The Natural History of Observed SDHx-Related Head and Neck Paragangliomas Using Three-Dimensional Volumetric Tumor Analysis

Abstract

Objective Characterize the natural history and clinical behavior of head and neck paragangliomas (HNPGLs) in subjects with succinate dehydrogenase (SDHx) pathogenic variants using volumetric tumor measurements. Study Design Cohort study. Setting Tertiary academic referral center. Patients Subjects with SDHx HNPGLs under observation for at least 6 months with 2 or more magnetic resonance imaging or computed tomography scans. Intervention(s) Diagnostic interventions include next-generation sequencing, magnetic resonance imaging, and computed tomography. Therapeutic interventions include microsurgical resection or stereotactic radiosurgery. Main Outcome Measure(s) Radiographic progression was defined as a 20% or greater increase in volume. Cranial nerve (CN) functional outcomes were assessed using clinical documentation. Results A total of 19 subjects with 32 tumors met the inclusion criteria. Median radiographic follow-up was 2.2 years, and the median volumetric growth rate was 0.47 cm3/yr. Kaplan-Meier estimated rates of survival free of radiographic progression for all SDHx tumors at 1, 2, and 3 years were 69, 50, and 22%, respectively. No tumors developed new CN palsies during the period of observation. Conclusions Over intermediate-term follow-up, observation of treatment-naive SDHx-related HNPGLs did not result in new cranial neuropathy. Although indefinite observation is only appropriate for select cases, these data support an interval of observation to characterize growth rate in asymptomatic to minimally symptomatic patients, who are at high risk of treatment-related morbidity. Given the early age at diagnosis and high risk of bilateral multifocal phenotypes in SDHx HNPGL mutation carriers, these data may aid in optimizing patient tumor control and CN functional preservation. Further studies are necessary to determine whether pretreatment growth rate is correlated with clinical outcomes.