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Small-cell lung cancer transformation from EGFR-mutant adenocarcinoma after EGFR-TKIs resistance: A case report
Yiqian Jiang1, Leyi Shou2, Qingmin Guo1
1Department of Radiotherapy, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China.
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.
Insights
Small-cell lung cancer (SCLC) transformation is a rare resistance mechanism in EGFR-mutant lung cancer treated with EGFR-tyrosine kinase inhibitors (TKIs). Repeat biopsies are crucial for diagnosing this transformation and guiding treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective for EGFR-mutant cancers.
- Acquired resistance to EGFR-TKIs is an inevitable challenge in cancer therapy.
- Transformation to small-cell lung cancer (SCLC) is a rare but significant resistance mechanism.
Observation:
- A 54-year-old male smoker with EGFR-mutant lung adenocarcinoma developed resistance to icotinib.
- Repeat biopsy revealed transformation to small-cell lung cancer with high Ki-67 index.
- The patient experienced disease progression, including brain and spine metastases, despite chemotherapy and radiotherapy.
Findings:
- EGFR-TKI resistance can manifest as SCLC transformation in EGFR-mutant lung adenocarcinoma.
- Immunohistochemistry confirmed the presence of both adenocarcinoma and small cell carcinoma components.
- Aggressive disease progression and metastasis occurred despite multimodal treatment.
Implications:
- This case underscores the importance of considering SCLC transformation as a cause of acquired resistance to EGFR-TKIs.
- Repeat biopsies are essential for accurate diagnosis and appropriate treatment selection in resistant lung cancer.
- Monitoring serum neuron-specific enolase may aid in early detection of SCLC transformation.
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