External Beam Radiation Therapy for Advanced/Unresectable Malignant Paraganglioma and Pheochromocytoma

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To evaluate the role of external beam radiation therapy (EBRT) for treatment of malignant paraganglioma (PGL) and pheochromocytoma (PCC). A retrospective review was performed of patients with malignant PGL or PCC treated with EBRT at our institution between 1973 and 2015. Treatment intent was considered “curative” if patients received EBRT +/- other local therapies to all known macroscopic sites of disease; all other EBRT was considered “palliative.” Biologic effective dose (BED) was calculated using alpha/beta of 10. Local control (LC) was determined per treated lesion and was defined as lack of radiographic progression. LC, overall survival (OS), and distant progression-free survival (dPFS) were estimated using the Kaplan Meier method. Acute and late toxicities were scored using the Common Toxicity Criteria for Adverse Events (CTCAE) version 4. The cohort included 41 patients with 107 sites treated. Treatment intention was curative in 20 patients (30 lesions) or palliative in 21 patients (77 lesions). Histology was PGL (63%) or PCC (37%). Median (range) age at EBRT was 33 (11-80) years. Gender was female for 59%. Previous local therapies were surgical resection (90%) and percutaneous ablation (19%). Seventeen patients (42%) had received medical therapies, the most common being cytotoxic chemotherapy (27%), octreotide (20%), denosumab (17%), and zoledronic acid (17%). The primary indications for EBRT were local control (66%), pain (22%), or spinal cord compression (12%). RT techniques were 2D/3D conformal RT (72%), intensity modulated RT (17%), stereotactic body RT (SBRT, 9%), intraoperative RT (3%), and intracranial stereotactic radiosurgery (SRS, 1%). Treatment site included bone (69%), soft tissue (30%), and liver (1%). Median (range) EBRT dose was 40 (6.5–70) Gy. Median BED10 was 53 (range 9-132). BED10was ≥ 50 for 63 lesions (59%). Median follow-up time was 3.7 years (range .03-40). OS at 5 years was 65% for all patients; 77% for curative and 53% for palliative patients (P = 0.039). For the curative intention patients, median dPFS was 1.6 (range .03-19.9) years and the 5 year dPFS was 30%. LC at 5 years for all lesions was 79%; 90% for lesions receiving BED10 ≥ 50, and 50% for lesions receiving BED10< 50 (P = 0.0002). All 10 lesions (in 7 patients) treated with SBRT/SRS had LC at a median of 2.0 (range 0.2-3.7) years. For the symptomatic lesions, symptoms improved in 94%. There were no acute grade ≥ 3 treatment-related AEs. One patient developed a late grade ≥ 3 AE (grade 3 pre-mature menopause). No patient received escalated pre-radiation alpha-blockade, and none experienced hypertensive crisis. EBRT is a useful treatment modality for malignant PGL and PCC. High-dose RT (BED10 ≥ 50) was associated with improved LC.