PMC7493011_01
Next-generation sequencing of tissue sample in July 2016.
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AKT serine/threonine kinase 1 (AKT1) mutations (Figure 1). Icotinib 125mg three times daily was administrated followed by stereotactic radiotherapy to the mediastinum and supraclavicular (50 Gy in 2 Gy fractions). After 7 months, he experienced disease progression with intrapulmonary metastasis.
Next-generation sequencing of plasma sample in February 2017.
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NGS analysis of plasma samples was performed, and a rare mutation of EGFR T751_I759delinsS located in exon 19 was found (Figure 2), accompanied by TP53 and AKT1 mutation.
Sagittal T1-weighted (T1w) spinal MRI showed multiple vertebral metastases in August 2017.. Notes: (A) C2-7 and T1-6 (white arrows). (B) L1, L3 and S2-4 (white arrows).
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Four cycles of pemetrexed, carboplatin and bevacizumab were administered, but multiple vertebral metastases were detected via MRI (Figure 3).
Axial T1w C+ craniocerebral MRI.. Notes: (A) Baseline MRI in January 2018 showed a patchy enhancement (white arrow). (B) Repeat MRI in May 2018 showed a shrunken lesion (white arrow). (C) Repeat MRI in January 2019 showed a reduced lesion (white arrow).
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However, brain metastasis was confirmed by MRI in January 2018 (Figure 4A). T751_I759delinsS along with TP53 and AKT1 mutation. The therapy was switched to osimertinib at 80 mg daily, which decreased the levels of multi-tumor markers (Figure 5), and stabilized the lesions of brain (Figure 4B and C) and pulmonary (Figure 6) for 16 months.
Changes of the concentrations of CEA, CYF211, NSE, CA125, CA153 in peripheral blood and the corresponding treatment.. Abbreviations: GP, gemcitabine and cisplatin; Ico, icotinib; Radio, radiotherapy; AP, pemetrexed and carboplatin; Beva, bevacizumab; Erlo, erlotinib; Osi, osimertinib.
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T751_I759delinsS along with TP53 and AKT1 mutation. The therapy was switched to osimertinib at 80 mg daily, which decreased the levels of multi-tumor markers (Figure 5), and stabilized the lesions of brain (Figure 4B and C) and pulmonary (Figure 6) for 16 months.
Chest CT showed stable lesions in the inferior lobe of left lung.. Notes: (A) In February 2017 (white arrow). (B) In January 2019 (white arrow).
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T751_I759delinsS along with TP53 and AKT1 mutation. The therapy was switched to osimertinib at 80 mg daily, which decreased the levels of multi-tumor markers (Figure 5), and stabilized the lesions of brain (Figure 4B and C) and pulmonary (Figure 6) for 16 months.
Leptomeningeal metastases (LM) was confirmed in June 2019.. Notes: (A) MRI showed enhancement of the spinal pia mater (white arrows). (B) CSF smear found tumor cell (hematoxylin and eosin staining).
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In June 2019, he showed symptoms of severe headache, nausea, weakness of the lower extremities and back pain, and leptomeningeal metastases (LM) was confirmed by the CSF cytology and MRI (Figure 7).
Treatment timeline.
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The whole course of treatment was constructed as a timeline (Figure 8).