Epidemiology of Central Nervous System Metastases

Introduction

Brain metastases are the most common type of brain tumors ( ) and are associated with significant mortality and morbidity ( ). The incidence of brain metastases varies by reporting institution, and different studies have reported different results. For example, the reported incidence varies from 2.8 to 14.3 individuals per 100 000 population ( ). At the same time, study-specific data indicate a rate of 9–17% of systemic cancers being complicated by brain metastases ( ). Autopsy studies also found that 8.7–24% of patients with systemic cancers had brain metastases ( ).

With the advent of new imaging modalities, the incidence of brain metastases increased over time due to earlier detection of the lesions ( ). In addition, improved treatment for the systemic cancers increased survival and therefore the likelihood of the patient developing brain metastases over time ( ). The cohort study in Sweden found that the incidence of brain metastases doubled from 1987 to 2006 ( ).

The most common sources of brain metastases are lung cancer, breast cancer, melanoma, renal cancer, and colorectal cancer ( ). However, virtually any cancer, including prostate cancer, ovarian cancer, and liver cancer can metastasize to the brain ( ). Sometimes, patients can present with brain metastases without evidence of primary cancer ( ). The primary tumor site, if eventually detected, is often the lung ( ).

The incidence of brain metastases from various cancers changed over time. For example, during the 1980s, men had a higher incidence of brain metastases than women. This was likely due to a higher incidence of lung cancer in men at the time due to smoking ( ). A more recent cohort study in Sweden reported that women had a higher incidence of brain metastases than men ( ). This study only investigated patients who were hospitalized and included all brain metastases. The reason for this change could be due to a decreased incidence of lung cancer in men due to smoking cessation and relative increase in incidence of lung cancer in women. In addition, a relative increase in the incidence of breast cancer in women over the study period from 1987 to 2006 also contributed to increased incidence of brain metastases. The incidence of breast cancer has increased slowly over the past 20 years. At the same time, it appeared that the incidence of brain metastases from breast cancer also increased ( ).

reported that the median age at first admission due to brain metastases from systemic cancer was 67 years old among men and 64 years old among women. Half of the patients were admitted because of brain metastases as the primary diagnosis, 43% were admitted as other systemic cancers with secondary brain metastases while 7% were admitted due to other non-cancer disorders and found to have brain metastases incidentally ( ). Brain metastases are rare in children. The most common brain metastases in children are secondary to germ cell tumors, sarcoma, and neuroblastoma ( ).

Incidence

Though the overall incidence of cancer as well as death due to cancer decreased recently between 2004 and 2012, there are still a total of 1 638 910 new cancer cases, and 577 190 deaths from cancer projected to occur in the USA in 2012 ( ). Brain metastases continue to remain the major type of brain tumor, about 3–5 times higher than the number of newly diagnosed primary malignant brain tumors each year ( ). It was estimated that almost 70 000 new brain metastases would occur over the remaining lifetime of individuals who received a diagnosis of primary invasive cancer in the USA in 2007 ( ). Although the exact incidence of brain metastases is unknown, it is estimated that the incidence ranges from 2.8–11.1 per 100 000 population in studies concluded before 1990 ( ) to 7–14.3 per 100 000 population in more recent studies ( ). The incidence of lifetime brain metastases from systemic cancers was estimated to increase yearly between 2003 and 2007 ( ).

In 1970, Guomundsson performed a population based epidemiologic study in Iceland that covered brain metastasis between 1954 and 1963. The annual incidence was 2.8 per 100 000 population ( ). A more extended study conducted from 1935 to 1968 by found the incidence in Minnesota in the USA was 11.1 per 100 000 population. Studies in the 1970s and 1980s showed the incidence of 3.4 per 100 000 population in Finland with 66 study subjects (1975–1983) ( ). More recent studies extended to the 1990s and 2000s showed a higher incidence than the studies conducted in the 1970s and 1980s. Materljan reported 9.9 per 100 000 population with 80 study subjects in Croatia ( ). Counsell reported 14.3 per 100 000 population with 214 study subjects in Scotland ( ). studied a large population with 15 517 subjects and clearly demonstrated that the incidence of brain metastases doubled from 7 per 100 000 in 1987 to 14 per 100 000 in 2006. Two other studies reported that the incidence proportion (also known as cumulative incidence) percentage (IP%) were 8.5% (1986–1995) in the Netherlands ( ) and 9.6% (1973–2001) in Michigan ( ).

Incidence by Demographic Features

As the incidence of the primary tumors varies with different demographic characteristics, so does the incidence of brain metastases. described that race, gender and age influence the incidence of brain metastases. The study was conducted on a population-based MDCSS (Cancer Surveillance System for the Metropolitan Detroit Area) on 16 210 patients who developed brain metastases after diagnosis with a single primary tumor between 1973 and 2001 ( ). It compared the IP% among different race, sex, age at the diagnosis and Surveillance Epidemiology and End Results Program (SEER) stage of the primary cancer.