Causes of Death in Patients With Brain Metastases

Abstract

BACKGROUND AND OBJECTIVES: Advances in targeted therapies and wider application of stereotactic radiosurgery (SRS) have redefined outcomes of patients with brain metastases. Under modern treatment paradigms, there remains limited characterization of which aspects of disease drive demise and in what frequencies. This study aims to characterize the primary causes of terminal decline and evaluate differences in underlying intracranial tumor dynamics in patients with metastatic brain cancer. These fundamental details may help guide management, patient counseling, and research priorities. METHODS: Using NYUMets-Brain—the largest, longitudinal, real-world, open data set of patients with brain metastases—patients treated at New York University Langone Health between 2012 and 2021 with SRS were evaluated. A review of electronic health records allowed for the determination of a primary cause of death in patients who died during the study period. Causes were classified in mutually exclusive, but collectively exhaustive, categories. Multilevel models evaluated for differences in dynamics of intracranial tumors, including changes in volume and number. RESULTS: Of 439 patients with end-of-life data, 73.1% died secondary to systemic disease, 10.3% died secondary to central nervous system (CNS) disease, and 16.6% died because of other causes. CNS deaths were driven by acute increases in intracranial pressure (11%), development of focal neurological deficits (18%), treatment-resistant seizures (11%), and global decline driven by increased intracranial tumor burden (60%). Rate of influx of new intracranial tumors was almost twice as high in patients who died compared with those who survived (P < .001), but there was no difference in rates of volume change per intracranial tumor (P = .95). CONCLUSION: Most patients with brain metastases die secondary to systemic disease progression. For patients who die because of neurological disease, tumor dynamics and cause of death mechanisms indicate that the primary driver of decline for many may be unchecked systemic disease with unrelenting spread of new tumors to the CNS rather than failure of local growth control.

Neuro-oncologic Emergencies

“…19 Herniation Herniation represents the most common cause of death secondary to CNS tumor progression. 23 FIGURE 11-1 is a schematic diagram of herniation syndromes. In the setting of supratentorial mass lesions, subfalcine herniation of the cingulate gyrus and uncal herniation, in which the mesial temporal region projects mass effect over the tentorial edge and midbrain, are the most common types of herniation.…”

“…More than 10% of neurologic causes of death in patients with brain metastasis are related to refractory seizures. 23 Overall, one-third of patients with malignant primary or secondary CNS tumors develop tumor-associated epilepsy 46,47 ; this risk is much lower in patients with meningiomas, with a cumulative risk of epilepsy of approximately 10% to 20%. 48,49 Seizure risk varies widely depending on the histopathologic type of tumor, particularly primary brain tumors.…”

“…Herniation represents the most common cause of death secondary to CNS tumor progression 23 figure 11-1 . is a schematic diagram of herniation syndromes.…”

“…Seizures and status epilepticus are highly morbid complications of CNS tumors and can be related to cortical irritation from the tumor, intratumoral hemorrhage, paraneoplastic syndromes, or treatment effects. More than 10% of neurologic causes of death in patients with brain metastasis are related to refractory seizures 23 . Overall, one-third of patients with malignant primary or secondary CNS tumors develop tumor-associated epilepsy 46,47 ; this risk is much lower in patients with meningiomas, with a cumulative risk of epilepsy of approximately 10% to 20% 48,49 .…”