Description of the condition
The development of brain metastases is a frequent complication in people with cancer. In brain metastases cancer cells migrate from the place where they first formed (primary tumour) and travel, mainly through the blood, to the brain and form one or more tumours. Approximately 9.6% of all primary sites combined may spread to the brain during the course of the disease. Although many different malignant tumours have the ability to infiltrate the central nervous system, the most common primary tumours responsible for brain metastases are lung cancer (19.9%), breast cancer (5.1%), renal cell carcinoma (6.5%) and melanoma (6.9%). In contrast, other carcinomas, for instance prostate, oesophageal, oropharyngeal or non-melanoma skin cancers, rarely infiltrate the brain (Barnholtz-Sloan 2004; Bouffet 1997; Nayak 2012; Sundermeyer 2005). Brain metastases occur in more than 64% of people with lung cancer, and approximately 20% of those with breast cancer (Lassman 2003).
The haematogenous spread (when cancer cells are transported through the blood to distant sites of the body) is the most common mechanism of metastasis to the brain (Gavrilovic 2005) and as a consequence, the junction of the grey matter and white matter is the most frequent location, probably because blood vessels have a narrow diameter, acting as a trap for clumps of tumour cells (Delattre 1988).
Brain metastases, in the majority of cases, are multiple lesions that are diagnosed in later stages of the disease. However, in some cases brain metastases appear as the only deposit detected, either as a solitary brain metastasis, defined as "the only known metastasis of a tumour in the whole body which happens to be localised in the central nervous system" or as a single (also named singular) brain metastasis, defined as "a single cerebral metastasis with additional metastases in other organ systems” (Westphal 2003).
Description of the intervention
The most widely used therapeutic modalities for single or solitary brain metastases are surgery and also some forms of radiosurgery.
Surgery consists of either a biopsy or a resection of the metastasis by means of a neurosurgical technique. Resection can be either partial or complete, as confirmed by postoperative imaging. Radiosurgery is a type of external radiation therapy where ionising radiation beams are precisely focused on the brain metastasis (Pannullo 2011). Radiosurgery includes different technical options, for example robotic delivery of radiation, multiple convergent sources of cobalt and other technical devices adapted to linear accelerators (LINACs) (Flickinger 1994; Joseph 1996; Suh 2010).
How the intervention might work
In people with multiple brain metastases palliative radiotherapy or steroids, or both are the treatment of choice (Bradley 2004; Patchell 2003). However, in people with solitary or single brain metastasis a more radical approach using surgery or radiosurgery has shown positive results. A Cochrane review (Patil 2012) including three clinical trials, concluded from one of them (Andrews 2004) that people with only one brain metastasis may live longer when they receive radiosurgery in addition to whole brain radiation therapy (WBRT) versus WBRT alone. Another Cochrane review (Hart 2005) including three clinical trials (Mintz 1996; Patchell 1990; Vecht 1993) concluded that surgery and WBRT may reduce the proportion of deaths due to neurological cause and functionally independent survival. However, it did not show a clear improvement in overall survival.
Management of people newly diagnosed with single or solitary brain metastasis varies widely with location and extension of the primary tumour, histological subtype of the tumour, location of the metastasis and treatment facilities of the referred centre being the most relevant factors (Bradley 2004; Patchell 2003). People having two or more brain metastases (oligometastasis) are not generally considered candidates for surgery, therefore we will not consider this subgroup in this review.
Some studies have described a significant survival extension when single brain metastases are managed aggressively using surgery or radiosurgery of the lesion with or without whole brain irradiation (WBI) (Andrews 2004; Aoyama 2003; Patchell 1998).
Why it is important to do this review
Single and solitary brain metastases are infrequent. However, since more people are living longer with a primary diagnosis, the incidence of brain metastasis is increasing (Nayak 2012).
Choosing the most appropriate treatment for people with brain metastases is always a clinical challenge. It is imperative to balance the risks and benefits due to the incurable nature of the vast majority of metastatic cancer patients, even with a single brain deposit. The best-described treatment strategies in the literature are surgery and radiosurgery, with or without WBI.
Surgery can be a reasonable option for some people with a solitary/single brain metastasis. However, morbidity and mortality associated with the procedure have to be taken into account. Complications include the increasing or onset of focal motor or sensory deficit, seizures and surgical wound and bone flap infection. In people with solitary and single brain metastasis, survival with surgery has been reported to be better than with radiosurgery (Bougie 2015; Muacevic 1999), although treatment-related complications have been shown to be higher with surgery Bougie 2015.
Radiosurgery has shown comparable local control compared to surgery, and survival rates may be similar to surgery if patients receive equally aggressive treatment of the primary tumour. Since radiosurgery is a non-invasive technique, complications are expected to be lower. Complications may include cerebral oedema, seizures and nausea (Muacevic 1999). Radiosurgery may also represent higher costs compared to surgery, due to set up expenses, and costs derived from follow-up imaging and a possible salvage therapy.
This review aims to assess the effectiveness and safety of surgery versus radiosurgery for people with single or solitary brain metastasis. It is also possible that the meta-analysis approach may overcome the limitations of small individual studies regarding rare conditions like solitary/single brain metastasis.