In Vivo Succinate Detection After External Beam Radiation Therapy in SDHx- Paragangliomas

Study Overview
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Brief Summary
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Qualitative and quantitative biomarker of response to radiotherapy is needed in paragangliomas. We aim at assessing the added value of 1H-SRM for the evaluation of early response to EBR therapy in patients with cervical SDHx PGL.

Detailed Description
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Paragangliomas (PGL) are rare neuroendocrine tumors inherited in 40% of cases. SDHx genes (SDHA, SDHB, SDHC, SDHD), encoding the 4 subunits of the mitochondrial enzyme succinate dehydrogenase (SDH), are the most frequently involved. Accumulation of succinate, the substrate for SDH, is a very specific biomarker for these mutations. Recently, we have demonstrated the feasability of detecting and quantifying succinate in tumors in vivo, by magnetic resonance spectroscopy (1H-SRM). Patients carrying these mutations frequently develop cervical PGL for which the treatment of choice is external beam radiation therapy (EBR). The objective of this project is to determine the feasibility of using 1H-SRM for the evaluation of early response to EBR therapy in patients with cervical SDHx PGL.

Official Title
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Evolution of Succinate Accumulation Detected in Vivo by Spectroscopic Magnetic Resonance Imaging (1H-SRM) After External Beam Radiation Therapy in SDHx-mutated Patients With Cervical Paragangliomas

Conditions
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Paraganglioma of Head and Neck

Intervention / Treatment
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* Diagnostic Test: 1H-Spectroscopy MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Signed informed consent Patient with cervical PGL with planning of treatment with EBR Patient with an SDHx mutation or unknown genetic status Patient affiliated to a social security scheme Exclusion Criteria: Pregnant woman Contraindication to MRI (implantable device, etc.) Impossibility of lying down without movement for 45 minutes (hyperalgesic patient, claustrophobia, etc.) PPGL having previously been the subject of local (excluding surgery) or systemic treatment PPGL <1 cm longest axis Patient under guardianship or curatorship

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Assigned Intervention<br>Addition to the cervical angio-MRI, of a sequence of 1H-SRM 3T (SUCCESS) centered on the lesion studied, performed according to the following parameters: PRESS asymmetric monovoxel PROBE, TE 144 ms, TR 2500 ms, 768 or 1024 medium. | Diagnostic Test: 1H-Spectroscopy MRI<br>* PRESS asymetric monovoxel  PROBE , TE 144 ms, TR 2500 ms, 768 or 1024 averages<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disappearance of succinate accumulation at M12 | Absence of succinate accumulation detected in vivo by 1H-SRM, in cervical PGLs with SDHx mutations, at 12 months after EBR, reviewed by 2 independant experts blinded to all other clinical and genetics data. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disapperance of succinate accumulation at M3 | Absence of succinate accumulation detected in vivo by 1H-SRM, in cervical PGLs with SDHx mutations, at 3 months after EBR, reviewed by 2 independant experts blinded to all other clinical and genetics data. | 3 months | 
| Performance of cervical MRI at M3 and M12 after EBR | Reference diagnostic for response assessed by MRI at 3 months and 12 months after EBR: 1/ Complete response : tumour disappearance ; 2/ Partial response : decrease by at least 30% of tumour volume and no clinical symptomatology worsening ; 3/ stable : stability of tumour size and no clinical symptomatology worsening; 4/ Progression : increase by at least 20% of tumour volume and/or clinical symptomatological worsening | 12 months | 
| Performance of PET/CT at M12 after EBR | PERCIST criteria (PET response criteria in solid tumors) assessed by PET/CT at 3 months and 12 months after EBR | 12 months | 
| Metastatic evolution or death at M12 | Occurence of an event related to the disease during 12 months follow-up (metastatic evolution of the disease or death). Metastases diagnostic is assessed remotely by presence in chromaffin tissue (http://www.sfendocrino.org/article/599/recommandations) | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paraganglioma,SDHx genes, 1H-Spectroscopy MRI