PD-1T TILs as precision biomarker in NSCLC 41 2 Cut-off Sensitivity Specificity NPV PPV <90 vs ≥90 79% 83% 89% 69% <90 vs ≥90 77% 67% 88% 49% <1 vs ≥1 41% 67% 74% 33% <50 vs ≥50 23% 95% 75% 63% <90 vs ≥90 92% 84% 96% 69% <90 vs ≥90 93% 65% 98% 37% <1 vs ≥1 57% 70% 88% 30% <50 vs ≥50 29% 94% 86% 50% Next, we compared the potential of PD-1T TILs to predict DC at 6 and 12 months in samples derived from either tumor resections or biopsies. Performing ROC analysis, we observed that the AUC for resected samples was higher than for biopsy samples though without reaching significance, in line with the notion that biopsies may be more prone to sampling errors (Fig. 3D,E). Next, we compared samples from primary and metastatic sites which performed similarly with respect to prediction of treatment outcome (Fig. 3D,E). Finally, we compared samples that were taken either directly before start of anti-PD-1 treatment or before prior systemic treatment. Samples that were taken directly before anti-PD-1 treatment showed better predictive value, reaching significance in the DC 12m subgroup (AUC 0.91; 95% CI: 0.82-0.99 versus 0.74; 95% CI: 0.61-0.88, P=0.04) for samples taken prior to at least one other systemic treatment (Fig. 3D,E). In summary, these explorative analyses suggest that the predictive performance of PD-1T TILs is even higher when assessed in a lesionspecific manner and in samples that were taken shortly before start of PD-1 blockade.
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