Brain metastases are the most frequently observed cancerous lesions in the brain and their incidence has grown as advances in imaging technologies and the treatment of extracranial disease has allowed the life expectancy of cancer patients to increase. For this reason, determining optimal treatment regimens for specific subsets of patients with brain metastases is imperative for clinicians. The purpose of this article is to review the randomized controlled trials analyzing patients with brain metastases treated with neurosurgery, WBRT, and SRS to determine future research directions for physicians and scientists. For patients who have a Karnofsky Performance Status (KPS) ≥70 and a single, surgically accessible brain metastasis, surgical resection followed by post-operative WBRT has proven to be a superior treatment modality when compared to WBRT alone and surgical resection alone. Evidence suggests that the addition of WBRT to SRS results in increased levels of survival for patients who have a single brain metastasis and increased levels of local tumor control for patients who have 1 to 4 brain metastases. Questions remain regarding survival and tumor control in patients treated with SRS with or without WBRT, which warrants further clinical investigation into this controversial matter. Although several randomized controlled trials have been published assessing the clinical outcomes of patients with brain metastases treated with a variety of treatment modalities, many studies are limited by poor patient accrual and further randomized evidence is needed to guide clinicians in their future treatment decisions.

Esophagectomy is the main treatment for esophageal cancer. The 2 histologic subtypes of esophageal cancer are squamous cell carcinoma and adenocarcinoma; these subtypes have different biologic features and treatment strategies. Although the prognosis of patients treated with surgery alone remains unsatisfactory, neoadjuvant therapy helps to improve outcome. A meta-analysis revealed that neoadjuvant chemoradiotherapy provides survival benefits for both histologic types, while neoadjuvant chemotherapy is useful for adenocarcinoma. In Western countries, neoadjuvant chemoradiotherapy is a standard treatment for resectable advanced esophageal cancer, while neoadjuvant chemotherapy has become the standard treatment in Japan. Esophagectomy can be performed by several different approaches, including McKeown (cervico-thoraco-abdominal), Ivor-Lewis (thoraco-abdominal), and transhiatal approaches. It has been suggested that Minimally Invasive Esophagectomy (MIE) contributes to the reduction of pulmonary complications. Cervico-thoraco-abdominal 3-field lymphadenectomy may prolong survival, but a randomized control study on this subject has not been conducted. Mortality and morbidity rates after esophagectomy remain high. Several meta-analyses demonstrated that esophagectomy at low-volume hospitals was associated with a significant increase in the incidence of in-hospital and 30-day mortality. The influence of hospital volume on long-term outcome continues to be a subject of debate.

In conclusion, surgical resection remains the main treatment for potentially curable esophageal cancer. Neoadjuvant treatment can improve long-term outcome after esophagectomy. Furthermore, MIE may improve shortterm outcome, and 3-field lymph node dissection may reduce the risk of recurrence. The effects of these surgical procedures should be confirmed by randomized prospective studies.