Radiosurgical management of SDHx-related paraganglioma.

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Abstract

BACKGROUND AND OBJECTIVES: Paragangliomas (PGLs) are rare neuroendocrine tumors which frequently occur in the head and neck. Mutations in subunits of the succinate dehydrogenase complex (SDHx) account for approximately 50% of hereditary PGLs and are associated with increased rates of malignancy, recurrence, and multifocality. While the use of stereotactic radiosurgery (SRS) for PGLs has expanded, there is a lack of data correlating genetic background with outcomes in this distinct patient population. We aimed to evaluate the safety and efficacy of SRS, specifically long-term local control and treatment-related complications, for management of the 3 major subtypes of SDHx-related PGL.METHODS: Patients with confirmed SDHx-related PGL who underwent SRS at a single institution were retrospectively reviewed. Lesions were stratified based on location and affected SDHx gene. Primary endpoints were local control, overall survival, and symptom improvement. The secondary endpoint was treatment-related adverse events. To contextualize our results, a review of prior studies assessing SRS for head and neck PGL was performed.RESULTS: Five female and 2 male patients with SDHx mutations received SRS for 10 total PGLs during the study period. Median age at PGL diagnosis was 32years (range: 16-56), with a median age at SRS treatment of 45.5years (range: 18-59). The cohort included 2 SDHB, 1 SDHC, and 4 SDHD patients. Subtotal resection was performed for 3 of 10 lesions prior to SRS. The glomus jugulare was the most common anatomic site, followed by the carotid body and glomus vagale. Treatment volume and maximum diameter ranged from 0.3 to 30.8cm3 and 11 to 50mm, respectively. Median marginal dose was 21Gy (range: 16-25). Median follow-up was 164, 160, and 21.8months for SDHB, SDHC, and SDHD patients, respectively, with an aggregate local control rate of 100%. Symptom improvement occurred in 80% of cases with preoperative symptoms. A single patient experienced a post-SRS adverse event, late dysphagia, requiring additional treatment. Our systematic review included 9 large SRS studies reporting a total of 593 patients. Median follow-up ranged from 35 to 102months, while the median local control rate was 94.8%.CONCLUSION: To our knowledge, this represents the first analysis correlating genetic subtype of SDHx-related PGL with SRS treatment outcomes. SRS appears to provide durable local control with minimal side effects across the 3 major subtypes of SDHx-related PGL, comparable to prior reports without genetically-defined cohorts. This reaffirms its applicability as a treatment strategy for this hereditary condition.

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