Gamma knife radiosurgery for elderly patients with brain metastases: evaluation of scoring systems that predict survival

Metastatic brain cancer is almost ten times more common than a primary malignant brain tumor and 20-40% of cancer patients will be diagnosed with a metastatic brain tumor [1]. If these patients are left untreated, the median survival time is 1–2 months [2], with a 1-year survival rate of 10.4% [3].

The incidence of cancer increases with age. In 2000, 12.6–18.1% of the population in developed countries was over 65 years of age [4]. In South Korea, the crude incidence rate of cancer development in this age group is 1,606 cases per 100,000 individuals [5]. However, with advances in imaging and chemotherapy, the detection and treatment of cancer, and thus the life expectancy of elderly cancer patients has improved. Among those with brain metastases, conventional treatment methods currently include surgical resection, whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or a combination thereof [6]. However, selection of the most suitable therapy is difficult and must consider factors such as patient’s age, neurologic performance, systemic disease status, and the size, volume, location, and number of metastases at presentation [1]. Advanced age is a poor prognostic factor for survival in patients with brain metastases [7], and the choice of treatment is complicated by the fact that elderly patients often have multiple, concurrent diseases that can restrict their physiological reserve and physical functioning.

Although WBRT has been generally accepted as a standard treatment for several decades, accumulated evidence suggests its association with a higher risk of neurocognitive deterioration in elderly patients with brain metastases [8,9]. Thus, as an alternative approach, gamma knife radiosurgery (GKRS) has gained increasing favor as the primary treatment modality [10]. The purpose of this study was to identify a scoring system able to predict survival outcome in patients age 70 years and older who underwent GKRS for brain metastases. The predictive power of four different scoring systems was evaluated: graded prognostic assessment (GPA), recursive portioning analysis (RPA), the score index for radiosurgery (SIR), and the basic score for brain metastases (BSBM) [11-15].

A cross-national comparison performed in 2000 showed that the proportion of individuals age ≥ 65 years was 12.6 to 18.1% [4], with the proportion predicted to reach 20–28% by 2030 [16]. Along with the growing size of the older population, the incidence of brain metastasis in elderly patients diagnosed with cancer has been rising for several reasons, including the longer survival of patients with a previously diagnosed localized cancer, and the improved detection of metastatic tumors by more sensitive imaging techniques. Nonetheless, in the majority of patients with malignant primary or metastatic brain tumors, age is an important prognostic factor [15,17].

For several decades, WBRT was the treatment of choice for metastatic brain tumors [18]. However, its use in elderly patients was hindered by impaired postoperative functional or cognitive status [9] and poor social services support [19,20] of treated patients. Moreover, although the prophylactic role of WBRT in some cancers has been demonstrated [21], prolonged treatment duration with multiple fractions may not be possible in elderly patients. In a comparison of SRS and WBRT, patients receiving SRS had better OS rates [22]. The preferred use of SRS is that it achieves repeated control of the target lesion without risk of detrimental neurocognitive effects after the therapy [8,23]. Because of its few side effects, GKRS is an excellent treatment option for patients with metastatic brain tumors, including elderly patients. Other advantages of GKRS are that it is minimally invasive, substantially reduces hospitalization time, is relatively inexpensive, and is associated with minimal pain and post-treatment complications [24].

Well-known prognostic scoring systems used to assess patients treated with GKRS for brain metastases are RPA, SIR, BSBM, and GPA, which were created from databases containing 65–1200 patients with brain metastases from a variety of primary tumors [12-15]. GPA was developed to address the limitations of the three other scoring systems; specifically, RPA and BSBM do not consider the number of metastases; RPA, BSBM, and SIR require estimation of the degree of control of the systemic disease, including a primary malignancy, which leads to inconsistencies due to variation in the type and timing of imaging tests. The SIR takes into account treatment factors, such as the volume of the largest lesion at the time of radiosurgery, to predict outcome before treatment decisions are made [25-27]. In the GPA, components of the other scoring systems that are difficult to quantify, such as the control of extracranial disease, were removed as part of the general removal of treatment-related factors such that treatment choice rather than treatment result was reflected [26,27]. The GPA system considers different combinations of diagnosis-specific prognostic factors, and thus better predicts the outcome that can be expected in elderly patients treated with various therapeutic options [28]. The KPS is included in several meaningful scoring systems; in other studies targeting elderly patients, it was shown to be the strongest predictor of prognosis [11].

To identify prognostic factors specific for elderly patients, it is necessary to examine their clinically based prognostic scores and then compare those values with other prognostic scores. Minniti et al. [7] reported that patients with a KPS > 70 and stable extracranial disease had significantly longer survival. Kim et al. [29] found that survival was significantly influenced by the number of brain metastases at the time of SRS, and the primary lung tumor type of the patients. However, while these studies identified KPS, extracranial disease, and the number of brain metastases as significant factors for survival, they did not specify which scoring system most accurately predicted survival in elderly patients with brain metastasis treated with GKRS. A recent report suggested the use of the modified RPA to select favorable candidates for GKRS, even among patients age 80 years and older [30]. In our study, KPS ≥ 90 and no extracranial metastasis at the time of brain-metastasis diagnosis were the most important factors predicting survival. Although in the multivariate analysis both the GPA score and the SIR were statistically significant in predicting survival, the GPA score may be the more powerful independent prognostic factor because it takes into account both the KPS and the presence of extracranial metastasis. Many oncologists and neurosurgeons may hesitate to recommend aggressive treatment for brain metastasis in elderly cancer patients. The results of this and previous studies support the use of GKRS in patients age 70 years and older and even in those 80 years and older. However, although chemotherapy for primary cancer increased the survival of elderly patients according to some studies [31], in our series there were no significant differences between GKRS and GKRS followed by chemotherapy.

This study was based on a retrospective investigation; thus, selection bias due to missed cases was a possibility. Additionally, there was no information on the quality of life or the control of treated lesions in patients who underwent GKRS. Nevertheless, our results identified extracranial metastases and KPS as independent prognostic factors for survival in elderly patients with brain metastasis treated with GKRS. Among the scoring systems analyzed in this study, the GPA was the most powerful and most specific prognostic scoring system. These are important considerations that influence treatment choice and patient outcome and should be taken into account in therapeutic decision-making.