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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Histological transformation of non-small cell lung cancer: Clinical analysis of nine cases
1Department of Thoracic Oncology, Hubei Cancer Hospital, Wuhan 430000, Hubei Province, China.
Background:
Histological transformation is one of the numerous mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Given its rarity, the underlying transformational mechanisms, clinical features, and therapeutic prognoses are only studied through limited case reports.
Aim:
To analyze the clinical characteristics and underlying mechanisms in non-small cell lung cancer (SCLC) patients with histological transformation after treatment with EGFR-TKIs.
Methods:
We retrospectively investigated nine patients diagnosed with non-SCLC transforming to SCLC, large-cell neuroendocrine carcinoma (LCNEC), or squamous cell carcinoma on re-biopsy after first- or third-generation EGFR-TKIs.
Results:
The median age of nine patients was 60 years. Among them, six patients had the EGFR 19del mutation, one had the L858R mutation, and one had wild-type EGFR. The level of plasma NSE was measured in six patients with SCLC or LCNEC transformation when transformation occurred, and five patients had elevated plasma NSE levels. All patients received standard chemotherapy after transformation with the exception of one patient who received chemotherapy and anlotinib.
Conclusion:
Tumor re-biopsy should be performed routinely when EGFR-TKI therapy fails in lung cancer patients to avoid ignoring histological transformation and to select a subsequent therapeutic strategy. The transformed tumor retained the original EGFR mutation, indicating that histological transformation represents an evolution from the initial tumor.
Insights
Histological transformation in lung cancer is a rare resistance mechanism to EGFR-TKIs. Re-biopsy is crucial for identifying these transformations and guiding treatment for better outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Histological transformation is a resistance mechanism to EGFR-TKIs in lung cancer.
- Limited data exists on transformation mechanisms, clinical features, and prognosis due to rarity.
Purpose of the Study:
- To analyze clinical characteristics and mechanisms of histological transformation in non-small cell lung cancer (NSCLC) after EGFR-TKI treatment.
Main Methods:
- Retrospective analysis of nine NSCLC patients who transformed to SCLC, LCNEC, or squamous cell carcinoma post-EGFR-TKI therapy.
- EGFR mutation status and plasma NSE levels were assessed.
Main Results:
- Median age was 60; most patients had EGFR 19del or L858R mutations.
- Five of six patients with SCLC/LCNEC transformation showed elevated plasma NSE.
- Most patients received chemotherapy post-transformation.
Conclusions:
- Routine re-biopsy is recommended upon EGFR-TKI failure to detect histological transformation.
- Transformed tumors retain original EGFR mutations, suggesting evolutionary resistance.
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