Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy.

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities.

[Radiation therapy in veterinary medicine at the University of Liège]. / Radiothérapie en médecine vétérinaire à l'Université de Liège.

Radiation therapy has many indications in veterinary oncology and allows a multidisciplinary approach for the treatment of canine and feline patients. Radiation therapy can be recommended as a sole therapy in case of radiosensitive tumors or can be associated to surgery and/or chemotherapy after marginal excision for example. It can also be recommended as a palliative treatment for patients with an inoperable or painful tumor or disseminated disease. Radiation therapy significantly improves the quality of life and survival time of treated animals and should be part of the therapeutic modalities in veterinary medicine. The University of Liège developed the first veterinary center of radiation therapy in Belgium and can therefore participate in improving therapeutic management of cancerous animal patients.

La radiothérapie présente de nombreuses indications en oncologie vétérinaire et permet une approche multidisciplinaire pour le traitement de nos patients cancéreux canins et félins.La radiothérapie peut être recommandée seule pour le traitement de tumeurs radiosensibles, ou associée à la chirurgie et/ou la chimiothérapie notamment lors d'exérèse marginale. Elle a également sa place dans une prise en charge palliative de certains patients présentant une tumeur inopérable ou douloureuse, ou encore une maladie disséminée. La radiothérapie permet d'améliorer significativement la qualité et l'espérance de vie des animaux traités et à ce titre, doit faire partie de l'arsenal thérapeutique vétérinaire. L'Université de Liège possède, depuis peu, l'unique centre de radiothérapie vétérinaire en Belgique et peut ainsi participer à l'amélioration de la prise en charge des animaux cancéreux.

Blood pressure in hyperthyroid cats before and after radioiodine treatment.

BACKGROUND: Hyperthyroid cats commonly have systemic hypertension, with a reported prevalence of 7% to 48%. Although hypertension might be expected to resolve once treatment restores euthyroidism, it can persist or only first develop after treatment. OBJECTIVES: To determine the proportion of hyperthyroid cats with hypertension (systolic blood pressure [SBP] ≥160 mm Hg), persistence or first development of hypertension after successful radioiodine treatment, and correlation of post-treatment hypertension with azotemia or hypothyroidism. ANIMALS: Four hundred one hyperthyroid nonazotemic cats were included in the study. METHODS: Prospective, cross-sectional and before-and-after studies. All hyperthyroid cats had SBP measured by Doppler; 255 had SBP rechecked 6 months after successful radioiodine (131I) treatment. RESULTS: Of untreated hyperthyroid cats, 108/401 (27%) were hypertensive. A higher proportion of hypertensive cats were nervous/excited compared with normotensive cats (47% vs 12%; P < .001). Of the initially hypertensive cats, 87/108 cats were reexamined after 131I treatment; 43/87 (49%) cats normalized SBP, whereas 44/87 (51%) remained hypertensive. Of the initially normotensive cats, 16/168 (9.5%) first developed hypertension after successful 131I treatment. 7/60 (12%) of the 131I-treated hypertensive cats were azotemic and 9/60 (15%) were hypothyroid. A higher proportion of cats remaining hypertensive had nervous/excited demeanor than did normotensive cats (50% vs 17%; P < .001). CONCLUSIONS/CLINICAL IMPORTANCE: Hypertension, when present, resolves in many hyperthyroid cats after successful treatment. Hyperthyroid cats uncommonly develop new hypertension after treatment. Persistent or newly detected hypertension was unrelated to azotemia or iatrogenic hypothyroidism. More frequently perceived nervousness/anxiety in radioiodine-treated hypertensive cats suggests that many of these cats might have "situational" hypertension, as hyperthyroid-induced hypertension should resolve after treatment.

Characteristics and outcomes for 61 cats that underwent either surgery or stereotactic radiotherapy as treatment for intracranial meningioma (2005-2017).

OBJECTIVE: To report clinical features and outcomes of cats undergoing either stereotactic radiotherapy (SRT) or surgical excision for the treatment of intracranial meningioma. ANIMALS: 61 client-owned cats. METHODS: Medical records were retrospectively reviewed of cats with intracranial meningiomas that were treated with surgical removal and/or SRT between 2005 and 2017. Signalment, clinical signs, duration of clinical signs, diagnostic imaging reports, histopathology reports, treatment protocol, complications, recurrence or progression, and survival time were obtained from the medical record and through follow-up phone calls. RESULTS: Of the 61 patients, 46 had surgery, 14 had SRT, and 1 had surgery followed by SRT for initial treatment. Significantly more cats that underwent surgery had peritreatment complications compared to the SRT group (P < .0001). Cats that received surgery initially had a significantly longer median survival time (MST) of 1,345 days compared to the MST of 339 days for the SRT cats (P = .002). Fourteen (30%) cats in the surgery group and 4 cats in the SRT group (28%) had MRI- or CT-confirmed tumor regrowth or new tumor growth (P = 1.00). Five cases that had SRT for subsequent recurrence had an MST of 700 days (range, 335 to 1,460 days) after the last treatment. CLINICAL RELEVANCE: SRT proved to be a safe, alternative treatment option for feline patients with intracranial meningiomas; however, the survival times with surgery alone were significantly longer. SRT for the treatment of recurrence following initial surgery may show promising results.

Extracellular heat shock protein 70 levels in tumour-bearing dogs and cats treated with radiation therapy and hyperthermia.

Hyperthermia is a form of a cancer treatment which is frequently applied in combination with radiotherapy (RT) to improve therapy responses and radiosensitivity. The mode of action of hyperthermia is multifactorial; the one hand by altering the amount of the blood circulation in the treated tissue, on the other hand by modulating molecular pathways involved in cell survival processes and immunogenic interactions. One of the most dominant proteins induced by hyperthermia is the major stress-inducible heat shock protein 70 (Hsp70). Hsp70 can be found in the blood either as a free-protein (free HSP70) derived from necrotic cells, or lipid-bound (liposomal Hsp70) when it is actively released in extracellular vesicles (EVs) by living cells. The aim of the study was to evaluate the levels of free and liposomal Hsp70 before and after treatment with RT alone or hyperthermia combined with radiotherapy (HTRT) in dogs and cats to evaluate therapy responses. Peripheral blood was collected from feline and canine patients before and at 2, 4, 6 and 24 h after treatment with RT or HTRT. Hsp70 enzyme-linked immunosorbent assays (ELISAs) were performed to determine the free and liposomal Hsp70 concentrations in the serum. The levels were analysed after the first fraction of radiation to study immediate effects and after all applied fractions to study cumulative effects. The levels of free and liposomal Hsp70 levels in the circulation were not affected by the first singular treatment and cumulative effects of RT in cats however, after finalizing all treatment cycles with HTRT free and liposomal Hsp70 levels significantly increased. In dogs, HTRT, but not treatment with RT alone, significantly affected liposomal Hsp70 levels during the first fraction. Free Hsp70 levels were significantly increased after RT, but not HTRT, during the first fraction in dogs. In dogs, on the other hand, RT alone resulted in a significant increase in liposomal Hsp70, but HTRT did not significantly affect the liposomal Hsp70 when cumulative effects were analysed. Free Hsp70 was significantly induced in dogs after both, RT and HTRT when cumulative effects were analysed. RT and HTRT treatments differentially affect the levels of free and liposomal Hsp70 in dogs and cats. Both forms of Hsp70 could potentially be further investigated as potential liquid biopsy markers to study responses to RT and HTRT treatment in companion animals.

Treatment of a nasal angiofibroma in a cat using stereotactic body radiation therapy.

A 14-year-old cat presented with right-sided epistaxis, right facial swelling, hyporexia, and sneezing. A right nasal mass was diagnosed based on dental radiography and computed tomography (CT), and nasal angiofibroma was diagnosed based on histopathology. Treatment consisted of stereotactic body radiation therapy in three consecutive daily doses. Self-limiting grade 3 oral mucositis developed which resolved within 6 weeks. Recheck CT 169 days after treatment confirmed a partial response by RECIST(1) based on digital CT measurements . Disease progression was confirmed on CT 642 days after treatment, per RECIST criteria, with the longest tumor diameter measuring 3.4 cm.

Urine concentrating ability in cats with hyperthyroidism: Influence of radioiodine treatment, masked azotemia, and iatrogenic hypothyroidism.

BACKGROUND: Hyperthyroid cats often have urine specific gravity (USG) values <1.035. It remains unclear how USG changes after treatment, if USG can be used to predict azotemia after treatment, or how iatrogenic hypothyroidism influences USG values. OBJECTIVES: To determine the proportion of hyperthyroid cats with USG <1.035 vs ≥1.035; if USG changes after treatment; and whether USG <1.035 correlated with unmasking of azotemia or hypothyroidism. ANIMALS: Six hundred fifty-five hyperthyroid cats treated with radioiodine; 190 clinically normal cats. METHODS: Prospective, before-and-after study. Hyperthyroid cats had serum thyroxine, thyroid-stimulating hormone, and creatinine concentrations, and USG measured before and 6 months after successful treatment with radioiodine. RESULTS: Of untreated hyperthyroid cats, USG was ≥1.035 in 346 (52.8%) and <1.035 in 309 (47.2%). After treatment, 279/346 (80.6%) maintained USG ≥1.035, whereas 67/346 (19.4%) became <1.035; 272/309 (88%) maintained USG <1.035, whereas 37/309 (12%) became ≥1.035. Only 22/346 (6.4%) with USG ≥1.035 developed azotemia after treatment, compared with 136/309 (44%) with <1.035 (P < .001). Of cats remaining nonazotemic, 38% had USG <1.035, compared with 20% of normal cats (P < .001). The 137 cats with iatrogenic hypothyroidism had lower USG after treatment than did 508 euthyroid cats (1.024 vs 1.035), but USGs did not change after levothyroxine supplementation. USG <1.035 had high sensitivity (86.1%) but moderate specificity (65.2%) in predicting azotemia after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperthyroidism appears not to affect USG in cats. However, cats with evidence of sub-optimal concentrating ability before radioiodine treatment (USG < 1.035) are more likely to develop azotemia and unmask previously occult chronic kidney disease. Iatrogenic hypothyroidism itself did not appear to affect USG values.

Changes in symmetric dimethylarginine and glomerular filtration rates in hyperthyroid cats undergoing radioiodine therapy.

OBJECTIVES: The aims of this study were to evaluate concentrations of symmetric dimethylarginine (SDMA) in hyperthyroid cats before and after radioiodine treatment, and to compare results with other variables used to assess kidney function in cats (creatinine, urine specific gravity [USG] and glomerular filtration rate [GFR] measured by renal scintigraphy). METHODS: Thirteen cats diagnosed with hyperthyroidism based on clinical signs and increased serum total thyroxine (TT4) were included in this prospective study. Study design included physical examination, complete blood count, serum chemistry, TT4, urinalysis and SDMA before treatment (T0) and at 1 month (T1) and 3 months post-treatment (T3). GFR was quantified by renal scintigraphy at T0 and T3. RESULTS: Median GFR decreased significantly from baseline (3.18 ml/kg/min; range 1.35-4.87) at T3 (2.22 ml/kg/min; range 1.81-3.42 [P = 0.005]). While median creatinine and serum urea nitrogen increased post-treatment (creatinine: T0 = 0.8 mg/dl [range 0.4-1.1], T1 = 1.3 mg/dl [range 0.9-2]; T3 = 1.65 mg/dl [range 0.8-2.8]; P <0.001; serum urea nitrogen: T0 = 23 mg/dl [range 15-26]; T1 = 27 mg/dl [range 20-40]; T3 = 27.5 mg/dl [range 20-36]; P <0.001), SDMA and USG did not change significantly (SDMA: T0 = 11 µg/dl [range 7-15]; T1 = 12 µg/dl [range 6-16]; T3 = 10.5 µg/dl [range 8-21]; P = 0.789; USG: T0 = 1.030 [range 1.011-1.059]; T1 = 1.035 [range 1.012-1.044]; T3 = 1.030 [range 1.007-1.055]; P = 0.792). CONCLUSIONS AND RELEVANCE: Our data suggest that factors other than GFR may affect serum SDMA in hyperthyroid cats and that SDMA does not offer an advantage over other biomarkers traditionally used to predict changes in renal function following radioiodine therapy.

Radioiodine treatment in hyperthyroid cats: insights into the characteristics of owners and their cats, and owner motivation and perceptions.

OBJECTIVES: Radioiodine (131I) therapy is the most appropriate treatment option for many hyperthyroid cats, as it is minimally invasive and often curative. Nevertheless, 131I treatment is not always pursued by owners. Hence, it is important to obtain more insight into owner satisfaction during and after 131I treatment, and their decision-making process. In this study, we describe the characteristics of owners and their hyperthyroid cats referred for 131I therapy, and determine owners' motivation and how they experienced the 131I treatment of their cat. METHODS: A survey was sent to owners whose cats underwent 131I therapy (n = 1071) between 2010 and 2017 at Ghent University. The survey contained 35 questions with tick-box or free-text answer options concerning family situation, pet insurance, previous therapy, comorbidities, motivation for 131I therapy and owner perception of this treatment. RESULTS: In total, 438 owners completed 94% or more of the questionnaire. Over half of the cats (55%) had received previous medical, dietary or surgical treatment. Motivations for changing the initial therapy to 131I therapy included difficulties in administering medication (31%), insufficient improvement in clinical signs (23%), side effects (16%) and following the referring veterinarian's advice (16%). Almost a fifth of owners (18%) were not informed about the existence of 131I therapy by their veterinarian and found information on 131I treatment online or through friends. Hospitalising their cat was very distressing for 17% of owners. Most owners (92%) were satisfied with the treatment. Reasons for dissatisfaction were insufficient communication, iatrogenic hypothyroidism, persistent hyperthyroidism and comorbidities post-treatment. CONCLUSIONS AND RELEVANCE: Our study stresses the importance of communication regarding the possible outcome of 131I treatment, the importance of managing underlying comorbidities before treatment and anticipating the stress of owners during their cat's hospitalisation period. The results of this study could help in improving client communication when advising on 131I treatment.

Evaluation of mega-voltage CT images for completed radiotherapy treatments for dogs and cats reveals uncommon but potentially consequential dose deviation in thoracic and abdominal tumors.

As advanced delivery techniques such as intensity-modulated radiation therapy (IMRT) become conventional in veterinary radiotherapy, highly modulated radiation delivery helps to decrease dose to normal tissues. However, IMRT is only effective if patient setup and anatomy are accurately replicated for each treatment. Numerous techniques have been implemented to decrease patient setup error, however tumor shrinkage, variations in the patient's contour and weight loss continue to be hard to control and can result in clinically relevant dose deviation in radiotherapy plans. Adaptive radiotherapy (ART) is often the most effective means to account for gradual changes such as tumor shrinkage and weight loss, however it is often unclear when adaption is necessary. The goal of this retrospective, observational study was to review dose delivery in dogs and cats who received helical radiotherapy at University of Wisconsin, using detector dose data (D2%, D50%, D98%) and daily megavoltage computed tomography (MVCT) images, and to determine whether ART should be considered more frequently than it currently is. A total of 52 treatment plans were evaluated and included cancers of the head and neck, thorax, and abdomen. After evaluation, 6% of the radiotherapy plan delivered had clinically relevant dose deviations in dose delivery. Dose deviations were more common in thoracic and abdominal targets. While adaptation may have been considered in these cases, the decision to adapt can be complex and all factors, such as treatment delay, cost, and imaging modality, must be considered when adaptation is to be pursued.

Solitary intraventricular tumors in dogs and cats treated with radiotherapy alone or combined with ventriculoperitoneal shunts: A retrospective descriptive case series.

BACKGROUND: Intraventricular tumors are rare, optimal treatment is not defined. Symptomatic patients often exhibit life-threatening hydrocephalus. With several months time-to-effect after radiotherapy (RT), increased intracranial pressure is concerning. This increase in pressure can be overcome by ventriculoperitoneal shunting (VPS). OBJECTIVES: Retrospective evaluation of outcome and complications in dogs and cats with intracranial tumors treated with either RT or VPS/RT. ANIMALS: Twelve client-owned cats and dogs. METHODS: Dogs and cats with symptomatic intraventricular tumors treated with definitive-intent RT or VPS/RT were included in a retrospective, descriptive case series. Complications, tumor volume evolution, time-to-progression, and survival time were determined. RESULTS: Twelve animals were included: 1 cat and 5 dogs treated with single-modality RT and 4 cats and 2 dogs treated with VPS/RT. Neurological worsening seen in 4/6 animals during single-modality RT and 2/6 died during RT (suspected brain herniation). All dogs with VPS normalized clinically by the end of RT or earlier. Complications occurred in 4/6 animals, all but 1 were successfully managed surgically. Imaging follow-up in 8 animals surviving RT showed a marked decrease in tumor volume. Median survival time was 162 days (95% confidence interval [CI]: 16; infinity) for animals treated with RT and 1103 days (95%CI: 752; infinity) for animals treated with VPS/RT. Median time-to-progression was 71 days (95%CI: 7; infinity) and 895 days (95%CI: 704; infinity) for each group, respectively. Two dogs died because of intraventricular metastasis 427 and 461 days after single-modality RT. CONCLUSIONS AND CLINICAL IMPORTANCE: Ventriculoperitoneal shunting led to rapid normalization of neurological signs and RT had a measurable effect on tumor volume. Combination of VPS/RT seems to be beneficial.

Palliative radiation therapy as a treatment for feline urinary bladder masses in four cats.

CASE SERIES SUMMARY: Urinary bladder masses in four cats were treated with palliative radiation therapy (RT). Three cats were previously diagnosed with chronic kidney disease (CKD): International Renal Interest Society (IRIS) stage 2 in two cats and IRIS stage 3 in one cat. One cat had a diagnosis of hyperthyroidism and inflammatory bowel disease. Three cats had urinary tract infections diagnosed by urine culture and susceptibility testing prior to or during treatment. All patients had urine cytospin cytology performed; one case showed suspect urothelial carcinoma and three had no cytological evidence of neoplasia. All clients declined further sampling from the bladder masses. Therefore, cytologic/histologic diagnosis in all cases was not available. An abdominal ultrasound was performed in all cats, which revealed urinary bladder mass(es) prior to referral for RT. Three cats had pretreatment thoracic radiographs, which revealed no evidence of pulmonary metastasis. An abdominal CT was performed in all cases and one case had thoracic CT performed for staging. The thoracic CT showed a focal lesion of unknown etiology in the right caudal lung lobe. Palliative RT was performed with four weekly 6 Gy fractions (24 Gy in total). The urinary signs in all cats resolved over the course of RT: after the first RT treatment in two cats and after the second RT treatment in two cats. There were two Veterinary Radiation Therapy Oncology Group grade 1 gastrointestinal and one grade 2 genitourinary acute RT side effects. RELEVANCE AND NOVEL INFORMATION: This is the first report in the literature of a standardized RT protocol as a treatment option for feline urinary bladder masses.

Effect of radioiodine treatment on muscle mass in hyperthyroid cats.

BACKGROUND: Approximately 75% of hyperthyroid cats lose muscle mass as accessed with a muscle condition scoring (MCS) system. After treatment, MCS improves as the cats regain muscle mass. OBJECTIVES: To quantify the degree of muscle loss in hyperthyroid cats using ultrasonography and evaluate changes in muscle mass after treatment. ANIMALS: Forty-eight clinically normal cats and 120 cats with untreated hyperthyroidism, 75 of which were reevaluated after radioiodine-131 therapy. METHODS: Prospective cross-sectional and before-after studies. All cats underwent ultrasonography and measurement of epaxial muscle height (EMH), with subsequent calculation of vertebral and forelimb epaxial muscle scores (VEMS and FLEMS). A subset of hyperthyroid cats underwent repeat muscle imaging 6 months after treatment. RESULTS: Untreated hyperthyroid cats had a lower EMH than did clinically normal cats (median [25th-75th percentile], 0.98 [0.88-1.16] cm vs 1.34 [1.23-1.58] cm, P < .001). Seventy-seven (64.2%) untreated cats had subnormal EMH. Similarly, compared to normal cats, hyperthyroid cats had lower VEMS (0.93 [0.84-1.07] vs 1.27 [1.18-1.39], P < .001) and FLEMS (1.24 [1.10-1.35] vs 1.49 [1.39-1.63], P < .001). After treatment, EMH increased (1.03 [0.89-1.03] cm to 1.33 [1.17-1.41] cm, P < .001), with abnormally low EMH normalizing in 36/41 (88%). Both VEMS (0.94 [0.87-1.10] to 1.21 [1.10-1.31], P < .001) and FLEMS (1.31 [1.17-1.40] to 1.47 [1.38-1.66], P < .001) also increased after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Almost two-thirds of hyperthyroid cats have abnormally low muscle mass when measured quantitatively by ultrasound. Successful treatment restores muscle mass in >85% of cats. EMH provided the best means of quantitating muscle mass in these cats.

Combined Hypofractionated Radiotherapy and Chemotherapy Versus Hypofractionated Radiotherapy Alone for Cats with Localized Sinonasal Lymphoma.

Despite considering hypofractionated radiotherapy (HRT) a useful treatment option for feline localized sinonasal lymphoma (stage I), the benefits of additional chemotherapy remain controversial. This retrospective cohort study evaluated the efficacy of the early initiation of chemotherapy in combination with HRT (HRTC) to prolong the progression-free survival (PFS) and overall survival (OS) in cats with localized sinonasal lymphoma compared with HRT alone. While 24 eligible cats received HRT alone (HRT group), 18 received HRTC (HRTC group). The total median administered dose was 35 Gy, with one fraction per week, for a median of five fractions. In the HRTC group, the chemotherapy protocol was cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based and cyclophosphamide, vincristine, and prednisolone (COP)-based in 14 (78%) and 4 cats (22%), respectively. Cats in the HRTC group had significantly longer PFS (677 versus 104 days; P = .04) and OS (983 versus 263 days; P = .04) than those in the HRT group. Considering the poor outcome in the HRT group despite the cats having received rescue chemotherapy for progressive disease, the early initiation of additional chemotherapy along with HRT may be recommended for feline localized sinonasal lymphoma.

A model to determine at-home restrictions for cats after treatment of hyperthyroidism with radioiodine.

OBJECTIVES: Felinehyperthyroidism is the most common endocrine disease of older cats and radioiodine is considered to be the gold standard treatment. Isolation periods following treatment vary depending on both individual treatment facilities and the relevant legislation of the country; therefore, there is no recognised standardised protocol defining the length of isolation. This work describes how our institution validated that its owner restrictions met dose constraints by using a model of iodine retention to calculate the required duration and nature of owner restrictions. MATERIALS AND METHODS: The retained radioactivity of cats at the point of discharge was used to simulate the radiation dose to owners in the 90 days following release. The model created was used to calculate the minimum duration of isolation for a range of administered activities and owner restrictions. RESULTS: Using the model, it was found that when injected with the maximum dose used, 222 MBq radioiodine, it was possible to release cats after 14 days of isolation and keep owner doses below 0.30 mSv (whole-body effective dose constraint for a single radiation source) with some restrictions. It was possible to release after 23 days with no restrictions. CLINICAL SIGNIFICANCE: The present study provides clinicians with a consistent and verified method in which they can calculate the isolation periods for radioiodine-treated cats.

Radioiodine treatment of hyperthyroidism in cats: results of 165 cats treated by an individualised dosing algorithm in Spain.

OBJECTIVES: Although radioiodine (131I) is the treatment of choice for feline hyperthyroidism, 131I-dosing protocols commonly induce iatrogenic hypothyroidism and expose azotaemia. A recently reported patient-specific 131I dosing algorithm minimised the risk of 131I-induced hypothyroidism and azotaemia, while maintaining high cure rates. The aim of the study was to report results of 131I treatment in a European population of hyperthyroid cats using this patient-specific dosing algorithm. METHODS: This prospective case series (before-and-after study) evaluated 165 hyperthyroid cats referred for 131I treatment. All cats had serum concentrations of thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH) measured (off methimazole ⩾1 week). Thyroid volume and percentage uptake of 99mTc-pertechnetate (TcTU) were determined using thyroid scintigraphy. An initial 131I dose was calculated by averaging dose scores for T4/T3 concentrations, thyroid volume and TcTU; 70% of that composite dose was then administered. Twenty-four hours later, percentage 131I uptake was measured, and additional 131I administered as needed to deliver an adequate radiation dose to the thyroid tumour(s). Serum concentrations of T4, TSH and creatinine were determined 6-12 months later. RESULTS: Median calculated 131I dose was 2.15 mCi (range 1.2-7.5), with only 51 (30.9%) receiving ⩾2.5 mCi. Of 165 cats, 124 (75.2%) became euthyroid, seven (4.2%) became overtly hypothyroid, 27 (16.4%) became subclinically hypothyroid and seven (4.2%) remained hyperthyroid. A higher proportion of overtly (85.7%) and subclinically (26.9%) hypothyroid cats developed azotaemia than euthyroid cats (13.6%; P = 0.0002). Hypothyroid cats were older (P = 0.016) and more likely to have detectable TSH concentrations (P = 0.025) and symmetrical bilateral distribution of 99mTc-pertechnetate uptake (P = 0.0002), whereas persistently hyperthyroid cats had higher severity scores (P = 0.012). CONCLUSIONS AND RELEVANCE: Our results confirm that 131I dosing with this new algorithm results in high cure rates, with a lowered prevalence of 131I-induced overt hypothyroidism and azotaemia. Age, serum TSH concentrations, bilateral, symmetrical uptake and severity score help predict outcome.

Non-injection-site soft tissue sarcoma in cats: outcome following adjuvant radiotherapy.

OBJECTIVES: Biological behaviour and treatment options of non-injection-site soft tissue sarcomas (nFISS) in cats are less well understood than in dogs. The aim of this retrospective study was to assess the outcomes of cats with nFISS following treatment with adjuvant radiotherapy. METHODS: The medical records of cats with soft tissue sarcomas in locations not associated with, and histology reports not suggestive of, injection-site sarcomas were reviewed. All cats underwent adjuvant radiotherapy, either hypofractionated (32-36 Gy delivered in weekly 8-9 Gy fractions) or conventionally fractionated (48-54 Gy delivered in 16-18 3 Gy fractions) to microscopic disease. RESULTS: In total, 18 cats were included in the study, 17 with extremity nFISS and one with facial nFISS. Nine received radiotherapy after a single surgery and nine after multiple surgeries for recurrent nFISS. Eight cats were treated with a hypofractionated protocol and 10 with a conventionally fractionated protocol. The median follow-up time was 540 days (range 51-3317 days). The tumour recurred in eight (44.4%) cats following adjuvant radiotherapy; it recurred in three (37.5%) cats following a hypofractionated protocol and in five (50%) cats following a conventionally fractionated protocol. The overall median progression-free interval (PFI) for 17/18 cats was 2748 days, while the median PFI for the 7/8 cats with recurrence was 164 days. The recurrence for one cat was reported, but the date was unknown and it was therefore censored from these data. When stratifying based on the protocol, the median PFI for hypofractionated and conventionally fractionated protocols was 164 days and 2748 days, respectively. Statistically, there was no significant difference between the two protocols (P = 0.636). CONCLUSIONS AND RELEVANCE: Adjuvant radiotherapy resulted in good long-term tumour control in 12/18 cats with nFISS. Further studies in larger populations are required to assess the significance of radiation dose and fractionation on tumour control and the effect of multiple surgeries prior to initiation of radiotherapy on outcome.

Outcome of radioiodine therapy for feline hyperthyroidism: Fixed dose versus individualized dose based on a clinical scoring system.

Background: Hyperthyroidism is the most frequent endocrinopathy in older cats. To date, there is no consensus on how to best calculate the dose of radioiodine to administer to hyperthyroid cats. Aim: The goals of this study were to compare thyroid function, renal function, and survival time between hyperthyroid cats receiving a fixed dose of radioiodine and those receiving an individualized dose calculated using a clinical scoring system. Methods: Medical records of 110 cats treated with radioiodine therapy at the University of Bern between 2010 and 2020 were reviewed. Thyroid function, renal function, and survival of cats treated with a fixed dose of radioiodine (2010-2015; n = 50) were compared to those of cats treated with an individualized dose (2015-2020; n = 60) at different time points after therapy. Results: Treatment with a fixed dose of radioiodine (mean = 168 ± 26 MBq) was associated with 69% of euthyroidism, 19% persistent hyperthyroidism, and 12% hypothyroidism, whereas treatment with an individualized dose (mean = 120 ± 30 MBq) led to 54% euthyroidism, 23% hyperthyroidism, and 23% hypothyroidism (p = 0.73). More than 12 months after treatment, the incidence of azotemia was comparable between cats treated with a fixed dose (37%) and those treated with an individualized dose (31%) (p = 0.77). No factors were found to be predictive of treatment failure (hypothyroidism or hyperthyroidism) after therapy. Median survival time after radioiodine therapy was 44 months. In a multivariate analysis, persistent hyperthyroidism was the only variable independently associated with a shorter survival time (HR = 6.24, p = 0.002). Conclusion: The method of calculating the dose of radioiodine (fixed vs. individualized) to treat feline hyperthyroidism does not appear to be decisive for posttreatment thyroid function, renal function, or survival.

Combining radiation therapy with zoledronate for the treatment of osteo-invasive feline oral squamous cell carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is the most common oral tumour diagnosed in pet cats and carries a poor prognosis with <10% one-year survival despite multi-modal therapies. Tumours of the mandible or maxilla are frequently osteo-invasive and pain can result from osteolysis. Zoledronate is a bisphosphonate that inhibits osteoclasts and reduces bone resorption. Radiation therapy (RT) is used to treat FOSCC due to anti-cancer activity and ability to improve quality of life. We hypothesized RT can be safely combined with zoledronate, and that this combinatory therapy would be efficacious, well tolerated, and result in decreased bone resorption in cats with FOSCC. SCCF1 cell line was treated with zoledronate before, concurrently, or after RT, and clonogenic assays were performed to determine if an optimal dosing schedule would be identified. Nine cats with osteoinvasive FOSCC were recruited for treatment with 4 weekly doses of 8 Gy RT combined with zoledronate administered at the first and fourth treatments. Serial CT scans were performed to assess tumour response. Safety and tolerability were monitored with hematologic and biochemical parameters, and acute radiation effects were characterized. Serum c-telopeptide (CTx) and relative bone mineral density (rBMD) by dual -energy X-ray absorptiometry (DEXA) quantified bone resorption. In vitro studies showed no clear benefit to timing of zoledronate with RT, therefore all zoledronate was administered concurrently with RT in FOSCC patients. Based on tumour volume, 4/9 (44.4%) cats achieved partial remission, 4/9 (44.4%) stable disease and 1/9 (11.1%) had progressive disease. The combinatory therapy was well-tolerated based on biochemical measurements, and all patients experienced decreased serum CTx. Combining RT with zoledronate in tumour-bearing cats is safe, well-tolerated, results in a partial remission rate of up to 44%, and decreases serum CTx, a marker of bone resorption.

Use of a cyclical hypofractionated radiotherapy regime ('QUAD shot') for the treatment of feline sinonasal carcinomas.

OBJECTIVES: Radiation therapy is the treatment of choice for cats with sinonasal carcinomas. Different protocols have been described in the literature, though a clear consensus regarding the optimal protocol is lacking. The aim of the study was to describe the tolerability, efficacy and outcome of cats treated with a cyclical hypofractionated protocol. METHODS: Cats with histologically diagnosed sinonasal carcinomas in a single institution were retrospectively included. All patients were treated with a cyclical hypofractionated protocol ('QUAD shot' regime). Cats were treated with 4 Gray (Gy) delivered in four fractions within 48 h, with a minimum of 6 h between two treatments, and repeated every 3-4 weeks for a total dose of 48 Gy in three cycles. RESULTS: Seven cats met the inclusion criteria. Nasal discharge and sneezing were the most common presenting complaints. All cats presented with advanced stage of disease with CT examination (three with modified Adams stage 3 and four with stage 4). Clinical improvement was seen in six cats. Five cats had a follow-up CT; one had a complete response, two had partial responses, one had stable disease and one had progressive disease. Two cats were still alive at the time of writing while four were euthanased owing to tumour-related causes. The median overall survival time was 460 days. The 1-year survival time was 80% and the 2-year survival time was 0%. Severe acute or late toxicity was not reported. CONCLUSIONS AND RELEVANCE: This is the first report of a cyclical hypofractionated protocol in the veterinary literature that can provide prolonged survival in cats with advanced stage sinonasal carcinoma. Its use should be considered in patients when prolonged hospitalisation can be detrimental to quality of life, while still delivering a therapeutic total dose of radiation therapy.