Comparing circulating biomarkers with PD-L1 expression on CTCs for monitoring tumor dynamics. Each panel represents data from a different patient. (A): Case 4: A patient with hepatocellular carcinoma (HCC) who received combined therapy had SD at the first response evolution, and PR occurred 52 weeks after treatment. (B): Case 1: A patient with a sacrococcygeal neuroendocrine tumor who received monotherapy had SD at the first response evolution, and SD occurred at 18 weeks after treatment. (C): Case 23: A patient with a gastric neuroendocrine carcinoma who received monotherapy had PR at the first response evolution, and SD occurred at 21 weeks after treatment. (D): Case 9: A patient with rectal cancer who received monotherapy had SD at the first response evolution, and PD occurred at 16 weeks after treatment. (E): Case 46: A patient with HCC who received monotherapy had PD as defined by RECIST at the first response evolution, but she did not have PD according to iRECIST, and SD occurred at 38 weeks after treatment. (F): Case 3: A patient with HCC who received monotherapy was also classified as having PD as defined by RECIST at the first response evolution, but she was not classified as having PD according to iRECIST; then, PD occurred at 20 weeks after treatment. Top panels show the plasma levels of circulating biomarkers. Middle panels show the counts of total CTCs (black lines), PD-L1-positive CTCs (blue lines) and PD-L1-high CTCs (red lines) in the blood. Bottom panels show the proportion of PD-L1-positive CTCs (blue lines) and PD-L1-high CTCs (red lines) relative to total CTCs. Abbreviations: AFP, alpha fetoprotein; CA72-4, Carbohydrate Antigen 72-4; CEA, Carcinoembryonic Antigen, or CA199, Carbohydrate Antigen 199; CTCs, circulating tumor cells; CYFR21-1, Cytokeratin 19 Fragment Antigen21-1; IU, international unit; NSE, neuron-specific enolase; PD-L1, programmed death-1 ligand; PD, progressive disease; PR, partial response.
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