PMC8114361_01
Diagram of the course of disease management.
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The treatment history of the patient is summarized in Figure 1.
(A) Baseline CT Scan at diagnosis in Jan, 2013. (B) PD on chemotherapy in Aug, 2014. (C) PR after icotinib treatment in Feb, 2015. (D) PD on icotinib in Dec, 2015. (E) PR after osimertinib treatment in Sep, 2016. (F) PD on osimertinib in Dec, 2017. (G) PD on chemotherapy in Apr, 2018. (H) PR after the combined treatment of afatinib and apatinib in Nov, 2018. (I) PD on afatinib combined with apatinib treatment in Feb, 2019. (J) PR on albumin-bound paclitaxel and toripalimab treatment in Jul, 2019.
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Positron emission tomography/computed tomography (PET/CT) scan showed a left-lobe lung lesion with mediastinal lymphadenopathy and multiple bone metastasis (Figure 2A). In August 2014, the patient experienced progressive disease (PD) (Figure 2B). Tumors 1.1 (RECIST 1.1) with a PFS of 13.5 months (Figure 2C and D). Then he was switched to gemcitabine and nedaplatin for 4 cycles and achieved SD with a PFS of 7.5 months. After 1 month, the patient achieved PR (Figure 2E and F) and lasted for 16 months. After progression, he was switched to vinorelbine in combination with lobaplatin and experienced PD 2.5 months later (Figure 2G). In April 2018, afatinib combined with apatinib was administered and the patient achieved PR (Figure 2H) with a PFS of more than 10 months. In February 2019, the patient experienced PD with an enlargement of the left lobe mass (Figure 2I). After 2.5 months of treatment, the patient achieved PR (Figure 2J).
The distribution of gene copy number (purple blot: HER2 (ERBB2) amplification). Gene copy number variation (CNV) was identified based on the depth of coverage data of capture intervals. Because of GC content and target probe density, the coverage depth was corrected for the sequencing bias, and the average coverage of all capture regions was calculated as internal control. Gene amplification was defined when it met the following three criteria: 1. Gene copy number is equal or greater than 2.75; 2. The adjusted coverage depth of the gene in tumor samples is higher than internal control significantly (z-test). 3. The coverage of the whole gene region is significantly higher than internal control (t-test).
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In addition, EGFR C797S in cis with the EGFR T790M was only detected from plasma, while HER2 (ERBB2) amplification with a copy number of 3.5 was only observed in the tissue sample (Figure 3).