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

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 GyRBE 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.

Long Term Outcome and Quality of Life of Intracranial Meningioma Patients Treated with Pencil Beam Scanning Proton Therapy

“…It must be noted that almost all of our patients were referred by other radiation oncology departments due to the complexity of the case. Taking into account the mostly complicated location and tumor geometry of our patients and the relatively large average PTV (102.3 cm 3 ), the high-grade toxicity rate is acceptable and comparable with the recently published results of the high-risk cohort of RTOG 0539 [54].…”

“…As a result of the rare occurrence of high-grade visual toxicity, we have modified our dose constraints to apply a strict maximum dose point of 50 Gy (RBE) to both the optic nerves and chiasma. We have assessed the clinical and therapeutic factors associated with visual toxicity in a larger cohort of patients receiving at least 45 Gy (RBE) on the optic apparatus [ 54 ]. In this analysis, a rate of 2.8% of high-grade radiation-induced optic neuropathy was detected.…”

A Rare Case of Unilateral Auditory Neuropathy Induced by Proton Therapy

“…Surprisingly, optic toxicities highlighted on visually evoked potentials increase with the distance of the target irradiated area. These results confirm uncertainties regarding the relative biological effectiveness of proton therapy, particularly due to the more heterogeneous linear energy transfer, especially in areas near the target volumes [16,17].…”

Possible association of dose rate and the development of late visual toxicity for patients with intracranial tumours treated with pencil beam scanned proton therapy

“…The strong limitation of this study is the size of the data set. Fortunately, the incidence of optic apparatus toxicities is low in our patients with intracranial disease [ 11 , 12 ]. Therefore, the possibility to acquire a sufficiently large data set to prove or disprove the hypothesis will require a multi-institutional collaboration, similar as suggested in the European Particle Therapy Toxicity Workshop (Leuven, Belgium, 04.10.2022).…”

“…Rare, unexpected severe toxicities can occur in patients following proton therapy [ 11 , 12 ]. A dedicated workshop on these remarkable toxicities was organized by the European Particle Therapy Network in 2022 ( https://www.estro.org/Science/EPTN ).…”