ESPEYB21 8. Adrenals New Hope (3 abstracts)
8.15. Metastatic pheochromocytoma and paraganglioma: somatostatin receptor 2 expression, genetics, and therapeutic responses
Fischer A , Kloos S , Maccio U , Friemel J , Remde H , Fassnacht M , Pamporaki C , Eisenhofer G , Timmers HJLM , Robledo M , Fliedner SMJ , Wang K , Maurer J , Reul A , Zitzmann K , Bechmann N , Žygienė G , Richter S , Hantel C , Vetter D , Lehmann K , Mohr H , Pellegata NS , Ullrich M , Pietzsch J , Ziegler CG , Bornstein SR , Kroiss M , Reincke M , Pacak K , Grossman AB , Beuschlein F & Nölting S
J Clin Endocrinol Metab. 2023; 108(10): 2676-2685. https://pubmed.ncbi.nlm.nih.gov/36946182/
Brief Summary: This study explored the relationship between Somatostatin Receptor 2 (SSTR2) immunoreactivity and succinate dehydrogenase complex iron sulfur subunit B (SDHB) immunoreactivity, mutational status, and clinical behavior of paragangliomas (PPGLs), and evaluated SSTR-based therapies in metastatic PPGLs. The findings highlight SSTR2 expression as a novel biomarker for metastatic behavior in PCC, PGL and SDHB/ SDHx mutations. They also suggest that SSTR-based therapies may provide superior therapeutic outcomes in metastatic PPGLs with a higher disease control rate.
Comment: Pheochromocytomas (PCC) and paragangliomas (PPGLs) caused by pathogenic mutations in succinate dehydrogenase subunit B ( SDHB ) gene are rare inheritable neuroendocrine tumors with a high propensity for metastasis, making their management particularly challenging (1). Therefore, identifying biomarkers of potential malignant risk is of great clinical importance.
This retrospective study focuses on the expression of somatostatin receptor 2 (SSTR2), which is present in both non-metastatic and metastatic PPGLs, as a potential key biomarker in the diagnosis and treatment of neuroendocrine tumors, as it is the target for imaging (2-4). The study’s primary objectives were to evaluate the correlation between SSTR2 immunoreactivity, SDHB immunoreactivity, mutational status and the clinical phenotype of PPGLs. Additionally, the study assessed the efficacy of SSTR based therapies, including peptide receptor radionuclide therapy (PRRT) and cold SSTR2 analogues, in treating metastatic PPGLs.
SSTR2 was positive in 50% of patients (n=101), although with considerable variability in intensity. SSTR2 positivity was not linked to tumor location, size, or a higher proliferation index (Ki-67>3%). However, it was associated with SDHB and SDHx related PPGLs, with the highest intensity observed in SDHB related PPGLs, and with metastatic disease independent of SDHB/SDHx mutation status. Furthermore, the disease control rate in metastatic PPGLs was 67% with first-line SSTR-based radionuclide therapy (n=22, n=11SDHx) and 100% with first line “cold” somatostatin analogues (n=6, n=3 SDHx).
In conclusion, this study offers valuable insights into the potential of SSTR2 expression particularly as a novel biomarker for diagnosing metastatic behavior in PCC, PGL and SDHB/ SDHx mutations. It also suggests that SSTR-based therapies may provide superior therapeutic outcomes in metastatic PPGLs with a higher disease control rate.
References: 1. Crona J, Lamarca A, Ghosal S, Welin S, Skogseid B, Pacak K. Genotype-phenotype correlations in pheochromocytoma and paraganglioma: a systematic review and individual patient meta-analysis. Endocr Relat Cancer. 2019; 26(5): 539–550. 2. Reubi J, Waser B, Schaer JC, Laissue JA. Somatostatin receptor sst1–sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001; 28(7): 836-846.3. Taïeb D, Jha A, Treglia G, Pacak K. Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups. Endocr Relat Cancer. 2019; 26(11): R627-R652.4. Janssen I, Blanchet EM, Adams K, et al. Superiority of [68Ga]-DOTATATE PET/CT to other functional imaging modalities in the localization of SDHB -associated metastatic pheochromocytoma and paraganglioma. Clin Cancer Res. 2015; 21(17): 3888-3895.
Volume 21
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more