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

Abstract

The prognosis for canine sinonasal tumors remains rather poor despite definitive‐intent radiotherapy (RT). Theoretical calculations predicted improved outcomes with simultaneously integrated boost (SIB) protocols. With the hypothesis of clinically detectable differences in outcome between groups, our retrospective study evaluated prognostic variables and outcome in dogs treated with regular versus SIB RT. Dogs with sinonasal tumors treated with either a regular (10 × 4.2 Gy) or new SIB protocol (10 × 4.83 Gy to macroscopic tumor) were included. Information regarding signalment, tumor stage, type, clinical signs, radiation toxicity, response, and outcome was collected. Forty‐nine dogs were included: 27 treated regularly and 22 treated with SIB RT. A total of 69.4% showed epistaxis, 6.1% showed epileptic seizures, 46.9% showed stage IV tumors, and 6.1% showed lymph node metastases. Early toxicity was mostly mild. Late grade 1 skin toxicity (alopecia/leucotrichia) was seen in 72.1% of dogs, and a possible grade 3 ocular toxicity (blindness) was seen in one dog. Complete/partial resolution of clinical signs was seen in 95.9% of patients as best clinical response and partial remission was seen as best imaging response in 34.7%. The median progression‐free survival (PFS) was 274 days (95% CI: 117–383) for regular and 300 days (95% CI: 143–451) for SIB RT, which was not significantly different (P = 0.42). Similarly, the median overall survival (OS) was 348 days (95% CI: 121–500) for regular and 381 days (95% CI: 295–634) for the SIB RT (P = 0.18). Stratified by protocol, the hazard ratio of stage IV versus stage I–III tumors was 2.29 (95% CI: 1.156‐4.551, P = 0.02) for OS but not PFS. All dogs showed acceptable toxicity. In contrast to theoretical predictions, however, we could not show a statistically significant better outcome with the new protocol.

Relative tumor volume has prognostic relevance in canine sinonasal tumors treated with radiation therapy: A retrospective study

“…Whereas a theoretical study predicted an increased tumor control probability with a boost approach applied in 10 fractions [17], an earlier study was not able to see a positive effect of the boost protocol on TTP [7]. Also in a recent (although not randomized) study we were not able to detect a benefit of increased dose (via SIB) in dogs with sinonasal tumors [8]. While there is no randomized prospective clinical trial evaluating different treatment protocols in sinonasal tumors in dogs, most resulted in similar median survival times of 6.7 to 19.7 months after definitive-intent, finely fractionated radiation therapy [4,16].…”

“…Datasets from a previous study were evaluated for this single institution retrospective cohort study [8]. The mentioned study was non-randomized and included dogs between June 2014 and May 2020 with non-lymphomatous, sinonasal tumors treated with either our regular radiation therapy protocol (10x4.2 Gy) or with a simultaneously-integrated boost protocol (SIB; GTV boosted to 10x4.83 Gy) and was approved by the Animal Ethics Council of the Canton of Zurich, Switzerland (permit number: ZH075/17).…”

“…Treatment set-up (rigid bite-block system and vacuum cushion), radiation equipment (Varian Clinac iX 6MV linear accelerator and ECLIPSE planning software version 10.0.28 or 15.1.25 (Varian Oncology Systems, Palo Alto, USA)), contouring of target volumes and organs at risk, and treatment planning was performed as described by Meier at al. [8]. In short, the GTV included the contrast enhancing mass seen in the co-registered contrast-enhanced CT images, as well as the lytic bone visualized in the bone window.…”

“…Dose maxima up to 107% of the respective dose levels in any volume and dose maxima of >110% in a small volume (<2%) within the PTV were allowed. Dose to target volumes as recommended by Rohrer Bley et al and Keyerleber et al [9,10] was described in the original study [8].…”

Treatment of intracranial neoplasia in dogs using higher doses: A randomized controlled trial comparing a boosted to a conventional radiation protocol

“… 23 These improvements are based predominantly on refined technology, and investigating its use on brain tumors is warranted. 23 , 24 , 25 …”