Brain Metastases from Esophageal Cancer in the Presence of HER-2 Overexpression

Introduction

The standard approach to locally advanced esophageal carcinoma has evolved in recent years and currently involves the use of a multimodality approach with the use of concurrent chemotherapy and radiation followed by esophagectomy. Although the treatment goal is to cure the disease, recurrence rates are high and usually involve the liver, abdomen, lungs, and bone ( ). In a study by 65% of the relapses in patients who underwent neoadjuvant concurrent chemoradiation and esophagectomy were in distant organs rather than locoregional failure.

More common carcinomas, namely, breast and non-small cell lung carcinomas have the highest rates of metastases to the brain. The incidence of metastatic disease within the central nervous system (CNS) has continued to increase in recent years ( ), and this is likely attributable to several factors: better radiographic detection methods, increased clinician awareness of this disease aspect, as well as improved and prolonged patient survival due to advancing systemic therapies. As overall survival numbers continue to increase, rates of clinically detectable metastatic deposits within the CNS have also risen ( ). In breast cancer, overexpression of human epidermal growth factor receptor 2 (HER-2), a membrane-bound tyrosine kinase, has been shown to be a risk factor for development of brain metastases. demonstrated that amplification of HER-2 on the surface of breast cancer tumor cells conveyed a four times greater risk of developing brain metastases than matched breast cancer counterparts (hazard ratio = 4.23).

Brain metastases from esophageal carcinomas have been reported in the medical literature, though this has been a common event ( ). Recent advances in testing and understanding of esophageal carcinoma have led to the discovery of overexpression of HER-2 in a subset of gastric, esophageal, and gastroesophageal (GE) junction tumors that was initially found to be a poor prognostic factor ( ).

Brain metastases in esophageal cancer

Brain metastasis from locally advanced esophageal cancer is uncommon ( ; ; ; ). In one of the largest series (27 patients) describing the characteristics of patients developing brain metastases from esophageal carcinoma, showed that the predominant underlying histology of the patients was adenocarcinoma and that the median overall survival from the time of brain metastasis diagnosis was 3.8 months. also published a series describing 17 esophageal cancer patients with CNS metastases and found that 76% had concurrent systemic metastases at the time of diagnosis. In contrast to the series from these patients experienced a prolonged median survival after the diagnosis of CNS metastases. Those patients who were found to have a preserved performance status (Karnofsky performance status (KPS) score > 70) had a median survival of 26.2 months, whereas those with a more limited performance status had a median survival of 19.4 months ( ). Also in contrast to the Weinberg series, the most common histology to metastasize was found to be squamous carcinoma ( ).

The pattern of CNS metastases seen at the time of diagnosis is varied; patients with solitary metastases as well as multiple, scattered intracranial lesions have both been observed. Among the patients with multiple sites of disease, no set distribution pattern was noted, as cerebellar as well as cerebral involvement have both been described ( ; ).

Various factors have been identified to be prognostic in esophageal cancer outcomes. These include response to the neoadjuvant treatment ( ; ), cancer grade, stage, and tumor length ( ; ; ), and possibly, the use of perioperative chemoradiation ( ).

Currently, no standard treatment approach exists for the management of brain metastases from esophageal carcinoma. As this is such an uncommon event, randomized trials have not been done to compare available treatment options. In the retrospective series that have described this relatively rare clinical occurrence, several treatment approaches have been used: surgical resection, stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and surgical resection followed by SRS ( ; ; ). Two of these series ( ; ), described the longest median survivals with a combined treatment approach with surgery and SRS: however, these observations were based on a small number of patients.