PMC6664872_01
Chest CT and cranial MRI. (Left) Chest CT performed on the day of admission (day 1) and after treatment with afatinib for 71 days (day 98) and 190 days (day 217). The lung lesions (blue arrows) were reduced in size after treatment with afatinib for 71 days (day 98), and the effect was maintained after a further 119 days of treatment (day 217). (Right) Enhanced cranial MRI T2 FLAIR scans performed on day 21 and after treatment with afatinib for 77 days (day 104) and 194 days (day 221). The cranial MRI scan on day 21 showed high-intensity linear shadows in the medulla oblongata, pons, and ventral and dorsal midbrain, which were considered to be leptomeningeal metastases. The cranial scan on day 104 revealed similar abnormalities to those detected on day 21. However, the abnormal signals in the medulla oblongata, pons, and ventral and dorsal midbrain on day 221 were decreased in comparison to those on days 21 and 104.
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Chest CT on day 1 revealed lung lesions (Figure 1), while cranial CT showed dilation of the supratentorial ventricular system and widening of the cerebral sulcus and cistern. Enhanced cranial MRI T2 fluid-attenuated inversion recovery (FLAIR) scans on day 21 showed high-intensity linear shadows in the medulla oblongata, pons, and ventral and dorsal midbrain, indicating leptomeningeal metastasis (Figure 1). Follow-up on 25th July 2018 (day 98) demonstrated reduced pulmonary lesions (chest CT; Figure 1) and improved supratentorial ventricular dilation.
Changes in the concentrations of CEA in peripheral blood and CSF between day 1 (the initial admission) and day 216. Therapy with afatinib was commenced on day 27.
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On 21st April 2018 (day 3), a ventriculoperitoneal shunt was placed in the right lateral ventricle, and carcinoembryonic antigen (CEA) levels in peripheral blood were 717 ng/mL (Figure 2). On 8th May 2018 (day 20), lumbar puncture revealed a CSF pressure of 8 mmHg, and CSF CEA levels were 9,470 ng/mL (Figure 2). November 2018 (day 216), peripheral blood CEA level was 93 ng/mL; CSF CEA level was 1,590 ng/mL (Figure 2), with a CSF pressure of 6 mmHg, indicating maintenance of the response to afatinib therapy. NGS results for the CSF revealed an EGFR G719A mutation frequency of 23.1%, comparable to that measured on 10th August 2018, while liquid biopsy of peripheral blood indicated increased frequency of EGFR G873R mutation to 2.2% (Table 1).