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

Frontiers in Oncology

卷:9

Electron Kebebew¹  David Taieb²  M. Sue O'Dorisio³  Thomas O'Dorisio⁴  Ali Cahid Civelek⁶  Rami Alrezk⁷  Alice Chen⁸  Jiri Neuzil¹⁰  Corina Millo¹¹  Alexander Ling¹²  Kristine de Luna¹³  Leilani Mercado-Asis¹³  Charlene Ann Balili¹³  Cecilia Angela Paraiso¹³  Margarita Raygada¹⁴  Constantine A. Stratakis¹⁴  Karen T. Adams¹⁵  Karel Pacak¹⁵  Melissa K. Gonzales¹⁵  Bruna Viana¹⁵  Isabel Tena¹⁵  Abhishek Jha¹⁵ 

[1] 0Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States;

[2] 1Department of Nuclear Medicine, La Timone University Hospital, Aix-Marseille University, Marseille, France;

[3] 2Department of Pediatrics, RJ and LA Carver College of Medicine, University of Iowa, Iowa City, IA, United States;

[4] 3Neuroendocrine Tumor Program, Division of Endocrinology and Metabolism, Department of Medicine, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA, United States;

[5] 4Nuclear Medicine Division, Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, United States;

[6] 5Nuclear Medicine, Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, MD, United States;

[7] Clinical Endocrine Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States;

[8] Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States;

[9] Mitochondria, Apoptosis and Cancer Research Group, School of Medical Science, Menzies Health Institute Queensland, Griffith University, Southport, QLD, Australia;

[10] Molecular Therapy Group, Institute of Biotechnology, Czech Academy of Sciences, Prague, Czechia;

[11] Positron Emission Tomography Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, United States;

[12] Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, United States;

[13] Section of Diabetes, Endocrinology and Metabolism, Department of Medicine, University of Santo Tomas Hospital, Manila, Philippines;

[14] Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States;

[15] Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States;

关键词: paraganglioma;    pheochromocytoma;    SDHA;    68Ga-DOTATATE;    PET/CT;    18F-FDG;   

DOI  :  10.3389/fonc.2019.00053

来源: DOAJ

【 摘 要 】

Background: 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 (SDHA)-related metastatic PHEO/PGL, currently there exists insufficient clinical information, especially with regards to its diagnostic and treatment characteristics.Methods: Ten patients with SDHA-related metastatic PHEO/PGL were followed-up prospectively and/or retrospectively between January 2010–July 2018. They underwent biochemical tests (n = 10), 123I-MIBG (n = 9) scintigraphy, and multiple whole-body positron emission tomography/computed tomography (PET/CT) scans with 68Ga-DOTATATE (n = 10), 18F-FDG (n = 10), and 18F-FDOPA (n = 6).Results: 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 68Ga-DOTATATE (n = 10/10), 18F-FDG (n = 10/10), 18F-FDOPA (n = 5/6) PET/CT, and 123I-MIBG (n = 7/9) scintigraphy were 100, 100, 83.33, and 77.77%, respectively. Five out of 7 123I-MIBG positive patients had minimal 123I-MIBG avidity or detected very few lesions compared to widespread metastatic disease on 18F-FDG PET/CT, implying that diagnosis and treatment with 123/131I-MIBG is not a good option. 68Ga-DOTATATE PET/CT was found to be superior or equal to 18F-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, 131I-MIBG, peptide receptor radionuclide therapy) in addition to surgery showed disease progression.Conclusion: In our cohort of patients, SDHA-related metastatic PHEO/PGL followed a disease-course similar to that of SDHB-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.

【 授权许可】

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