PMC7428409_01
Magnetic resonance imaging (MRI) scan regarding the clinical response of metastatic spine lesions during whole course of treatment. (A) Baseline MRI scan of the patient with spinal metastasis before the combination treatment. (B) Observation of stable disease (SD) after four-month gefitinib treatment. (C) Observation of the deterioration of the spine metastasis before osimertinib treatment. (D) Observation of stable disease (SD) after four-month osimertinib treatment. (E) Observation of progressive disease (PD) before the combination treatment of osimertinib and dabrafenib plus trametinib. (F) Observation of progressive disease (PD) after the nine-month combination treatment of osimertinib and dabrafenib plus trametinib.. Note: Red arrow indicates spinal metastasis.
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A 63-year-old man with more than 40-year history of second-hand smoking presented with recurrent pain in his left lumbar back for more than half a year, and was diagnosed with stage IV lung adenocarcinoma with metastases to the spine (Figure 3A). In addition, the magnetic resonance imaging (MRI) after 4 months of gefitinib treatment showed the patient reached a stable disease (SD) (Figure 3B). But his disease progressed after a progression-free survival (PFS) of 17 months and an MRI scan revealed the deterioration of bone metastasis (Figure 3C). Subsequently, the patient was treated with osimertinib (80 mg qd), and achieved a stable disease (SD) after 4 months based on criteria in Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 (Figure 3D). Results from computed tomography (CT) of his lung and MRI of his lumbar showed that the disease progressed (Figures 3E and 4A). CT scan and MRI showed an enlarged pulmonary lesion together with metastases in subcarinal lymph node and the aggravation of bone metastases lesions, respectively (Figures 3F and 4D).
Computed tomography (CT) scan regarding clinical response of multi-drug combination of targeted therapy. (A) Baseline CT scan of the patient before the combination treatment. (B) Observation of stable disease (SD) after two-month combination treatment. (C) Observation of continuing therapeutic response after four-month combination treatment. (D) Observation of progressive disease (PD) manifested as enlarged pulmonary lesion and metastases after nine-month combination treatment. (E) Observation of SD after one-month combination treatment. (F) Observation of continuing SD after three-month combination treatment.. Note: Red arrow indicates the lesion in the thorax.
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Results from computed tomography (CT) of his lung and MRI of his lumbar showed that the disease progressed (Figures 3E and 4A). The follow-up CT reexamination also demonstrated his lung lesions decreased and reached SD (Figure 4B and C). CT scan and MRI showed an enlarged pulmonary lesion together with metastases in subcarinal lymph node and the aggravation of bone metastases lesions, respectively (Figures 3F and 4D). In August and September 2019, a CT scan showed that the pulmonary lesion had shrunk and reached SD (Figure 4E and F).
Dynamic monitoring of integrative genomics viewer (IGV) regarding the acquired resistance mutations during the combination treatment. (A) Integrated genomics viewer showing the 1799T>A at codon V600E (BRAF V600E) mutation (red) before combination treatment. (B) Integrated genomics viewer highlighting the presence of the 2369C>T at codon 790 (EGFR-T790M) mutation (red) without accompanying with EGFR-C797S mutation before combination treatment. (C) Integrated genomics viewer showing the 1799T>A at codon V600E (BRAF V600E) mutation (red) after combination treatment. (D) At disease progression, integrative genomics viewer highlighting the 2369C>T at codon 790 (EGFR-T790M) mutation (red) oriented in cis with a 2389T>A at codon 797 (EGFR-C797S) mutation (green) and 2390G>C at codon 797 (EGFR-C797S) mutation (blue).
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In this case, we advised him to take a plasma next-generation sequencing (NGS) testing, and eventually, a BRAFV600E (AF=8.78%) mutation was identified in addition to EGFR-19 del and EGFR-T790M (AF=2.38%) mutation (Figure 5A and B). Liquid biopsy of plasma revealed the acquired mutation of EGFR cis-C797S (AF=6.17% and 7.76%), in addition to the original mutations (19Del/T790M/BRAFV600E) (Figure 5C and D).