External Beam Radiation Therapy for Pheochromocytoma and Non-Head and Neck Paraganglioma: A Single-Institution Experience and Systematic Review

Background/Objectives: Paragangliomas (PGLs) and pheochromocytomas (PCCs) are rare neuroendocrine tumors. While external beam radiation therapy (EBRT), particularly stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT), is established for head and neck PGLs (HNPGLs), its efficacy for non-head and neck PGLs (non-HNPGLs) and PCCs is less defined. We aimed to compare treatment outcomes of EBRT across these anatomic sites. Methods: We retrospectively reviewed patients with confirmed PGL or PCC treated with EBRT at a single institution between 1998 and 2025. Treated lesions were classified as non-HNPGL or HNPGL based on the radiation treatment field. Outcomes included local control (LC), distant progression-free survival (dPFS), overall survival (OS), symptomatic/biochemical response, and toxicity. We also conducted a systematic review examining EBRT for non-HNPGLs and PCCs following PRISMA guidelines. Results: We included 74 patients with 129 lesions who were treated with EBRT, with 62 HNPGL lesions and 67 non-HNPGL lesions. Of the non-HNPGL lesions, 50.7% (34/67) received SRS/SBRT with a median BED10 of 50.8 Gy (range, 35.7–112.5). 5-year LC rate for non-HNPGL lesions was 95.3%, compared to 100% for HNPGL lesions, with 78% of lesions achieving symptomatic control. For non-HNPGL patients, median dPFS and OS were 37.6 and 131 months, respectively. There were no acute or late G ≥ 3 toxicities. Our systematic review (61 studies, 183 patients) showed LC and symptomatic improvement ranges of 76–100% and 76–94%, respectively. Conclusions: EBRT, including SRS and SBRT, provides excellent local control and symptomatic relief for both non-HNPGLs and HNPGLs. It represents a safe, effective treatment option for these rare tumors regardless of anatomic location.