Brain Metastases as Inaugural Sign of Non-Small Cell Lung Carcinoma: Case Series and Review of Literature

Simple Summary Treating non-small cell lung cancer (NSCLC) patients with brain metastases (BM) is challenging, especially when brain involvement is the first sign of cancer. This study retrospectively analyzed 25 patients with newly diagnosed brain metastatic NSCLC without EGFR or ALK alterations. The findings suggest that patients with symptomatic BM at diagnosis may have better survival outcomes due to increased use of multimodal local treatments. Combining local approaches with first-line immune checkpoint inhibitors (ICI) and chemotherapy appears to improve survival in these patients. Additionally, a nonsystematic literature review was conducted to better understand the topic and explore the potential benefits of various immunotherapy-based combinations for brain metastatic NSCLC. This research aims to highlight the survival outcomes of this underrepresented population and provide insights into optimal treatment strategies.Abstract In the era of immune checkpoint inhibitors (ICI), managing non-oncogene driven non-small cell lung cancer (NSCLC) with brain metastases (BM) is challenging, especially when brain involvement is the initial sign. Patients with newly diagnosed brain metastatic NSCLC without epidermal growth factor receptor (EFGR) nor anaplastic lymphoma kinase (ALK) alterations were retrospectively included. Twenty-five patients were analyzed; 15 (60%) had symptomatic BM as the first sign (group 1), while 10 (40%) had BM discovered during complementary examinations (group 2). Fourteen patients (56%) had concomitant extracerebral metastases, primarily in group 2. Eight (32%) had oligometastatic disease, with seven in group 1. Over half received chemotherapy and pembrolizumab as first-line treatment. BM surgical resection occurred in twelve (80%) patients in group 1 and one in group 2. Median cerebral progression-free survival was 10 months: 12 in group 1 and 5 in group 2. Median overall survival was 25 months: not reached in group 1 and 6 months in group 2. This case series highlights survival outcomes for patients with inaugural BM, a demographic underrepresented in pivotal trials. Oligometastatic disease and symptomatic BM as initial signs seem associated with better prognosis due to increased use of multimodal local approaches. Combining local approaches with first-line ICI+/- chemotherapy appears to improve survival in brain metastatic NSCLC. A literature review was conducted to explore key questions regarding upfront ICI alone or in combination with systemic drugs or local approaches in brain metastatic NSCLC.