A 66-year-old Chinese man experienced a cough and blood-tinged sputum for >5 months. On admission, the patient had an intermittent cough, a small amount of blood in sputum, a shortness of breath after activity, and mild pain in the left iliac region but no other complaints of obvious discomfort or disease history. He was generally in good health; the performance status (PS) score was 1, and the pain numerical rating scale (NRS) score was 1. The admission examination results of the tumor markers CEA (Carcinoembryonic antigen), CA19-9 (Carbohydrate antigen199), SCC (Squamous cell carcinoma antigen), NSE (Neuron-specific enolase), CYFRA21-1 (Cytokeratin 19 fragment), ProGRP(Progastrin releasing peptide), CA125 (Carbohydrate antigen 125), TPS (Tissue Polypeptide Specific Antigen) and Hsp90alpha (Heat Shock Protein 90 alpha) were negative, and the routine blood test results and the main indexes of liver and kidney function were basically normal. Admission positron emission tomography/computed tomography (PET/CT) showed signs of right lung upper lobe cancer and right ischium metastasis and high-density nodules in the right 8th posterior rib, 11th posterior rib, and left iliac bone; metastasis was considered. Tracheoscopy showed the orifice of the upper lobe of the right lung to be almost completely blocked by cauliflower-like tumors, with numerous dirty, white, and dead objects, which bled easily when touched. The biopsy of the upper lobe of the right lung revealed spindle cells arranged in a bundle and mat pattern, scattered lymphocyte infiltration, loose, and edema in some areas (Figure 1). Considering the immunohistochemical results: AE1/AE3 (-), vimentin (+), BCL-2 (-), CD34 (-), Ki67 (approximately 60% +), S-100 (-), SMA (-), TTF-1 (-), P63 (weak +), SATB2 (+), STAT6 (-), CK7 (focal weak +), ALK (D5F3) (+), and PD-L1 negative (22C3: TPS<1%) (Figure 2), which were consistent with those of malignant tumors, and a patient's pathological morphology, we suspected pulmonary mesenchymal tumor and established the diagnosis of right pulmonary inflammatory myofibroblastic tumor with bone metastasis. cT4N0M1c, the IVB stage, and the PS score was 1. DNA next-generation sequencing was carried out by using the hybridization capture method with the patient's tissue samples. We detected 556 cancer-related genes; the average sequencing depth of the target gene detection area was 2697X, and the sequencing depth was sufficient. The sequencing results showed that there was GCC2-ALK (G19:A20) fusion (Figure 3), and the mutation abundance was 7.11%. No other meaningful target mutations recommended for clinical medication were detected.
Based on the superior efficacy of ensartinib to crizotinib, the patient was started on ensartinib 225- mg QD, which targeted GCC2-ALK fusion, and denosumab 120-mg Q4w anti-bone metastasis. After 1 week, the patient reported significant improvement in cough and the disappearance of blood-tinged sputum. However, after approximately 2 weeks of treatment, the patient developed a grade III rash (according to NCI-CTCAE standard version 5.0) appearing first on the face and gradually involving the trunk and bilateral upper and lower limbs (Figure 4), with serious pruritus. Therefore, the ensartinib dose was reduced to 125-mg QD. After 2 weeks of drug reduction, the rash on the face and limbs gradually disappeared. In addition, the patient experienced mild loss of taste and constipation during medication , no other discomfort. The patient continued to take the medicine at the stated dose. One month after treatment, the cough significantly improved, there was no blood in sputum, and pain in the left iliac region was relieved. The reexamination of chest CT showed that the focus volume was significantly reduced. According to RECIST 1.1, the better response evaluation was evaluated as partial response (PR). Follow-up chest CT revealed that the patient maintained PR after 7 months. After 11 months of follow-up, chest CT showed that the main focus of the lung tumor was slightly advanced, but the sum of the maximum diameter of the main focus of the tumor did not increase by 20%, and an evaluation of stable disease (SD) was achieved (Figure 5). In a whole-body bone scan, the metabolism of T6-T8 and T11, the eighth rib of the right rear was slightly increased, and the right ischium and left iliac bone were changed. A further check was suggested to exclude malignant tumor. The bone metastasis was significantly relieved, and there was no bone pain. After several follow-up visits, the patient's symptoms were stable, with a small amount of blood in sputum intermittently, which was relieved after symptomatic treatment. There were no major complaints of discomfort and no other drug-related side effects, and the routine blood routine examination and liver and kidney function were normal every time, suggesting the good clinical efficacy of ensartinib. The targeted therapy of ensartinib was continued, and regular outpatient follow-up continued.