Metastatic extraskeletal Ewing's sarcoma treated with trabectedin: A case report.

The Ewing's sarcoma family of tumors (ESFT) comprises a number of rare malignant tumors. Standard first-line treatment for patients with these tumors includes chemotherapy with a five-drug regimen of vincristine, doxorubicin (Adriamycin®) and cyclophosphamide, alternating with ifosfamide and etoposide (VAC/IE). In cases of inadequate response, there are a number of second-line regimens available. However, further treatment options are required for those patients with disease unresponsive to standard treatment. Trabectedin is a novel treatment option for patients with ESFT. The present study reports the case of a Caucasian 69-year-old female patient who presented with a soft tissue mass on the chest wall that had developed 7 months earlier. A computed tomography scan revealed a 9×8×7-cm mass on the anterior chest wall above the pectoral muscle. Histopathological evaluations and molecular analysis indicated that it was consistent with a metastatic extraskeletal Ewing's sarcoma. The patient was treated with an alternating VAC/IE regimen; however, an inadequate response was observed. The patient received second-line treatment with a gemcitabine and dacarbazine combination regimen, but the disease progressed. Subsequently, treatment with trabectedin (1.5 mg/m2 as a 24-h continuous infusion every 3 weeks) was initiated. Trabectedin treatment resulted in long-lasting (18 months) progression-free survival. It is vital that novel drugs continue to being developed for patients with ESFT following progression subsequent to standard chemotherapy. The current report presents a case of a patient with metastatic, pre-treated Ewing's sarcoma achieving disease stabilization with trabectedin. Based on these results and the observed tolerability profile, trabectedin represents an alternative treatment for patients with ESFT. Further studies are required in order to determine the efficacy of trabectedin as monotherapy or in combination with other drugs. It is also important to identify which tumor subtypes, specific translocations and patient profiles will benefit the most from treatment with trabectedin.

Rhombencephalitis due to Listeria monocytogenes: A Clinicopathologic Study of a Case.

INTRODUCTION: Central nervous system infections caused by Listeria monocytogenes usually manifest in the form of meningitis or meningoencephalitis, and are more common among immunosuppressed patients. Brainstem encephalitis (rhombencephalitis) is less common and fatal if not recognized and treated early. CASE REPORT: We describe the case of a 40-year-old, immunocompetent male patient, who presented with initial symptoms of high fever and productive cough. Signs of brainstem involvement appeared later. A magnetic resonance imaging of the brain revealed a lesion of inflammatory appearance in the right medulla oblongata, and the cerebrospinal fluid test showed mononuclear pleocytosis. Blood and cerebrospinal fluid cultures were negative. He presented with a significant improvement with the start of ceftriaxone and subsequent association of corticosteroids, until he developed respiratory failure and died. The third blood cultures grew after his death and they were positive for L. monocytogenes. An autopsy was carried out, which showed necrotizing inflammation, with gram-positive bacilli in the brainstem and the cerebellum. CONCLUSIONS: A fatal delay in the diagnosis occurred, mainly because of the favorable clinical response to ceftriaxone and corticosteroids. This case reminds us that a febrile clinical presentation with brainstem involvement must generate the suspicion of a Listeria infection, and therefore ampicillin must be a part of the empirical treatment.

Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab.

PURPOSE: Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for the proper identification of patients eligible for treatment with anti-HER2 targeted therapies. Today, the relationship remains unclear between the level of HER2 amplification and the outcome of HER2-positive gastric cancer treated with first-line chemotherapy with trastuzumab. The aim of this study was to determine whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio and HER2 gene copy number could significantly predict some benefit in overall survival and response to therapy in advanced gastric cancer treated with trastuzumab-based chemotherapy. PATIENTS AND METHODS: Ninety patients with metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy number (GCN) for discriminating positive results in terms of response and prolonged survival were determined using receiver operating characteristic curves analyses. RESULTS: In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27 to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80) were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff value discriminating sensitive and refractory patients (P = .005). Similarly, the optimal cutoff for predicting survival longer than 12 months was 4.45 (P = .005), and for survival longer than 16 months was 5.15 (P = .004). For HER2 GCN, the optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P = .02). CONCLUSION: The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy.