Treatment of oral squamous cell carcinoma with accelerated radiation therapy and concomitant carboplatin in cats

Background: Feline oral squamous cell carcinoma (SCC) carries a very poor prognosis with traditional treatments. Hypothesis/Objectives: To examine the effectiveness of adding carboplatin to a previously published accelerated radiation protocol in the treatments of oral SCC in cats. Animals: Thirty‐one cases of oral SCC in cats. Tumor sites included lingual (n = 9), mandible (n = 10), maxilla (n = 7), tonsil (n = 4), and cheek (n = 1). Methods: Prospective trial using a planned radiation protocol consisting of 14 fractions of 3.5 Gy given within a 9‐day period with the addition of carboplatin given at 90–100 mg/m² on day 1 and day 4.5. Treatments were twice daily with a 6‐hour delay between treatments. All cats presenting with oral SCC without evidence of distant metastasis were eligible. Results: Median survival for all cats was 163 days (range 53–770 days) with a mean of 319 ± 53 days with significant predictors of survival being site (P= .004) and whether there was a complete response at 30 days (P= .001). Cats with tumors of tonsil origin or cheek responded best to therapy and were long‐term survivors with a mean survival of 724 days and the median had not been reached because of continued survival of 4 cats. Conclusions and Clinical Importance: This protocol offers an aggressive yet tolerable treatment of oral SCC in cats that might offer improved survival as compared with previously reported treatments. The long‐term survival of cats with tonsillar SCC has not been reported previously.     

Environmental risk factors for the development of oral squamous cell carcinoma in cats

BackgroundRisk factors for oral squamous cell carcinoma (OSCC) in cats are derived from a single study dated almost 20 years ago. The relationship between inflammation of oral tissues and OSCC is still unclear.ObjectivesTo investigate previously proposed and novel potential risk factors for OSCC development, including oral inflammatory diseases.AnimalsHundred cats with OSCC, 70 cats with chronic gingivostomatitis (CGS), 63 cats with periodontal disease (PD), and 500 controls.MethodsProspective, observational case‐control study. Cats with OSCC were compared with an age‐matched control sample of client‐owned cats and cats with CGS or PD. Owners of cats completed an anonymous questionnaire including demographic, environmental and lifestyle information.ResultsOn multivariable logistic regression, covariates significantly associated with an increased risk of OSCC were rural environment (OR: 1.77; 95% CI: 1.03‐3.04; P = .04), outdoor access (OR: 1.68; 95% CI: 1.07‐2.63; P = .02), environmental tobacco smoke (OR: 1.77; 95% CI: 1.05‐3; P = .03), and petfood containing chemical additives (OR: 1.98; 95% CI: 1.04‐3.76; P = .04). Risk factors shared with CGS and PD were outdoor access and petfood containing chemical additives, respectively. A history of oral inflammation was reported in 35% of cats with OSCC but did not emerge as a risk factor.Conclusions and Clinical ImportanceThe study proposes novel potential risk factors for OSCC in cats. Although a history of inflammatory oral disease was not significantly more frequent compared with random age‐matched controls, OSCC shared several risk factors with CGS and PD.     

Oesophageal squamous cell carcinoma in two cats

Two cases of feline oesophageal squamous cell carcinoma are described. In both cases, diagnosis was achieved by radiography, endoscopy and cytology, and later confirmed by histology. One cat underwent oesophagectomy followed by end-to-end anastomosis, but died three days postsurgery; the second cat was euthanased after diagnosis.     

Environmental and lifestyle risk factors for oral squamous cell carcinoma in domestic cats

Oral squamous cell carcinoma (SCC) is a common malignancy in cats, but little currently is known about its etiology. We examined the relationship between risk of oral SCC and factors such as environmental tobacco smoke, flea control products, and diet in 36 domestic cats with histologically confirmed oral SCC and 112 renal disease control cats presented to a large veterinary referral hospital between 1994 and 2000. Questionnaires were mailed to owners of all study and control cats to assess demographic characteristics, lifestyle factors, and level of chemical exposures 2 years before diagnosis. Multivariate relative risks (RR) were used to estimate the relationships between the various factors and the risk of oral SCC. Flea control product use and diet were significantly associated with risk of oral SCC. Cats that wore a flea collar had 5 times the risk of oral SCC as nonusers, after adjustment for other factors (RR = 5.3; P = .002). In contrast, use of flea shampoo substantially reduced risk. Compared to cats eating mostly dry food, those with high canned food intake had a 3-fold increase in risk (RR = 3.6; P = .014); canned tuna fish intake was independently associated with risk (RR = 4.7; P = .004). Exposure to household environmental tobacco smoke was associated with a nonsignificant 2-fold increase in risk (P = .11). Results of this study suggest that flea control products, diet, and perhaps environmental tobacco smoke might be associated with risk of oral SCC and indicate that further investigation into these relationships is warranted.     

Evaluation of plasma folate and homocysteine concentrations in cats with and without oral squamous cell carcinoma

Feline oral squamous cell carcinoma (SCC) is a devastating disease with an extremely poor long‐term prognosis even with aggressive therapy. Folate and homocysteine derangements are identified in people diagnosed with head and neck SCC. The purpose of this study was to measure plasma folate and homocysteine concentrations in cats diagnosed with oral SCC (n = 13) and to compare these concentrations with those found in cats diagnosed with other tumour types (n = 25), cats with oral, non‐neoplastic disease (n = 6) and healthy cats (n = 24). The median plasma folate concentration in cats diagnosed with oral SCC was 14.7 ng mL^?1, while the median plasma homocysteine concentration was 2.61 μg mL^?1. These concentrations did not differ significantly from those of cats in the other groups. This suggests that different factors may contribute to the pathogenesis of this tumour in cats when compared with people, although evaluation of larger numbers of cats may still identify a difference between groups.     

The prognosis in cats bearing squamous cell carcinoma

During the past 2 years, follow-up studies have been carried out on twenty cats following surgery for the treatment of squamous cell carcinoma. An attempt has been made to correlate the permitted survival time of the animal with the site of the tumour, its degree of differentiation, and the length of time between initial detection and surgery. In seven cats with intra-oral tumours the prognosis was very poor. Four out of seven cats were destroyed within 7 weeks, and all were destroyed within 14 weeks. All animals had to be killed because of local recurrence and it did not appear that the degree of differentiation of the tumour was important. In animals with squamous carcinoma in the skin, the prognosis could be correlated with the degree of differentiation of the tumour, but not with the site. Fifty percent of animals with poorly differentiated tumours were destroyed within 12 weeks, and the longest survival time was 20 weeks. All animals with well-differentiated tumours survived for more than 36 weeks. Résumé. Pendant deux ans, nous avons suivi le progres de vingt chats apres une intervention chirurgicale pour traiter des carcinomes de cellules squameuses. Nous avons essaye d'établir un rapport entre la survie et le lieu du neoplasme, sa difierentiation et l'intervalle entre sa detection initielle et l'enlevement. Le prognostic etait tres mauvais chez sept chats avec des tumeurs burralles. Quatre sur sept sonts morts dans sept seamines et tous sonts morts avant quatorze semaines. Tous les animaux etarent mise a mort a cause des reapparitions locales et il ne semble pas que le degre de differentiation est important. Chez les animaux portant des carcinomes de cellules squameuses a la peau il y avait un rapport entre le prognostic et le degre de differentiation de la tumeur, mais pas avec sa location. Chez les animaux portant des tumeurs peu differencies, conquette pour cent sont morts en douze semaines et la survie la plus etendue etait de vingt semaines, tendis que tous les animaux portant dea tumeurs bien differencies sonts morts apres trente six semaines. Zusammenfassung. Innerhalb der latzten zwei Jahren sind Studien an 20 katzen, die wegen Plattenzeil carcinom in chirurgischer Behandlung waren, gemacht worden. Ein Versuch, die Überlebens-zeit des Tieres mit der Lage des Tumors, seinem Differenzierungs-grad, und der Zeitspanne zwishen Diagnose und Chirurgie in Zusammenhang zu bringen, wurde unternommen. Im Falle von 7 Katzen mit Mundhöhlen tumoren war die Prognose sehr schiecht. 4/7 Katzen starben innerhalb von 7 Wochen, und alle innerhalb von 14 Wochen. Alle Tiere wurden wegen localen Rezidivtumoren getötet, und der Differenzierungsgrad schien nicht massgebend zu sein. In Tieren mit Plattenzell carcinom der Haut hing die Prognose vom Differenzierungsgrad, aber nicht von der Lage, ab. 50% der Tiere mit schlecht differentierzen Tumoren starben innerhalb von 12 Wochen, und die Längste Uberlebens zeit war 20 Wochen, während alle Tierre mit gut differenzierte Tumoren mehr als 36 Wochen überlebten.     

Bone-invasive oral squamous cell carcinoma in cats: pathology and expression of parathyroid hormone-related protein

Feline oral squamous cell carcinoma (OSCC) is the most common oral tumor in cats. There is no effective treatment, and the average duration of survival after diagnosis is only 2 months. Feline OSCC is frequently associated with osteolysis; however, the mechanisms responsible are unknown. The objective of this study was to characterize the epidemiology and pathology of bone-invasive OSCC in cats and to determine the expression of select bone resorption agonists. In sum, 451 cases of feline OSCC were evaluated. There was no sex or breed predisposition, although there were more intact cats in the OSCC group compared to the control group. Gingiva was the most common site, followed by the sublingual region and tongue. Cats with lingual OSCC were younger (mean, 11.9 years) compared to cats with gingival OSCC (mean, 13.6 years). In addition to osteolysis, there was periosteal new bone formation, osseous metaplasia of tumor stroma, and direct apposition of OSCC to fragments of bone, suggestive of bone-binding behavior. Eighty-two cases were selected for immunohistochemical detection of parathyroid hormone-related protein (PTHrP). Specimens with osteolysis had increased PTHrP expression and nuclear localization, compared to OSCC without osteolysis. Thirty-eight biopsies of OSCC with osteolysis were evaluated for tumor necrosis factor α expression, and only 4 biopsies had such expression in a small proportion of tumor cells. Increased tumor expression of PTHrP and increased localization of PTHrP to the nucleus were associated with osteolysis and may play an important role in bone resorption and tumor invasion in cats with OSCC.     

In vivo and in vitro efficacy of zoledronate for treating oral squamous cell carcinoma in cats

BACKGROUND: Feline oral squamous cell carcinoma (OSCC) may cause painful bone destruction. Given the local invasiveness and rapid clinical progression of OSCC, conventional therapies are often palliative. In human cancer patients, zoledronate exerts anticancer effects by inhibiting tumor-induced angiogenesis and malignant osteolysis. HYPOTHESIS: Zoledronate will exert in vitro and in vivo anti-angiogenic and antiresorptive effects in feline OSCC. ANIMALS: Eight cats with OSCC were prospectively treated with zoledronate and conventional treatment modalities. METHODS: In vitro, zoledronate's effects in modulating soluble vascular endothelial growth factor (VEGF) secretion and receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) expression were investigated in a feline OSCC cell line (SCCF1). In vivo, basal serum C-telopeptide (CTx) concentrations were compared among normal and OSCC-bearing cats, and the biologic effects of zoledronate administration in cats with naturally occurring OSCC were quantified by serially assessing circulating serum VEGF and CTx concentrations. RESULTS: In vitro, zoledronate concentrations greater than 3 microM reduce soluble VEGF secretion in the SCCF1 cell line. The expression of RANKL in the SCCF1 cell line was also modulated by zoledronate, with low concentrations (3 microM) decreasing but higher concentrations (30 microM) increasing RANKL expression in comparison with untreated cells. In vivo, cats with bone-invasive OSCC had greater serum CTx concentrations in comparison with geriatric, healthy controls. Treatment with zoledronate rapidly decreased circulating serum VEGF and CTx concentrations in cats with spontaneously occurring OSCC. CONCLUSIONS AND CLINICAL IMPORTANCE: Zoledronate exerts in vitro and in vivo effects that may favor the slowing of tumor growth and pathologic bone turnover associated with OSCC.     

Toxicity and outcome in cats with oral squamous cell carcinoma after accelerated hypofractionated radiotherapy and concurrent systemic treatment

Recently, a multimodal approach to oral squamous cell carcinoma (SCC) in cats, combining medical treatment and accelerated radiation therapy, showed a substantial outcome improvement in a small pilot study. Herein we retrospectively review 51 cats with unresectable, histologically confirmed oral SCC and a complete initial staging work‐up: cats in group A (n = 24) received medical anti‐angiogenic treatment consisting of bleomycin, piroxicam and thalidomide, cats in group B (n = 27) received the anti‐angiogenic treatment and concurrent accelerated hypofractionated radiation therapy with 48Gy delivered in 10 fractions. Overall median progression‐free interval (PFI) was poor with 70 days (95% CI: 48;93). In the irradiated cats (group B), however, PFI was significantly longer with 179 days (95% CI: 58;301) days, vs 30 days (95% CI: 23;38) in medically only treated cats (P < .001). Overall median overall survival (OS) was 89 days (95% CI: 55;124), again significantly longer in the irradiated cats (group B) with 136 (95% CI: 40;233) vs 38 days (95% CI: 23;54) (P < .001). In 8 of the 27 (29.6%) cats in group B, however, severe toxicity (grade 3) occurred. Neither onset nor severity of toxicity could be associated with any of the tested variables, including anatomic site, tumour size, clinical stage and duration of neoadjuvant medical treatment. Given the potential severe acute effects and the impact on quality of life after chemo‐radiotherapy, owners must be clearly informed about the risks of treatment. With the overall poor outcome and high occurrence of acute toxicity, we cannot recommend the use of this accelerated radiation protocol combined with anti‐angiogenic therapy for oral SCC in cats.     

Male tortoiseshell cats in the United Kingdom

A questionnaire concerning the coat colour and sex of cats being vaccinated or neutered was sent to 2585 veterinary practices; 393 (15.2 per cent) were returned and information was obtained about 9816 cats. Of 4598 males, 20 were recorded as tortoiseshell (0.43 per cent). The frequency of the orange gene was 19.7 per cent assuming that male tortoiseshell cats had two X chromosomes. The chromosome complement and/or gonadal histology of 14 male tortoiseshell cats is described. Cytogenetic analysis of 11 animals revealed six with a 38,XX/38,XY complement, two with 39,XXY, two with 38,XX, and one with a 38,XY complement.     

Multiple squamous cell carcinoma of the digits in two cats

This paper describes the clinical and pathological features of two cats with squamous cell carcinoma affecting several digits. Similar lesions have been described in dogs and humans.     

Hematoporphyrin-based photodynamic therapy for cutaneous squamous cell carcinoma in cats

Photodynamic therapy (PDT) using a haematoporphyrin derivative (Photogem®, General Physics Institute and clustes Ltda) as photosensitizer and light emitting diodes (LEDs) as the light source was evaluated in 12 cats with cutaneous squamous cell carcinoma. Lesions were illuminated with LEDs, (300 J/cm for 30 min) 24 h after the administration of the photosensitizer. Clinical responses were classified as complete disappearance of the tumour with total re-epithelialization; partial response (a reduction greater than 50%); and no response (less than 50% reduction). Tumours localized to the pinna treated with one ( n  = 3) or two ( n  = 4) applications of PDT yielded no response. Highly invasive tumours of the nose and nasal planum also showed no response, after two treatments ( n  = 2). A combination of PDT and surgery was performed in three cases. Two cats showed partial response and one complete response with one application of therapy 30 days after nasal surgery. Small and noninfiltrative lesions ( n  = 3) of the nasal planum showed a PR with one application ( n  = 2) and a CR with two applications ( n  = 1). This study shows that PDT using Photogem® and LEDs can provide local control of low-grade feline squamous cell carcinoma. The addition of PDT to surgery in more invasive cases may help prevent recurrence.     

Hypocobalaminaemia is uncommon in cats in the United Kingdom

Recent work has highlighted the importance of cobalamin deficiency in cats with a range of alimentary tract diseases. The primary aim of our study was to determine the incidence of subnormal cobalamin concentrations in sick cats with and without alimentary system disorders. Firstly, serum cobalamin concentrations were measured in a population of cats, with and without gastrointestinal (GI) disease, evaluated at a referral hospital. In the second part of the study, the incidence of cobalamin deficiency was assessed in samples submitted to a commercial laboratory specifically for cobalamin measurement. For both studies, a validated radioimmunoassay was used to measure serum cobalamin concentrations (reference range: > 150 pg/ml). In the first part of the study, 132 cats were included and none of these cats had subnormal cobalamin concentrations (median=1,172; range: 278 to >2,000). There were no differences in cobalamin concentrations between cats with alimentary system disorders, and those with diseases of other organs. In the second part, 682 samples were submitted for cobalamin assay over a period of 3 years, and only one cat had a result below the reference range (median=794; range: 147 to >2,000). Cobalamin deficiency was rare in the population tested and this may suggest that the incidence of this biochemical abnormality is less common than reported in the USA.     

Metastasizing oral squamous cell carcinoma in an aged pig

A 10-year-old, female, pot-bellied pig (Sus scrofa) experienced a 3-month history of reduced appetite, dysphagia, and weight loss. Clinical examination revealed a mass in the left part of the oral cavity extending from the hard to the soft palate. At necropsy, a firm, white, poorly demarcated ulcerated mass at the left hard and soft palate with metastases to the left retropharyngeal lymph node and the lung was observed. Additional findings included a uterine adenocarcinoma, a hepatocellular adenoma, and nodular hyperplasias in spleen and adrenal glands. Histologically, the poorly demarcated, infiltrative growing oral mass consisted of islands, cords, and single epithelial cells with moderate squamous differentiation. Cells were strongly positive for cytokeratin by immunohistochemistry. Similar cells were found in the left retropharyngeal lymph node and the lung. The present findings represent the first report of a metastasizing oral squamous cell carcinoma in a pig.     

Hypercalcemia in two cats with squamous cell carcinomas

Hypercalcemia was identified in 2 cats with squamous cell carcinomas. One cat was referred because of multiple cutaneous tumors; the second cat had metastatic disease from an oral squamous cell carcinoma. In both cats, serum immunoreactive midmolecule parathyroid hormone concentration was within the range determined for clinically normal cats. The high serum calcium concentration in these cats may have resulted from the neoplastic disease, as evidenced by the reduction in serum calcium concentration after decrease in tumor size in response to treatment, and by failure to identify other known causes of hypercalcemia.     

Photodynamic therapy response in cats with cutaneous squamous cell carcinoma as a function of fluence

The response of advanced stage cutaneous squamous cell carcinomas (SCC) following treatment with photodynamic therapy (PDT) has been poor. It was the aim of this pilot study to determine whether an increase in the delivered fluence (i.e. energy density) would improve the duration of tumour remission in cats with advanced-stage SCC. Tumours were treated with aluminium phthalocyanine tetrasulphonate (AlPcS₄) PDT at a fluence of either 100 J cm⁻² or 200 J cm⁻² and tumour response was evaluated at regular intervals. Those feline tumours treated with a fluence of 100 J cm⁻² ( n = 8) had a significantly shorter median remission duration (69 days; range 0–619 days) than those feline tumours treated with 200 J cm⁻² ( n = 6; 522 days; range 151–1057 days). It is our conclusion that a fluence of 200 J cm⁻² is well tolerated and more effective when treating cats with advanced stage cutaneous SCC.     

Use of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II), a liposomal cisplatin analogue, in cats with oral squamous cell carcinoma

OBJECTIVE: To determine clinical response and toxic effects of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP) administered i.v. at escalating doses to cats with oral squamous cell carcinoma (SCC). ANIMALS: 18 cats with oral SCC. PROCEDURE: Cats that failed to respond to conventional treatment or had nonresectable tumors were included. Data included a CBC, serum biochemical analyses, urinalysis, cytologic examination of a fine-needle aspirate of enlarged lymph nodes, and thoracic and oral radiographs for clinical staging. A starting dose (75 to 100 mg/m2 of L-NDDP) was administered i.v.. At 21-day intervals, subsequent doses increased by the rate of 5 or 10 mg/m2. Response was evaluated every 21 days by tumor measurement and thoracic radiography. Quality of life was assessed by owners, using a performance status questionnaire. RESULTS: On average, cats received 2 treatments. Toxicoses included an intermittent, acute anaphylactoid-parasympathomimetic reaction, lethargy or sedation (< or = 24 hours), inappetence or signs of depression (< or = 72 hours), mild to moderate increase in hepatic enzyme activity, and melena. Pulmonary, renal, or hematopoietic abnormalities were not evident. Performance status surveys indicated normal behavior and grooming or decreased activity and self-care (19/20 assessments), ate well with or without assistance (15/20), and did not lose weight (15/20). Median survival time was 59.8 days (mean, 54.1 days). CONCLUSIONS AND CLINICAL RELEVANCE: L-NDDP was ineffective for treatment of cats with oral SCC. None of the cats had a complete or partial remission. Acute toxicoses and poor therapeutic response limit therapeutic usefulness of L-NDDP in cats, unless dosage, frequency, and administration procedures can be improved.