Brain metastases

Epidemiology

No reliable estimates are available on the incidence in cancer patients. This information is valuable for planning patient care and developing measures that may prevent or decrease the likelihood of metastatic brain disease.

Brain metastases are the most common cause of malignant brain tumours in adults. Of the nearly 1·5 million patients in the USA who received a primary diagnosis of cancer in 2007, about 70 000 of these primary diagnoses are estimated to eventually relapse in the brain ^{1) 2)}).

Between 20% and 40% of all patients with metastatic cancer will have brain metastases at autopsy ³⁾.

Rates of CNS involvement in metastatic cancer are believed to be increasing, possibly owing to better control of systemic disease with novel chemotherapies or improved metastasis detection.

However, controversies exist regarding demographic and clinical profile of brain metastases.

Analysis from the Kentucky and Alberta cancer registries similarly demonstrated the aggressive nature of lung cancer and its propensity for BM at initial presentation. Besides widespread organ involvement, no synchronous organ site predicted BM in lung cancer. BM is a common and important clinical outcome, and use of registry data is becoming more available ⁴⁾.

Trials

Despite the frequency of brain metastases, prospective trials in this patient population are limited, and the criteria used to assess response and progression in the CNS are heterogeneous ⁵⁾.

This heterogeneity largely stems from the recognition that existing criteria sets, such as RECIST ^{6) 7)}.

Types

Brain metastases from cancer of unknown primary site.

From different cancers.

For example:

Bladder cancer intracranial metastases.

Melanoma brain metastases.

Brain metastases from ovarian cancer.

Colorectal cancer (CRC) infrequently causes brain metastases (BM) (1.2%) ⁸⁾.

see Lung cancer intracranial metastases.

see Multiple brain metastases.

Distribution

The majority of brain metastases originate from primary cancers in the lung (40–50%) or breast (15–25%), or from melanoma (5–20%) ⁹⁾

They are common in elderly population and mostly due to primary lung. Adenocarcinoma was the most common histology of primary. Majority of lesions has been observed at parietal lobe ¹⁰⁾.

Genes involved

Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown.

Brastianos et al. detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases ¹¹⁾.

COX2

HBEGF

ST6GALNAC5

HK2

FOXC1

HER2

VEGFA

LEF1

HOXB9

CDH2, KIFC1, and FALZ3

STAT3

αvβ3

HDAC3, JAG2, NUMB, APH1B, HES4, and PSEN1

Clinical Features

see Brain metastases Clinical Features.

Diagnosis

see Brain metastases diagnosis.

Differential diagnosis

see Brain metastases differential diagnosis.

Guidelines

The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of NeuroOncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Soffietti et al. present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, they addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-small cell lung cancer, melanoma and breast and renal cancer), and supportive care ¹²⁾.

Treatment

see Brain metastases treatment.

Outcome

Brain metastases outcome.

Recurrence

see Brain metastases recurrence.

Case series

see Brain metastases case series.