Early radiation-induced oral pain signaling responses are reduced with pentoxifylline treatment.

Radiation-induced acute oral mucositis is associated with inflammation and pain. In other realms of pain research, nociceptors are known to be activated by inflammatory cytokines; for example, tumor necrosis factor alpha (TNF-α) can activate transient receptor potential ion channels on sensory neurons. But there is an unclear relationship between inflammatory cytokines and molecular mediators of pain in radiation-induced mucositis (RIM) and radiation-associated pain (RAP). In this prospective, analytical, experimental pilot study, a common drug (pentoxifylline [PTX]) was used with the goal of inhibiting TNF-α signaling in mice that underwent lingual irradiation to induce severe acute oral RIM/RAP. Body weight and glossitis scores were recorded daily. Eye wiping behaviors were assayed as a surrogate measure of oral discomfort (which is possible due to cross-sensitization of the mandibular and ophthalmic branches of the trigeminal nerve). Quantitative real-time reverse transcription polymerase chain reaction was performed on irradiated tongue tissue to measure changes in expression of TNF-α, its receptor, nuclear factor kappa-light-chain-enhancer of activated B cells, transient receptor potential vanilloid type 1 (TRPV1), and transient receptor potential vanilloid type 4 (TRPV4). Responsiveness of afferent sensory trigeminal neurons to TNF-α, a TRPV1 agonist (capsaicin), and a partial TRPV4 agonist (histamine) was measured via calcium imaging. Although PTX treatment did not reduce glossitis severity or mitigate weight loss in mice with RIM/RAP, it did inhibit the upregulation of TNF-α's receptor that normally accompanies RIM, and it also reduced neuronal responsiveness to each of the aforementioned chemical stimuli. These results provide provisional evidence that inhibition of TNF-α signaling with PTX treatment may serve as a useful tool for reducing pain in head and neck cancer patients.

Changes in target volume during irradiation of canine intranasal tumors can significantly impact radiation dosimetry.

Nasal tumor size can change during radiation therapy (RT). The amount of peritumoral fluid (eg, mucohemorrhagic effusions) can also fluctuate. How often this occurs and the magnitude of change are unknown. Likewise, there are no data which describe dosimetric effects of these changing volumes during a course of RT in veterinary medicine. This study addresses that gap in knowledge. Using pet dogs with nasal tumors, three CT image sets were created. Different Hounsfield units were applied to the gross tumor volume (GTV) of each image set: unchanged, -1000 (AIR), -1000 (to the portion of the GTV that actually underwent volume reduction during clinical RT; REAL). Two plans were created: 18-fraction three-dimensional conformal RT (3DCRT) and three-fraction intensity-modulated stereotactic RT (IM-SRT). For nearby normal tissues and GTV, near-maximum doses (D2% and D5% ) and volumes receiving clinically significant doses were recorded. To verify "AIR" results, thermoluminescent dosimeters recorded dose in cadavers that were irradiated using both 3DCRT and IM-SRT plans. "AIR" scenario had ≤1.5 Gray (Gy) increases in D2% and ≤3.2 cc increases of volume. "REAL" scenario had ≤0.97 Gy increases in D5% and ≤0.55 cc increases of volume at clinically relevant doses. Both were statistical significant. Results suggest that near-complete resolution of GTV warrants plan revision.

Implementation of total body photon irradiation as part of an institutional bone marrow transplant program for the treatment of canine lymphoma and leukemias.

A total body irradiation (TBI) protocol was developed to support a bone marrow transplant (BMT) program for the treatment of canine hematologic malignancies. The purpose of this prospective study is to describe implementation of the protocol and resultant dosimetry. Nongraphic manual treatment planning using 6 MV photons, isocentric delivery, 40 × 40 cm field size, wall-mounted lasers to verify positioning, a lucite beam spoiler (without use of bolus material), a dose rate of 8.75 cGy/min at patient isocenter, and a source-to-axis distance of 338 cm were used for TBI. A monitor unit calculation formula was derived using ion chamber measurements and a solid water phantom. Five thermoluminescent dosimeters (TLDs) were used at various anatomic locations in each of four cadaver dogs, to verify fidelity of the monitor unit formula prior to clinical implementation. In vivo dosimetric data were then collected with five TLDs at various anatomic locations in six patients treated with TBI. A total dose of 10 Gy divided into two 5 Gy fractions was delivered approximately 16 h apart, immediately followed by autologous stem cell transplant. The mean difference between prescribed and delivered doses ranged from 99% to 109% for various sites in cadavers, and from 83% to 121% in clinical patients. The mean total body dose in cadavers and clinical patients when whole body dose was estimated by averaging doses measured by variably placed TLDs ranged from 98% to 108% and 93% to 102% of the prescribed dose, respectively, which was considered acceptable. This protocol could be used for institutional implementation of TBI.

Teaching Tip: Virtual Oncology Clinic.

Due to limitations in traditional approaches to didactic and clinical learning, professional veterinary medical students face challenges in developing skills and competencies related to clinical practice. The Veterinary Information Network's (VIN) Virtual Clinic (VVC) aims to support learning by using gaming techniques to simulate clinical case management in a low-risk setting. The VVC lets students explore medical scenarios inside a virtual hospital. The purpose of this article is to describe the development and implementation of a learning approach that blends classroom instructor-directed learning with online simulation-based learning, using the VVC. We share challenges and successes of this approach. The case vignettes in the specific example described herein are for canine multicentric lymphoma. However, the lessons learned through the implementation of this oncology clinic module are expected to apply to a wide range of clinical disciplines.

Single fraction stereotactic radiation therapy (stereotactic radiosurgery) is a feasible method for treating intracranial meningiomas in dogs.

The aim of this retrospective, pilot study was to evaluate stereotactic radiosurgery as a method for treating intracranial meningiomas in dogs. Included dogs had an imaging diagnosis of presumed intracranial meningioma, were treated using a standardized stereotactic radiosurgery protocol, and had a follow-up time of >6 months after stereotactic radiosurgery. A single fraction of 16 Gy stereotactic radiosurgery was delivered to the tumor, with an internal simultaneously integrated boost to a total dose of 20-24 Gy to the central portion of the tumor. Thirty-two dogs were sampled. One dog was euthanized in the periprocedural period, and 10 of the remaining 31 dogs (31%) experienced an acute adverse event (defined as declining neurologic function due to tumor progression or treatment-associated complication within the first 6 months after stereotactic radiosurgery), three of which were fatal. Too few subjects (n = 6) had cross-sectional imaging after stereotactic radiosurgery to determine an objective response rate; however, 17/30 (57%) dogs assessed for response had a perceived clinical benefit from treatment. The overall median survival time was 519 days (95% confidence interval: 330-708 days); 64% and 24% of dogs were alive at 1 and 2 years after stereotactic radiosurgery, respectively. Dogs with infratentorial tumor location and high gradient indices had shorter survival. There were no factors identified which were predictive of acute adverse event. Survival times reported herein are similar to what has previously been reported for other stereotactic and traditional fractionated radiotherapy protocols. Findings therefore supported the use of stereotactic radiosurgery as an alternative method for treating dogs with presumed intracranial meningiomas.

Clinical and imaging findings, treatments, and outcomes in 27 dogs with imaging diagnosed trigeminal nerve sheath tumors: A multi-center study.

The clinical behavior of canine trigeminal nerve sheath tumors and benefits of previously reported treatments are incompletely defined. Aims of this retrospective, multicenter, observational study were to describe clinical signs, tumor localization characteristics, treatments, and clinical outcomes in a group of dogs with this neoplasm. Databases at four hospitals were reviewed for dogs with a trigeminal nerve sheath tumor diagnosis, magnetic resonance imaging (MRI) studies, and presentation between 2004 and 2014. A single observer recorded medical record findings and two observers recorded MRI characteristics by consensus. A total of 27 dogs met inclusion criteria (15 treated with stereotactic radiation therapy and 12 unirradiated). Two unirradiated dogs were excluded from outcome analyses. The most common presenting signs were masticatory muscle atrophy (26 dogs), neurologic signs referable to intracranial disease (13), and ocular disease (12). Based on MRI findings, all dogs had disease extending centrally at the level of the brainstem. The most commonly affected trigeminal nerve branches were the mandibular (26 dogs), maxillary (22), and ophthalmic (10). Of 15 dogs treated with stereotactic radiation therapy, one had improved muscle atrophy, and six had poor ocular health after treatment. Neurologic signs improved in 4/5 dogs with intracranial signs. Overall median survival time for the 10 unirradiated dogs with available follow-up was 12 days and 441 days for the 15 stereotactic radiation therapy dogs. Mean survival times between these groups were not significantly different (mean 95% CI for unirradiated dogs was 44-424 days and mean 95% CI for stereotactic radiation therapy dogs was 260-518 days).

RETROSPECTIVE EVALUATION OF INTERFRACTION URETERAL MOVEMENT IN DOGS UNDERGOING RADIATION THERAPY TO ELUCIDATE APPROPRIATE SETUP MARGINS.

Radiation-induced ureteral damage can result in serious complications (i.e., hydronephrosis). Also, ureters can be included in planning target volume (PTV) such as ureteral invasion of urinary bladder carcinoma. Therefore, knowing the interfractional movement of the ureters is critical for creation of appropriate planning organs at risk (pOAR) and PTV. This retrospective and descriptive study of 17 dogs with genitourinary carcinomas that underwent intensity-modulated, image-guided radiation therapy (IM-IGRT) was conducted to describe the movement and calculate suggested pOAR/PTV expansions at three locations (at the levels of third lumbar vertebra, immediately cranial to vesicoureteral junction [VUJ], and midway between those two) and from two perspectives: during a course of (1) IM-IGRT, where position verification is performed using soft tissue registration when the dogs underwent clinical IM-IGRT; (2) radiation therapy whereby position verification is performed using planar radiography with a corresponding bony registration. This registration was performed by fusing the radiation planning computed tomography (CT) and cone-beam CTs using bony landmarks. With soft tissue registration, findings supported the use of larger pOAR expansion (0.7-1.8 cm) for the mid region of the ureters compared to the areas near VUJ (0.7-1.1 cm). With bony registration, findings supported the use of larger pOAR/PTV expansions (1.6-1.7 cm) for dorsal direction bilaterally at areas near VUJ compared to those with soft tissue registration (0.9-1.0 cm). The results of this study should help radiation oncologists use appropriate ureter expansions for specific patient orientations and positioning verification methods.

DOSIMETRIC CONSEQUENCES OF USING CONTRAST-ENHANCED COMPUTED TOMOGRAPHIC IMAGES FOR INTENSITY-MODULATED STEREOTACTIC BODY RADIOTHERAPY PLANNING.

Potential benefits of planning radiation therapy on a contrast-enhanced computed tomography scan (ceCT) should be weighed against the possibility that this practice may be associated with an inadvertent risk of overdosing nearby normal tissues. This study investigated the influence of ceCT on intensity-modulated stereotactic body radiotherapy (IM-SBRT) planning. Dogs with head and neck, pelvic, or appendicular tumors were included in this retrospective cross-sectional study. All IM-SBRT plans were constructed on a pre- or ceCT. Contours for tumor and organs at risk (OAR) were manually constructed and copied onto both CT's; IM-SBRT plans were calculated on each CT in a manner that resulted in equal radiation fluence. The maximum and mean doses for OAR, and minimum, maximum, and mean doses for targets were compared. Data were collected from 40 dogs per anatomic site (head and neck, pelvis, and limbs). The average dose difference between minimum, maximum, and mean doses as calculated on pre- and ceCT plans for the gross tumor volume was less than 1% for all anatomic sites. Similarly, the differences between mean and maximum doses for OAR were less than 1%. The difference in dose distribution between plans made on CTs with and without contrast enhancement was tolerable at all treatment sites. Therefore, although caution would be recommended when planning IM-SBRT for tumors near "reservoirs" for contrast media (such as the heart and urinary bladder), findings supported the use of ceCT with this dose calculation algorithm for both target delineation and IM-SBRT treatment planning.

Surface characterization of gallium nitride modified with peptides before and after exposure to ionizing radiation in solution.

An aqueous surface modification of gallium nitride was employed to attach biomolecules to the surface. The modification was a simple two-step process using a single linker molecule and mild temperatures. The presence of the peptide on the surface was confirmed with X-ray photoelectron spectroscopy. Subsequently, the samples were placed in water baths and exposed to ionizing radiation to examine the effects of the radiation on the material in an environment similar to the body. Surface analysis confirmed degradation of the surface of GaN after radiation exposure in water; however, the peptide molecules successfully remained on the surface following exposure to ionizing radiation. We hypothesize that during radiation exposure of the samples, the radiolysis of water produces peroxide and other reactive species on the sample surface. Peroxide exposure promotes the formation of a more stable layer of gallium oxyhydroxide which passivates the surface better than other oxide species.

Update in Veterinary Radiation Oncology: Focus on Stereotactic Radiation Therapy.

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.

Outcomes of Stereotactic Radiation Therapy Versus Fractionated Radiation Therapy in 44 Dogs With Pituitary Masses: A Multi-Institutional Retrospective Study (2016-2022).

Although 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.

Accuracy of CT and MRI for contouring the feline optic apparatus for radiation therapy planning.

Consistency and accuracy in normal tissue contouring in radiotherapy planning is important for comparison of dosimetry and toxicity data between studies. The purpose of this study was to determine whether magnetic resonance imaging (MRI) improves the accuracy of optic apparatus contouring as compared with computed tomography (CT) in both normal and acromegalic cats, and to construct a reference contour of the feline optic apparatus. Both CT and MRI were performed on cadavers of four healthy cats, as well as on five radiotherapy patients with feline acromegaly. Contours of the optic apparatus were drawn for each imaging study. The volume, center of mass, and the degree of concordance and mismatch were determined for each, and compared with a reference standard. Precontrast CT was found to overestimate volume as compared with MRI in acromegalic cats; no other statistically significant differences were identified in the volume, concordance index or mismatch index values of normal or acromegalic cats. Contours derived from T2-wieghted MRI were subjectively considered to best match the reference standard. The caudal margin of the optic chiasm and the optic tracts were difficult to confidently contour regardless of which imaging modality and/or sequence was used. In conclusion, findings from the current study supported the use of a combination of CT and MR images and a priori knowledge of the shape of the optic apparatus to guide accurate contouring, especially where image contrast is not sufficient to clearly delineate the margins. Guidelines for feline optic apparatus contouring developed in this study can be used for future studies.

Acute radiotherapy-associated oral pain may promote tumor growth at distant sites.

Introduction: Patients 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. Methods: Mice 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. Results: Tongue 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). Discussion: This research points towards radiation-induced activation of capsaicin-responsive (TRPV1) neurons as the cause for accelerated growth of tumors at distant (unirradiated) sites.

Presumed pituitary apoplexy in 26 dogs: Clinical findings, treatments, and outcomes.

BACKGROUND: Pituitary apoplexy refers to hemorrhage or infarction within the pituitary gland resulting in acute neurological abnormalities. This condition is poorly described in dogs. OBJECTIVES: To document presenting complaints, examination findings, endocrinopathies, magnetic resonance imaging (MRI), treatments, and outcomes of dogs with pituitary apoplexy. ANIMALS: Twenty-six client-owned dogs with acute onset of neurological dysfunction. METHODS: Retrospective case series. Dogs were diagnosed with pituitary apoplexy if MRI or histopathology documented an intrasellar or suprasellar mass with evidence of hemorrhage or infarction in conjunction with acute neurological dysfunction. Clinical information was obtained from medical records and imaging reports. RESULTS: Common presenting complaints included altered mentation (16/26, 62%) and gastrointestinal dysfunction (14/26, 54%). Gait or posture changes (22/26, 85%), mentation changes (18/26, 69%), cranial neuropathies (17/26, 65%), cervical or head hyperpathia (12/26, 46%), and hyperthermia (8/26, 31%) were the most frequent exam findings. Ten dogs (38%) lacked evidence of an endocrinopathy before presentation. Common MRI findings included T1-weighted hypo- to isointensity of the hemorrhagic lesion (21/25, 84%), peripheral enhancement of the pituitary mass lesion (15/25, 60%), brain herniation (14/25, 56%), and obstructive hydrocephalus (13/25, 52%). Fifteen dogs (58%) survived to hospital discharge. Seven of these dogs received medical management alone (median survival 143 days; range, 7-641 days) and 8 received medications and radiation therapy (median survival 973 days; range, 41-1719 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with pituitary apoplexy present with a variety of acute signs of neurological disease and inconsistent endocrine dysfunction. Dogs that survive to discharge can have a favorable outcome.

Re-irradiation of canine non-lymphomatous nasal tumours using stereotactic radiation therapy (10 Gy x 3) for both courses: Assessment of outcome and toxicity in 11 dogs.

No uniformly beneficial treatments exist for dogs with non-lymphomatous nasal tumours (NLNT) that relapse after radiotherapy (RT). Reirradiation may prolong survival and improve quality of life. In this retrospective study, we describe outcomes for 11 dogs that had CT-confirmed locoregional progression of NLNT after an initial course of stereotactic RT (SRT#1; 10 Gy × 3) and were then re-treated with the same type of protocol (SRT#2, also 10 Gy × 3). The median time between SRT #1 and SRT #2 was 243 days (95% CI: 78-385 days). Ten dogs (91%) had a clinical benefit after SRT#1; five dogs (45%) had clinical benefit after SRT#2. Adverse events after SRT#2 included nasocutaneous or oronasal fistula formation (N = 3 at 180, 270, and 468 days), seizures (N = 2 at 78 and 330 days), bacterial or fungal rhinitis (N = 2 at 240 and 385 days), and facial swelling (N = 1 at 90 days). All 11 dogs have died, due to disease progression, presumed radiotoxicity, or declining quality of life; in most cases, it was difficult to discern between these conditions. The median overall survival time (OST) from SRT#1 was 745 days (95% CI: 360-1132). The median overall survival time (OST) from SRT #2 was 448 days (95% CI: 112-626). For these dogs, survival was prolonged, but adverse events after SRT#2 were common (8/11; 73%). Therefore, before consenting to re-irradiation with this protocol, pet owners should be counselled about survivorship challenges, including risk for severe toxicities, and persistence of clinical signs.

Intensity of perioperative analgesia but not pre-treatment pain is predictive of survival in dogs undergoing amputation plus chemotherapy for extremity osteosarcoma.

The purpose of this bi-institutional retrospective study was to determine whether, in dogs treated with limb amputation and adjunctive chemotherapy for osteosarcoma, oncologic outcomes are impacted by either: (1) baseline cancer pain severity, or (2) the approaches used for perioperative pain management. Data were extracted from the medical records of 284 dogs that underwent both limb amputation and chemotherapy (carboplatin and/or doxorubicin) between 1997 and 2017 for localized (non-metastatic) osteosarcoma of the appendicular skeleton. Kaplan-Meier survival curves and Cox proportional hazard (PH) models were used to determine the impact that retrospectively scored baseline pain levels (high vs. low) and various analgesic and local anaesthetic treatments had on both metastasis-free survival and all-cause mortality. For the entire population, the median disease free interval and median overall survival times were 253 and 284 days, respectively. Baseline pain was rated as "low" in 84 dogs, and "high" in 190 dogs; pain severity had no detectable effect on either metastasis-free survival or all-cause mortality. When accounting for the potential influences of known prognostic factors, dogs treated with what was characterized as a high-intensity perioperative analgesic plan (including both a non-steroidal anti-inflammatory drug [NSAID] and a bupivacaine-eluting soaker catheter placed at the amputation site) had a higher probability of survival than dogs treated with a low-intensity perioperative analgesic plan (neither an NSAID, nor a soaker catheter); the median overall survival times were 252 and 378 days, respectively (hazard ratio: 2.922; p = .020).

A retrospective study of 101 dogs with oral melanoma treated with a weekly or biweekly 6 Gy × 6 radiotherapy protocol.

One radiotherapy (RT) protocol used for canine oral melanoma (OM) gives 36 Gy total, in six weekly or biweekly fractions (6 Gy × 6). This retrospective study characterizes oncologic outcomes for a relatively large group of dogs treated with this protocol and determines whether radiation dose intensity (weekly vs. biweekly) affected either progression-free or overall survival (PFS and OS). Dogs were included if 6 Gy × 6 was used to treat grossly evident OM, or if RT was used postoperatively in the subclinical disease setting. Kaplan-Meier statistics and Cox regression modelling were used to determine the predictive or prognostic value of mitotic count, bony lysis, World Health Organization (WHO) stage (I, II, III, or IV), using systemic anti-cancer therapies, tumour burden at the time of RT (macroscopic vs. subclinical), radiation dose intensity (weekly vs. biweekly), and treatment planning type (manual vs. computerized). The median PFS and OS times for all dogs (n = 101) were 171 and 232 days, respectively. On univariate analysis PFS and OS were significantly longer (p = <.05) with subclinical tumour burden, WHO stages I or II, and weekly irradiation. On multivariable analysis, only tumour stage remained significant; therefore, cases were grouped by WHO stage (I/II vs. III/IV). With low WHO stage (I/II), PFS and OS were longer when irradiating subclinical disease (PFS: risk ratio = 0.449, p = .032; OS: risk ratio = 0.422, p = .022); this was not true for high WHO stage (III/IV). When accounting for other factors, radiation dose intensity had no measurable impact on survival in either staging group.

Stereotactic radiotherapy (10 Gy X 3) for canine nonlymphomatous intranasal tumors is associated with prolonged survival and minimal risk of severe radiotoxicity.

OBJECTIVE: To describe oncologic outcomes following administration of a uniform stereotactic radiotherapy protocol (SRT; 10 Gy X 3) for canine intranasal tumors and to identify whether any clinical or dosimetric factors were predictive of event-free or overall survival time (EFST or OST). ANIMALS: 129 dogs. PROCEDURES: In this single-institution retrospective study, the medical records database was searched for canine nonlymphomatous intranasal tumors treated with 10 Gy X 3 SRT between August 2013 and November 2020. Findings regarding adverse effects and outcomes were analyzed overall, for dogs grouped on the basis of life stage (mature adult, senior, or end of life), and for treatment-related or tumor-related variables to identify potential predictors of outcome. RESULTS: After SRT, most dogs clinically improved with minimal acute radiotoxicity. The median EFST was 237 days; median OST was 542 days. Receipt of other tumor-directed therapies before or after SRT was associated with improved EFST in senior dogs (hazard ratio [HR], 0.416) and improved OST in mature adult (HR, 0.241) and senior dogs (HR, 0.348). In senior dogs, administration of higher near-minimum radiation doses was associated with improved EFST (HR, 0.686) and OST (HR, 0.743). In senior dogs, chondrosarcoma was associated with shorter OST (HR, 7.232), and in dogs at end of life, having a squamous cell or transitional carcinoma was associated with worse EFST (HR, 6.462). CLINICAL RELEVANCE: This SRT protocol results in improved quality of life and prolonged OST for dogs of all life stages. Radiation protocol optimization or use of multimodal therapy may further improve outcomes.

Treatment outcomes and target delineation utilizing CT and MRI in 13 dogs treated with a uniform stereotactic radiation therapy protocol (16 Gy single fraction) for pituitary masses: (2014-2017).

Canine pituitary tumours are increasingly treated with stereotactic radiotherapy (SRT). Here, we report clinical outcomes in dogs treated with single-fraction SRT; we also explore technical aspects of SRT treatment planning. A single-institution retrospective study was performed, including any dog with a pituitary mass (PM) that was treated using a standardized single-fraction (16 Gy) SRT protocol between 2014 and 2017. Via medical records review, 13 cases were identified. Nine dogs neurologically improved after SRT. Four dogs experienced MRI-documented tumour volume reduction. Nine dogs experienced neurologic decline in 1.5 to 18 months after SRT and were euthanized. The median overall survival time was 357 days, with 15% alive 18 months after SRT. To better understand whether SRT target delineation is predictably altered by use of magnetic resonance imaging (MRI) in addition to computed tomography (CT), two radiation oncologists (RO) retrospectively re-evaluated all imaging studies used for SRT planning in these 13 cases. Gross tumour volume (GTV) was contoured on co-registered CT and MRIs for each case. In seven cases, CT alone was deemed inadequate for GTV contouring by at least one RO. T1 post-contrast MRI was considered the ideal image for GTV contouring in 11 cases. Contouring on MRI yielded larger GTV than CT for 11 cases. Inter-observer variability existed in each case and was greater for MRI. In summary, use of co-registered CT and MRI images is generally considered advantageous for PM delineation when using SRT. Notably, survival times reported herein are shorter than what has previously been reported for PM treated with finely fractionated full-course RT protocols.

Behavioral phenotyping of cancer pain in domesticated cats with naturally occurring squamous cell carcinoma of the tongue: initial validation studies provide evidence for regional and widespread algoplasticity.

Feline oral squamous cell carcinoma (FOSCC) is a common and naturally occurring condition that recapitulates many features of human head and neck cancer (HNC). In both species, there is need for improved strategies to reduce pain caused by HNC and its treatment. Research to benefit both species could be conducted using pet cats as a comparative model, but this prospect is limited by lack of validated methods for quantifying FOSCC-associated pain. A prospective non-randomized pilot study was performed for initial validation of: (1) a pet owner administered quality of life questionnaire and visual assessment scoring tool (FORQ/CLIENT); (2) a clinician assessment questionnaire (UFEPS/VET); (3) electronic von Frey testing [EVF]; and (4) Cochet-Bonnet (COBO) aesthesiometry. To assess intra-rater reliability, discriminatory ability, and responsiveness of each assay, 6 cats with sublingual SCC and 16 healthy control cats were enrolled. The intra-rater reliability was moderate-to-good for the clinical metrology instruments and EVF (intraclass correlation coefficient [ICC] ≥ 0.68), but poor for COBO (ICC = 0.21). FORQ/CLIENT scores were higher (worse quality of life) in FOSCC cats vs healthy controls. The internal reliability of FORQ/CLIENT scoring was high (Cronbach α = 0.92); sensitivity and specificity were excellent (100% when using cut-offs determined using receiver operating characteristic [ROC] curves). For the FORQ/CLIENT, there was strong and inverse correlation between scores from the questions and visual assessment (r =  - 0.77, r 2 = 0.6, P < 0.0001). For the UFEPS/VET, Cronbach's α was 0.74 (high reliability). Sensitivity and specificity were 100% and 94%, respectively, when using a cut-off score (3.5) based on ROC curves (Youden index of 0.94). Total UFEPS/VET scores were positively correlated with FORQ/CLIENT scores (r 2 = 0.72, P < 0.0001). Sensitivity of EVF and COBO ranged from 83 to 100% and specificity ranged from 56 to 94%. Cats with cancer were more sensitive around the face (lower response thresholds) and on the cornea (longer filament lengths) than control animals (P < 0.03). Reduced pressure response thresholds were also observed at a distant site (P = 0.0002) in cancer cats. After giving buprenorphine, EVF pressure response thresholds increased (P = 0.04) near the mandible of cats with OSCC; the length of filament required to elicit a response in the COBO assay also improved (shortened; P = 0.017). Based on these preliminary assessments, the assays described herein had reasonable inter-rater reliability, and they were able to both discriminate between cats with and without oral cancer, and respond in a predictable manner to analgesic therapy. In cats with tongue cancer, there was evidence for regional peripheral sensitization, and widespread somatosensory sensitization. These results provide a basis for multi-dimensional assessments of pain and sensitivity in cats with oral SCC.