title: Current and future treatments for malignant pheochromocytoma and sympathetic paraganglioma.
abstract: Pheochromocytomas (PHs) and sympathetic paragangliomas (SPGs) are rare neuroendocrine tumors. Approximately 17 % of these tumors are malignant, but because no molecular or histologic markers for malignancy exist, patients are often diagnosed with malignant PHs or SPGs after unresectable disease has formed. Patients with progressive metastatic tumors and overwhelming symptoms are currently treated with systemic chemotherapy and radiopharmaceutical agents such as metaiodobenzylguanidine. These therapies lead to partial radiographic response, disease stabilization, and symptomatic improvement in approximately 40 % of patients, and systemic chemotherapy is associated with a modest improvement in overall survival duration. However, over the past decade, substantial progress has been made in clinical, biochemical, and radiographic diagnosis of PHs and SPGs. Approximately 50 % of patients with malignant PHs and SPGs have been found to carry hereditary germline mutations in the succinate dehydrogenase subunit B gene (SDHB), and anti-angiogenic agents such as sunitinib have been found to potentially play a role in the treatment of malignant disease, especially in patients with SDHB mutations. In some patients, treatment with sunitinib has been associated with partial radiographic response, disease stabilization, decreased fluorodeoxyglucose uptake on positron emission tomography, and improved blood pressure control. These findings have led to the development of prospective clinical trials of new targeted therapies for metastatic disease. Here, we provide an updated review of the clinical and genetic predictors of malignant disease, radiographic diagnosis of malignant disease, and information from the most relevant studies of systemic therapies, as well as proposed treatment guidelines for patients with metastatic or potentially malignant PHs and SPGs.
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, Unit 1461, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. cjimenez@mdanderson.org
authors.forename: Camilo
authors.initials: C
authors.lastname: Jimenez
authors.forename: Eric
authors.initials: E
authors.lastname: Rohren
authors.forename: Mouhammed Amir
authors.initials: MA
authors.lastname: Habra
authors.forename: Thereasa
authors.initials: T
authors.lastname: Rich
authors.forename: Paola
authors.initials: P
authors.lastname: Jimenez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Ayala-Ramirez
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D010235:Paraganglioma / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase