Assessment of Radiation-Induced Optic Neuropathy in a Multi-Institutional Cohort of Chordoma and Chondrosarcoma Patients Treated with Proton Therapy

SIMPLE SUMMARY: Proton therapy is an effective therapeutic option for the treatment of skull-base tumors that require high radiation doses to be controlled. On rare occasions, patients suffer from radiation-induced optic neuropathy (RION) to the detriment of their post-treatment quality-of-life. We have collected multi-institutional data of 289 skull-base patients having received high doses to the optic apparatus from proton therapy or proton–photon mixed treatments and have observed a RION incidence rate (all grades) of 4.2% (12). We have furthermore confirmed older age and hypertension as risk factors for the onset of this side effect, with tumor involvement or its proximity to the optic apparatus and repeated surgical procedures showing moderate association. Our findings were consolidated into a NTCP model that can support pre-treatment patient segmentation into risk groups and the planning of necessary treatment countermeasures. However, further data and validation are necessary to confirm validity of the model. ABSTRACT: Radiation-induced optic neuropathy (RION) is a rare side effect following radiation therapy involving the optic structures whose onset is, due to the low amount of available data, challenging to predict. We have analyzed a multi-institutional cohort including 289 skull-base cancer patients treated with proton therapy who all received >45 Gy(RBE) to the optic apparatus. An overall incidence rate of 4.2% (12) was observed, with chordoma patients being at higher risk (5.8%) than chondrosarcoma patients (3.2%). Older age and arterial hypertension, tumor involvement, and repeated surgeries (>3) were found to be associated with RION. Based on bootstrapping and cross-validation, a NTCP model based on age and hypertension was determined to be the most robust, showing good classification ability (AUC-ROC 0.77) and calibration on our dataset. We suggest the application of this model with a threshold of 6% to segment patients into low and high-risk groups before treatment planning. However, further data and external validation are warranted before clinical application.