Abstract
Central nervous system (CNS) metastases occur frequently in oncogene-driven non-small cell lung cancer (NSCLC). Standard treatment approaches can potentially delay systemic treatment (surgical intervention) or result in neurocognitive impairment (radiotherapy). Recently, next-generation tyrosine kinase inhibitors (TKIs) have demonstrated remarkable intracranial activity. However, most clinical trials did not enroll patients suffering neurological symptoms. Our study aimed to assess the CNS activity of targeted therapies in this patient population. We present a case series of nine NSCLC patients with either EGFR mutation or ALK rearrangement and symptomatic CNS metastases that were treated with TKIs. Clinicopathological characteristics, treatment, and outcomes were analyzed. Most patients presented with symptomatic CNS metastases at time of metastatic disease presentation (6/9). Additionally, the majority of patients had leptomeningeal disease (6/9) and multiple parenchymal metastases. Patients presented with a variety of CNS symptoms with the most common being nausea, vomiting, headache, and confusion. Most patients (6/9) responded rapidly both clinically and radiographically to the targeted treatment, with a marked correlation between systemic and intracranial radiographic response. In conclusion, upfront use of next-generation TKIs in patients with oncogene-driven NSCLC with symptomatic CNS metastases is associated with reasonable intracranial activity and represents a valuable treatment option.
Highlights
Central nervous system (CNS) metastases occur in 24–44% of patients with advanced non-small cell lung cancer (NSCLC) [1]
All patients presented with stage IV disease with dissemination to metastatic sites, except one patient who presented with localized disease and had a brain-only relapse two years after primary definitive therapy
Leptomeningeal disease was diagnosed by brain imaging or cerebrospinal fluid cytology or both
Summary
Central nervous system (CNS) metastases occur in 24–44% of patients with advanced non-small cell lung cancer (NSCLC) [1]. Incidence of CNS metastases is even higher (24–58%) among patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) rearrangement, or c-ROS oncogene 1 (ROS1) rearrangement [2,3,4,5,6,7,8]. Brain metastases negatively affect survival and quality of life [9]. The standard approach to the treatment of brain metastases was primarily local and included options such as surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). A frequent shortcoming of the local strategies is the necessity to delay systemic treatment which can be crucial in patients with rapidly progressing tumors [10]. WBRT has recently been demonstrated to have no impact on overall survival or quality of life [13]
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