Brain metastases are identified either as part of a staging workup for a newly diagnosed cancer or due to a workup for new neurologic signs and symptoms, either with or without a known primary disease. The presence of brain metastases will usually alter therapy, depending on clinical aspects as well as performance status and patient decisions. Brain metastases can arise from all sites, with the most common being small cell lung cancers, other lung cancers, followed by breast cancers. The choice of treatment is based on number and location of metastases, which may be identified by MRI with gadolinium contrast and T2, FLAIR or diffusion weighted imaging or a combination. Alterntatively, and sometimes expeditiously, a contrast enhanced high resolution CT can be used instead of an MRI, despite its reduced sensitivity, as a symptomatic metastases will probably appear. CT identifies a solitary lesion in 50% based on historical data, and MRI demonstrates solitary lesion much less frequently at around 20%
Histologic Confirmation
Frequently brain metastases are found in the setting of a known extra-cranial primary tumor or imaging findings highly suggestive of a malignancy elsewhere. This is one of the few sites where it may be appropriate to treat without pathologic confirmation under this circumstance. One study looked at the question of determining histology in the case of a solitary imaging finding. This study reported 11% of these patients where found to have non-malignant histology or lesions of infectious or inflammatory origin. Commonly, neurosurigical consultation is in order regarding surgical intervention and pathologic confirmation, especially when there is impending cerebral or cerebellar herniation.
Steroid Treatment
Steroids are an established mechanism in the treatment of symptoms related to brain metastases. Dexamethasone is commonly used, but there is no consensus on the appropriate dose and taper schedule. A single center patterns of practice survey revealed 55% of physicians prescribe corticosteroids based on presence or absence of neurologic symptoms. The others started steroids at 4 mg QID. 60% tapered the dose in the 4 weeks after radiation therapy completed. An older RTOG study demonstrated patients with moderate neurologic signs experienced more rapid improvement when steroids were added to radiation treatments. No study to date has demonstrated any change in progression free survival or overall survival with the use or lack of use of steroids.
Steroids have significant side effects. With increased dose, toxicity becomes more common. A study looked at toxicy and effectiveness of 4, 8 and 16 mg dexamethasone per day and found no advantage in patients without impending herniation. Steroid toxicity tended to diminish after 28 days. The authors attributed improvement in the high dose group to early taper in the low dose group (the reference group). They recommend 4 mg/day without a taper for 28 days in patients without mass effect, signs or symptoms.
Another study looked at patients treated with steroids and found various toxicities including hyperglycemia (47%), Cushing's, candidiasis, peripheral edema, psychosis, proximal motor weakness. The ACR panel, based on this data concluded that there is little compelling evidence to start steroids routinely in asymptomatic patients prior to or during radiation therapy. They recommend starting at 4 - 8 mg per day in minimally symptomatic patients or 16 mg/day with a short interval taper.
The number of metastases may drive the type of therapy recommended. Some advocate stereotactic radiosurgery for 1-3 lesions, neurosurgery for solitary lesions which are amenable to resection, or whole brain radiotherapy for multiple lesions.
Anticonvulsants
The ACR cites a meta-analysis that estiamtes 15% of patients with brain metastases present with seizures. Most if these patients have supratentorial lesions and are generally started on anitseizure medications. Randomized prospective trials have not shown a significant reduction in incidence of first seizures in brain tumor patients placed on prophylactic anticonvulsants. New onset seizures in this study matched the 25% of patients who were on prophylactic anticonvulsants. More than 20% of patients on anti-convulsants had side effects severe enought to warrant a change in regimen. Thus the ACR consensus is to avoid anticonvulsants prophylactically with brain metastases due to any primary tumor.
Summary of ACR Recommendations
- Pre-treatment determination of number, location and size of mets.
- MRI is preferred modality, particularly if potential neurosurgical or radiosurgical candidates.
- Systemic workup to identify primary disease site, progression, age and performance status
- Hydrocephalus or impending herniation is an indication for high dose steroids and immediate neurosurgical evaluation.
- Moderate symptoms: 4-8 mg /day n divided doses
- Asymptomatic: No routine steroids needed
No proven benefit for prophylactic anticonvulsants