Given its tendency to abut and infiltrate critical skull base anatomy, pediatric esthesioneuroblastoma (EN) presents a local control challenge, particularly given the high dose of radiation historically utilized in adult patients and the sensitivity of developing pediatric normal tissue. The purpose of this study was to report the outcomes of pediatric EN treated with proton radiotherapy. Using an IRB-approved, single institutional prospective outcomes registry, we analyzed disease control and toxicity in pediatric patients with non-metastatic EN treated with a multimodality approach, including proton radiotherapy, between March 2008 and March 2022. Of the 15 patients, 8 were female, and 7 were male. The median age was 16 years (range, 3-21 years). Patients were Kadish stage B (n = 2), C (n = 8), and D (n = 5) and Hyams low-grade (n = 9), high-grade (n = 5), and not specified (n = 1). Six patients had intracranial involvement, 4 had cranial nerve deficits, and 4 had positive cervical lymph nodes. Prior to radiation, 2 patients had a subtotal resection and 13 had a gross total resection via either endoscopic (n = 8) or craniofacial (n = 7) approaches. Two patients underwent neck dissection (one unilateral and one bilateral). A total of 11 patients received chemotherapy before (n = 5), concurrent (n = 4) with radiation, or both (n = 2). The median total radiation dose delivered to the primary site was 66 Gy/CGE (range, 59.4-72.8 Gy/CGE) for patients with gross disease and 54 Gy/CGE (range, 54-74.4 Gy/CGE) for patients with microscopic disease. With a median follow-up of 4.8 years (range, 0.1-12.2 years), both the 5-year disease free and overall survival rates were 86%. There were no local or regional recurrences. Two patients with Kadish D, high grade tumors developed vertebral metastases and died with disease. Serious acute toxicity included 2 patients requiring a temporary feeding tube for oral mucositis/dysphagia. Serious late toxicity included symptomatic retinopathy (n = 3), major reconstructive surgery (n = 2), cataracts requiring intervention (n = 2), chronic otitis media (n = 2), chronic keratoconjunctivitis (n = 2), hypothyroidism (n = 2), and in-field basal cell skin cancer (n = 1). A multimodality approach to pediatric EN results in excellent local control. Despite the use of moderate dose proton therapy, serious radiation toxicity was observed and thus select patients may benefit from further dose and target volume reduction. Longer follow-up and comparative data from modern photon series are necessary to fully characterize any relative advantage of proton therapy.
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