Canine Anal Sac Adenocarcinoma Research Articles

Pilot study evaluating the feasibility of stereotactic body radiation therapy for canine anal sac adenocarcinomas.

The use of stereotactic body radiation therapy (SBRT) to treat many canine tumors is rapidly expanding. However, published studies are lacking regarding use of SBRT for management of canine anal sac adenocarcinoma (ASAC), primarily due to concerns regarding intolerable late effects. The objective of this retrospective, pilot study was to describe the efficacy and safety profile of coarse fractions administered with an SBRT regime to manage a group of dogs with ASAC. A total of 12 dogs with ASAC that received SBRT as a component of their treatment were sampled. Three patients had macroscopic primary tumors irradiated, while nine patients received SBRT following incomplete surgical resection. Seven patients also received metastatic regional lymph node irradiation. Primary tumor and nodal irradiation sites received three fractions totaling 22-24Gy and 22.5-24Gy, respectively, over three consecutive days. All patients developed acute effects including mild colitis, alopecia, and erythema. Late effects included alopecia, variable dermal pigmentation and leuko- or melanotrichia within radiation fields, and rectal stricture in one patient. A median progression free survival time of 549 days and median survival time of 991 days were achieved in this study. These results should be considered preliminary data suggesting that coarse fractionation administered with an SBRT technique is a safe and effective treatment regime for the management of canine ASAC, with the aim to conduct prospective studies in the future.

Expression of Phosphorylated Signal Transducer and Activator of Transcription 3 and its Prognostic Significance in Canine Anal Sac Adenocarcinoma

Prognostication in canine anal sac adenocarcinomas (ASACs) is difficult due to conflicting evidence regarding metastatic rates and median survival times (MSTs). The transcription factor signal transducer and activator of transcription 3 (STAT3) is a prognostic predictor in several human cancers. The aim of this retrospective study was to assess STAT3 expression in ASACs and to explore its association with clinical presentation and outcome. We hypothesized that STAT3 expression would distinguish tumours with early versus late metastasis. Records from The Queen's Veterinary School Hospital, Cambridge, UK, were searched for dogs diagnosed with ASAC from 2008 to 2019. Immunohistochemical expression of phosphorylated STAT3 (pSTAT3) was assessed in primary tumours (n=57) and metastatic lymph nodes (n=30) and MSTs were calculated for cases with low and high pSTAT3 expression. Of the 57 cases assessed, 27 presented with primary tumours but no metastasis and 30 with both primary and local metastatic disease. Most cases (50/57) expressed nuclear pSTAT3 within neoplastic cells in both primary tumour and metastatic lymph nodes. pSTAT3 expression was predominantly observed in neoplastic cells at the edges of neoplastic lobules, suggesting a potential role in invasion. There was no significant difference in pSTAT3 expression between cases metastatic at presentation and those that did not have detectable metastasis at presentation. There was no significant difference between the MSTs in cases with high and low pSTAT3 expression. Cases that presented with metastatic disease had shorter MSTs (395 days) than those with primary tumours alone (623 days). Although pSTAT3 is variably expressed in primary and metastatic ASAC cells, pSTAT3 did not provide prognostic information for canine ASAC.

A complication probability study for a definitive‐intent, moderately hypofractionated image‐guided intensity‐modulated radiotherapy protocol for anal sac adenocarcinoma in dogs

Previous trials showed the importance of administering radiation therapy (RT) with small doses per fraction in canine pelvic tumours to maintain acceptable toxicity levels. With increased accuracy/precision of RT, namely intensity-modulated RT (IMRT), this approach might be challenged. Theoretical toxicity calculations for a new definitive-intent moderately hypofractionated RT protocol for canine anal sac adenocarcinomas (ASAC) were performed, focussing on the risk of toxicity in pelvic organs at risk (OAR). Computed tomography datasets of 18 dogs with stage 3b ASAC were included. Re-planning with margins for daily image-guidance/IMRT was performed and a new protocol isoeffective to previously described definitive-intent protocols was computed. Dose-volume information were derived from individual plans and used for normal tissue complication probability (NTCP) computations. A 12 × 3.8 Gy protocol was computed for risk estimation. Tumour volumes ranged from 27.9 to 820.4 cm3 (mean 221.3 cm3 ± 188.9). For late rectal toxicity/bleeding ≥grade 2, median risk probability was 2.3% inter quartile range (IQR: 5.9; 95% confidence interval (CI): 1.2, 8.4) (rho = 0.436) and 3.4% (IQR: 0.96; 95%CI: 3.1, 4.0) (rho = 0.565), respectively. Median late toxicities in urinary bladder, kidneys and small bowel were <1%, except in one kidney. Myelopathy/myelonecrosis had a median risk probability of 4.1% (IQR: 23.5; 95%CI: 2.1, 25.2) (rho = 0.366) and 5.6% (IQR: 13.5; 95%CI: 3.1, 14.1) (rho = 0.363), respectively. However, graded risk showed a probability estimate for late spinal cord toxicity of ≥5% in 8/18 patients. The daily-imaging IMRT 12 × 3.8 Gy protocol for canine ASAC seems tolerable for most cases, even in advanced disease. Theoretical dose computations serve as estimate, but are safe measures before implementing new protocols into clinical use.

Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999-2013).

Currently no standard of care exists for advanced, inoperable or metastatic anal sac adenocarcinoma (ASAC). The objective of this retrospective study was to assess the role of hypofractionated radiation therapy (RT) in 77 dogs with measurable ASAC. A total of 38% of dogs experienced a partial response to RT. For dogs presenting with clinical signs related to the tumour, improvement or resolution of signs was noted in 63%. For dogs presenting with hypercalcemia of malignancy, resolution was noted in 31% with RT alone and an additional 46% with radiation, prednisone, and/or bisphosphonates. Median overall survival was 329 days (range: 252-448 days). Median progression free survival was 289 days (range: 224-469). There was no difference in survival based on radiation protocol, use of chemotherapy, previous surgery or advanced stage. Radiation toxicities were mild and infrequent. Hypofractionated RT is well tolerated and is applicable in the treatment of advanced primary, locoregional or metastatic ASAC.

COX-2 expression in canine anal sac adenocarcinomas and in non-neoplastic canine anal sacs

Anal sac adenocarcinoma (ASAC) is a clinically significant canine neoplasm characterized by early lymphatic invasion. Up-regulation of cyclooxygenase isoform 2 (COX-2) has been confirmed in several animal and human neoplastic tissues. The aim of the current study was primarily to evaluate COX-2 expression in canine ASAC and compare it to COX-2 expression in non-neoplastic canine anal sac tissue using immunohistochemistry with scoring for percentage positivity and intensity. Twenty-five ASAC samples and 22 normal anal sacs were available for evaluation.All canine ASAC samples and the normal anal sac tissues stained positively for COX-2. However, while normal anal sac tissue showed strong staining of the ductal epithelial cells, ASAC samples showed staining of the neoplastic glandular epithelial cells, with varying percentage positivity and intensity between ASAC samples. COX-2 immunoreactivity of ASAC samples was of low intensity in 52% and high in 12% of the cases; the remaining samples were of intermediate intensity. Seventy-six per cent of the ASAC had over 50% of the neoplastic glandular cells staining positive. These results confirm that COX-2 is expressed in the neoplastic glandular epithelial cells in canine ASAC and suggest a potential role for COX-2 inhibitors in the management of ASAC. Furthermore, the results indicate that COX-2 is expressed in ductal epithelial cells of the normal anal sac.

Expression of E‐cadherin in Canine Anal Sac Apocrine Gland Adenocarcinoma and its Association with Survival

Introduction: Inverse associations have been shown between E‐cadherin expression and degree of differentiation in canine mammary tumours and with the acquisition of malignancy in human epithelial cancers. The purpose of this study was to examine whether there was an association between prognosis, and the distribution or intensity of immunohistochemical staining for E‐cadherin in anal sac adenocarcinoma.Methods: Formalin‐fixed paraffin‐wax embedded canine anal sac adenocarcinoma specimens were obtained for 36 patients for whom clinical data, including survival statistics, were available. Canine mammary adenoma tissue was employed as the positive and negative controls with antibody diluent replacing the primary antibody in the latter. Samples were scored according to proportion of cells showing positive cytoplasmic membranous staining, intensity of cytoplasmic membranous staining and proportion of nuclei staining. As quality control, a sample of 10 slides was randomly selected for repeat evaluation; results exactly matched those obtained in the first assessment.Results: All anal sac adenocarcinoma cells expressed E‐cadherin to varying degrees. There was no evidence of an association between survival time and the intensity of staining or the proportion of nuclei staining. Patients whose tumours exhibited &gt;75% positive cytoplasmic membranous staining survived significantly longer than those exhibiting &lt;75% staining with median survival times of 1100 and 479 days respectively (log rank test: χ2 = 3.89, 1 DF, p = 0.049).Conclusion: Immunohistochemical evaluation of the proportion of cells in anal sac adenocarcinoma samples exhibiting positive cytoplasmic membranous staining for E‐cadherin may allow improved determination of prognoses and could aid clinical decision making.

Canine anal sac adenocarcinomas: clinical presentation and response to therapy.

A retrospective study of 43 dogs with anal sac adenocarcinoma (ASAC) was performed to characterize the clinical presentation and response to treatment. Clinical signs at presentation varied considerably, with signs related either to sublumbar nodal metastasis (tenesmus or constipation) or hypercalcemia (polyuria-polydipsia and anorexia) being the most frequent findings. At the time of presentation, 23 (53%) dogs had hypercalcemia and 34 (79%) had metastases, with the regional lymph nodes (31 dogs, 72%) being the most common site of metastasis. A variety of chemotherapeutic agents were administered, with partial remission (PR) recorded in 4 of 13 (31%) dogs treated with cisplatin and in 1 of 3 (33%) dogs treated with carboplatin. The median survival for all dogs was 6 months (range, 2 days-41 months). There was no statistical association between the presence of hypercalcemia and survival, although the power of the study to detect an increase in survival of 3 months was low (.33). We conclude that platinum chemotherapy has antitumor activity in canine apocrine gland carcinoma and that further study of these agents is warranted.

Canine Anal Sac Adenocarcinomas: Clinical Presentation and Response to Therapy

A retrospective study of 43 dogs with anal sac adenocarcinoma (ASAC) was performed to characterize the clinical presentation and response to treatment. Clinical signs at presentation varied considerably, with signs related either to sublumbar nodal metastasis (tenesmus or constipation) or hypercalcemia (polyuria‐polydipsia and anorexia) being the most frequent findings. At the time of presentation, 23 (53%) dogs had hypercalcemia and 34 (79%) had metastases, with the regional lymph nodes (31 dogs, 72%) being the most common site of metastasis. A variety of chemotherapeutic agents were administered, with partial remission (PR) recorded in 4 of 13 (31%) dogs treated with cisplatin and in 1 of 3 (33%) dogs treated with carboplatin. The median survival for all dogs was 6 months (range, 2 days‐41 months). There was no statistical association between the presence of hypercalcemia and survival, although the power of the study to detect an increase in survival of 3 months was low (.33). We conclude that platinum chemotherapy has antitumor activity in canine apocrine gland carcinoma and that further study of these agents is warranted.