PMC5951221_01
IGV screenshots displaying the reads of each mutation subtype identified by NGS.. Notes: (A) EGFR exon 19 insertion K745_E746insIPVAIK. (B) EGFR double-site mutation H835L+L833V located in cis. (C) PCM1-RET fusion. (D) KIF5B-RET fusion. (E) ADD3-RET fusion.. Abbreviations: IGV, Integrative Genomics Viewer; NGS, next-generation sequencing.
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First, a 40-year-old advanced adenocarcinoma patient harbored both a PCM1-RET fusion and an EGFR exon 19del (Figure 2C). We also identified a 60-year-old female with advanced adenocarcinoma who harbored two different RET fusions - ADD3-RET and KIF5B-RET (Figure 2D and E).
Correlation of patient baseline characteristics, baseline somatic aberrances, and PFS.. Notes: (A) The correlation of EGFR mutation occurrence frequency and smoking status. (B) Patients who received MTT commonly achieved longer PFS. (C) Allelic fraction of EGFR T790M was inversely correlated with PFS. Difference of EGFR mutation percentage between subgroups (never smoker vs smoker) was calculated with Student's t-test; a two-sided p-value of <0.05 was considered statistically significant. A Kaplan-Meier analysis was used to estimate survival, and a log-rank test was used to determine the difference in survival curve between subgroups.. Abbreviations: AF, allelic fraction; MTT, matched targeted therapy; PFS, progression-free survival.
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Of the patients analyzed, EGFR sensitizing mutations were significantly more frequent in never smokers (51%) than in smokers (24%, p=0.023; Figure 3A). The result revealed that patients who received mutation-MTT achieved significantly longer median PFS than patients who did not (275 vs 80 days, p<0.0001; Figure 3B). The result showed that patients with a higher T790M allelic fraction had a shorter median PFS than patients with a lower T790M allelic fraction (238 vs 378 days, p=0.059; Figure 3C). Therefore, the allelic fraction may be a prognostic indicator of response to osimertinib for patients with the T790M mutation.
A lung squamous cell carcinoma patient is presented here to illustrate the value of ctDNA in predicting disease progression earlier than radiographic imaging.. Notes: With the development of EGFR L858R and KRAS amplification, which leads to icotinib resistance, he was treated with Pem+Carb+Bev therapy and achieved clinical SD. Afterwards, sequencing of liquid biopsy revealed the increased allelic fraction of EGFR L858R, KRAS amplification, and ctDNA level, which were earlier than clinical PD detected by radiographic imaging for a period of 46 days. This case demonstrated the value of ctDNA for early detection of disease progression than radiological PD.. Abbreviations: amp, amplification; ctDNA, circulating tumor DNA; PD, progressive disease; Pem+Carb+Bev, pemetrexed+carboplatin+bevacizumab; SD, stable disease.
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This ctDNA change preceded the detection of clinical PD revealed by radiographic imaging by 46 days (Figure 4).