Surgery

In the past, few patients with brain metastases were considered for surgery. The role of surgical resection has increased with the improvements in anaesthesia, surgical technique and the recognition of benefit in selected patients mainly with single brain metastases. The goal of surgery is to provide immediate relief of symptoms, to establish histologic diagnosis and to improve local control. A series of trials ^17,18,19 comparing patients who received surgical resection, with or without radiotherapy, have shown that combined treatment increases the median survival time to nine and 10 months versus three to six months for patients undergoing radiation treatment alone. Patchell reported in a randomised trial that resection was superior to WBRT in well selected patients. A critical prognostic factor was the degree of control of the primary tumour.¹⁷ The role of postoperative WBRT in single brain metastases was addressed in a randomised study by Patchell,²⁰ where he demonstrated that recurrence of tumour in the brain was less frequent in the group of patients treated with surgery and WBRT than the group who received surgery alone. Patients treated with surgery had a lower incidence of local relapse (20% versus 52%) and a longer time of functional independence. Despite these encouraging results, few patients can benefit from surgical resection due to tumour location in a surgically accessible region, size, age and extensive systemic disease.

Complete surgical resection offers an immediate relief of symptoms of intracranial oedema and of seizures and a reduction of focal neurological deficits.

Radiotherapy

Whole brain radiotherapy has traditionally been the standard treatment for patients with brain metastases since 1950. WBRT has been shown to effectively improve neurologic symptoms and function for patients with minimum co-morbidity. This palliative approach does not offer survival benefit and the median survival ranges from three to six months. The published overall response rate is symptomdependent but ranges from 64% to 85%.^21,22 Complications of modern WBRT are relatively uncommon and acute toxicity is unusual. Hypofractionated treatments as 30Gy in 10 fractions for two weeks are generally employed because of short life-expectancy. Several recent trials failed to demonstrate improvement of both local control and survival by dose escalation.^23,24 The reason might be either suboptimal patient selection or failure to achieve local control due to application of insufficient total doses. The optimal dose fractionation schedules for patients with brain metastases have been evaluated in randomised trials conducted by the Radiation Therapy Oncology Group (RTOG).25 The median response and median survival were equivalent in all arms of these studies. Median survival ranged between 15 and 18 weeks and brain metastasis was the cause of death in 40% of the patients. While the RTOG trials failed to identify the best fractionation schedule, they enabled the identification for clinical factors associated with better survival.²⁶ The RTOG developed three prognostic classes for brain metastases using recursive partitioning analysis (RPA) of a large database. These classes were based on Karnofsky performance status (KPS), primary tumour status, presence of extracranial systemic metastases and age. RPA class I included patients with KPS >70, less than 65 years of age with controlled primary and no extracranial metastases. Patients with KPS <70 were classified as RPA class III and all others were class II. This classification made the comparison between different trials possible and enabled the selection of aggressive treatments in specific patient populations. In patients with good prognosis who are likely to survive more than one year, a more protracted radiation schedule (eg, 40Gy in 2Gy fraction) may offer better response and better progression-free survival.

Stereotactic Radiosurgery

Stereotactic radiosurgery is a technique of external irradiation that utilises multiple convergent beams to deliver a high single dose of radiation to a radiographically discrete treatment volume.²⁷ Radiosurgery has several advantages over surgery. It can be used to treat metastases in surgically inaccessible areas of the brain, such as the brainstem. Because radiosurgery is a non-invasive procedure it is associated with less morbidity than surgery. In a multi-institutional trial ²⁸ involving 116 patients treated with radiosurgery for a single brain metastasis, local tumour control was obtained in 99 patients (85%). Multivariate analysis showed that better local control was obtained in patients who received (WBRT) in addition to radiosurgery and in patients with radioresistant histologies (melanoma and renal carcinoma).

In a recently reported RTOG 95-08 trial the benefits of radiosurgery for patients with single brain metastasis were demonstrated.²⁹ In this trial, 333 patients from 55 institutions with single brain metastasis were entered and were randomised to receive whole brain irradiation (37.5Gy in 2.5 fractions) with or without radiosurgery. Improved survival was found in 186 patients with single brain metastasis receiving radiosurgery (6.5 months versus 4.9 months, p=0.04). There was an important finding that patients receiving radiosurgery were more likely to improve and maintain their KPS. Radiosurgery combined with WBRT is recommended in patients with small lesions up to three in patients with good performance status and well controlled primary disease. Radiosurgery also has an important role in patients who experience recurrence of brain metastases following WBRT.