AUTHOR=Jha Abhishek , de Luna Kristine , Balili Charlene Ann , Millo Corina , Paraiso Cecilia Angela , Ling Alexander , Gonzales Melissa K. , Viana Bruna , Alrezk Rami , Adams Karen T. , Tena Isabel , Chen Alice , Neuzil Jiri , Raygada Margarita , Kebebew Electron , Taieb David , O'Dorisio M. Sue , O'Dorisio Thomas , Civelek Ali Cahid , Stratakis Constantine A. , Mercado-Asis Leilani , Pacak Karel 

TITLE=Clinical, Diagnostic, and Treatment Characteristics of SDHA-Related Metastatic Pheochromocytoma and Paraganglioma

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00053

DOI=10.3389/fonc.2019.00053

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Pheochromocytoma and paraganglioma (PHEO/PGL) are rare neuroendocrine tumors which may cause potentially life-threatening complications, with about a third of cases found to harbor specific gene mutations. Thus, early diagnosis, treatment, and meticulous monitoring are of utmost importance. Because of low incidence of succinate dehydrogenase complex subunit A (<italic>SDHA</italic>)-related metastatic PHEO/PGL, currently there exists insufficient clinical information, especially with regards to its diagnostic and treatment characteristics.</p><p><bold>Methods:</bold> Ten patients with <italic>SDHA</italic>-related metastatic PHEO/PGL were followed-up prospectively and/or retrospectively between January 2010–July 2018. They underwent biochemical tests (<italic>n</italic> = 10), <sup>123</sup>I-MIBG (<italic>n</italic> = 9) scintigraphy, and multiple whole-body positron emission tomography/computed tomography (PET/CT) scans with <sup>68</sup>Ga-DOTATATE (<italic>n</italic> = 10), <sup>18</sup>F-FDG (<italic>n</italic> = 10), and <sup>18</sup>F-FDOPA (<italic>n</italic> = 6).</p><p><bold>Results:</bold> Our findings suggest that these tumors can occur early and at extra-adrenal locations, behave aggressively, and have a tendency to develop metastatic disease within a short period of time. None of our patients had a family history of PHEO/PGL, making them appear sporadic. Nine out of 10 patients showed abnormal PHEO/PGL-specific biochemical markers with predominantly noradrenergic and/or dopaminergic phenotype, suggesting their utility in diagnosing and monitoring the disease. Per patient detection rates of <sup>68</sup>Ga-DOTATATE (<italic>n</italic> = 10/10), <sup>18</sup>F-FDG (<italic>n</italic> = 10/10), <sup>18</sup>F-FDOPA (<italic>n</italic> = 5/6) PET/CT, and <sup>123</sup>I-MIBG (<italic>n</italic> = 7/9) scintigraphy were 100, 100, 83.33, and 77.77%, respectively. Five out of 7 <sup>123</sup>I-MIBG positive patients had minimal <sup>123</sup>I-MIBG avidity or detected very few lesions compared to widespread metastatic disease on <sup>18</sup>F-FDG PET/CT, implying that diagnosis and treatment with <sup>123/131</sup>I-MIBG is not a good option. <sup>68</sup>Ga-DOTATATE PET/CT was found to be superior or equal to <sup>18</sup>F-FDG PET/CT in 7 out of 10 patients and hence, is recommended for evaluation and follow-up of these patients. All 7 out of 7 patients who received conventional therapies (chemotherapy, somatostatin analog therapy, radiation therapy, <sup>131</sup>I-MIBG, peptide receptor radionuclide therapy) in addition to surgery showed disease progression.</p><p><bold>Conclusion:</bold> In our cohort of patients, <italic>SDHA</italic>-related metastatic PHEO/PGL followed a disease-course similar to that of <italic>SDHB</italic>-related metastatic PHEO/PGL, showing highly aggressive behavior, similar imaging and biochemical phenotypes, and suboptimal response to conventional therapies. Therefore, we recommend careful surveillance of the affected patients and a search for effective therapies.</p>