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Chunhua Ma1, Juncheng Zhang2,3, Dongjiang Tang2,3
1Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Disease, Department of Intervention, Tianjin HuanHu Hospital, Tianjin, China.
Abstract:
Background: The significance of uncommon epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) and brain metastasis (BM) remains unclear. Cerebrospinal fluid (CSF) liquid biopsy is a novel tool for assessing EGFR mutations in BM. This study aimed to evaluate the EGFR mutations in patients with NSCLC and newly diagnosed BM and to examine the effect of EGFR tyrosine kinase inhibitors (TKI) on BM harboring CSF-tested uncommon EGFR mutations. Methods: This was a prospective study of 21 patients with NSCLC and BM diagnosed between 04/2018 and 01/2019. CSF was obtained to detect the BM EGFR mutations by next-generation sequencing. BM characteristics at magnetic resonance imaging (MRI) and EGFR-TKI response were examined. Results: Of 21 patients with NSCLC, 10 (47.6%) had leptomeningeal metastasis (LM), while 11 (52.4%) had brain parenchymal metastasis (BPM); 13 (61.9%) had confirmed EGFR mutation-positive primary tumors. The uncommon mutation rate in CSF ctDNA was 33.3% (7/21). Among those with EGFR mutation-positive primary tumors, the rate of uncommon EGFR mutations in CSF was 53.8% (7/13). Uncommon EGFR mutations were more common in patients with LM than in patients with PBM (6/11, 54.5% vs. 1/10, 10%), and included G719A, L861Q, L703P, and G575R. TKI was effective for four patients with BMs harboring uncommon EGFR mutations. Conclusion: In patients with NSCLC and LM, the rate of uncommon EGFR mutation was high. The BMs with uncommon EGFR mutations seem to respond to EGFR-TKI treatment. CSF liquid biopsy could reveal the EGFR genetic profile of the BM and help guide treatment using small-molecule TKI.
Insights
Uncommon epidermal growth factor receptor (EGFR) mutations are frequent in non-small cell lung cancer (NSCLC) with brain metastasis (BM). Cerebrospinal fluid (CSF) liquid biopsy can detect these mutations, and EGFR tyrosine kinase inhibitors (TKI) show effectiveness in treating BM with uncommon EGFR mutations.
Area of Science:
- Oncology
- Genetics
- Neurology
Background:
- The clinical significance of uncommon epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) is not well understood.
- Cerebrospinal fluid (CSF) liquid biopsy offers a novel approach for detecting EGFR mutations within brain metastases.
- Understanding these mutations is crucial for guiding targeted therapy in NSCLC patients with brain involvement.
Purpose of the Study:
- To evaluate the spectrum of EGFR mutations in patients diagnosed with NSCLC and newly identified BM.
- To assess the efficacy of EGFR tyrosine kinase inhibitors (TKI) in treating BM that harbor uncommon EGFR mutations detected via CSF liquid biopsy.
- To correlate CSF-detected EGFR mutations with BM characteristics and treatment response.
Main Methods:
- A prospective study involving 21 patients with NSCLC and BM between April 2018 and January 2019.
- Next-generation sequencing of CSF was performed to identify EGFR mutations in BM.
- Magnetic resonance imaging (MRI) was used to characterize BM, and the response to EGFR-TKI treatment was evaluated.
Main Results:
- Among 21 NSCLC patients, 10 had leptomeningeal metastasis (LM) and 11 had brain parenchymal metastasis (BPM).
- The uncommon EGFR mutation rate in CSF circulating tumor DNA (ctDNA) was 33.3% (7/21), rising to 53.8% (7/13) in patients with EGFR mutation-positive primary tumors.
- Uncommon mutations (G719A, L861Q, L703P, G575R) were more prevalent in LM (54.5%) than PBM (10%), and EGFR-TKI showed efficacy in four patients with uncommon mutations.
Conclusions:
- Patients with NSCLC and LM exhibit a high incidence of uncommon EGFR mutations.
- BM harboring uncommon EGFR mutations appear to be responsive to EGFR-TKI therapy.
- CSF liquid biopsy is a valuable tool for profiling the EGFR genetic landscape of BM, aiding in the selection of small-molecule TKI treatments.
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