From Patchell to Brown: An Evidence-Based Evolution of the Role of Radiotherapy on the Management of Brain Metastases

Abstract

About 1,658,370 new cancer cases are expected to be diagnosed in the United States in 2015, and 589,430 Americans are expected to die of cancer. Despite those dreadful numbers, the 5-year survival rate for all cancers diagnosed in 2004 2010 was 68%, up from 49% in 1975 1977. The steady improvement in survival seen throughout those past 4 decades can be attributed to a combination of early diagnosis and better treatment modalities. Brain metastases occur in 20% 40% of patients with systemic cancer and are the most common type of intracranial tumor, outnumbering primary tumors by 10 to 1. They are multifocal in more than 70% of cases. Notwithstanding the improvements in survival in stage IV (metastatic) patients as a whole, the occurrence of brain metastases is often considered a sign of uncontrolled or treatment resistant disease and carries a dismal prognosis. As a case in point, the median overall survival is 1 2 months with corticosteroids, which can be extended to 6 months with whole brain radiation therapy (WBRT). The treatment algorithm for brain metastases typically involves some combination of surgical resection, radiotherapy, radiosurgery, and corticosteroids. With few exceptions, systemic therapies like chemotherapy are usually not an effective first-line treatment modality. The utility of the surgical management of single brain metastases was described by Patchell et al. in 1990. In this small, double-arm, randomized, prospective trial, 48 patients were randomized to either surgical removal of the brain tumor followed by WBRT (surgical group) or needle biopsy and WBRT (radiation group). Same-site recurrence was less frequent in the surgical group (20% vs. 52%). More importantly, the overall survival was significantly longer in the surgical group (median 40 weeks vs. 15 weeks in the radiation group) and those patients remained functionally independent longer (38 weeks vs. 8 weeks in the radiation group). When death from systemic causes was used as the survival end point, the differences between the surgical and radiation groups were not statistically significant. Twenty-five years after its publication, the first Patchell et al. randomized study remains one of the most cited articles on the theme, with more than 2100 indexed citations. Because most cases of brain metastases are multifocal, surgical resection is limited to only 10% 20% of the patients. In situations where surgical resection is not indicated or of limited benefit, WBRT has historically been the mainstay of treatment. The decision to use WBRT revolves around its impact on 3 interrelated components: 1) overall survival, 2) intracranial control, and 3) neurocognitive sequelae. While a large volume of retrospective reports support the effectiveness of WBRT on the management of brain metastases, there are no high-level