Revised: June 2014
Cerebral metastasis is the most common malignancy affecting the brain. The 3 most common sites of the primary tumour are the lung, breast and gastrointestinal tract. Seventy percent of the patients with cerebral metastasis have 1 or 2 lesions and 80% are located in the cerebral hemispheres (1).
Patients with good a neurologic function, a long disease free interval between the diagnosis of the primary tumour and development of the metastases, and lack of progressive systemic disease, tend to have the best prognosis. Therefore, the management of patients with cerebral metastases depends on following factors: the performance status of the patient, the status of the systemic disease, and the number of cerebral lesions.
For patients with progressive systemic disease and/or poor performance status, palliative WBRT or supportive management with dexamethasone alone is considered the most appropriate treatment. On the other hand, patients with solitary brain metastasis, who otherwise have no or stable systemic disease and a good performance status, should be considered for palliative surgical resection prior to whole brain radiotherapy (WBRT). Surgery followed by WBRT has shown to significantly improve both the survival time and the quality of life of patients in this category, when compared to treatment with WBRT alone (2).
Stereotactic Radiosurgery (SRS) followed by whole brain therapy has been investigated in randomized trials (3,4). The largest of these, RTOG 9508, showed that in patients with single metastasis, survival and disease control was improved with SRS + WBRT over WBRT alone (3). For patients with 2-3 metastases, local control was improved with SRS but overall survival was not improved. A smaller clinical trial in patients with 1-4 metastases comparing SRS alone vs SRS + WBRT did not show improvement in survival but better local control with combined SRS and WBRT(5). This trial also showed MMSE scores declined more rapidly in the SRS group. A conflicting randomized study suggested that combined WBRT +SRS had inferior neuro-cognitive outcomes compared to SRS alone but it is uncertain if this has significant impact on functional outcomes compared to the high risk of brain recurrence (6). Currently it is reasonable to consider using a radiosurgery boost in addition to WBRT as initial treatment for patients with the following circumstances: 1) inoperable solitary brain metastasis, 2) up to 3 cerebral lesions, provided that the performance status is good and there is no progressive systemic disease. It may also be useful in the palliation of recurrent cerebral metastases following WBRT in carefully selected cases which there are no more than 3 lesions, performance status is good and there is no progressive systemic disease. Whether SRS or even surgery alone are reasonable first options with WBRT deferred to relapse remains controversial.
References:
Delattre JY, Krol G, Thaler HT, et al. Distribution of brain metastases. Arch Neurol 45:741-744,1988
Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494-500,1990.
Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363:1665-1672, 2004.
Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 45:427-434, 1999.
Aoyama H, Shirato H, Tago M, et al. Stereotactic Radiosurgery plus whole brain therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295:2483-91, 2006.
Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomized controlled trial. Lancet Oncol 2009;10:1037-1044
