Squamous Cell Carcinoma In Cats Research Articles

Treatment of Oral Squamous Cell Carcinoma with Accelerated Radiation Therapy and Concomitant Carboplatin in Cats

Feline oral squamous cell carcinoma (SCC) carries a very poor prognosis with traditional treatments. To examine the effectiveness of adding carboplatin to a previously published accelerated radiation protocol in the treatments of oral SCC in cats. 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). 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/m(2) 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. 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. 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.

Abstract 3293: Activity and safety of an antiangiogenic peptide in spontaneous head and neck squamous cell carcinoma in cats

Abstract Anginex is a rationally designed, synthetic peptide that inhibits proliferation of human and mouse endothelial cells and demonstrates anti-tumor activity in murine tumor models. The anti-tumor and anti-angiogenic activity of Anginex is attributable, at least in part, to its interaction with galectin-1, a carbohydrate binding protein. As an intermediate step in the clinical translation of Anginex and related anti-vascular agents, we are investigating the effects of Anginex in spontaneous feline head and neck squamous cell carcinoma (HNSCC). Feline HNSCC shares morphology, clinical behavior, and biologic features such as intratumoral hypoxia and expression of EGFR, COX-2, and mutant p53 with its human counterpart. Our objectives were to investigate the activity of Anginex in feline cells and provide evidence of its safety in a phase I trial in cats with HNSCC. To establish Anginex activity in vitro, we evaluated the effect of 24 hour exposure to Anginex doses ranging from 2.5 – 25 uM on proliferation of both feline aortic endothelial cells (FAECs) and feline HNSCC cells (SCCF1) using flow cytometry and labeling with propidium iodide and bromodeoxyuridine (BrdU). With increasing Anginex dose, we observed accumulation of FAECs in G1 and decreased uptake of BrdU. We observed no effect in SCCF1 cells. To investigate safety, cats were treated with Anginex in cohorts of at least three animals at doses of 1, 3, and 9 mg/kg daily for 5 days. Clinical, laboratory and histologic features were evaluated before and after treatment. There were no serious adverse events during treatment. Continuous variables including body weight and laboratory variables were compared before and after treatment using a Wilcoxon signed rank test. No statistically significant changes occurred in these parameters. These data indicate that Aniginex is active against feline endothelial cells specifically and appears to be safe in cats. We are currently investigating the effects of Anginex on tumor physiology and in combination with radiation therapy for feline HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3293. doi:10.1158/1538-7445.AM2011-3293

Bone-Invasive Oral Squamous Cell Carcinoma in Cats

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.

Computed tomographic features of oral squamous cell carcinoma in cats: 18 cases (2002–2008)

To describe the computed tomographic features of oral squamous cell carcinoma (SCC) in cats and identify imaging characteristics associated with survival time. Retrospective case series. 18 cats with a diagnosis of oral SCC. Information on history; clinical, laboratory, and diagnostic imaging findings; treatment; and survival time was obtained from medical records of 18 cats with oral SCC. Computed tomography (CT) studies were examined to identify features associated with oral SCC. The association of CT features with survival time was evaluated. On CT images, SCC was centered at the following sites: sublingual or lingual region (n = 7), maxilla (5), buccal mucosa (4), mandible (4), pharyngeal mucosa (2), soft palate mucosa (1), and lip (1). These results were in agreement with the results of oral examination for all sites, except the soft palate (CT, 1 cat; oral examination, 4 cats). On CT images, extension of maxillary masses was most often observed to affect the orbit (5 cats). Heterogeneous contrast enhancement was most commonly identified (8/18). Osteolytic mass lesions were identified on CT images in 9 cats. None of the quantitative CT features that were identified, including mass size, attenuation, or lymph node width, were correlated with survival time. Common CT features of oral SCC in cats included sublingual and maxillary locations, marked heterogeneous contrast enhancement, and osteolysis. Computed tomography may be used to determine mass extension and lymph node enlargement, but results did not correlate with survival time.

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.

5.08] Fluorescence diagnosis and photodynamic therapy of superficial squamous cell carcinomas in cats using topical 5-aminolevulinic acid and incoherent light sources

Objective In human medicine photodynamic therapy (PDT), utilizing the topical administration of 5-aminolevulinic acid (5-ALA) has generated widespread interest in the past several years and is rapidly becoming the standard treatment for multiple actinic keratosis in several countries. In cats, UV-induced superficial squamous cell carcinomas have been treated with PDT using systemic sensitizers and diode lasers. The effect of topical 5-ALA as a 20%-creamor as 10%-gelin squamous cell carcinomas in cats is demonstrated. Material and methods In total 15 cats with squamous cell carcinomas on the pinna or the nose have been treated with PDT. 5-ALA was applied topically for 4–6 h under occlusion while the animals were sedated. Before radiation with an incoherent light source and a fluence of 180 J/cm 2 was applied, photographs of the fluorescence were taken using a digital camera with a mounted long pass filter. Results In more than 80% of the cases, one single treatment was curative. Conclusion Superficial squamous cell carcinomas in cats can be effectively treated with topical 20%-ALAcream or 10%-ALAgel and using incoherent light sources.

Photodynamic Therapy of Superficial Nasal Planum Squamous Cell Carcinomas in Cats: 55 Cases

Squamous cell carcinomas (SCCs) are common skin tumors in cats. We investigated photodynamic therapy (PDT) using the photosensitizing agent 5-aminolaevulinic acid (5-ALA) topically and a high-intensity red light source. PDT is a safe and effective treatment for feline SCCs. Fifty-five client-owned cats with superficial nasal planum SCCs. Prospective, uncontrolled clinical trial. PDT was performed using topical 5-ALA and light of peak wavelength 635 nm. Adverse effects, response, and tumor control were evaluated. 53/55 (96%) cats responded to therapy, and there was a complete response in 47/55 (85%). Six cats (11%) had a partial response. Of the 47 cats with complete response to a single treatment, 24 recurred (51%), with a median time to recurrence of 157 days (95% confidence interval, 109-205 days). Repeat PDT was performed in 22 cats, and at a median follow-up of 1,146 days, 23 (45%) cats were alive and disease free, 17 (33%) had to be euthanized due to tumor recurrence, and 11 (22%) were euthanized for other reasons. Only transient mild local adverse effects were observed after treatment. PDT using 5-ALA and a red light source was safe, well tolerated, and effective in the treatment of superficial nasal planum SCCs of cats and offers an alternative to conventional therapy. Although initial response rates were high, this treatment did not lead to a durable remission or cure in all cases.

Use of imiquimod 5% cream (Aldara™) in cats with multicentric squamous cell carcinoma in situ: 12 cases (2002–2005)*

Multicentric squamous cell carcinoma in situ (MSCCIS) is a variant of squamous cell carcinoma in cats, commonly referred to as Bowen's-like disease. Imiquimod 5% cream (Aldara) is a novel immune response modifier (IRM) that has been reported as a successful treatment for Bowen's disease in humans. The purpose of this study was to describe clinical findings, treatment protocols and survival in cats with MSCCIS treated with imiquimod 5% cream and to examine the effects of imiquimod 5% cream in cats with MSCCIS. The expression of papillomavirus group-specific antigen in the study population was also determined. From review of medical records, 12 cats were identified with a histologic diagnosis of MSCCIS and treatment with imiquimod 5% cream. Initial lesions responded to imiquimod 5% cream in all cats. Most cats (75%) developed new lesions. New lesions also responded to imiquimod 5% cream in all cats treated. Five cats (41%) had side effects suspected to be associated with the use of imiquimod 5% cream, including local erythema (25%), increased liver enzymes and neutropenia (8%), and partial anorexia and vomiting (8%). Kaplan-Meier median treatment duration and median survival time probabilities for cats in this study were 1189 days, respectively. A time to failure model was generated as many cats were censored from analysis well before the aforementioned projected median. This model resulted in a shorter median survival time of 243 days. No patient-related, tumour-related or treatment-related prognostic variables were identified. No expression for papilloma group-specific antigen was found. Imiquimod 5% cream appears to be well tolerated in the majority of cats, and further studies are warranted to further examine its usefulness in cats with this disease.

In Vivo and In Vitro Efficacy of Zoledronate for Treating Oral Squamous Cell Carcinoma in Cats

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. Zoledronate will exert in vitro and in vivo anti-angiogenic and antiresorptive effects in feline OSCC. Eight cats with OSCC were prospectively treated with zoledronate and conventional treatment modalities. 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. 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. Zoledronate exerts in vitro and in vivo effects that may favor the slowing of tumor growth and pathologic bone turnover associated with OSCC.

Electrochemotherapy for the treatment of squamous cell carcinoma in cats: A preliminary report

Squamous cell carcinomas (SCC) of the skin are commonly described in cats. Reported treatments include surgery, radiation therapy and photodynamic therapy. This preliminary study reports on the management of these lesions combining the local administration of bleomycin (plus hyaluronidase for a more uniform distribution) with permeabilizing biphasic electric pulses. Nine cats with SCC graded T 2–T 4 were treated over a 5 year period, and each cat received two sessions of electrochemotherapy (ECT) 1 week apart. The side effects of this treatment were minimal and limited to mild erythema of the nose. Seven of the cats (77.7%) had a complete response lasting up to 3 years. ECT seems to be a safe and effective option for the treatment of feline sun-induced squamous cell carcinomas and warrants further investigation.

Photodynamic Therapy of Feline Cutaneous Squamous Cell Carcinoma Using a Newly Developed Liposomal Photosensitizer: Preliminary Results Concerning Drug Safety and Efficacy

Background: Squamous cell carcinomas are common skin tumors in cats. We investigated photodynamic therapy (PDT) using a new liposomal photosensitizer as a minimally invasive, effective treatment that can be easily performed while achieving good cosmetic results. Aim: The goal of this study was to assess and describe possible toxicities using a liposomal formulation of the photosensitizer meta‐(Tetrahydroxyphenyl)Chlorin (m‐THPC) and investigate if favorable pharmacokinetics translate into favorable tumor response and control. Animals: Eighteen client‐owned cats with 20 spontaneous cutaneous squamous cell carcinomas were included in the study. Methods: PDT was performed using a new, liposomal formulation of the photosensitizer. Toxicity, tumor response, and tumor control were evaluated retrospectively. Results: No general adverse effects were observed in cats treated with the new liposomal formulation. Mild local toxicity such as erythema and edema were seen in 15% of the patients. All cats responded to therapy, with a complete response rate of 100%. The overall 1‐year control rate was 75%. The tumor recurrence rate was 20% with a median time to recurrence of 172.25 (±87.1) days. Conclusions and Clinical Importance: A new liposomal photosensitizer was successfully used for squamous cell carcinoma in cats and was well tolerated. There were no systemic adverse effects observed with the liposomal formulation. The favorable pharmacokinetics of the liposomal drug resulted in a favorable tumor response.

Photodynamic Therapy of Feline Cutaneous Squamous Cell Carcinoma Using a Newly Developed Liposomal Photosensitizer: Preliminary Results Concerning Drug Safety and Efficacy

Squamous cell carcinomas are common skin tumors in cats. We investigated photodynamic therapy (PDT) using a new liposomal photosensitizer as a minimally invasive, effective treatment that can be easily performed while achieving good cosmetic results. The goal of this study was to assess and describe possible toxicities using a liposomal formulation of the photosensitizer meta-(Tetrahydroxyphenyl)Chlorin (m-THPC) and investigate if favorable pharmacokinetics translate into favorable tumor response and control. Eighteen client-owned cats with 20 spontaneous cutaneous squamous cell carcinomas were included in the study. PDT was performed using a new, liposomal formulation of the photosensitizer. Toxicity, tumor response, and tumor control were evaluated retrospectively. No general adverse effects were observed in cats treated with the new liposomal formulation. Mild local toxicity such as erythema and edema were seen in 15% of the patients. All cats responded to therapy, with a complete response rate of 100%. The overall 1-year control rate was 75%. The tumor recurrence rate was 20% with a median time to recurrence of 172.25 +/-87.1) days. A new liposomal photosensitizer was successfully used for squamous cell carcinoma in cats and was well tolerated. There were no systemic adverse effects observed with the liposomal formulation. The favorable pharmacokinetics of the liposomal drug resulted in a favorable tumor response.

Terapêutica no carcinoma de células escamosas cutâneo em gatos

O carcinoma de células escamosas é uma neoplasia cutânea de grande relevância em países de clima tropical como o Brasil, uma vez que a exposição crônica à radiação ultravioleta é um dos fatores importantes para o desenvolvimento da doença. Esta revisão tem por objetivo discorrer sobre alternativas de tratamento do carcinoma de células escamosas em gatos, com ênfase à terapia fotodinâmica. A escolha da modalidade terapêutica deve ser estabelecida de acordo com o estadiamento do tumor, o estado geral do paciente, a colaboração do proprietário e a disponibilidade de equipamentos e fármacos. A precocidade no diagnóstico tem efeito fundamental no prognóstico.

Ki67 Reactivity in Nasal and Periocular Squamous Cell Carcinomas in Cats Treated with Electron Beam Radiation Therapy

Squamous cell carcinomas of sparsely haired skin are relatively common tumors in cats, and these tumors likely exhibit a rapid growth rate. Thus, we evaluated response and duration of response in relation to the Ki67 proliferative reactivity in such tumors. Seventeen cats with confirmed squamous cell carcinomas and treated with an accelerated, hypofractionated electron beam radiation protocol were included in the study. For all of them histologic grading, Ki67 reactivity, response, and disease‐free interval (DFI) were evaluated. Response to therapy was excellent (94% complete response rate) with a median DFI of 414 days. Only moderate acute and few long‐term adverse effects were seen. Cats with tumors with a low Ki67 reactivity had markedly shorter DFIs than cats with tumors with high Ki67 reactivity. We concluded that an accelerated, hypofractionated electron beam radiation therapy protocol is well suited for feline squamous cell carcinomas. The protocol appears especially efficacious in tumors with a high Ki67 reactivity.

Ki67 Reactivity in Nasal and Periocular Squamous Cell Carcinomas in Cats Treated with Electron Beam Radiation Therapy

Squamous cell carcinomas of sparsely haired skin are relatively common tumors in cats, and these tumors likely exhibit a rapid growth rate. Thus, we evaluated response and duration of response in relation to the Ki67 proliferative reactivity in such tumors. Seventeen cats with confirmed squamous cell carcinomas and treated with an accelerated, hypofractionated electron beam radiation protocol were included in the study. For all of them histologic grading, Ki67 reactivity, response, and disease-free interval (DFI) were evaluated. Response to therapy was excellent (94% complete response rate) with a median DFI of 414 days. Only moderate acute and few long-term adverse effects were seen. Cats with tumors with a low Ki67 reactivity had markedly shorter DFIs than cats with tumors with high Ki67 reactivity. We concluded that an accelerated, hypofractionated electron beam radiation therapy protocol is well suited for feline squamous cell carcinomas. The protocol appears especially efficacious in tumors with a high Ki67 reactivity.

Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonography

One principal mechanism of photodynamic therapy (PDT) in tumors is destruction of tumor-associated vasculature. In the present study, the vascular effects of PDT in tumors were investigated with power Doppler ultrasonography. Seven cutaneous squamous cell carcinomas in cats were treated. Tumors were examined via power Doppler ultrasonography before, 5 minutes, 1 hour, and 24 hours after PDT. Images were digitized for computer-aided assessment of vascularity and blood volume. Mean baseline tumor vascularity and blood volume were moderate. During PDT, a significant decrease in vascularity and blood volume was noted. Lowest values were found 24 hours after PDT. Power Doppler ultrasonography represents a non-invasive modality to successfully monitor the vascular effects and thus, treatment efficacy, of PDT.

Abstracts

Treatment of superficial squamous cell carcinoma in cats by photodynamic therapy Stell, A. J., Dobson, J. M. & Langmack, K. (2001) Photodynamic therapy of feline superficial squamous cell carcinoma using...

Photodynamic therapy of facial squamous cell carcinoma in cats using a new photosensitizer.

Photodynamic therapy has been shown to be an effective treatment modality for surface-oriented neoplasms of the skin, respiratory, gastrointestinal, and urogenital systems. The purpose of this study was to assess the safety and efficacy of photodynamic therapy using a new photosensitizer in the treatment of squamous cell carcinomas of the feline facial skin. Cats with naturally occurring squamous cell carcinomas of the facial skin were entered into the study. Tumors were staged using a modification of the World Health Organization (WHO) system for classification of feline tumors of epidermal origin. Photodynamic therapy was delivered to the tumors using an argon-pumped dye laser 24 hours after the administration of the photosensitizer pyropheophorbide-alpha-hexyl-ether (HPPH-23). Following treatment, tumors were evaluated for complete response rates and local control durations. Fifteen tumors were staged T1a (< 1.5 cm diameter, noninvasive), 18 T1b (< 1.5 cm, invasive), and 28 T2B (> 1.5 cm, invasive). Complete response rates as well as local control durations were significantly (P < 0.05) related to stage. Complete response was achieved in 100% of T1a tumors, 56% of T1b tumors, and 18% of T2b tumors. One-year local control rates were 100% for T1a tumors and 53% for T1b tumors; overall 1-year local control rate for all treated tumors was 62%. Clinical, hematological, and biochemical evidence of toxicity was not seen in any cat following drug administration. However, morbidity was observed following treatment of large, invasive tumors of the nasal plane. Photodynamic therapy with the photosensitizer HPPH-23 was safe and effective in treating early stage squamous cell carcinomas of the feline nasal plane and facial skin. However, toxicity was encountered following treatment of large neoplasms.

Photodynamic therapy of facial squamous cell carcinoma in cats using a new photosensitizer

Photodynamic therapy of facial squamous cell carcinoma in cats using a new photosensitizer

Photodynamic therapy for nasal and aural squamous cell carcinoma in cats

Summary: Eighteen random-bred cats with a total of 19 nasal or aural squamous cell carcinomas were treated with photodynamic therapy, using aluminum phthalocyanine tetrasulfhonate as the photosensitizer. Cats were irradiated at power densities of 100 mW/cm2 and energy densities of 100 J/cm2. Successful outcome was obtained in 10 tumors after 1 treatment, and 2 more tumors had complete responses after 1 or 2 additional treatments. Treatments were more effective in tumors of stage T2 or earlier. Five tumors had partial responses, and the response of 2 tumors could not be evaluated. The treatment was safe and well tolerated by most cats, although we found that cats should be kept out of sunlight for 2 weeks after treatment.