Clinical, diagnostic, and treatment characteristics of SDHA-related metastatic pheochromocytoma and paraganglioma

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number53
JournalFrontiers in Oncology
Volume9
Issue numberFEB
DOIs
StatePublished - Jan 1 2019

Fingerprint

Paraganglioma
Succinate Dehydrogenase
Pheochromocytoma
3-Iodobenzylguanidine
Fluorodeoxyglucose F18
Therapeutics
Radionuclide Imaging
Phenotype
Peptide Receptors
Neuroendocrine Tumors
Somatostatin
Radioisotopes
Disease Progression
Early Diagnosis
Radiotherapy
Biomarkers
Positron Emission Tomography Computed Tomography
Drug Therapy

Keywords

  • 123I-MIBG
  • 18F-FDG
  • 18F-FDOPA
  • 68Ga-DOTATATE
  • Paraganglioma
  • PET/CT
  • Pheochromocytoma
  • SDHA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Clinical, diagnostic, and treatment characteristics of SDHA-related metastatic pheochromocytoma and paraganglioma. / 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; Stratakis, Constantine A.; Mercado-Asis, Leilani; Pacak, Karel.

In: Frontiers in Oncology, Vol. 9, No. FEB, 53, 01.01.2019.

Research output: Contribution to journalArticle

Jha, A, De Luna, K, Balili, CA, Millo, C, Paraiso, CA, Ling, A, Gonzales, MK, Viana, B, Alrezk, R, Adams, KT, Tena, I, Chen, A, Neuzil, J, Raygada, M, Kebebew, E, Taieb, D, O'Dorisio, MS, O'Dorisio, T, Civelek, A, Stratakis, CA, Mercado-Asis, L & Pacak, K 2019, 'Clinical, diagnostic, and treatment characteristics of SDHA-related metastatic pheochromocytoma and paraganglioma', Frontiers in Oncology, vol. 9, no. FEB, 53. https://doi.org/10.3389/fonc.2019.00053
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 ; Stratakis, Constantine A. ; Mercado-Asis, Leilani ; Pacak, Karel. / Clinical, diagnostic, and treatment characteristics of SDHA-related metastatic pheochromocytoma and paraganglioma. In: Frontiers in Oncology. 2019 ; Vol. 9, No. FEB.
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abstract = "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.",
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TY - JOUR

T1 - Clinical, diagnostic, and treatment characteristics of SDHA-related metastatic pheochromocytoma and paraganglioma

AU - Jha, Abhishek

AU - De Luna, Kristine

AU - Balili, Charlene Ann

AU - Millo, Corina

AU - Paraiso, Cecilia Angela

AU - Ling, Alexander

AU - Gonzales, Melissa K.

AU - Viana, Bruna

AU - Alrezk, Rami

AU - Adams, Karen T.

AU - Tena, Isabel

AU - Chen, Alice

AU - Neuzil, Jiri

AU - Raygada, Margarita

AU - Kebebew, Electron

AU - Taieb, David

AU - O'Dorisio, M. Sue

AU - O'Dorisio, Thomas

AU - Civelek, Ali

AU - Stratakis, Constantine A.

AU - Mercado-Asis, Leilani

AU - Pacak, Karel

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - 123I-MIBG

KW - 18F-FDG

KW - 18F-FDOPA

KW - 68Ga-DOTATATE

KW - Paraganglioma

KW - PET/CT

KW - Pheochromocytoma

KW - SDHA

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