EGFR-Mutant Non-Small-Cell Lung Cancer [Neurosurgery Wiki]

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====== EGFR-Mutant Non-Small-Cell Lung Cancer ======

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/12Ek7-__ImvHhbya5JBSNEa2Ngc87YPKiD5Sj53oLlptYA5E-S/?limit=15&utm_campaign=pubmed-2&fc=20250402144056}}

The discovery of [[epidermal growth factor receptor]] (EGFR) mutations is one of the most promising advances for the treatment of [[NSCLC]]
((Luo D, Ye X, Hu Z, Peng K, Song Y, Yin X, Zhu G, Ji Q, Peng Y. EGFR mutation
status and its impact on survival of Chinese non-Small-cell lung cancer patients 
with brain metastases. Tumour Biol. 2014 Mar;35(3):2437-44. doi:
10.1007/s13277-013-1323-9. Epub 2013 Nov 7. PubMed PMID: 24197981.
)).

Patients with EGFR-mutant tumors are more likely to experience [[brain metastases]] than patients with wild-type tumors
((Shin DY, Na II, Kim CH, Park S, Baek H, Yang SH. EGFR mutation and brain
metastases in pulmonary adenocarcinomas. J Thorac Oncol. 2014 Feb;9(2):195-9.
doi: 10.1097/JTO.0000000000000069. PubMed PMID: 24419416.
)).
----

----
Chiang et al. prospectively enrolled patients with EGFR-mutant NSCLC who underwent [[CSF sampling]] for suspected [[Leptomeningeal metastases]] (LM). The supernatant of [[CSF]] after routine [[cytology]] examination was collected. The diagnosis of LM was established according to EANO-ESMO criteria. CSF and plasma cell-free DNA ([[cfDNA]]) were retrieved for [[Epidermal growth factor receptor mutation]] testing.

Fifty-one patients with a median age of 62.7 years were enrolled. The median duration from the initial diagnosis to CSF sampling was 23.0 months and most patients (94.1%) had received at least one [[Epidermal growth factor receptor tyrosine kinase inhibitor]]. [[Adenocarcinoma]] cells were found in 37 CSF samples (72.5%), and 48 (94.1%) patients had confirmed or probable LM. Thirty-five of these 48 patients (72.9%) had valid EGFR mutation-testing results using CSF cfDNA and tended to have higher [[white blood cell count]]s and positive cytology in their CSF compared to those with invalid mutation testing results. The overall detection rate of EGFR mutation in CSF cfDNA was 68.8%, and the [[T790M]] detection rate was 14.6%. In 37 patients with paired CSF and plasma samples, the concordance rate of the EGFR mutation results was 29.7%.

For patients with EGFR-mutant NSCLC with LM, CSF supernatant is a valuable source for EGFR mutation testing and may provide important information
((Chiang CL, Lee CC, Huang HC, Wu CH, Yeh YC, Shen CI, Luo YH, Shiao TH, Chang HJ, Huang YT, Chen YM, Chou TY, Chiu CH. Utility of Cerebrospinal Fluid Cell-Free DNA in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer with Leptomeningeal metastases. Target Oncol. 2021 Feb 10. doi: 10.1007/s11523-021-00791-9. Epub ahead of print. PMID: 33566300.)).

===== Prognosis =====
Non-small cell lung cancer patients with [[EGFR]] mutation have a high rate of [[brain metastases]], and [[Epidermal growth factor receptor tyrosine kinase inhibitor]]s (TKIs) are the principal therapeutic approach.

However, acquired [[targeted therapy resistance]] is the main reason for EGFR-TKIs' treatment failure. At present, the mechanism of intracranial acquired targeted therapy resistance is limited, mainly due to the lack of a [[cell line]] that can be used for its study.
----
====== Lung adenocarcinoma with epidermal growth factor receptor mutation ======

Kwon et al. investigated the risk factors for [[leptomeningeal carcinomatosis]] (LMC) and compared clinical efficacies of various treatment modalities including [[intrathecal]] [[chemotherapy]] in patients with [[lung adenocarcinoma]] harboring [[epidermal growth factor receptor mutation]]s.

Using clinical research [[data]] from the [[Asan Medical Center]], they retrospectively analyzed data of patients diagnosed with LMC, confirmed via [[cerebrospinal fluid]] (CSF) analysis from January 2008 to December 2017.

They identified 1189 patients with [[lung adenocarcinoma]] harboring [[EGFR]] [[mutation]]s. Among these, 9.8% had a median duration of 13.5 (interquartile range [IQR] 6.8-23.6) months from the initial [[lung cancer]] diagnosis to LMC occurrence. Younger age (hazard ratio [HR] 1.043, P < 0.001), initial metastatic disease (HR 3.768, P < 0.001), and metastases to the brain (HR 8.682, P < 0.001) or lung (HR 2.317, P = 0.004) were risk factors associated with LMC. The [[median survival]] duration from LMC diagnosis was 3.8 (IQR 1.5-8.6) months. Eastern Cooperative Oncology Group performance status score ≤ 2 (HR 0.505, P = 0.007) and insertion of the [[Ommaya reservoir]] (HR 0.445, P = 0.005) were associated with longer survival. EGFR-[[tyrosine kinase inhibitor]] (TKI) conferred survival benefits compared to cytotoxic chemotherapy or best supportive care (HR 2.222, P = 0.018; HR 5.638, P < 0.001, respectively). Although IT chemotherapy showed no survival benefit, it was associated with improved neurologic symptoms and signs and CSF negative conversion.

Younger age, an initial diagnosis of metastatic disease, and metastases to the brain or different lobes were associated with LMC in patients with EGFR-mutant lung adenocarcinoma. Therapeutic interventions including EGFR-TKIs, cytotoxic chemotherapy, or Ommaya reservoir, and good performance status were related to favorable survival outcomes.

Age and disease status were associated with LMC in patients with EGFR-mutant adenocarcinoma, and EGFR-TKI, [[Ommaya reservoir]], and good [[performance status]] were related to survival benefit
((Kwon BS, Cho YH, Yoon SK, Lee DH, Kim SW, Kwon DH, Lee JC, Choi CM. Impact of 
clinicopathologic features on leptomeningeal metastases from lung adenocarcinoma 
and treatment efficacy with epidermal growth factor receptor tyrosine kinase
inhibitor. Thorac Cancer. 2020 Jan 7. doi: 10.1111/1759-7714.13296. [Epub ahead
of print] PubMed PMID: 31910497.
)).

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