In dogs with sinonasal cancer, lymph node (LN) metastasis can affect prognosis and treatment. Hence, despite uncertain cost effectiveness, staging often includes regional LN cytology. This retrospective study evaluates how well physical examination and computed tomography (CT) perform as surrogates for regional LN cytology in dogs with sinonasal carcinomas and sarcomas. Dogs were included if their staging included physical examination, CT, and cytology of at least one regional LN. Physical examination parameters and tomographic appearance of the LNs were compared with cytologic descriptions to enable calculation of sensitivity and specificity, plus positive and negative predictive values (PPV and NPV). A total of 150 dogs were included. Fourteen dogs had cytologically confirmed LN metastasis; all 14 had carcinomas. Metastases were detected ipsilaterally in 12 dogs and bilaterally in two dogs. The sensitivity, specificity, PPV, and NPV of LN palpation alone were 71.4, 64, 17, and 96%, respectively; for CT alone, these were 100, 46.3, 16.1, and 100%; and for the combination of palpation and CT, these were 100, 59.5, 23.8, and 100%. Based on these results, detection of a palpably and tomographically normal LN in a dog with sinonasal carcinoma or sarcoma appears sufficient to confidently rule out cytologically detectable metastasis.

BACKGROUND:Idiopathic cystitis (IC) accounts for the majority of lower urinary tract (LUT) disease in cats and is characterized by recurrent clinical signs or urethral obstruction (UO), presenting ongoing challenges in clinical management. HYPOTHESIS/OBJECTIVES:Determine the feasibility of using single-fraction low-dose radiotherapy (RT) to reduce rate of re-obstruction and recurrence of clinical signs in cats with feline idiopathic cystitis. ANIMALS:Fifteen client-owned male cats with recent history of severe IC and historical UO that remained symptomatic despite environmental modification and pharmacological management. METHODS:An IACUC-approved, single-arm, single-institution, prospective clinical trial was conducted to evaluate the clinical effects of irradiating the entire LUT with a single 6 Gy fraction. RESULTS:One cat was immediately lost to follow-up, and 1 died 516 days after RT. The remaining 13 cats were alive at the time of data analysis, with a median follow-up of 548 (range 70-1307) days. All but 1 had symptomatic improvement. Six had a single flare-up of signs of IC at a median of 243 days after RT (range 4-395 days). After RT, 1 cat had a recurrent UO, which occurred at 11 months and was managed surgically. CONCLUSIONS AND CLINICAL IMPORTANCE:In this cohort of severely affected cats, >90% had apparent improvement in clinical signs after RT, with no documented adverse effects, demonstrating that in addition to environmental modification, RT is a promising tool for managing IC in male cats.

Radiation-associated pain (RAP) after head and neck cancer treatment often results in significant discomfort, yet the mechanisms underlying this pain remain poorly understood. Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8) channels, known to mediate cold sensation, have been implicated in RAP. Previous studies suggested that inhibition of TRPM8 might offer a therapeutic approach for alleviating radiation-induced pain. We tested the effects of PBMC, a small molecule inhibitor of TRPM8, on radiation-induced glossitis and associated pain behaviors in C57BL/6J mice following tongue irradiation. We evaluated the impact of phenylethyl(2-aminoethyl)(4-(benzyloxy)-3-methoxybenzyl)carbamate (PBMC) on weight loss, burrowing, grooming behavior, and nest building. Additionally, mRNA expression of TRPM8 and other relevant ion channels was assessed in the trigeminal ganglion (TG) using qRT-PCR and in situ hybridization (ISH). Irradiated mice exhibited significant glossitis, weight loss, and altered behaviors, including impaired burrowing and grooming. PBMC treatment provided no measurable protection against glossitis and only weakly mitigated weight loss and abnormal burrowing behavior. Exposure to radiation led to downregulation of TRPM8 expression in the TG, contrasting with previous findings of upregulation. Interestingly, female mice showed greater susceptibility to RAP than males, highlighting a sex-dependent response. Our findings suggest that TRPM8 inhibition with PBMC does not alleviate radiation-induced pain or glossitis in the C57BL/6J murine model. The observed downregulation of TRPM8 expression challenges prior assumptions, and our results suggest that compensatory mechanisms or model-specific factors may contribute to the failure of PBMC to impact pain outcomes. Future studies incorporating genetic models and evaluating protein expression are necessary to better understand the role of TRPM8 in radiation-induced pain and to explore more effective therapeutic strategies.

Intranasal respiratory epithelial adenomatoid hamartomas (REAHs) and chondro-osseous respiratory epithelial adenomatoid hamartomas (COREAHs) are rare in dogs. Affected dogs are often treated surgically but published outcomes data are scant. Here, 3 cases are described. An 11-year-old Siberian Husky with advanced REAH underwent stereotactic radiosurgery (17 Gy); had no acute radiotoxicity and experienced short-lived clinical improvement before loss to follow-up. An 8-year-old mixed breed dog with advanced COREAH causing cribriform lysis received stereotactic body radiotherapy (SBRT) (30 Gy in 3 fractions); had no acute radiotoxicity, a strong partial response to treatment, and was euthanized 26 months after irradiation. A 5-year-old Border Collie with sinonasal COREAH and cribriform lysis was treated with 3D conformal radiotherapy (45 Gy in 12 fractions); the dog had stable disease for 18 months with ongoing follow up at the time of publication. These experiences provide evidence that REAH/COREAH could be radioresponsive with potential for prolonged survival.

Radiation therapy (RT) has emerged as a promising non-surgical approach for treating canine adrenal tumours. This multi-institutional, retrospective study describes clinical outcomes for 21 dogs having been prescribed a course of hypofractionated image-guided intensity-modulated RT (IMRT) entailing delivery of 25-35 Gy total in 5 fractions given over 5-15 days for an adrenal tumour. Diagnoses were based on imaging (abdominal ultrasound or computed tomography) and biochemical testing. All dogs had unilateral or bilateral irregular adrenal masses with evidence of vessel compression or invasion. Adrenal masses were incidentally identified in 11 dogs. The clinical diagnoses included pheochromocytoma (n = 13, 61.9%), adrenocortical adenocarcinoma (n = 2, 9.5%) and unspecified (n = 6, 28.6%). Among the 16 dogs with available follow-up imaging, the rates of partial response and stable disease were 37.5% (6/16) and 62.5% (10/16), respectively. Mild gastrointestinal side effects related to RT were reported in four dogs (19%). Early death that could have been attributable to tumour or complications of treatment occurred in two dogs (9.5%) at 21 and 52 days post-RT; one presenting with acute vomiting, and the other presenting with vomiting, tremors, and shock before death. Of the 15 deceased dogs, 4 (26.7%) died due to tumour-related causes and 11 died due to unknown (n = 2) or unrelated (n = 9) causes. The median overall survival time was 377 days, with a median follow-up time of 458 days for censored patients (n = 6). The one- and two-year survival rates were 59.4% and 34.7%, respectively. These data build upon prior published reports, demonstrating that RT can be associated with prolonged survival in dogs with adrenal tumours. Hypofractionated IMRT appears to offer a potential survival benefit even in dogs with major vessel invasion or comorbidities. Future research should focus on identifying risk factors for early death and determining which patient populations are most likely to benefit from RT.

Supplemental Figure 2. Pre- and post-LITT images of patient gliomas

The goal of this prospective, single-arm pilot study was to assess tolerability and clinical benefit for cats with histologically confirmed lymphocytic lymphoma/chronic inflammatory enteropathy complex (FLL/CIE) treated with low-dose abdominal cavity radiation therapy (RT; 8 Gy total dose administered in four 2 Gy fractions). No cats received steroids or chemotherapy prior to RT. Fourteen cats were enrolled and 13 completed the study. Eight cats had enteropathy-associated T cell lymphoma type II (FLL), and 6 cats had CIE (lymphoplasmacytic enteritis, 3 with concurrent eosinophilic enteritis). Nine of 13 cats (69%) had transient worsening of GI signs in the 1-3 weeks after RT, presumed secondary to RT and/or stress of travel/anaesthesia. Eight were managed as outpatients and one cat died after being syringe fed by the owner. Nine of the 12 remaining cats (75%; N = 6 with FLL and N = 3 with CIE) had a clinical benefit to treatment (resolution or improvement of GI signs as defined by owner surveys and body weight) that was sustained for > 340 days. Three cats experienced presumed or confirmed disease progression at 341, 465 and 449 days after RT and were treated with steroids. Six cats remained asymptomatic (N = 5) or stable (N = 1) at a median of 635 days after RT (range, 447-1014 days). Low-dose abdominal cavity RT could be considered for cats that cannot tolerate steroids and/or for owners that cannot pill cats routinely. Further optimisation of the protocol and use of RT as a rescue treatment for cats that fail traditional therapies are considerations for further study.

Hypofractionated radiotherapy (hRT) is often used to treat dogs with oral malignant melanoma (OMM); however, there is no consensus as to whether clinically uninvolved regional lymph nodes should be prophylactically irradiated. The objective of this retrospective study is to compare outcomes for dogs with OMM treated with hRT+/- elective nodal irradiation (ENI). Dogs with nonmetastatic OMM undergoing hRT+/- ENI with a prescription of ≥ 30 Gy were included. Survival statistics were evaluated with Kaplan-Meier curves and log-rank testing. Univariable and multivariable Cox proportional hazard models were used to assess how survival was impacted by the use of ENI, WHO T-stage, mitotic count, RT technique, and use of Oncept melanoma vaccine. Data from four institutions and 100 dogs (80 with ENI and 20 without) were included. In the ENI group, nodal and distant metastases were documented in 4 and 30 dogs, respectively. In the non-ENI group, nodal and distant metastases were documented in 6 and 4 dogs, respectively. There was no significant difference in the 1-year nodal or distant progression-free intervals (p = 0.174, and 0.563, respectively). The only variable maintaining significance on multivariable analysis was T-stage (overall progression-free survival, HR 1.393, p = 0.006; overall survival time, HR 1.426, p = 0.005; distant progression-free interval, HR 1.521, p = 0.033). ENI did not measurably alter the oncologic outcomes in this study population. Results should be interpreted cautiously given the lack of standardised staging/restaging and the heterogenous nature of this clinical population. Future investigations are needed to clarify the role of ENI in the treatment of canine OMM.

Supplemental Figure 1. Surgical workflow for tumor biopsy and placement of minibolt

Oxygen microbubbles (OMB) are lipid-shelled ultrasound contrast agents with an oxygen gas core that show promise as theranostic agents for diagnostic imaging and enhancing radiotherapy efficacy in preclinical rodent models. By improving oxygenation in hypoxic tumor regions, OMBs may increase radiosensitivity. However, their safety, tolerability, and potential to act as vascular imaging contrast agents have yet to be assessed in larger animals. In this study, four healthy beagle dogs received intravenous OMBs at escalating doses 1, 10, and 100 μl/kg at 1-week intervals. Over a 4-week observation period, key physiological parameters, including temperature, pulse, and respiration, were monitored alongside complete blood counts, blood biochemistry, coagulation panels, and urinalysis. Additionally, the ability of OMBs to enhance contrast during kidney ultrasound imaging was evaluated, and pharmacokinetic parameters were estimated. Across all doses, OMB administration was well tolerated, with no clinically significant changes in vital signs or laboratory values. Ultrasound imaging revealed dose-dependent increases in renal contrast enhancement. Pharmacokinetic analyses confirmed that higher doses prolonged contrast enhancement and improved image quality. This study provides an initial safety and diagnostic benchmark for OMB administration in dogs, laying the groundwork for future investigations into their theranostic potential.

A common complication of therapeutic radiotherapy for head and neck cancer is the development of severe pain. The biological mechanisms underlying acute orofacial radiation-associated pain (RAP) are unknown but may involve cold-sensing and cold-signaling pathways. A key cold receptor is TRPM8 (Transient Receptor Potential Melastatin family member 8), whose activation might be mediated by the neurotrophic factor artemin (ARTN) acting on its primary receptor, GFRα3. To test the hypothesis that radiation triggers release of ARTN, which results in activation of TRPM8 to cause RAP, we performed tongue-irradiation in mice that had been treated with either monoclonal anti-ARTN-neutralizing antibody or control (IgG). Lingual ARTN expression (IHC) increased after lingual irradiation, and this was mitigated by anti-ARTN treatment. Assessments of glossitis severity, body weight, and behavioral pain measures indicated that irradiation caused severe pain, which ARTN depletion failed to mitigate. However, after topical ophthalmic application of cold saline solution, tongue-irradiated anti-ARTN treated mice wiped their eyes less than their IgG-treated counterparts, and as assessed via ex vivo calcium imaging of trigeminal ganglia neurons, their afferent sensory nerves were less responsive to cold buffer. We therefore conclude that at the molecular level, ARTN depletion reduced radiation-induced cold sensitivity, but was insufficient to reduce behavioral indicators of RAP. Ongoing work in tissues from these mice is exploring whether changes in cold sensitivity correlated with TRPM8 expression, and future experiments are planned to assess: (1) whether genetic deletion of ARTN reduces RAP, and (2) if modulation of ARTN leads to upregulation of alternative TRPM8 activators. Faihaa A. Ahmed, Thitsana Ingkasri, Sophi Schofield, Elizabeth Wright, B. Duncan X. Lascelles, Santosh K. Mishra, Michael Nolan. The impact of artemin depletion on acute radiation-associated oral pain [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1835.

PURPOSE:Laser interstitial thermal therapy (LITT) is a minimally invasive surgical intervention permitting thermal ablation of intracranial targets such as tumors, radiation necrosis, or epileptogenic brain, including lesions that are deep, difficult to access, or recurrent that would otherwise have few viable surgical options. Despite its advantages, LITT has several limitations, including a restricted effective treatment zone (approximately 3 cm) and a limited ability to distinguish tumor margins from healthy brain tissue. Few viable animal models of appropriate size exist for studying LITT's impact on these disorders or for optimizing the technology and obviating its current limitations. Pet dogs develop these same disorders at similar rates to humans. We hypothesized that LITT could be made feasible in dogs, creating a unique model for in vivo LITT research and development. EXPERIMENTAL DESIGN:Canine cadaveric specimens and live dogs, including canine patients with spontaneously occurring intracranial gliomas, were used in this study. Commercially available equipment was used for neuronavigation (Curve, Brainlab) and to perform LITT (NeuroBlate, Monteris Medical). RESULTS:Canine cadavers and two end-of-life laboratory dogs allowed adaptation of the neuronavigation and LITT systems to dogs, with successful targeting and ablation of intracranial targets. Four canine patients with intracranial gliomas were subsequently successfully treated with these same technologies. CONCLUSIONS:This work establishes a unique canine model for in vivo LITT research and development using commercially available systems, as well as creating a viable cutting-edge therapeutic intervention for pet dogs with intracranial lesions.

Head and neck cancer encompasses a diverse group of malignant neoplasms originating in regions such as the oral cavity, oropharynx, hypopharynx, larynx, sinonasal cavities, and salivary glands. HNC represents a significant public health challenge, and recent reports indicate an increment in the incidence of HNC in young adults. In 2020, approximately 377,700 new HNC cases and 177,800 HNC-related deaths were reported globally. Major risk factors include tobacco smoking, alcohol consumption, and human papillomavirus (HPV) infections. HNC impacts vital functions such as breathing, swallowing, and speech. Treatments for this type of cancer within this complex anatomy include surgery, radiotherapy, and chemotherapy combinations. Radiotherapy is often an essential component of both curative and palliative HNC treatment, balancing tumor control with the preservation of function and appearance. However, its use can damage adjacent normal tissues, causing acute or chronic toxicity. One complication of HNC irradiation is VF fibrosis, which leads to severe voice impairments, significantly affecting patients’ quality of life. Fibrosis involves excessive and aberrant deposition of extracellular matrix, driven by factors such as TGF-β1 and inflammatory cytokines, which ultimately impair the flexibility and function of VF. Current radiation-induced fibrosis treatments primarily focus on symptom management and include systemic therapies like corticosteroids, anti-inflammatory drugs, and antioxidants. However, these treatments have limited efficacy. Experimental approaches targeting molecular pathways involved in fibrosis are being explored. Given the limitations of these treatments, advancing research is crucial to develop more effective therapeutic strategies that can significantly improve the quality of life for HNC patients, especially those vulnerable to VF fibrosis.

ABSTRACTAlthough canine pituitary masses (PM) are increasingly treated with stereotactic radiotherapy (SRT), historical literature supports superior outcomes with conventional full‐course fractionated radiation therapy (FRT). A multi‐institutional retrospective study was performed, including dogs with PM treated from 2016 to 2022 with SRT (total dose 30 or 35 Gy in 5 daily fractions) or FRT (total dose 50–54 Gy in 19–20 daily fractions). The influence of potential prognostic/predictive factors was assessed, including pituitary: brain height, pituitary: brain volume, sex, age and endocrine status (functional [F] vs. nonfunctional [NF] PM). Forty‐four dogs with PM were included (26 F, 14 NF, 4 unknown). All patients completed protocols as scheduled (SRT = 27, FRT = 17) and two dogs had suspected Grade 1 acute neurotoxicity. During the first 6 months after RT, 5/27 (19%) dogs treated with SRT (4 F, 1 NF) and 3/17 (18%) dogs treated with FRT (all F) died or were euthanised because of progressive neurologic signs. The overall median survival time was 608 days (95% CI, 375–840 days). Young age at the time of treatment was significant for survival (p = 0.0288); the overall median survival time was 753 days for dogs <9 years of age (95% CI, 614–892 days) and 445 days for dogs ≥9 years of age (95% CI, 183–707 days). Survival time was not associated with treatment type or any other factor assessed herein. A prospective study using standardised protocols would further validate the results of the present study and potentially elucidate the predictors of early death.

Radiotherapy (RT) is increasingly utilised for definitive-intent treatment of canine genitourinary carcinomas (CGUC). At our institution, the standard approach is to irradiate tomographically abnormal tissues gross tumour volume (GTV) plus a clinical target volume (CTV) expansion of 2 cm. Cystourethroscopy is often incorporated into the treatment planning workflow, though an optimal approach has yet to be defined. This observational study evaluated cystourethroscopy as a tool for identifying gross lesions that can be targeted with RT. We hypothesised that in most cases, addition of cystourethroscopy would result in a larger GTV than would be drawn with computed tomography (CT) alone. Medical records from 54 dogs diagnosed with CGUC between 2013 and 2023 were reviewed; each had been evaluated before RT using CT and cystourethroscopy. The GTV was initially defined as the tomographically evident disease on a post-contrast sagittal plane CT scan, and then lesions visualised with cystourethroscopy (suspected or confirmed to be tumour) were added. Beyond what was visible on CT, cystourethroscopy extended the GTV by a median of 6.5 cm distally into the urethra (range: 1.5-31.8 cm) and therefore resulted in GTV enlargement in 26 of 54 (48%) cases. Addition of our standard 2 cm CTV expansion to a CT-defined GTV (without use of data from cystourethroscopy) would have underestimated the extent of grossly abnormal tissue in 35% (19/54) of cases. These results suggest that incorporating cystourethroscopy into treatment planning workflows may improve local tumour control by reducing the risk of a geographic miss.

Stereotactic radiotherapy (SRT) involves the precise delivery of highly conformal, dose-intense radiation to well-demarcated tumors. Special equipment and expertise are needed, and a unique biological mechanism distinguishes SRT from other forms of external beam radiotherapy. Families find the convenient schedules and minimal acute toxicity of SRT appealing. Common indications in veterinary oncology include nasal, brain, and bone tumors. Many other solid tumors can also be treated, including spinal, oral, lung, heart-base, liver, adrenal, and prostatic malignancies. Accessibility of SRT is improving, and new data are constantly emerging to define parameters for appropriate case selection, radiation dose prescription, and long-term follow-up."

Stereotactic radiotherapy (SRT) involves the precise delivery of highly conformal, dose-intense radiation to well-demarcated tumors. Special equipment and expertise are needed, and a unique biological mechanism distinguishes SRT from other forms of external beam radiotherapy. Families find the convenient schedules and minimal acute toxicity of SRT appealing. Common indications in veterinary oncology include nasal, brain, and bone tumors. Many other solid tumors can also be treated, including spinal, oral, lung, heart-base, liver, adrenal, and prostatic malignancies. Accessibility of SRT is improving, and new data are constantly emerging to define parameters for appropriate case selection, radiation dose prescription, and long-term follow-up.

Abstract Background To ameliorate anticipated or ongoing neurological deficits, dogs undergoing brain tumor irradiation often are prescribed lengthy courses of prednisone PO during and after radiotherapy (RT). This practice can contribute to unwanted corticosteroid‐associated morbidity and may be unnecessary. Objective Determine whether long‐term corticosteroid dependency can be minimized by use of succinct prednisone tapering. Animals Fifty‐five pet dogs undergoing brain tumor irradiation. Methods Nineteen dogs were treated using a “rapid‐taper” protocol wherein corticosteroid dose reduction began 0 to 20 days after completing RT. Outcomes were compared with a retrospectively studied control group (“slow‐taper”; N = 36 dogs) in which corticosteroids were tapered more slowly according to individual clinician recommendations. Results Patient demographics were similar between groups. Mean time to lowest prednisone dose was 41 days postirradiation in the rapid‐taper group and 117 days in the slow‐taper group (P = .003). In the rapid‐taper group, 15 of 19 dogs (84%) were completely tapered off prednisone, vs 18 of 36 (50%) in the slow‐taper group (P = .04). Rates at which corticosteroids had to be reinstituted later were similar for the 2 groups (approximately 1 in 3 dogs). Adverse effect rates were similar for the 2 groups. Although no comparable questionnaire‐derived data were available for the “slow‐taper” group, overall and neurologic quality of life remained stable after RT in the rapid‐taper group. Conclusions and Clinical Importance For many dogs, lengthy courses of PO prednisone are avoidable after intracranial RT. Future efforts should aim to identify which dogs benefit most from accelerated prednisone tapering.

IntroductionPatients developing acute radiotherapy induced dermatitis or oral mucositis commonly experience pain. When severe, this radiotherapy-associated pain (RAP) can necessitate treatment breaks; unfortunately, in a variety of cancers, prolongation of the radiotherapy course has been associated with early cancer relapse and/or death. This is often attributed to accelerated repopulation, but it is unknown whether pain or pain signaling constituents might alter tumor behavior and hasten metastatic disease progression. We studied this by testing the hypothesis that severe acute RAP at one site can hasten tumor growth at a distant site.MethodsMice underwent single fraction tongue irradiation (27 Gy, or 0 Gy “sham” control) to induce severe glossitis. At the time of maximal oral RAP, one of three luciferase-transfected tumor cell lines were injected via tail vein (4T1, B16F10, MOC2; each paired to their syngeneic host: BALB/c or C57BL/6); tumor burden was assessed via in vivo transthoracic bioluminescence imaging and ex vivo pulmonary nodule quantification. Survival was compared using Kaplan-Meier statistics.ResultsTongue irradiation and resultant RAP promoted lung tumor growth of 4T1-Luc2 cells in BALB/c mice. This effect was not a result of off-target radiation, nor an artefact of environmental stress caused by standard (subthermoneutral) housing temperatures. RAP did not affect the growth of B16F10-Luc2 cells, however, C57BL/6 mice undergoing tail vein injection of MOC2-Luc2 cells at the time of maximal RAP experienced early lung tumor-attributable death. Lung tumor growth was normalized when RAP was reduced by treatment with resiniferatoxin (300 µg/kg, subcutaneously, once).DiscussionThis research points towards radiation-induced activation of capsaicin-responsive (TRPV1) neurons as the cause for accelerated growth of tumors at distant (unirradiated) sites.