PMC9096128_01
A schematic diagram of the course of management highlighting (A) radiographic, histopathologic, and molecular findings, and (B) carcinoembryonic antigen (CEA) levels at key time points. Red circles indicate the target lesion. CT, computed tomography. H & E, hematoxylin and eosin. LLL, left upper lobe. LN, lymph node. LUAD, lung adenocarcinoma. Met, metastasis. PD, progressive disease. PR, partial response. TPR, translocated promoter region.
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A neoplasm in the left lower trachea was found on bronchoscopy, and biopsy of the neoplasm revealed a poorly differentiated adenocarcinoma (Figure 1A). Frontline treatment with crizotinib (250 mg bid) started in May and after 1 month elicited a rapid response consistent with partial response (PR) per RECIST v1.1 guidelines, manifested as a 46% reduction (59x53 mm to 31x20 mm) of the LLL mass (Figure 1A). CEA level also lowered to 24.8 ng/ml (Figure 1B). Follow-up CT in August found newly emerged right lung nodules despite continued reduction of the target lesion (25x14 mm; Figure 1A). CT and enlarged brain lesions on MRI, which were consistent with progressive disease (Figure 1A). CEA level also rose to 43.9 ng/ml. TPR-ROS1 as the only aberration. The patient was subsequently started on ceritinib (450 mg qd) but did not appear to respond, as follow-up CT one month later indicated growing and new bilateral lung lesions and enlarged supraclavicular LN and brain metastasis, accompanied by continued rise in CEA level (65.2 ng/ml; Figure 1). There was also a minor drop in CEA level (Figure 1B).
Detection of a novel TPR-ROS1 (T4:R35) gene rearrangement using next-generation sequencing. (A) Identification of a TPR-ROS1 gene fusion. (B) Structural illustration of the resultant putative chimeric protein. TPR, translocated promoter region.
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A novel translocated promoter region (TPR)-ROS1 (T4:R35) gene fusion was detected from both samples (Figure 2).