Ocular Sparing Using Intensity Modulated Radiation Therapy (IMRT) in a Canine Model of Spontaneous Sinonasal Cancer: Proof–of–Principle of Conformal Avoidance

Abstract

Abstract: : Purpose: Safe and effective external beam radiotherapy is challenging when tumor is close to, or surrounds, normal critically sensitive structures such as the eye, especially if the tumor margins are ill–defined. Rather than conventionally conforming the radiation dose to the size and shape of the tumor, conformal avoidance "carves out" dose–limiting structures (eye, brain), and gives a full–dose to arbitrarily shaped treatment volumes representing "everything in between". IMRT, the newest and most advanced form of conformal avoidance, can achieve almost any dose distribution, regardless of the shape of the target, and can abruptly vary doses at specified borders. We used a canine model of naturally occurring sinonasal cancer to evaluate the potential of IMRT to reduce acute and late ocular toxicity. Methods: 10 client–owned dogs with sinonasal cancer were treated with IMRT using helical tomotherapy (HT) and/or dynamic multileaf collimator (DMLC) delivery. For each dog, treatment plans were devised using HT and DMLC that achieved the target dose to the primary tumor volume and limited critical normal tissues to prescribed dosed–volume constraints (15 Gy to no > 50% of ocular volume). Ocular toxicity was prospectively evaluated, and compared to that in 36 comparable historical control dogs treated with conventional two–dimensional (2D) radiotherapy. Results: Median follow–up for IMRT–treated dogs was 10.8 months (vs 8.1 months for 2D–treated dogs), allowing adequate time to assess acute (< 3 mo) and late (> 3 mo) ocular toxicity in this model. No dog receiving IMRT experienced clinically significant ophthalmic complications involving the globe, whereas 56% of 2D–treated dogs lost vision in 1 or both eyes. Similar marked differences in ocular morbidity were present between the 2 groups in the frequency of conjunctivitis, blepharitis, keratitis, corneal ulceration, KCS, anterior uveitis, cataracts and radiation retinopathy. Conclusions: Compared with conventional techniques, IMRT reduced the dose delivered to the eyes, resulting in bilateral ocular sparing in this model. These data provide proof–of–principle that conformal avoidance radiotherapy can be delivered through the high conformity of IMRT, resulting in improved clinical outcome with respect to toxicity.

Keywords: radiation therapy • tumors • oncology