A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases

Brian Patrick O'Neill *ANancy J. Iturria †, Michael J. Link ‡, Bruce E. Pollock ‡, Karla V. Ballman † and Judith R. O'Fallon † Rochester, MN 55905, USA., Department of Neurology, Mayo Clinic and Foundation, 200 SW First Street, Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA

To determine whether neurosurgery (NS) or stereotactic radiosurgery (RS) provided better local tumor control and enhanced patient survival.Retrospective review of all solitary brain metastases (SBM) patients newly diagnosed at Mayo Clinic Rochester between 1991 and 1999. Eligible patients satisfied tumor size and SBM site criteria to qualify for both NS and RS.There were no significant differences between 74 NS and 23 RS patients in terms of baseline characteristics (age, gender, systemic disease type, systemic disease status, signs/symptoms at SBM presentation) or percent of patients who received whole brain radiotherapy. Median follow-up for alive patients was 20 months (range 0–106 months). There was no significant difference in patient survival; the 1-year survival rate was 56% for the RS patients and 62% for the NS patients. Multivariate Cox regression analysis found that a significant prognostic factor for survival was a performance score of 0 or 1. There was a significant (p = 0.020) difference in local tumor control between NS and RS for solitary brain metastasis; none of the RS group had local recurrence compared to 19 (58%) of the NS group.     IJROBP 2003;55:1169

Brain metastases are an important clinical problem for cancer patients, with approximately 25% of patients with brain metastases dying from neurologic causes. In addition, because of their disabling impact on cognition, memory, language, mobility, and adaptive skills, brain metastases are responsible for disproportionate morbidity and mortality for this patient population. Approximately 200,000 cancer patients in the United States will develop brain metastases this year, and roughly half of these will be solitary. As the treatments for systemic disease improve, it is reasonable to assume that the number of cancer patients who develop brain metastases will increase, as well as the fraction of brain metastases that are solitary. Because solitary brain metastases (SBM) are being detected earlier in the cancer patient's illness, the potential to improve the duration and quality of life is greatest in these patients. Unlike the patient with multiple brain metastases, local therapies should be applicable. However, it is not clear which local therapy produces superior results.

It is thought that patients with SBM benefit from more aggressive care than whole brain radiation therapy (WBRT) alone. Compared with WBRT, both neurosurgery (NS) and stereotactic radiosurgery (RS) appear to provide to the patient improved local tumor control, longer survival, and better quality of life. However there is no class 1 evidence to support the use of one technique over the other for patients with SBM not suffering from symptomatic mass effect. The purpose of this study was to compare local tumor control and survival for patients with SBM having NS or RS. Typically, SBM patients have been treated with WBRT after or instead of craniotomy and removal. In a 1990 report, Patchell et al. concluded that surgical resection combined with postoperative radiotherapy was more effective than treatment with radiotherapy alone. In a follow-up study, the same authors concluded that patients with cancer and single metastases to the brain who receive treatment with surgical resection and postoperative radiotherapy have fewer recurrences of cancer in the brain and are less likely to die of neurologic causes than are similar patients treated with surgical resection alone. However, in this study there was no significant difference between the two groups in overall length of survival or the length of time that patients remained functionally independent.

Furthermore there are good data to support an increased risk of late complications from WBRT. In 1989, DeAngelis and Posner described ''radiation-induced dementia'' in patients cured of brain metastases . In addition, the experiences with prophylactic cranial irradiation (PCI) involved field radiotherapy in glioblastoma multiforme and therapeutic whole-brain radiotherapy in primary CNS lymphoma are relevant. As many as 30% of lung cancer survivors who received PCI had a functionally significant subcortical dementia syndrome. In 1980, Hochberg and Slotnick described neuropsychologic impairment in astrocytoma survivors. Last, significant neurocognitive decline is seen in primary central nervous system lymphoma patients treated with WBRT either alone or in combination with chemotherapy. Although the decline is likely a combination of the disease, comorbidity, and its treatment, the irony remains that the patients most in need of treatment may be the patients most at risk of damage from it.

Although there are compelling data to support resection for SBM, roughly only half of SBM patients are surgical candidates because of comorbidity. Alternatively, many patients with brain metastases have undergone RS primarily with either the gamma knife (GK) or a linear accelerator-based system (Linac). A summary of 21 independent reports of GK or Linac radiosurgery involving more than 1700 patients and more than 2700 lesions reported by Boyd and Mehta  found a mean local control rate of 83% and median patient survival of 9.6 months. Factors significantly associated with improved survival were controlled extracranial disease, three or fewer lesions, and higher performance scores. A dose–response curve was suggested, and these authors recommended using tumor margin doses of 18 Gy or more whenever it was deemed safe.

To the best of our knowledge, there has not been a Phase III trial comparing NS and SR for patients with SBM. Ideally, a prospective trial could be performed to better understand the relative roles that these two techniques should play in the management of this patient population. Such a study would better control for the heterogeneous nature of this patient population with respect to factors that correlate with survival but are not neurologic in nature. It would also minimize other confounding variables and treatment selection bias. Nonetheless, retrospective reviews, such as our study and others, should be able to provide some useful information regarding local tumor control and treatment-related morbidity. The result of our study found neither NS nor RS was superior for patients with small- to moderate-size tumors. Thus a prospective trial appears to be warranted to compare these treatment modalities.