Deciphering F-DOPA uptake in SDH-related head and neck paragangliomas: a radiomics approach. - National Genomics Data Center (CNCB-NGDC)

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Deciphering F-DOPA uptake in SDH-related head and neck paragangliomas: a radiomics approach.

Valentina Berti, Elsa Fasciglione, Anne Charpiot, Flavio Montanini, Miriam Pepponi, Andrea Leo, Fabrice Hubele, David Taieb, Karel Pacak, Bernard Goichot, Alessio Imperiale

Author Information

Valentina Berti: Nuclear Medicine Unit, Careggi University Hospital, Florence, Italy.
Elsa Fasciglione: Endocrinology, Diabetology, Nutrition, Strasbourg University Hospitals, Strasbourg University, Strasbourg, France.
Anne Charpiot: Otolaryngology and Maxillofacial Surgery, Strasbourg University Hospitals, Strasbourg University, Strasbourg, France.
Flavio Montanini: Nuclear Medicine Unit, Careggi University Hospital, Florence, Italy.
Miriam Pepponi: Nuclear Medicine Unit, Careggi University Hospital, Florence, Italy.
Andrea Leo: Experimental and Clinical Biomedical Sciences 'Mario Serio', Florence University, Florence, Italy.
Fabrice Hubele: Nuclear Medicine and Molecular Imaging, ICANS, Strasbourg University Hospitals, Strasbourg University, Strasbourg, France.
David Taieb: Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, Marseille, France.
Karel Pacak: Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, MD, USA.
Bernard Goichot: Endocrinology, Diabetology, Nutrition, Strasbourg University Hospitals, Strasbourg University, Strasbourg, France.
Alessio Imperiale: Nuclear Medicine and Molecular Imaging, ICANS, Strasbourg University Hospitals, Strasbourg University, Strasbourg, France. a.imperiale@icans.eu. ORCID

PMID: 39666255 DOI: 10.1007/s40618-024-02515-y

PURPOSE: To investigate the influence of germline succinate dehydrogenase (SDHx) pathogenic variants on 6-[F]-fluoro-3,4-dihydroxyphenylalanine (F-DOPA) Positron Emission Tomography (PET) radiomic signature of head and neck paragangliomas (HNPGLs).
METHODS: Forty-seven patients (20 SDH pathogenic variants carriers) harboring 55 HNPGLs were retrospectively included. HNPGLs were delineated using Nestle adaptive threshold. 128 radiomic features were extracted and harmonized to correct for batch effects. Principal Component Analysis (PCA) was performed to remove redundancy and avoid collinearity. The most representative feature of each component was tested with multivariate stepwise logistic binary regression analysis (LBRA) to identify variables predictive of genetic status.
RESULTS: F-DOPA Positron Emission Tomography/Computed Tomography (PET/CT) detected 28/29 carotid body HNPGLs, 23/23 jugulotympanic HNPGLs, and 4/4 vagal HNPGLs. SUVmax was significantly higher in SDH-related HNPGLs (p = 0.003). PCA allowed identification of 4 Components. The most representative variables of Component 1 and 2 (including intensity and intensity-related textural features, and not intensity-related textural features, respectively) were Intensity-based (IB)-SUVmedian and Grey Level Run Length Matrix-Long Run Low Gray Level Emphasis (GLRLM-LRLGLE). SDHx HNPGLs exhibited higher activity scores and more homogeneous texture. At patient level, SDHx cases showed significantly higher IB-SUVmedian values (p < 0.001), and lower GLRLM-LRLGLE than sporadic patients (p = 0.005). IB-SUVmedian was found to be an independent predictor of genetic status at lesion (71.0%) and patient level (77.8%).
CONCLUSION: The present study pioneers the application of F-DOPA PET radiomics for HNPGLs, suggesting the influence of germline SDH pathogenic variants on F-FDOPA uptake intensity and textural heterogeneity. Integrating radiomics with genetic data provides new insights into the correlation between PET features and underlying molecular dysregulation.

18F-DOPA Head and neck PET Paraganglioma Radiomics Succinate dehydrogenase

Cass ND, Schopper MA, Lubin JA, Fishbein L, Gubbels SP (2020) The changing paradigm of head and neck paragangliomas: what every otolaryngologist needs to know. Annals Otology Rhinology Laryngology 129:1135–1143 [DOI: 10.1177/0003489420931540]

Lin EP, Chin BB, Fishbein L, Moritani T, Montoya SP, Ellika S et al (2022) Head and Neck paragangliomas: an update on the molecular classification, state-of-the-art imaging, and Management recommendations. Radiol Imaging Cancer 4:e210088 [DOI: 10.1148/rycan.210088]

Richter S, Qiu B, Ghering M, Kunath C, Constantinescu G, Luths C et al (2022) Given the potential hereditary component, genetic counseling and testing are necessary Head/neck paragangliomas: focus on tumor location, mutational status and plasma methoxytyramine. Endocr Relat Cancer 29:213–224 [DOI: 10.1530/ERC-21-0359]

Taïeb D, Imperiale A, Pacak K (2016) (18)F-DOPA: the versatile radiopharmaceutical. Eur J Nucl Med Mol Imaging 43:1187–1189 [DOI: 10.1007/s00259-016-3354-0]

Castinetti F, Kroiss A, Kumar R, Pacak K, Taieb D (2015) 15 YEARS OF PARAGANGLIOMA: imaging and imaging-based treatment of pheochromocytoma and paraganglioma. Endocr Relat Cancer 22:T135–T145 [DOI: 10.1530/ERC-15-0175]

Amodru V, Guerin C, Delcourt S, Romanet P, Loundou A, Viana B et al (2018) Quantitative (18)F-DOPA PET/CT in pheochromocytoma: the relationship between tumor secretion and its biochemical phenotype. Eur J Nucl Med Mol Imaging 45:278–282 [DOI: 10.1007/s00259-017-3833-y]

Moog S, Houy S, Chevalier E, Ory S, Weryha G, Rame M et al (2018) 18F-FDOPA PET/CT uptake parameters correlate with catecholamine secretion in human pheochromocytomas. Neuroendocrinology 107:228–236 [DOI: 10.1159/000491578]

Taïeb D, Jha A, Treglia G, Pacak K (2019) Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups. Endocr Relat Cancer 26:R627–R652 [DOI: 10.1530/ERC-19-0165]

Timmers HJ, Chen CC, Carrasquillo JA, Whatley M, Ling A, Havekes B et al (2009) Comparison of 18F-Fluoro-L-DOPA, 18F-Fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma. J Clin Endocrinol Metab 94:4757–4767 [DOI: 10.1210/jc.2009-1248]

Gabriel S, Blanchet EM, Sebag F, Chen CC, Fakhry N, Deveze A et al (2013) Functional characterization of no metastatic paraganglioma and pheochromocytoma by (18)F-FDOPA PET: focus on missed lesions. Clin Endocrinol 79:170–177 [DOI: 10.1111/cen.12126]

Reichert T, Fakhry N, Lavieille JP, Amodru V, Sebag F, Romanet P et al (2019) Exploring the link between tumour metabolism and succinate dehydrogenase deficiency: a 18 F-FDOPA PET/CT study in head and neck paragangliomas. Clin Endocrinol (Oxf) 91:879–884 [DOI: 10.1111/cen.14086]

Hatt M, Le Rest CC, Tixier F, Badic B, Schick U, Visvikis D (2019) Radiomics: Data are also images. J Nucl Med 60:38S–44S [DOI: 10.2967/jnumed.118.220582]

Bera K, Braman N, Gupta A, Velcheti V, Madabhushi A (2022) Predicting cancer outcomes with radiomics and artificial intelligence in radiology. Nat Rev Clin Oncol 19:132–146 [DOI: 10.1038/s41571-021-00560-7]

Li S, Zhou B (2022) A review of radiomics and genomics applications in cancers: the way towards precision medicine. Radiat Oncol 17:217 [DOI: 10.1186/s13014-022-02192-2]

Lambin P, Rios-Velazquez E, Leijenaar R, Carvalho S, van Stiphout RG, Granton P et al (2022) Radiomics: extracting more information from medical images using advanced feature analysis. Eur J Cancer 48:441–446 [DOI: 10.1016/j.ejca.2011.11.036]

Ansquer C, Drui D, Mirallié E, Renaudin-Autain K, Denis A, Gimenez-Roqueplo AP et al (2020) A usefulness of FDG-PET/CT-Based Radiomics for the characterization and genetic orientation of Pheochromocytomas before surgery. Cancers (Basel) 12(9):2424. https://doi.org/10.3390/cancers12092424

Noortman WA, Vriens D, de Geus-Oei LF, Slump CH, Aarntzen EH, van Berkel A et al (2022) [18F]FDG-PET/CT radiomics for the identification of genetic clusters in pheochromocytomas and paragangliomas. Eur Radiol 32:7227–7236 [DOI: 10.1007/s00330-022-09034-5]

Taïeb D, Hicks RJ, Hindié E, Guillet BA, Avram A, Ghedini P et al (2019) European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging 46:2112–2137 [DOI: 10.1007/s00259-019-04398-1]

Nioche C, Orlhac F, Boughdad S, Reuzé S, Goya-Outi J, Robert C et al (2018) LIFEx: a freeware for radiomic feature calculation in multimodality imaging to accelerate advances in the characterization of tumor heterogeneity. Cancer Res 78:4786–4789 [DOI: 10.1158/0008-5472.CAN-18-0125]

Orlhac F, Boughdad S, Philippe C, Stalla-Bourdillon H, Nioche C, Champion L et al (2018) Postreconstruction Harmonization Method for Multicenter Radiomic studies in PET. J Nucl Med 59:1321–1328 [DOI: 10.2967/jnumed.117.199935]

Toledo RA, Burnichon N, Cascon A, Benn DE, Bayley JP, Welander J et al (2017) Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas. Nat Rev Endocrinol 13:233–247 [DOI: 10.1038/nrendo.2016.185]

Zhi Y, Gerhard-Hartmann E, Hartrampf PE, Weich A, Higuchi T, Bley TA et al (2023) Somatostatin receptor-Directed PET/CT can differentiate between different subtypes of Head and Neck Paragangliomas. Clin Nucl Med 433:48:923–927 [DOI: 10.1097/RLU.0000000000004870]

Pepponi M, Berti V, Fasciglione E, Montanini F, Canu L, Hubele F et al (2024) [68Ga]DOTATOC PET-derived radiomics to predict genetic background of head and neck paragangliomas: a pilot investigation. Eur J Nucl Med Mol Imaging. 51(9):2684–2694. https://doi.org/10.1007/s00259-024-06735-5

van Berkel A, Vriens D, Visser EP, Janssen MJR, Gotthardt M, Hermus ARMM et al (2019) Metabolic subtyping of Pheochromocytoma and Paraganglioma by (18)F-FDG pharmacokinetics using dynamic PET/CT scanning. J Nucl Med 60:745–751 [DOI: 10.2967/jnumed.118.216796]

De Rycke O, Perrier M, Ouvrard É, Mennetrey C, Lachachi C, Bando-Delaunay A et al (2023) High Tumor Uptake on 18F-FDOPA PET/CT indicates poor prognosis in patients with metastatic midgut neuroendocrine tumors: a study from the Groupe d’étude Des Tumeurs endocrines and ENDOCAN-RENATEN Network. J Nucl Med 64:1699–1705 [DOI: 10.2967/jnumed.123.265584]

Humans

Male

Female

Head and Neck Neoplasms

Middle Aged

Succinate Dehydrogenase

Dihydroxyphenylalanine

Retrospective Studies

Paraganglioma

Adult

Positron Emission Tomography Computed Tomography

Radiopharmaceuticals

Aged

Prognosis

Radiomics

Succinate Dehydrogenase

Dihydroxyphenylalanine

fluorodopa F 18

Radiopharmaceuticals

Journal Article