Five-Fraction Stereotactic Radiation for Head and Neck Paragangliomas

Abstract

Paragangliomas of the head and neck (HN) are benign, slow-growing neoplasms that are rarely functional. Treatment is often indicated for patients presenting with mass effect, cranial neuropathies, or pulsatile tinnitus. Radiotherapy, traditionally conventionally fractionated, is often used for primary, post-operative, and salvage therapy, given its excellent control rates and reduced risks to adjacent neurovascular structures. Stereotactic ablative radiation (SAbR) offers shorter treatment time, and modern techniques eliminate margins to improve organ-at-risk avoidance. SAbR may offer additional radiobiological sparing of normal structures over single-fraction SAbR. We aimed to evaluate tumor and symptom response, acute and late toxicity rates, and recurrence patterns in HN paraganglioma patients treated with 25 Gy in 5 fractions. Retrospective chart review collected baseline patient and tumor information, treatment and dosimetry details, acute and long-term toxicity grades (per the CTCAE v. 5.0), symptom and tumor response, and survival. Local control was defined as the absence of local enlargement (per RECIST v. 1.1) or marginal failure and was estimated using the Kaplan-Meier method. Between December 2009-March 2020, 39 patients received 25 Gy in 5 fractions to 43 HN paragangliomas, of which 17 were treated in 11 patients with hereditary paraganglioma-pheochromocytoma syndrome. Fifteen targets were post-operative recurrent or residual tumors. There were 27 jugulotympanic tumors, 4 jugular, 1 tympanic, 8 vagal, 5 carotid body, and 2 jugulotympanic or vagal. Median follow-up time was 3.3 years (range 0-11.4 years), and 21 targets had at least 4 years of follow-up. Tumor volume decreased by a median of 37%. Three-year local control was 100%. One patient, known to harbor an SDHD mutation, had 2 out-of-field recurrences within the post-operative bed at 7.1 years. Two patients experienced 2 marginal recurrences within the post-operative bed at 6.1 and 8.4 years: one had an SDHB mutation and developed metastatic disease, and the other did not have genetic testing. The most common grade 1-2 acute toxicities were headache and fatigue; the most common grade 1-2 late toxicities were dysphagia and otalgia. There were no grade >2 acute toxicities. A late grade 3 aspiration event was seen in 1 patient who presented with paralyzed vocal cord requiring multiple medialization laryngoplasties. Within 6 months of SAbR, 18% of symptoms or toxicities improved or resolved; 34% improved or resolved more than 6 months after SAbR. This is the largest series of HN paragangliomas treated with SAbR, detailing a 10-year experience with a 5-fraction regimen that is well-tolerated and achieves excellent local control. Post-SAbR recurrences occurred outside of the radiation field but within the post-operative bed, suggesting that some post-operative patients may benefit from expanded radiation volumes or close surveillance for salvage therapy.