Brain Metastases: Can We Do More?

Brain metastases are by far the most common intracranial tumors. They represent a major cause of morbidity and mortality for cancer patients who may develop a brain involvement in up to 40% of cases. Surgical resection, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or a combination, are the possible treatments for brain metastases. Thirty years ago, WBRT was still the standard treatment for patients with brain metastases, although many retrospective series published in the 1980s suggested a survival benefit from resection of single brain metastases and in a subgroup of patients with multiple metastases, but good functional status and controlled or indolent extracranial disease. Ten years later, in the 1990s, two randomized trials, confirmed that surgical resection followed by WBRT was an effective treatment for patients with single, surgically accessible, brain metastases who presented a controlled extracranial disease and are in good general condition 9 and 11. Together, studies performed on multiple metastases again suggest that a highly selected subset of patients with a limited number of metastases may benefit from aggressive surgical management (2). In the same decade, SRS became a widely available option for patients with a single brain metastasis, the first treatment option for patients with two to four metastases and an alternative to WBRT to treat the surgical resection cavity. The best treatment of brain metastases should maximize survival and neurological function recovery yet avoiding unnecessary invasive procedures. The treatment strategy, including the selection of palliation versus aggressive management, should take into account several prognostic factors whose influence on survival and quality of life have been demonstrated. A three-tiered prognostic categorization was formulated by the Radiation Therapy Oncology Group database from 1200 patients, using recursive partitioning analysis. The Radiation Therapy Oncology Group stratification has proven to be valid in several studies 1, 3, 4 and 7 and represents an effective approach to address patients to the most suitable care in relation to the clinical status and life expectancy. In the past decade different studies, including randomized trials, have been performed to address which treatment and/or combination of treatments should be used in patients with newly diagnosed metastatic brain tumors and in what clinical settings. The literature rather clearly demonstrates that surgery is effective in prolonging survival in solitary and surgically accessible metastases when the systemic disease is controlled and the performance status is good 5 and 10. Surgical resection may be also considered for multiple lesions when one lesion is large, symptomatic, or life threatening, or when tumors display cystic or necrotic aspects or are surrounded by considerable edema. Furthermore, surgery may have a diagnostic role, in the absence of histologic documentation of the primary disease, if the radiologic aspect is atypical to rule out differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system) or in case of suspicion of progression after irradiation to differentiate radionecrosis from a progression of brain disease. Radiosurgery has an efficacy that is comparable to that of surgery. Because SRS can treat more than one tumor per session, and, at present, most tumors are detected while small in size, the number of patients treated by SRS is increasing. In addition, SRS is considered less invasive. Thus, to represent an alternative to SRS, surgery should reach the highest outcome standard including fast postoperative course and best cosmetic result. To these aims, advanced preoperative planning by means of a sophisticated morphologic and functional imaging to achieve an accurate preoperative motor and language mapping, integrated with neuronavigation and intraoperative cortical and subcortical brain monitoring, should become the standard of care. With regard to the prognosis, median survival after WBRT varies between 15 and 24 weeks, with good palliation of symptoms 8, 9 and 11, whereas an aggressive treatment, surgery, and/or SRS, combined with WBRT, grants a median survival of 40–44 weeks 6, 9 and 11. Therefore, we have improved the results in terms of survival, and, even if the outcome of these patients with is still generally poor, this does not necessary reflect a failure of these treatments in controlling cerebral disease, but often a failure in controlling the systemic disease. In the near future, we will able to use targeted therapies and our patients will have much more benefit from a multidisciplinary approach, including the integration of novel chemotherapy to surgical and radiation treatments. Song et al. described the results of 26 consecutive patients with brain metastasis out of 1612 patients with esophageal primary carcinoma, approximately 1.61% of the entire series, who were surgically treated. They provided a comprehensive discussion about the surgical treatment of brain metastases from primary esophageal cancer. Surgical treatment was offered to patients with good performance status and limited extracranial disease. Despite its retrospective design, the study is well conducted with results that are credible, appropriately interpreted, and consistent with those reported in the literature. Furthermore, this study has the merit of providing useful information on the treatment and prognosis of a specific histologic type of brain metastasis. What we know about the treatments and prognosis of metastases derives from studies not specifically addressing the issue of the nature of the primitive disease. For this reason, similar studies are welcome to improve our prognostic evaluation and decision-making process.