PMC7393232_01
Saliva-based EFIRM for detection of exon19 del EGFR and p.E545K PIK3CA in Case 1. (A) The volume of metastatic tumor showed a sharp decline after the initiation with 80 mg osimertinib. At the time point of day 280 (black arrow), LAT and followed osimertinib re-initiation were performed. The tumor volume increased to a high level eventually. (B) The curve of exon19 del EGFR EFIRM has a strong similarity to that of exon19 del EGFR ddPCR (R = 0.53, P = 0.01). (C) The curve of p.E545K PIK3CA EFIRM has a strong similarity to that of p.E545K PIK3CA NGS (R = 0.72, P = 0.00), respectively.
fonc-10-01240-g0002.jpg
PMC7393232_01_fonc-10-01240-g0002.jpg
F2
As shown in Figure 2A, after the initiation with osimertinib treatment, there was a sharply partial response (PR) period (from day 0 to 42) for the volume of metastatic tumor (from 30 to 7 mm3). As shown in Figure 2B, in the sharply PR period of tumor volume, exon19 del EGFR ctDNA detected by both plasma-based ddPCR and saliva-based EFIRM was also markedly decreased (ddPCR from 60 to 3%; EFIRM from 310 to 150 nA). As shown in Figure 2C, p.E545K PIK3CA mutant tested by both plasma-based NGS and saliva-based EFIRM also decreased sharply in the PR period of tumor volume after the initiation of osimertinib (NGS from 19 to 2%; EFIRM from 179 to 0 nA).
PMC7393232_02
Saliva-based EFIRM for detection of p.L858R EGFR and p.E545K PIK3CA in Case 2. (A) The volume of metastatic tumor showed an obvious decrease after LAT and initiation with 80 mg osimertinib. (B) The change trends of p.L858R EGFR EFIRM data have significant similarities with plasma-based ddPCR for p.L858R EGFR (R = 0.467, P = 0.04). (C) The p.E545K PIK3CA tested by plasma-based NGS remained undetectable till to day 315, which showed the only and unapparent peak (from 0 to 0.2%). On the contrary, the EFIRM signal of p.E545K PIK3CA mutation increased gradually from the beginning.
fonc-10-01240-g0003.jpg
PMC7393232_02_fonc-10-01240-g0003.jpg
F3
As shown in Figure 3A, the PR with regression of metastatic tumor size was found after the treatment of LAT and osimertinib. As shown in Figure 3B, accompanying changes in the PR period of tumor volume, p.L858R EGFR mutation detected by both plasma-based ddPCR and saliva-based EFIRM demonstrated a brief decline, then remained at an undetectable level until day 287. As shown in Figure 3C, the allele fraction of p.E545K PIK3CA mutation tested by NGS remained undetectable till to day 315 in the SD period of tumor, at which showed the only peak of signal (from 0 to 0.2%).