Fig. 4

Serial measurement of BRAF V600mut ctDNA from plasma in 5 patients (a–e) with advanced melanoma during targeted therapy. Treatment with dabrafenib (dabra, 150 mg BID) and trametinib (trame, 2 mg QD) was initiated after obtaining the baseline plasma sample. The left y-axis represents the BRAF V600mut ctDNA copy number per milliliter (solid line), the right y-axis represents the BRAF V600mut ctDNA fraction to the total amount of cfDNA (dashed line). SD, PR and PD respectively denote stable disease, partial response and progressive disease according to RECIST v1.1. a The BRAF V600mut ctDNA copy number and fraction dropped after treatment initiation. After 40 days, no BRAF V600mut ctDNA could be detected anymore, and CT body showed a PR. The BRAF V600mut ctDNA fraction reappeared after 96 days and increased on day 124, although an ongoing PR was reported on PET–CT. PET–CT showed PD, 50 days after the reappearance of BRAF V600mut ctDNA in plasma. b BRAF V600mut ctDNA remained detectable from treatment initiation until PD was detected after 89 days. c At baseline, no BRAF V600mut ctDNA was detected in plasma. BRAF V600mut ctDNA appeared after 28 days, 35 days prior to the detection of PD on CT body. d At baseline, no BRAF V600mut ctDNA was detected in plasma. After 168 days, PD was detected in a gallbladder metastasis, and BRAF V600mut ctDNA was detected concomitantly. The only other lesion, a lung metastasis, had remained strictly stable. After resection of the gallbladder metastasis, the BRAF V600mut ctDNA fraction could not be detected until PD occurred in the remaining lung metastasis. e Five days after treatment initiation, BRAF V600mut ctDNA could not be detected anymore. Brain MRI showed a new millimetric brain lesion on the first response evaluation, while PET–CT showed clear regression of all liver and lung metastases. Subsequent MRI’s showed ongoing slow PD in the brain, while liver and lung lesions showed ongoing PR. No BRAF V600mut ctDNA was detected during PD in this patient