Clinical-dosimetric relationship between lacrimal gland dose and ocular toxicity after intensity-modulated radiotherapy for sinonasal tumours

Objective:

To characterise the relationship between lacrimal gland dose and ocular toxicity among patients treated by intensity-modulated radiotherapy (IMRT) for sinonasal tumours.

Methods:

40 patients with cancers involving the nasal cavity and paranasal sinuses were treated with IMRT to a median dose of 66.0 Gy. Toxicity was scored using the Radiation Therapy Oncology Group morbidity criteria based on conjunctivitis, corneal ulceration and keratitis. The paired lacrimal glands were contoured as organs at risk, and the mean dose, maximum dose, V₁₀, V₂₀ and V₃₀ were determined. Statistical analysis was performed using logistic regression and the Akaike information criterion (AIC).

Results:

The maximum and mean dose to the ipsilateral lacrimal gland were 19.2 Gy (range, 1.4–75.4 Gy) and 14.5 Gy (range, 11.1–67.8 Gy), respectively. The mean V₁₀, V₂₀ and V₃₀ values were 50%, 25% and 17%, respectively. The incidence of acute and late Grade 3+ toxicities was 23% and 19%, respectively. Based on logistic regression and AIC, the maximum dose to the ipsilateral lacrimal gland was identified as a more significant predictor of acute toxicity (AIC, 53.89) and late toxicity (AIC, 32.94) than the mean dose (AIC, 56.13 and 33.83, respectively). The V₂₀ was identified as the most significant predictor of late toxicity (AIC, 26.81).

Conclusion:

A dose–response relationship between maximum dose to the lacrimal gland and ocular toxicity was established. Our data suggesting a threshold relationship may be useful in establishing dosimetric guidelines for IMRT planning that may decrease the risk of acute and late lacrimal toxicities in the future.

Advances in knowledge:

A threshold relationship between radiation dose to the lacrimal gland and ocular toxicity was demonstrated, which may aid in treatment planning and reducing the morbidity of radiotherapy for sinonasal tumours.The majority of tear fluid is produced by the paired lacrimal glands, which are located in the superior temporal quadrants of the orbits. Each bilobed lacrimal gland is anatomically divided into the larger orbital and smaller palpebral parts, both of which contain excretory components consisting of ductal cells that mechanically assist in the secretion of tears on to the ocular surface by modifying the fluid secreted by acinar and myoepithelial cells [1]. The glands of Krause and Wolfring are smaller accessory lacrimal glands located in the superior fornix that secrete additional tear fluid. Functionally, the lacrimal gland is responsible for the secretion of fluid that continually moistens, lubricates and protects the surface of the eye.An increasingly recognised complication of radiotherapy to the periorbital region is dry eye syndrome, defined by the International Dry Eye WorkShop as a “multi-factorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface accompanied by increased osmolarity of the tear film and inflammation of the ocular surface” [2]. Although previous research has suggested a variable association between radiation dose to the lacrimal gland and incidence of dry eye syndrome [3–11], the exact nature of this dose–response relationship remains undetermined. This is particularly relevant given the ability of intensity-modulated radiotherapy (IMRT) to limit dose to normal structures designated as organs at risk (OARs). The aim of the present study was to characterise this relationship between various dosimetric parameters related to the lacrimal gland and ocular toxicity in patients treated with IMRT for sinonasal tumours.