Risk Factors for Radiation-Induced Keratoconjunctivitis Sicca in Dogs Treated with Hypofractionated Intensity-Modulated Radiation Therapy for Intranasal Tumors

Radiation-induced keratoconjunctivitis sicca (KCS) is a significant late complication in dogs receiving radiation therapy for intranasal tumors, particularly with hypofractionated intensity-modulated radiation therapy (IMRT). This retrospective case-control study was performed to identify anatomical...

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Main Authors: Akihiro Ohnishi, Soichirou Takeda, Yoshiki Okada, Manami Tokoro, Saki Kageyama, Yoshiki Itoh, Taketoshi Asanuma
Format: Article
Language:English
Published: MDPI AG 2025-08-01
Series:Animals
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Online Access:https://www.mdpi.com/2076-2615/15/15/2258
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author Akihiro Ohnishi
Soichirou Takeda
Yoshiki Okada
Manami Tokoro
Saki Kageyama
Yoshiki Itoh
Taketoshi Asanuma
author_facet Akihiro Ohnishi
Soichirou Takeda
Yoshiki Okada
Manami Tokoro
Saki Kageyama
Yoshiki Itoh
Taketoshi Asanuma
author_sort Akihiro Ohnishi
collection DOAJ
description Radiation-induced keratoconjunctivitis sicca (KCS) is a significant late complication in dogs receiving radiation therapy for intranasal tumors, particularly with hypofractionated intensity-modulated radiation therapy (IMRT). This retrospective case-control study was performed to identify anatomical and dosimetric risk factors for KCS in 15 canine patients treated with IMRT delivered in 4–6 weekly fractions of 8 Gy. Orbital structures were retrospectively contoured, and dose–volume metrics (D50) were calculated. Receiver operating characteristic (ROC) curve analysis and odds ratios were used to evaluate the associations between radiation dose and KCS development. Six dogs (33%) developed KCS within three months post-treatment. Statistically significant dose differences were observed between affected and unaffected eyes for the eyeball, cornea, and retina. ROC analyses identified dose thresholds predictive of KCS: 13.8 Gy (eyeball), 14.9 Gy (cornea), and 17.0 Gy (retina), with the retina showing the highest odds ratio (28.33). To ensure clinical relevance, KCS was diagnosed based on decreased tear production combined with corneal damage to ensure clinical relevance. This study proposes dose thresholds for ocular structures that may guide treatment planning and reduce the risk of KCS in canine patients undergoing IMRT. Further prospective studies are warranted to validate these thresholds and explore mitigation strategies for high-risk cases.
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spelling doaj-art-930bf61b6b204877ba00cd94fc621fcf2025-08-20T03:36:01ZengMDPI AGAnimals2076-26152025-08-011515225810.3390/ani15152258Risk Factors for Radiation-Induced Keratoconjunctivitis Sicca in Dogs Treated with Hypofractionated Intensity-Modulated Radiation Therapy for Intranasal TumorsAkihiro Ohnishi0Soichirou Takeda1Yoshiki Okada2Manami Tokoro3Saki Kageyama4Yoshiki Itoh5Taketoshi Asanuma6Department of Veterinary Medicine, Faculty of Veterinary Medicine, Okayama University of Science, Imabari 794-0085, JapanDepartment of Veterinary Medicine, Faculty of Veterinary Medicine, Okayama University of Science, Imabari 794-0085, JapanDepartment of Veterinary Medicine, Faculty of Veterinary Medicine, Okayama University of Science, Imabari 794-0085, JapanDepartment of Veterinary Medicine, Faculty of Veterinary Medicine, Okayama University of Science, Imabari 794-0085, JapanDepartment of Veterinary Medicine, Faculty of Veterinary Medicine, Okayama University of Science, Imabari 794-0085, JapanChushikoku Animal Eye Clinic, Fukuyama 729-0111, JapanDepartment of Veterinary Medicine, Faculty of Veterinary Medicine, Okayama University of Science, Imabari 794-0085, JapanRadiation-induced keratoconjunctivitis sicca (KCS) is a significant late complication in dogs receiving radiation therapy for intranasal tumors, particularly with hypofractionated intensity-modulated radiation therapy (IMRT). This retrospective case-control study was performed to identify anatomical and dosimetric risk factors for KCS in 15 canine patients treated with IMRT delivered in 4–6 weekly fractions of 8 Gy. Orbital structures were retrospectively contoured, and dose–volume metrics (D50) were calculated. Receiver operating characteristic (ROC) curve analysis and odds ratios were used to evaluate the associations between radiation dose and KCS development. Six dogs (33%) developed KCS within three months post-treatment. Statistically significant dose differences were observed between affected and unaffected eyes for the eyeball, cornea, and retina. ROC analyses identified dose thresholds predictive of KCS: 13.8 Gy (eyeball), 14.9 Gy (cornea), and 17.0 Gy (retina), with the retina showing the highest odds ratio (28.33). To ensure clinical relevance, KCS was diagnosed based on decreased tear production combined with corneal damage to ensure clinical relevance. This study proposes dose thresholds for ocular structures that may guide treatment planning and reduce the risk of KCS in canine patients undergoing IMRT. Further prospective studies are warranted to validate these thresholds and explore mitigation strategies for high-risk cases.https://www.mdpi.com/2076-2615/15/15/2258keratoconjunctivitis siccacanine intranasal tumorintensity-modulated radiation therapydosimetric analysisradiation-induced ocular toxicitydose threshold
spellingShingle Akihiro Ohnishi
Soichirou Takeda
Yoshiki Okada
Manami Tokoro
Saki Kageyama
Yoshiki Itoh
Taketoshi Asanuma
Risk Factors for Radiation-Induced Keratoconjunctivitis Sicca in Dogs Treated with Hypofractionated Intensity-Modulated Radiation Therapy for Intranasal Tumors
Animals
keratoconjunctivitis sicca
canine intranasal tumor
intensity-modulated radiation therapy
dosimetric analysis
radiation-induced ocular toxicity
dose threshold
title Risk Factors for Radiation-Induced Keratoconjunctivitis Sicca in Dogs Treated with Hypofractionated Intensity-Modulated Radiation Therapy for Intranasal Tumors
title_full Risk Factors for Radiation-Induced Keratoconjunctivitis Sicca in Dogs Treated with Hypofractionated Intensity-Modulated Radiation Therapy for Intranasal Tumors
title_fullStr Risk Factors for Radiation-Induced Keratoconjunctivitis Sicca in Dogs Treated with Hypofractionated Intensity-Modulated Radiation Therapy for Intranasal Tumors
title_full_unstemmed Risk Factors for Radiation-Induced Keratoconjunctivitis Sicca in Dogs Treated with Hypofractionated Intensity-Modulated Radiation Therapy for Intranasal Tumors
title_short Risk Factors for Radiation-Induced Keratoconjunctivitis Sicca in Dogs Treated with Hypofractionated Intensity-Modulated Radiation Therapy for Intranasal Tumors
title_sort risk factors for radiation induced keratoconjunctivitis sicca in dogs treated with hypofractionated intensity modulated radiation therapy for intranasal tumors
topic keratoconjunctivitis sicca
canine intranasal tumor
intensity-modulated radiation therapy
dosimetric analysis
radiation-induced ocular toxicity
dose threshold
url https://www.mdpi.com/2076-2615/15/15/2258
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