Proof of principle of ocular sparing in dogs with sinonasal tumors treated with intensity-modulated radiation therapy

Abstract

Intensity-modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared with a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT-treated and 2D-treated dogs was 420 and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared with historical controls treated with 2D-RT.

Figure 1

Typical image of the tomotherapy operator station showing alignment of the MVCT (top left) with the original planning kVCT (bottom left) of a dog treated with helical tomotherapy. In the correlated image (large image, right) the yellow squares represent the MVCT image obtained prior to treatment and the grey areas represent the planning kVCT. The round yellow and green contours represent the right and left eyes, respectively. The blue contour is the rostral brain and the red contour is the PTV.

Figure 2

Typical IMRT isodose distributions and dose volume histogram are shown. The IMRT plan shown was designed using helical tomotherapy treatment planning software. The red line represents the PTV, and yellow, lime green and blue lines represent the left eye, right eye and brain, respectively.

Figure 3

Kaplan-Meier survival curves for the IMRT and control group of dogs and progression free survival curve for the IMRT cohort of dogs. The median PFS and median survival time (MST) for dogs receiving IMRT were 194 and 420 days, respectively. The MST for dogs after 2D radiation therapy was 411 days. Vertical hatch marks denote censorings.