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Small-cell lung cancer transformation from EGFR-mutant adenocarcinoma after EGFR-TKIs resistance: A case report
Authors:Yiqian Jiang  Leyi Shou  Qingmin Guo  Yanhong Bao  Xiaoping Xu  Suhong An  Jianfeng Lu
Affiliation:aDepartment of Radiotherapy, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China;bDepartment of Pathology, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China;cDepartment of Infectious Disease, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China.
Abstract:Rationale:With the recent advancements in molecular biology research, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have emerged as excellent therapies for patients with EGFR-mutant cancers. However, these patients inevitably develop cross-acquired resistance to EGFR-TKIs. Transformation to small-cell lung cancer (SCLC) is considered a rare resistance mechanism against EGFR-TKI therapy. Here, we report a case of TKI resistance due to SCLC transformation and demonstrate its mechanisms and clinical features.Patient concerns:A 54-year-old Chinese man with a history of smoking for 40 years complained of an intermittent cough in March 2019.Diagnosis:Transbronchial lung biopsy was performed on the basal segment of the left lower lobe, which confirmed lung adenocarcinoma. In January 2020, repeat biopsy was performed, and the results of immunohistochemistry (IHC) staining showed TTF-1 (+), CK7 (+), napsin A (+), syn (+), and CD56 (+), with a Ki-67 (+) index 80% of small cell carcinomas. Infiltrating adenocarcinomas and small cell carcinomas were observed.Interventions:Icotinib (125 mg thrice daily) was administered as a first-line treatment from June 2019. We subsequently administered a chemotherapy regimen consisting of etoposide (180 mg, days 1–3) plus cisplatin (45 mg, days 1–3) every 3 weeks for 1 cycle after recurrence. As the patient could not tolerate further chemotherapy, he continued taking icotinib orally and received whole-brain radiotherapy 10 times to a total dose of 30 Gy after brain metastases.Outcomes:The patient relapsed after successful treatment with icotinib for 9 months. A partial response was achieved after 4 cycles of chemotherapy, and despite the brief success of chemotherapy, our patient exhibited brain metastasis and metastases of the eleventh thoracic spine and the second lumbar vertebra with pathological fracture. The patient eventually died of aggressive cancer progression.Lessons:Our case highlights the possibility of SCLC transformation from EGFR-mutant adenocarcinoma and the importance of repeat biopsy for drug resistance. Serum neuron-specific enolase levels may also be useful for detecting early SCLC transformation.
Keywords:epidermal growth factor receptor-mutant adenocarcinoma   small-cell lung cancer   transformation
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