Clinical‐dosimetric relationship between lacrimal gland dose and keratoconjunctivitis sicca in dogs with sinonasal tumors treated with radiation therapy

Abstract

Background Dogs with sinonasal tumor can develop keratoconjunctivitis sicca (KCS) after radiation therapy (RT). In humans, the incidence of xerophtalmia is associated with the mean radiation dose received by the ipsilateral lacrimal gland (LG). Hypothesis/Objectives The eyes receiving a higher mean LG dose are more likely to develop KCS. The aim of the study was to determine a starting threshold dose to use as dose constraint for intensity‐modulated radiation therapy (IMRT). Animals Dogs with nasal tumors treated with RT between August 2013 and December 2016. Methods Case control retrospective study of dogs with sinonasal tumor treated with 42 Gray (Gy) in 10 fractions using IMRT. Dogs were included if development of KCS after RT was documented (cases) or adequate follow‐up information with Schirmer tear test (STT) result for ≥6 months after RT was available (controls). Lacrimal glands were contoured and dose distribution was calculated using the original treatment plan to determine prescribed doses to LGs. Results Twenty‐five dogs were treated with RT and 5 dogs (20%) developed KCS. Fifteen dogs met the inclusion criteria including 5 unilateral KCS and 10 control dogs, resulting in 5 KCS eyes and 25 control eyes. KCS developed at a median of 111 days (84‐122) after 1st RT. The mean LG dose reached using a 4.2 Gy per fraction was 33.08 Gy (range: 23.75‐42.33) for KCS eyes and 10.33 Gy (1.8‐24.77) for control eyes (P < .001). The minimum LG mean dose for developing KCS was 23.75 Gy. No eyes that received a mean LG dose <20 Gy developed KCS versus 5/7 (71%) developed with >20 Gy. Conclusion and Clinical Importance Contouring and applying a dose constraint on LGs should be performed when using IMRT in dogs with sinonasal tumors to reduce the risk of KCS.

Dose‐escalated simultaneously integrated boost radiation protocol fails to result in a survival advantage for sinonasal tumors in dogs

“…A recent study evaluated the relationship between keratoconjunctivitis sicca (KCS) and lacrimal gland dose in dogs treated with 10 × 4.2 Gy, with 33% (5/15) developing KCS after a median of 111 days. The mean lacrimal gland dose was 33.08 Gy for dogs developing KCS versus 10.33 Gy for healthy dogs 34 . The mean dose to the lacrimal gland was 14.72 (±8.65) on the left and 15.10 (±9.91) on the right in our study.…”

“…The mean lacrimal gland dose was 33.08 Gy for dogs developing KCS versus 10.33 Gy for healthy dogs. 34 The mean dose to the lacrimal form plate in previous studies, which was eliminated in their study (and ours) with adequate target dose coverage. 29 The question of whether GTV/CTV was adequate in our study remains unanswered, as mentioned below.…”

Can volumetric modulated arc radiation therapy reduce organ at risk dose in stage 4 sinonasal tumors in dogs treated with boost irradiation?

“…In order to adjust for fraction size and fraction number in the new 10-fraction protocol, the parameter gEUD was then converted to a biologically equivalent gEUD using the linear-quadratic model [18][19][20]. Next, we aimed at fulfilling the following constraints for (peri-) ocular organs at risk: dose volume constraint of D60<15 Gy for the ocular bulb [5], dose volume constraint of Dmean<20 Gy for the lacrimal glands [13], dose volume constraint D2<35.4 Gy for the cornea [12,21]. Further minimization to OAR doses, as done in clinical routine, was undertaken, if this was possible without losing target coverage.…”

“…Lacrimal gland toxicity was examined in 15 dogs treated with 10x4.2 Gy and did not result in keratoconjunctivitis sicca (KCS) if mean dose to the lacrimal gland was <20 Gy, in contrast to 5/7 lacrimal glands with dose >20 Gy. Mean dose was also significantly lower in eyes that did not develop KCS (mean 11.6 Gy) versus eyes that developed KCS later on (mean 30.8 Gy) [13]. Since ocular toxicity up to (unacceptable) loss of an eye was described in earlier studies and since this could have been due to KCS and/or keratitis, we decided to add a separate constraint for the cornea [21].…”

“…A dosevolume constraint of less than 15 Gy to 60% of the OAR volume (D60<15 Gy) for the ocular bulb has been recommended, when treating nasal tumors with a commonly used protocol of 10x4.2 Gy [5,12]. With the same protocol, a threshold dose to avoid keratoconjunctivitis sicca of a mean dose of less than 20 Gy (D mean <20 Gy) was proposed as dose constraint for lacrimal glands [13]. In advanced stage 4 sinonasal tumors, also dose to normal brain could be of concern, since the tumor extends up to the lytic cribriform plate or even shows intracranial extension [14].…”