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Long-term prediction of radiation-induced optic neuropathy: A mixed-effects analysis of visual field kinetics following proton therapy.

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Title: Long-term prediction of radiation-induced optic neuropathy: A mixed-effects analysis of visual field kinetics following proton therapy.
Authors: Pham, Thao-Nguyen1 (AUTHOR) pham.thaonguyen4497@gmail.com, Mathis, Thibaud2 (AUTHOR), Azemar, Nathan3 (AUTHOR), Vela, Anthony4 (AUTHOR), Quintyn, Jean-Claude5 (AUTHOR), Thariat, Juliette1,3 (AUTHOR) jthariat@gmail.com
Source: Radiotherapy & Oncology. Dec2025, Vol. 213, pN.PAG-N.PAG. 1p.
Subjects: Proton therapy, Prediction models, Optic nerve diseases, Longitudinal method, Visual acuity, Disease risk factors, Multilevel models, Medical dosimetry
Abstract: • RION is a delayed complication of RT, trackable via visual field sensitivity loss. • Visual sensitivity declined over time after radiotherapy, best captured by a quadratic model. • Older age and larger target volumes predicted faster visual field deterioration. • Chiasma V40 (≥40 Gy) improved model performance for predicting field loss. • Simulated risk of grade 2+ RION increased from 4.6 % at 2 years to 28.3 % at 5 years. Radiation-induced optic neuropathy (RION) is a rare but serious complication of radiotherapy, leading to progressive vision loss. The temporal dynamics of RION are poorly understood, limiting effective monitoring and intervention. We developed a predictive mixed-effects model of visual field deterioration, a sensitive surrogate marker for clinically-reported RION, by integrating longitudinal clinical and dosimetric data, to anticipate long-term visual outcomes. Out of a prospective database of 238 patients, 179 eyes from 105 patients treated with pencil beam scanning proton therapy were included. All selected eyes had no significant visual field deficit at baseline, defined as a mean visual sensitivity loss better than −6 dB. Baseline clinical characteristics, detailed dosimetric data, and longitudinal visual field assessments were collected. Temporal changes in mean visual sensitivity were analyzed using feature selection through random forest models and linear regression. A nonlinear mixed-effects model was then developed to predict the trajectory of visual field deterioration over time. Visual field deterioration progressed significantly over time, with a quadratic model best capturing the kinetics. Mean sensitivity loss accelerated with increasing age and clinical target volume. Incorporating the full dose-volume histogram, the volume of the optic chiasma received at least 40 Gy (V 40 /chiasma), improved model performance. Simulation based on this model showed that the probability of RION increased sharply over time: 4.6 % at 2 years, and 28.3 % at 5 years. This model confirms and expands upon prior work by showing that clinical factors can outweigh dosimetric ones in predicting RION progression. Our model was capable of predicting long-term visual outcomes even in patients with limited follow-up. [ABSTRACT FROM AUTHOR]
Copyright of Radiotherapy & Oncology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
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  Data: Long-term prediction of radiation-induced optic neuropathy: A mixed-effects analysis of visual field kinetics following proton therapy.
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  Data: <searchLink fieldCode="AR" term="%22Pham%2C+Thao-Nguyen%22">Pham, Thao-Nguyen</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> pham.thaonguyen4497@gmail.com</i><br /><searchLink fieldCode="AR" term="%22Mathis%2C+Thibaud%22">Mathis, Thibaud</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Azemar%2C+Nathan%22">Azemar, Nathan</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vela%2C+Anthony%22">Vela, Anthony</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Quintyn%2C+Jean-Claude%22">Quintyn, Jean-Claude</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Thariat%2C+Juliette%22">Thariat, Juliette</searchLink><relatesTo>1,3</relatesTo> (AUTHOR)<i> jthariat@gmail.com</i>
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  Data: <searchLink fieldCode="JN" term="%22Radiotherapy+%26+Oncology%22">Radiotherapy & Oncology</searchLink>. Dec2025, Vol. 213, pN.PAG-N.PAG. 1p.
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– Name: Abstract
  Label: Abstract
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  Data: • RION is a delayed complication of RT, trackable via visual field sensitivity loss. • Visual sensitivity declined over time after radiotherapy, best captured by a quadratic model. • Older age and larger target volumes predicted faster visual field deterioration. • Chiasma V40 (≥40 Gy) improved model performance for predicting field loss. • Simulated risk of grade 2+ RION increased from 4.6 % at 2 years to 28.3 % at 5 years. Radiation-induced optic neuropathy (RION) is a rare but serious complication of radiotherapy, leading to progressive vision loss. The temporal dynamics of RION are poorly understood, limiting effective monitoring and intervention. We developed a predictive mixed-effects model of visual field deterioration, a sensitive surrogate marker for clinically-reported RION, by integrating longitudinal clinical and dosimetric data, to anticipate long-term visual outcomes. Out of a prospective database of 238 patients, 179 eyes from 105 patients treated with pencil beam scanning proton therapy were included. All selected eyes had no significant visual field deficit at baseline, defined as a mean visual sensitivity loss better than −6 dB. Baseline clinical characteristics, detailed dosimetric data, and longitudinal visual field assessments were collected. Temporal changes in mean visual sensitivity were analyzed using feature selection through random forest models and linear regression. A nonlinear mixed-effects model was then developed to predict the trajectory of visual field deterioration over time. Visual field deterioration progressed significantly over time, with a quadratic model best capturing the kinetics. Mean sensitivity loss accelerated with increasing age and clinical target volume. Incorporating the full dose-volume histogram, the volume of the optic chiasma received at least 40 Gy (V 40 /chiasma), improved model performance. Simulation based on this model showed that the probability of RION increased sharply over time: 4.6 % at 2 years, and 28.3 % at 5 years. This model confirms and expands upon prior work by showing that clinical factors can outweigh dosimetric ones in predicting RION progression. Our model was capable of predicting long-term visual outcomes even in patients with limited follow-up. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Radiotherapy & Oncology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.radonc.2025.111205
    Languages:
      – Code: eng
        Text: English
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        PageCount: 1
        StartPage: N.PAG
    Subjects:
      – SubjectFull: Proton therapy
        Type: general
      – SubjectFull: Prediction models
        Type: general
      – SubjectFull: Optic nerve diseases
        Type: general
      – SubjectFull: Longitudinal method
        Type: general
      – SubjectFull: Visual acuity
        Type: general
      – SubjectFull: Disease risk factors
        Type: general
      – SubjectFull: Multilevel models
        Type: general
      – SubjectFull: Medical dosimetry
        Type: general
    Titles:
      – TitleFull: Long-term prediction of radiation-induced optic neuropathy: A mixed-effects analysis of visual field kinetics following proton therapy.
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            NameFull: Pham, Thao-Nguyen
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            NameFull: Mathis, Thibaud
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            NameFull: Azemar, Nathan
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            NameFull: Quintyn, Jean-Claude
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            – D: 01
              M: 12
              Text: Dec2025
              Type: published
              Y: 2025
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              Value: 01678140
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              Value: 213
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