In November 2020, a 73-year-old Chinese woman with no history of smoking was referred to the authors’ hospital for a one-month history of severe chest and back pain, cough, dyspnea, asthenia, anorexia, weight loss, and multiple masses observed on chest radiography.
Positron emission tomography-computed tomography (PET-CT) revealed 18-fluoro-2-deoxy-d-glucose (FDG) showing abnormally increased radiopharmaceutical uptake at a 4.7- × 4.2 cm mass in the right upper lobe of the lung with a maximum standardized uptake value 11.9, accompanied by multiple metastases in bilateral lungs, bilateral adrenal nodules, liver, bones, bilateral hilar, mediastinal, supraclavicular lymph nodes, and right pleural metastases with pleural effusion (Fig. 1). Pathological examination of the CT-guided core needle biopsy of the liver metastases specimen revealed undifferentiated cancer with a mild tendency of squamous differentiation (hematoxylin and eosin staining [Fig. 2]). Upon immunohistochemical analysis, the tumor cells exhibited strong positive staining for cytokeratin and p63 (Fig. 2), but negative for thyroid transcription factor-1 (TTF-1) (Fig. 2). These findings led to the final diagnosis of advanced LSCC, grade 3, cT4N3M1c, stage IVB.
Targeted next-generation sequencing (NGS) of 16 lung cancer-related genes (Repu Gene Technology Company, China) was performed on DNA isolated from the tumor biopsy specimen, and results indicated that the cancer cells harbored both the EML4-ALK variant 1 rearrangement (E13;A20) and TP53 exon10 p.L348S (c. 1043T > C) mutation accounted for 70.04% (Fig. 3).
At that time, the patient was too ill to undergo conventional chemotherapy due to severely deteriorated liver function and poor physical constitution. According to the Eastern Cooperative Oncology Group criteria, her performance status (PS) was 4. Carbohydrate antigen (CA) 125 and CA19-9 levels were 16,125 U/mL (reference value < 35 U/mL) and 181.7 U/mL (reference value < 40 U/mL), respectively. Considering the molecular results, first-line therapy with the new second-generation ALK inhibitor, ensartinib (225 mg once per day), was administered on December 3, 2020. The accompanying treatment plan consisted of zoledronic acid injections for bone metastasis. On February 24, 2021, CT (performed after 83 days of ensartinib therapy) revealed good partial response in most target lesions according to the Response Evaluation Criteria in Solid Tumors scores (Fig. 4). The levels of CA125 and CA19-9 were reduced to 107 U/mL and 4.1 U/mL, respectively. Moreover, adverse events experienced by the patient were diminished during treatment, and only involved a mild rash. Her physical condition improved significantly, and PS recovered to 2. At the latest follow-up, 3.5 months after commencing ensartinib treatment, there was no evidence of progression or any remarkable toxicity.