PMC6292407_01
Correlation between plasma levels of G1202R mutations detected by ctDNA assay and radiological findings.. Notes: The figure shows the sequential strategy of ALK TKIs and the time correlation between radiological findings at CT scan and the corresponding molecular profiling in liquid biopsy. In April, CT scan did not show progression of the left lower lobe mediastinal pathological tissue, however, for the first time we detected the resistance mutation G1202R in the ctDNA with 11% MAF. In May, progression was radiologically evident and for this reason, patient stopped brigatinib and entered into a clinical trial with lorlatinib. In June, CT scan demonstrated a partial remission of the left lower lobe pathological tissue, consistently with liquid biopsy, where we found a decreased amount of G1202R, 2.5% MAF. In August, G1202R MAF increased again to 12% with minor radiological progression, which was significant in September. Bypassing signaling pathways were explored in search of secondary resistance mutations, even in a tumor tissue sample, but no new activating mutations were detected and we decided to switch to chemotherapy. The white boxes show how left lower lobe mediastinal pathological tissue is increased or reduced during oncological treatments.. Abbreviations: Jan, January; Feb, February; Apr, April; Aug, August; Sept, September; Oct, October; Nov, November; Dec, December; ctDNA, circulating tumor DNA; CTY, chemotherapy; MAF, mutant allelic frequency; nd, not detected; -, negative.
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Nine different liquid biopsies were performed as depicted in Figure 1. We explored ROS-1 (exon 36-37-38), EGFR (exons 18, 19, 20, 21), KRAS (exons 2, 3, 4), and BRAF (exon 15), but mutations were not detected by plasma-based ctDNA assay during lorlatinib treatment in none of the analyzed liquid biopsies (Figure 1).