each box corresponds to an individual patient. Axes indicate the variant allele fractions (VAFs) of each mutation (x-axis: pre-treatment; y-axis: on-treatment); oncogenic mutations highlighted in blue; (n = 18 patients). (b) Differences in on-treatment density of (TTF1+/CK5+) tumor cells as determined by mIF between treatment arms; (SBRT n = 6 patients, SBRT+Ipi/Nivo n = 6 patients); two-sided Wilcoxon test. The top and bottom edges represent the 1st and 3rd quartiles, respectively; the center line represents the median; whiskers extend to the farthest data points which do not represent outliers (within 1.5x the interquartile range); outliers are plotted as points above and below the box-and-whisker plot. (c) On treatment changes in purity and ploidy; two-sided paired Wilcoxon test. Patient #12 was excluded from the SBRT+ipi/nivo group because the tumor purity could not accurately be determined for the on-treatment sample (SBRT+Ipi/Nivo n = 7 patients, SBRT n = 10 patients). Boxplot elements are defined in the legend of panel b. (d) Changes in ssGSEA Hallmark pathway scores on-treatment (SBRT n = 8 patients, SBRT+Ipi/Nivo n = 7 patients); two-sided paired Wilcoxon P<0.05 are highlighted in blue. (e) Plots illustrating patient-level changes in ssGSEA Hallmark pathways determined to be significantly differentially changed between treatment arms (see Fig. 2d); (SBRT n = 8 patients, SBRT+Ipi/Nivo n = 7 patients); two-sided paired Wilcoxon test. Box plot elements are defined in the legend of panel b. (f) Changes in ESTIMATE stromal score on treatment in each treatment arm; (SBRT n = 8 patients, SBRT+Ipi/Nivo n = 7 patients); two-sided paired Wilcoxon test. Box plot elements are defined in the legend of panel b.