Fig. 1: Genomic and molecular features of differential responses to immunotherapy and radioimmunotherapy.
Participants are stratified by control versus SBRT arm and therapy response within each arm (CR + PR versus SD + PD); rows represent distinct features and columns represent individual participants. TMB correlated with radiographic response in the control arm (Mann–Whitney U-test, P = 0.023) but not the SBRT arm (Mann–Whitney U-test, P = 0.53). Similarly, PDL1 expression was associated with therapy response in the control arm (Mann–Whitney U-test, P = 0.00041), with a trend noted in the SBRT arm (Mann–Whitney U-test, P = 0.07). In line with the TMB findings, a mutational smoking signature was enriched in responding tumors in the control arm (Mann–Whitney U-test, P = 0.019) but not the SBRT arm (Mann–Whitney U-test, P = 0.12). Tumor aneuploidy (represented as the fraction of genome with allelic imbalance) was not correlated with response in the control or SBRT arms (Mann–Whitney U-test, P = 0.43 and P = 0.87, respectively). Key NSCLC driver genes are shown together with annotations for hotspot mutations. We did not identify a differential enrichment in the overall number or in oncogenic mutations in STK11, KRAS or TP53 by treatment arm; however, KRAS;TP53 comutations were enriched in responding tumors in the control arm. A total of 16 tumors harbored STK11 mutations, 13 of which are characterized as oncogenic in the literature (10 in the control arm and 3 in the SBRT arm). Of these 13 participants, there was 1 responding participant with an STK11-mutant tumor in the control arm and 1 responding participant with an STK11-mutant tumor in the SBRT arm (1/10, 10% versus 1/3, 33%; Fisher’s exact test, P = 0.42). Notably, we observed an enrichment of Wnt pathway mutations in participants with tumors responding to SBRT (OS > 12 months; Fisher’s exact test, P = 0.047).
