Two thirds of brain metastases are symptomatic during the patient’s lifetime. The signs and symptoms are the same as for any other slowly expanding intracranial lesion ultimately resulting in raised intracranial pressure. There are three main symptoms: seizures, focal symptoms and signs and headaches.

Headache may also occur where the lesions are attached to the dural surface towards the midline or in the middle fossa or to the falx itself. Probably local inflammation and associated direct trigeminal innervation are responsible (see ◘ Fig. 51.1).

Most importantly in patients with known primary or metastatic breast cancer, any patient with unexpected new neurological symptoms should be carefully screened and imaged for spread of disease to the CNS. For patients without a history or evidence of previous or coexisting cancer, the likelihood of a single brain lesion being a metastasis is less than 15%.

Immediate screening of patients with suspicious symptoms and signs is frequently performed with CT head scans. To enhance and expedite MDT decision-making where intracranial lesions are seen, MRI head scanning is essential, and in some tumour types, or where symptoms are suggestive of CNS involvement outside the cranium, e.g. thoracic pain, imaging should include the whole cranio-spinal axis. Commonly patients with isolated cranial lesions will need staging or screening with CT of the chest, abdomen and pelvis for the multidisciplinary team/tumour board (MDT) to be in a position to decide on action. Contrast-enhanced MRI is more specific and much more sensitive at showing up small or multiple lesions. It is also critical for determining lesions in the cerebellar or posterior fossa area where bone shadows make CT interpretation unreliable. MRI slice thickness tends to be finer, and hence the chance of visualising small lesions for both radiotherapy planning and monitoring is improved. Increasingly units offering access to both stereotactic radiosurgery (SRS) and surgery for these patients will request specific thin cut planning scans that can be used for image-directed surgery and/or fused with CT scans or alone for RT planning. With enhanced T1-weighted MRI scans, metastatic deposits show as discrete areas of increased signal intensity (white spots) with a tendency to a ringlike appearance as the size of the lesions increases. Not infrequently contrast penetration and retention is time- and dose-dependent, and where there is doubt about a lesion’s nature or presence, then the use of double-dose contrast can be useful. This latter approach is especially useful for SRS planning. Tumour-related oedema is often considerably greater than one might expect for the size of the lesion and is usually well seen on T1-weighted (decreased intensity) imaging but often more measurable and visible on T2 scans where the parenchymal «white signal» is seen. Cystic metastatic tumours may have a thicker wall than that seen in high-grade gliomas, but there is little to separate these from the appearances of an abscess cyst except the obvious clinical presentation. Tumours adherent to the dura or falx need careful anatomical review to clarify the local extent on this surface for both surgical and SRS planning. It is not possible to resolve the degree of local invasion of the tumour deposits from either very clear or fuzzy margins on MRI imaging. There is some suggestion paradoxically that sharp imaging margins may need more careful examination of adjacent vessels at surgery for tumour involvement.

Diffusion-weighted imaging may offer some help with deciding on the extent of additional resection required, but the data so far is anecdotal. MRI/ADC mapping may offer information on very early responses to treatment in residual lesions and hence may be a method for evaluating new (medical) therapies. Magnetic resonance spectroscopy (MRS) can be helpful in particular situations where the differentiation between glioma, abscess, lymphoma and metastasis is in question.

The use of whole brain radiation therapy for the treatment of brain metastases offers a seemingly simple and non-invasive way of treating the entire brain and hence would appear ideally suited to treating multiple metastases, and there is good evidence that breast and lung cancers demonstrate relative radiosensitivity by comparison with melanoma or renal cell tumours.

For many patients the presence of multiple deposits with very small or apparently microscopic collections makes this the only really viable treatment that can be offered. However it is increasingly recognised that large volumes of normal brain are exposed to ionising radiation, and in situations where the expectation of good control or cure means that life expectancy is increased, then it might be questioned whether preservation of normal function may be threatened despite fractionated treatments. Brain tissue sensitivity to RT is variable and depends on the total dose, fraction size, volume and dosing interval. Acute side effects from a multiple fraction course to the brain include hair loss, headaches, nausea, otitis media and very commonly lethargy with all-pervading tiredness and on occasion acute skin irritation and desquamation. The symptoms of fatigue can take several weeks to abate after the RT course, and patients may be left with this as their major chronic symptom. A further acute issue can be dramatic brain swelling that can require large (even very large) dose of steroids, and on occasion acute decompressive surgery may be considered appropriate. A number of patients see their lethargy develop into a «somnolence syndrome» characterised by a chronic debilitating fatigue [12]. Late effects are also well recognised including atrophic change in the brain with associated memory or cognitive deficits, radiation necrosis that can masquerade as a new or recurrent tumour mass, progressive white matter disease (leucoencephalopathy) and with mainly frontal RT, a dementing disease which may or may not be associated with apparent small vessel inflammatory or vasculopathic changes. The risk of secondary induced tumours runs at approximately 1 in 2000 cases. Numerous attempts to understand the critical factors have pointed clearly to dose and particularly fraction sizes as related to neurocognitive problems, with induced leucoencephalopathy, and damage to small blood vessels markedly increasing above fraction doses of >2 Gy [13, 14]. There thus becomes the issue of the burden of radiation therapy duration in palliative-intent patients versus the increased risk of side effects from shortening treatment regimens by using higher dose fractions. Usual current fractionation schedules thus compromise to deliver 30 Gy in 10 fractions where the aim is rapid stabilisation for palliative control and 40 Gy in 20 fractions where the aim is longer-term disease control.