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).
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).
From different cancers.
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).
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).
CDH2, KIFC1, and FALZ3
HDAC3, JAG2, NUMB, APH1B, HES4, and PSEN1
Presenting symptoms include headache (49%), focal weakness (30%), mental disturbances (32%), gait ataxia (21%), seizures (18%), speech difficulty (12%), visual disturbance (6%), sensory disturbance (6%), and limb ataxia (6%) 12).
Neuropsychological testing demonstrates cognitive impairment in 65% of patients with brain metastases 13) 14) , which might be a result of destruction or displacement of brain tissue by the expanding tumor, peritumoral edema leading to further disruption of surrounding white matter tracts, increased intracranial pressure, and/or vascular compromise.
Magnetic resonance imaging with contrast enhancement is the imaging procedure of choice to diagnose and characterize brain metastases. Multiple lesions with marked vasogenic edema and mass effect are typically seen in patients with brain metastases. The classical appearance of a metastasis is a solid enhancing mass with well-defined margins and extensive edema. Occasionally, central necrosis produces a ring enhancing mass.
The MR assessment should include T1-weighted images with and without enhancement and T2/FLAIR images. They usually appear as multiple lesions with nodular or annular enhancement and are surrounded by edema. They are hypervascularized and have no restriction of their diffusion coefficient in their necrotic area and contain lipids on 1H spectroscopy. Metastases can be distinguished from primary tumors by the lack of malignant cell infiltration around the tumor 15).
The main differential diagnosis includes primary tumours, abscesses, vascular and inflammatory lesions.
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 16).
Brain metastases are associated with a dismal prognosis. Treatment options for patients with brain metastases (BM) have limited efficacy and the mortality rate is virtually 100%.
Overall prognosis depends on age, extent and activity of the systemic disease, number of brain metastases and performance status. In about half of the patients, especially those with widespread and uncontrolled systemic malignancy, death is heavily related to extra-neural lesions, and treatment of cerebral disease doesn't significantly improve survival.
In such patients the aim is to improve or stabilize the neurological deficit and maintain quality of life. Corticosteroids and whole-brain radiotherapy usually fulfill this purpose. By contrast, patients with limited number of brain metastases, good performance status and controlled or limited systemic disease, may benefit from aggressive treatment as both quality of life and survival are primarily related to treatment of brain lesions.
Strong positive prognostic factors include good functional status, age <65 years, no sites of metastasis outside of the central nervous system (CNS), controlled primary tumor 17), the presence of a single metastasis in the brain, long interval from primary diagnosis to brain relapse, and certain cancer subtypes such as HER2 positive breast cancer brain metastases and EGFR-mutant non-small-cell lung cancer (NSCLC) 18) 19) 20)
It is presently unknown whether patients with brain metastases from heavily pre-treated cancers have a significantly different prognosis than those with less pre-treatment 22).