FIG 4.

ctDNA molecular response in pseudoprogression versus true progressive disease. (A) Patient with metastatic non–small-cell lung cancer and a dominant 7.0-cm RUL mass (red line) initiated pembrolizumab monotherapy; a 9-week (T1) scan showed an increase in the size of the RUL mass to 7.8 cm along with the development of mediastinal adenopathy. 9-week ctDNA analysis showed a reduction in identified variants with an AF > 0.3% and associated reduction the mean VAF with a molecular response = 17%. Pembrolizumab was continued and a follow-up scan at 16 weeks (T2) showed a reduction in the RUL mass to 6.2 cm and resolution of mediastinal adenopathy. The overall clinical picture was consistent with radiologic pseudoprogression to anti–PD-1 therapy. (B) Patient with newly diagnosed advanced NSCLC with a dominant 1.7-cm nodule in the RUL (red asterisk) initiated pembrolizumab monotherapy; a 9-week (T1) scan showed an increase in this lesion to 3.1 cm suggestive of progressive disease. 9-week ctDNA analysis shows an increase in ctDNA (molecular response = 189%). Pembrolizumab was continued and a repeat chest computed tomography at 13 weeks (T2) showed continued radiographic progression, and pembrolizumab was subsequently discontinued. ctDNA, circulating tumor DNA; RUL, right upper lobe; VAF, variant allele fraction.