A 71-year-old never-smoker man presented to our hospital complaining of abdominal hidden pain for 1 week. There was no atony, fever, fleshless or other symptoms. A history of gastric ulcers was noted. He had undergone left upper lobectomy and thymectomy 18 months ago. Pathology reported a (left lung) adenocarcinoma. The tumor invaded the pleura and thymic lymph nodes; thus 6 cycles of pemetrexed 800 mg (d1) and carboplatin 400 mg (d1) were subsequently delivered until January 2019. Then he agreed to undergo the accurate Gamma Knife (GK) radiosurgery to the lesions in the upper left side of the mediastinum (DT 38.4 GY/12F). Then the patient took a Chinese medicine to recuperate, the specific details were unknown.
A computed tomography (CT) scan performed immediately detected multiple lung and lymph nodes lesions (Fig. 1②-④), and CEA level increased to 14.8 ng/ml (normal range, 0‑4.7 ng/ml), and CA153 level increased to 28.6 U/ml (normal range, 0‑26.4 U/ml) and CA125 level increased to 47.8 U/ml (normal range, 0‑35.0 U/ml). Ultrasound-guided needle biopsy of the intraperitoneal lymph node was performed. Pathology reported metastatic adenocarcinoma originated from the lung. Immunohistochemically, the tumor cells tested positive for cytokeratin 7 (CK7), NapsinA, Ki-67 (labeling index = 30%), P40, and CKAE1/AE3 and the tumor cells were negative for cytokeratin 20 (CK20) and CK5/6. The next generation sequencing (NGS) was performed and the molecular results from intraperitoneal lymph node tissue biopsy did not show any abnormality (EGFR, KRAS, NRAS, ALK, ROS1, MET, HER-2, FGFR2, NTRK1, NTRK2, RET, PIK3CA) except BRAF exons 15 (p.D594N pathogenic mutation). The patient developed symptoms of right progressive hypotonia to grade 1 and distortion of right commissure. MRI brain showed that there was a mass (about 1.3 cm in diameter) in the left frontal lobe with brain edema, which was deemed metastatic (Fig. 1①). Furosemide and 20% mannitol were used to treat cerebral edema and the muscle tone recovered to grade 2. The patient refused the treatment of whole brain radiotherapy and systemic chemotherapy.
The patient started to take trametinib (2 mg orally, once daily) based on the molecular results. There have been systemic pruritus and hand-foot syndrome during the treatment, which was evaluated as grade 2 adverse reaction according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. and no other adverse reactions were observed. He got relieved after taking positive measures. A CT scan performed 8 months after medication showed a partial response of brain metastasis, pulmonary nodule, portal lymph node metastasis and peritoneal lymph node metastasis (Fig. 1⑤-⑧). CEA, CA125, and CA153 all returned to normal level. The improvement of quality of life of the patient was dependent on the recovery of muscle tone. In November 2020, the patient developed melena without an obvious cause, and gastroscopy showed compound ulcer, so he stopped taking trimetinib. The patient eventually died of gastrointestinal bleeding. He had an 8 months progression-free survival on trametinib.