Introduction

Brain metastases are the most common intracranial tumours in adults, affecting up to 20% to 40% of all cancer patients, and representing one of the most frequent neurological complications of systemic cancer as a major cause of morbidity and mortality.^1–3 Patients with lung or breast cancer and melanoma are at the greatest risk of developing brain metastases. In a small percentage of patients, brain metastases are discovered incidentally with a computed tomography (CT) scan or magnetic resonance imaging (MRI) and occasionally at autopsy.⁴ In patients with brain metastases the median survival is approximately one month without any treatment. With corticosteroids it can be prolonged to two months and with cranial irradiation three to six months.⁵ For decades, the standard treatment has been whole brain radiotherapy (WBRT), resulting in symptomatic improvement in the majority of patients ⁶ but longterm local control has been poor (0% to 14% at one year).^7,8 A review of survival following WBRT in a selected large series of patients reported over the last 30 years indicates little change in the results.^6,9,10 Approximately 25% to 50% of patients treated with brain irradiation will eventually die from intracranial progression.^9,11 The incidence of brain metastases has increased over time, probably as a result of advances in neuroimaging procedures and improvements in the treatment of primary tumour and systemic disease, which has led to an increase of survival. Treatment for brain metastases patients includes corticosteroids, anticonvulsants to control seizures, surgery, radiotherapy, radiosurgery and chemotherapy. The appropriate aim of treatment is improvement or maintenance of quality of life. Surgical resection followed by WBRT may yield longer survival but is generally reserved for a minority of patients with a single brain lesion, well controlled primary disease and good prognosis.

Despite the recent advances in the diagnosis and treatment of brain metastases, it remains difficult to document an important change in overall outcome, neurological function and quality of life in this cohort of patients.

Diagnosis

The clinical presentation of brain metastases is similar to that of patients with any intracranial mass lesion. Most patients experience debilitating neurologic symptoms, including headaches, focal weakness, cognitive dysfunction or altered mental status; 20% or more develop seizures. Severe neurologic dysfunctions frequently develop in patients, and up to 50% will die as a direct consequence of cerebral metastases. For many patients, brain metastases causes relatively mild symptoms and some may die as a result of progressive systemic, extracranial disease. One-third of the patients developing symptomatic brain metastases do not have any previous cancer history.^12,13 The reports in the literature refer to patients in whom brain metastases were the first symptom of tumour discovered at diagnosis and to patients in which the primary site remained undetected after a thorough investigation. Contrastenhanced MRI is more sensitive than enhanced CT scanning in detecting brain metastases, particularly small lesions or metastases situated in the posterior fossa.^14,15 MRI is particularly recommended for patients with an apparently single metastasis on a CT or for patients with limited disease (i.e lung tumours) in whom the detection of asymptomatic brain metastases would alter the therapeutic management. Radiographically, metastases are ring-enhancing lesions, most often located at the grey-white matter junction followed usually by significant oedema. About half of brain metastases are single lesions, the remainder being multiple. In the majority (80%) of patients, brain metastases develop after diagnosis of systemic cancer (metachronous presentation). When a brain metastasis from an undetected primary site is discovered at the first investigation on CT scan or MRI, it should be considered carefully. In most cases, the primary tumour is located in the lung and a chest CT scan is always recommended.¹⁶.