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 language | English (US) |
|---|---|
| Article number | 53 |
| Journal | Frontiers in Oncology |
| Volume | 9 |
| Issue number | FEB |
| DOIs | |
| State | Published - Jan 1 2019 |
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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 journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=85063267843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063267843&partnerID=8YFLogxK
U2 - 10.3389/fonc.2019.00053
DO - 10.3389/fonc.2019.00053
M3 - Article
C2 - 30854332
AN - SCOPUS:85063267843
VL - 9
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
IS - FEB
M1 - 53
ER -