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Temozolomide is a novel oral alkylating agent that has schedule-dependent clinical activity in human malignant glioma and metastatic melanoma. Little is known about the efficacy of temozolomide in the treatment of canine solid cancers, where broad range of dosages have been used but no maximally tolerated dose (MTD) had been established. The aim of this this open-label, dose-escalating study was to determine MTD and dose-limiting toxicity (DLT) of a single temozolomide cycle in dogs with advanced solid tumours. Temozolomide was administered as a 5-days course starting at 70 mg/m2 , using escalation of 10 mg/m2 increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Safety evaluation was performed 10 days after dosing. Thirty-three client-owned dogs were enrolled. MTD was established at 150 mg/m2 and the most frequent adverse events (AEs) were hematologic and hepatic, followed by gastrointestinal, with the majority being self-resolving and of mild grade. VCOG grade 3 hepatic toxicity and grade 4 thrombocytopenia were defined as DLTs at 160 mg/m2 . A subcohort of dogs received multiple temozolomide doses on a 4-week cycle and no cumulative toxicity was documented. Conclusions of this study define temozolomide MTD at 150 mg/m2 when given once daily over 5 days. Future trials on the efficacy of temozolomide administered at its MTD are warranted.

Failure rate and site are not well defined in localized sinonasal lymphoma in cats treated with radiotherapy. In this study, we describe (a) failure pattern, (b) outcome, (c) influence of previously reported prognostic variables on the outcome in cats with suspected localized sinonasal lymphoma. In this multi-institutional retrospective study, we included 51 cats treated with single-modality radiotherapy. Cats were irradiated using 10x4.2Gy (n = 32), 12x3Gy (n = 11) or 5x6Gy (n = 8). Regional lymph nodes were prophylactically irradiated in 24/51 cats (47.1%). Twenty-five cats (49.0%) developed progressive disease: progression was local (nasal) in five (9.8%), locoregional (nodal) in two (3.9%), local and locoregional in three (5.9%), systemic in nine (17.6%) and both local and systemic in six cats (11.8%). No cat receiving prophylactic nodal irradiation had progression in the locoregional lymph nodes. The median time to progression was 974 days (95%CI: 283;1666), with 58% and 53% of cats free of progression at 1 and 2 years, respectively. Median overall survival was 922 days (95%CI: 66;1779) with 61% and 49% alive at 1 and 2 years, respectively. Half of the cats that died of relapse/progression (13/26) died within 6 months of treatment, suggesting possible shortcomings of staging, rapid dissemination of disease or sequential lymphomagenesis. None of the prognostic factors evaluated were predictive of outcome (prednisolone use, anaemia, nasopharyngeal involvement, modified canine Adams tumour stage, protocol, total dose). Radiotherapy is an effective treatment for localized sinonasal lymphoma with a long time to progression. However, in one-third of the cats, systemic disease progression occurs soon after radiotherapy.

Image‐guided, intensity modulated radiation therapy (IG‐IMRT) reduces dose to pelvic organs at risk without losing dose coverage to the planning target volume (PTV) and might permit margin reductions potentially resulting in lower toxicity. Appropriate PTV margins have not been established for IG‐IMRT in abdominopelvic tumours in dogs, and herein we explore if our usual PTV 5 mm margin can be reduced further. Datasets from dogs that underwent IG‐IMRT for non‐genitourinary abdominopelvic neoplasia with 5 mm‐PTV expansion were included in this retrospective virtual study. The clinical target volumes and organs at risk (OAR) colon, rectum, spinal cord were adapted to each co‐registered cone‐beam computed tomography (CBCT) used for positioning. New treatment plans were generated and smaller PTV margins of 3 mm and 4 mm evaluated with respect to adequate dose coverage and normal tissue complication probability (NTCP) of OAR. Ten dogs with a total of 70 CBCTs were included. Doses to the OAR of each CBCT deviated mildly from the originally planned doses. In some plans, insufficient build‐up of the high dose‐area at the body surface was found due to inadequate or missing bolus placement. Overall, the margin reduction to 4 mm or 3 mm did not impair dose coverage and led to significantly lower NTCP in all OAR except for spinal cord delayed myelopathy. However, overall NTCP for spinal cord was very low (