Incidence and real-world burden of brain metastases from solid tumors and hematologic malignancies in Ontario: a population-based study

Abstract

Background: Although intracranial metastatic disease (IMD) is a frequent complication of cancer, most cancer registries do not capture these cases. Consequently, a data-gap exists, which thwarts system-level quality improvement efforts. The purpose of this investigation was to determine the real-world burden of IMD.

Methods: Patients diagnosed with a non-CNS cancer between 2010 and 2018 were identified from the Ontario Cancer Registry. IMD was identified by scanning hospital administrative databases for cranial irradiation or coding for a secondary brain malignancy (ICD-10 code C793).

Results: 25,478 of 601,678 (4.2%) patients with a diagnosis of primary cancer were found to have IMD. The median time from primary cancer diagnosis to IMD was 5.2 (0.7, 15.4) months and varied across disease sites, for example, 2.1 months for lung, 7.3 months for kidney, and 22.8 months for breast. Median survival following diagnosis with IMD was 3.7 months. Lung cancer accounted for 60% of all brain metastases, followed by breast cancer (11%) and melanoma (6%). More advanced stage at diagnosis and younger age were associated with a higher likelihood of developing IMD (P < .0001). IMD was also associated with triple-negative breast cancers and ductal histology (P < .001), and with small-cell histology in patients with lung cancer (P < .0001). The annual incidence of IMD was 3,520, translating to 24.2 per 100,000 persons.

Conclusion: IMD represents a significant burden in patients with systemic cancers and is a significant cause of cancer mortality. Our findings support measures to actively capture incidents of brain metastasis in cancer registries.

Keywords: brain imaging; brain metastases; incidence; intracranial metastatic disease.

Figure 1.

Cohort creation. Cohort creation from the Ontario Cancer Registry (OCR), excluding primary cancers of the brain and CNS (ICD Oncology version 3 codes C70-C72). Means and medians are the time from primary cancer diagnosis until brain metastasis was identified. ^aPostal code was derived from the OCR, which corresponds to the patients’ postal code at the time of diagnosis. ^b709 identified from CIHI databases only; 4,379 identified from the Activity Level Reporting database only. ICD-10—International Classification of Diseases, 10th revision; C793—ICD-10 diagnostic code “Secondary malignant neoplasm of brain and cerebral meninges”; IQR—25th, 75th percentile.

Figure 2.

Intracranial metastatic disease by disease site. (A) Percent of all brain metastasis by disease site (minimum 50 metastases). (B) Probability of brain metastasis by disease site (minimum 50 metastases). (C) Time from primary diagnosis until metastasis (select disease sites). SEER, Surveillance, Epidemiology, and End Results.

Figure 2.

Intracranial metastatic disease by disease site. (A) Percent of all brain metastasis by disease site (minimum 50 metastases). (B) Probability of brain metastasis by disease site (minimum 50 metastases). (C) Time from primary diagnosis until metastasis (select disease sites). SEER, Surveillance, Epidemiology, and End Results.

Figure 3.

Rate of intracranial metastatic disease (IMD) over time by disease site. (A) Timing of occurrence of brain metastasis since original primary cancer diagnosis. (B) Timing of occurrence of brain metastasis since original primary cancer diagnosis by disease site (logarithmic scale). For a given year, the number of brain metastases is equal to 2.23% of the number of incident cancer diagnosis occurring the previous year plus 1.07% of cases diagnosed the previous year, and so on. Disease-site specific estimates can be derived from the percentages in Supplementary Table S8. To permit sufficient follow-up across disease sites to develop IMD, only primary cancers diagnosed between 2010 and 2012 were included.

Figure 4.

Association of intracranial metastatic disease (IMD) and overall survival. (A) Kaplan–Meier plot for survival in patients with (bottom line) or without (top line) IMD. (B) Kaplan–Meier plot for survival following IMD, by disease site.