Development of Brain Metastases Following Definitive Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer

Abstract

<h3>Purpose/Objective(s)</h3> To describe the time course and likelihood of symptomatic presentation of brain metastases in the setting of locally advanced non-small cell lung cancer (LA-NSCLC) following definitive therapy. <h3>Materials/Methods</h3> Patients with LA-NSCLC treated with chemoradiation as definitive therapy between 2013-2020 (n = 219) were reviewed. Features including histologic subtype, T, N and clinical prognostic stage, presence of brain metastases and symptoms at time of presentation were recorded. Descriptive statistics were used to characterize the patient population, including incidence of brain metastases by histology, and the method of Kaplan and Meier was used to estimate brain metastasis free survival at 24 months. Fisher's exact tests were used to compare proportions between symptomatic and asymptomatic patients. <h3>Results</h3> A total of 219 patients met inclusion criteria. Histology including squamous cell carcinoma (SCC) (96), adenocarcinoma (88), and NSCLC-Not Otherwise Specified (NOS) (35). Median age was 67 years; 210 (96%) were current/former smokers, T stage was T0 (11.9%), T1 (21.9%), T2 (26.5%), T3 (18.3%), and T4 (21.5%). The majority of patients were N2 or N3 at treatment: N0 (5%), N1 (14.2%), N2 (60.7%), and N3 (20.1%). In total, 39 patients (17.8%) developed brain metastases. Incidence by histology varied with NSCLC-NOS showing the highest incidence (34.3%), followed by adenocarcinoma (23.9%), and SCC (6.2%). Brain metastasis free survival at 24 months was 72.9% (95% CI: 62.5-84.9%) for adenocarcinoma, 92.2% (95% CI: 86.3 – 98.5%) for SCC, and 53.3% (95% CI: 35.4 – 80.1%) for NSCLC-NOS. Median time to development of brain metastasis was 7.7 months (adenocarcinoma), 5.7 months (SCC), and 8.3 months (NSCLC-NOS). Overall, 85% of brain metastases occurred within 1 year. Ninety percent of patients were diagnosed with brain metastases after development of neurologic symptoms. Only 4 total patients had brain metastases discovered without symptoms. For patients presenting with symptomatic brain metastases, 91.4% required steroids versus 0% for those without symptoms (p <0.001). Symptomatic patients were more likely to require hospitalization at presentation, 65.7% vs 0% (p = 0.02). All asymptomatic patients with brain metastases were able to undergo stereotactic radiosurgery (SRS) alone, while only 40% of symptomatic patients received SRS monotherapy (p = 0.04). There was no statistically significant difference brain metastasis incidence based on treatment with adjuvant immunotherapy vs none for any histology (17.1% vs 18.1%, p = 1). <h3>Conclusion</h3> Brain metastases are a common source of morbidity and mortality in the setting of LA-NSCLC; however, there is no standard recommendation for surveillance brain imaging following therapy. Presentation with symptomatic brain metastases was significantly associated with need for more invasive management. This could strengthen an argument for the potential utility of surveillance brain imaging in the post-definitive setting.