AUTHOR=Gordon Konstantin , Gulidov Igor , Smyk Daniil , Semenov Alexey , Golubev Kirill , Lemaeva Alyona , Koryakin Sergey , Jumaniyazova Enar , Vishnyakova Polina , Eremina Irina , Fatkhudinov Timur , Kaprin Andrey TITLE=Upright proton therapy for esthesioneuroblastoma: a single-institution experience JOURNAL=Frontiers in Oncology VOLUME=Volume 14 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1348291 DOI=10.3389/fonc.2024.1348291 ISSN=2234-943X ABSTRACT=Aim: This study presents an analysis (efficacy and toxicity) of outcomes in patients with esthesioneuroblastoma after pencil beam proton therapy with a fixed beamline in the upright position. Background: Esthesioneuroblastoma (ENB) is an extremely rare tumor of sinonasal area located in critical proximity to vital structures. Proton therapy (PT) is often considered the optimal radiation treatment for head-and-neck tumors, although of limited availability. Upright PT delivered using fixed pencil beamline and rotating chair is a fairly promising option. Methods: This is a single-center experience describing the outcomes of PT in 14 patients with ENB treated between January 2016 and October 2022; half of the cases had a history of previous irradiation. The therapy was applied using a fixed pencil beamline with 6D-chair for positioning. The median dose was 63 GyRBE (total range 48-70 GyRBE; based on 1.1 RBE multiplier for protons) with 2.0 GyRBE per fraction. The mean gross tumor volume was 109.5 cm 3 (17.1-257.7 cm 3 ). Patient demography, pathology, treatment parameters and toxicity data were analyzed. Radiationinduced reactions were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. Results: The median follow-up time was 28 months. The 1-and 2-year locoregional control rates constituted 100% and 88.9%, respectively; the median duration of local control was 52 months. The 1-and 2-year progression-free survival (PFS) rates constituted 92.9% and 75.0%, respectively; the median PFS duration was 52 months. The 1-and 2-year overall survival (OS) rates constituted 92.9% and 84.4%, respectively. Two patients died of non-cancer-related causes (coronavirus-induced pneumonia) and 1 patient died of tumor progression. All patients tolerated PT well without any treatment gaps. Serious late toxicity reactions included glaucoma in 1 patient and cataract in 2 patients, in over half a year since irradiation. Conclusion: PT with upright design of the unit affords promising outcomes in terms of disease control and toxicity rates in ENB, a sinonasal tumor of complicated localization.