Prognostic value of peripheral blood and bone marrow infiltration assessed by flow cytometry in dogs with de novo nodal peripheral T-cell lymphoma receiving alkylating-rich chemotherapy.

Peripheral T-cell lymphoma (PTCL) is highly aggressive in dogs and demonstrates a poor response to traditional chemotherapy. The aim of this retrospective study was to assess the prognostic significance of peripheral blood (PB) and bone marrow (BM) infiltration evaluated by flow cytometry (FC) in dogs with treatment-naïve and histologically confirmed PTCL. To be included, dogs had to undergo complete staging, including FC on lymph nodes, PB and BM samples. Additionally, dogs had to receive an alkylating-rich protocol and have a complete follow-up. Treatment response was evaluated based on RECIST criteria at each chemotherapy session, and the end-staging was conducted at the completion of treatment. Endpoints were time to progression (TTP) and lymphoma-specific survival (LSS). The relationship between TTP/LSS and the percentage of PB and BM infiltration, categorized as > 1%, > 3%, > 5%, > 10%, > 15% and > 20% was investigated. Fifty dogs were included: based on imaging and FC, 78.0% had stage 5 disease, 14.0% had stage 4, 6.0% had stage 3 and 2.0% had stage 1. By multivariable analysis, the CD4-negative phenotype was the only factor associated with a shorter TTP (P = 0.049), while BM infiltration was significantly associated with LSS (P = 0.037). Dogs with BM infiltration > 5% had shorter median LSS (114 days; 95%CI: 0-240) compared to dogs with BM infiltration ≤ 5% (178 days; 95%CI: 145-211). Lack of complete response (P = 0.039) and administration of corticosteroids before chemotherapy (P = 0.026) also significantly worsened LSS. BM flow cytometric evaluation could be considered an essential part of staging work-up for dogs with PTCL and has prognostic relevance.

A retrospective study on bone metastasis in dogs with advanced-stage solid cancer.

OBJECTIVES: To review clinical characteristics, treatment, outcome and prognostic factors in dogs with solid cancer-bearing bone metastases. MATERIALS AND METHODS: Records were reviewed from dogs with histologically-proven solid cancer and bone metastases. Clinicopathologic variables, bone metastases characteristics and skeletal-related events were recorded. Endpoints were time to bone metastases and survival. RESULTS: Fifty dogs were included, 20 of them with synchronous and 30 of them with metachronous bone metastases. In the latter group, median time to diagnosis of bone metastases was 210 days (range, 30 to 1835). Most common primary cancer locations included mammary gland (n=6), spleen (n=5) and tonsil (n=5). Most common histotypes were carcinoma (n=32) and hemangiosarcoma (n=10). Nineteen dogs had multiple bones involvement, with humeri and vertebrae more commonly affected. Twenty-four dogs received antitumoural therapy, five symptomatic treatment and 21 were not treated. Overall median survival after bone metastases diagnosis was 30 days (range, 11 to 49); 83% of dogs died because of skeletal-related events. Lack of antitumoural therapy was significantly associated with shorter survival (hazard ratio: 2.7; 95% confidence interval: 1.3 to 5.6) and with increased risk of skeletal-related death (hazard ratio: 3.3; 95% confidence interval: 1.4 to 7.4). Dogs with endocrine/neuroendocrine tumours (odds ratio: 8.8; 95% confidence interval: 1.2 to 63.9), without appendicular metastases (odds ratio: 5.1; 95% confidence interval: 1.0 to 25.8), without extra-skeletal metastases (odds ratio: 5.2; 95% confidence interval: 1.1 to 24.5) and receiving antitumoural therapy (odds ratio: 14.8; 95% confidence interval: 1.7 to 131.4) had an increased chance of surviving more than 100 days. CLINICAL SIGNIFICANCE: Bone metastases in dogs with solid cancers are associated with poor prognosis and a high risk of skeletal-related events. Treatment appears to have an impact on survival.

Lymphadenectomy improves outcome in dogs with resected Kiupel high-grade cutaneous mast cell tumours and overtly metastatic regional lymph nodes.

INTRODUCTION: Historically, the prognosis for dogs with stage II Kiupel high-grade cutaneous mast cell tumours has been considered poor. OBJECTIVES: The aim of this study was to explore the impact of lymphadenectomy on outcome in dogs with Kiupel high-grade cutaneous mast cell tumours and overt regional lymph node metastasis. MATERIAL AND METHODS: Data from dogs with completely staged Kiupel high-grade cutaneous mast cell tumours with overt and/or certain regional lymph node metastasis undergoing excision of the primary tumours and adjuvant medical treatment were extracted. Dogs with a cytological diagnosis of regional lymph node metastasis that did not undergo lymphadenectomy were compared with dogs that underwent lymphadenectomy and had a histological diagnosis of overt lymph node metastasis. RESULTS: Forty-nine dogs were included, 18 did not undergo lymphadenectomy while 31 underwent lymphadenectomy. Median time to progression was significantly shorter in dogs that did not undergo lymphadenectomy (150 days, 95% confidence interval: 129 to 170) compared to the other dogs (229 days, 95% confidence interval: 191 to 266). Median survival time was also shorter in dogs that did not undergo lymphadenectomy (250 days, 95% confidence interval: 191 to 308) compared to dogs that underwent lymphadenectomy (371 days, 95% confidence interval: 311 to 430). On multivariable analysis, lack of lymphadenectomy was associated with higher risk of overall tumour progression (hazard ratio: 2.05, 95% confidence interval: 1.02 to 4.13), nodal progression (hazard ratio: 3.4, 95% confidence interval: 1.65 to 7.02) and tumour-related death (hazard ratio 3.63, 95% confidence interval: 1.72 to 7.66), whereas tumour size was associated with higher risk of local recurrence (hazard ratio: 3.61, 95% confidence interval: 1.06 to 13). CLINICAL SIGNIFICANCE: Regional lymphadenectomy may improve outcome in dogs with biologically aggressive cutaneous mast cell tumours.

[New concepts in human oncology: is it possible to use them in veterinary medicine as well?]. / Neue Konzepte in der humanen Onkologie: Können sie in der Veterinärmedizin eingesetzt werden?

In human oncology, novel targeted therapy focusing on monoclonal antibodies and tyrosine kinase inhibitors has become an attractive anticancer strategy. The introduction of antiangiogenetic drugs and metronomic chemotherapy has also increased the therapeutic arsenal. Chemotherapy still plays a key role in the treatment of many tumors affecting dogs and cats. However, novel anticancer strategies (including tyrosine kinase inhibitors and monoclonal antibodies, as well as antiangiogenetic treatments) are becoming relevant in veterinary medicine, too. The goal of this review is to describe new therapeutic strategies for cancer treatment in veterinary medicine, including less well-known chemotherapeutic drugs.

Association between waste management and cancer in companion animals.

BACKGROUND: Increased cancer rates have been documented in people residing in areas around Naples characterized by illegal dumping and incineration of waste. HYPOTHESIS: Risk of cancer in dogs and cats is associated with waste management. ANIMALS: Four hundred and fifty-three dogs and cats with cancer and 1,554 cancer-free animals. METHODS: Hospital-based case-control study in Naples (low danger) and nearby cities having a history of illegal waste dumping (high danger). Odds ratio (OR) between high- and low-danger areas was calculated for all tumors and various malignancies in dogs and cats. RESULTS: An increased risk for cancer development was identified in dogs but not in cats residing in high-danger areas (OR: 1.55; 95% confidence interval: 1.18-2.03; P < .01). A 2.39-fold increased risk of lymphoma (P < .01) accounted for the greater tumor frequency in dogs residing in high-danger areas. The risk of mast cell tumor and mammary cancer did not differ in dogs residing in high- or low-danger areas. CONCLUSIONS AND CLINICAL IMPORTANCE: Waste emission from illegal dumping sites increases cancer risk in dogs residing in high-danger areas. An increased prevalence of lymphoma has been previously recognized in humans living close to illegal waste dumps. Thus, epidemiological studies of spontaneous tumors in dogs might suggest a role for environmental factors in canine and human carcinogenesis and can predict health hazards for humans.

Aberrant phenotypes and quantitative antigen expression in different subtypes of canine lymphoma by flow cytometry.

Flow cytometry may be a useful tool to analyze lymphoma samples that are obtained from fine needle aspirations (FNA). This study aimed to determine if flow cytometric analysis add more objective and standardized information on the cellularity and morphology of lymphoma cells to conventional cytology. The typical immunophenotype of different lymphoma subtypes was assessed and leukocyte marker expression was evaluated to determine which antigens were more frequently over- or under-expressed in these lymphoma subtypes. Fifty FNA lymph node samples were evaluated from canine lymphomas. Thirty-one samples were identified to be of B-cell origin, sixteen were identified to be of T/NK-cell origin and three cases were classified as acute lymphoblastic leukaemia with lymph nodes involvement. The most common B-cell lymphoma subtypes were centroblastic lymphomas, whereas three cases were atypical and classified as B-large cell pleomorphic lymphomas. Among the T/NK lymphomas, small clear cells, large and small pleomorphic mixed cells, large granular lymphocytic cells and small pleomorphic cells were identified. Aberrant phenotypes and/or antigen under/over regulation was identified in thirty out of forty-seven lymphoma cases (64%; 18/31 B-cell=58% and 12/16 T-cell=75%). In B-cell lymphomas the most frequent finding was the diminished expression of CD79a (45%). CD34 expression was also observed in four cases (13%). Among T-cell lymphomas the prevalent unusual phenotype was the under-expression or absence of CD45 (25%). These findings reveal flow cytometry may be useful in confirming the diagnosis of lymphoma, as the technique allows one to add useful information about morphology of the neoplastic cells and identify antigenic markers and aberrant phenotypes.

Clinicopathological features and outcome for dogs with mast cell tumors and bone marrow involvement.

BACKGROUND: Mast cell tumors (MCTs) with bone marrow (BM) involvement are poorly documented in dogs and are associated with a poor prognosis. Successful treatment strategies have not been described. HYPOTHESIS: Clinicopathologic findings of affected dogs are not specific. Administration of lomustine or imatinib is beneficial. ANIMALS: Fourteen dogs with MCT and BM involvement. METHODS: Clinical and laboratory evaluations were performed in each dog on admission and during follow-up. All dogs received prednisone. Additionally, 8 dogs received lomustine and 3 dogs received imatinib. Imatinib was administered if tumor-associated tyrosine kinase KIT was aberrant. RESULTS: On admission, 11 dogs had a single cutaneous nodule and 3 dogs had multiple nodules. Involvement of regional lymph nodes, liver, or spleen was observed in each dog. BM infiltration with mast cells (MCs) was observed in all dogs. On CBC, nonregenerative anemia, leukopenia, or thrombocytopenia was common. Four dogs had circulating MCs. Increased alkaline phosphatase or alanine transferase activity was observed in 12 and 10 dogs, respectively. Treatment with lomustine induced partial remission in 1 of 8 dogs. Median survival time was 43 days (range, 14-57). Dogs on imatinib experienced complete remission. Two dogs survived for 117 and 159 days, and the third was alive after 75 days. Dogs treated symptomatically did not improve and were euthanized after 1, 14, and 32 days. CONCLUSIONS AND CLINICAL IMPORTANCE: A combination of clinical and laboratory evaluation helps in identifying dogs with MCT and BM infiltration. Administration of lomustine is not helpful in affected dogs. The beneficial effect of imatinib warrants further investigation.

The impact of toceranib, piroxicam and thalidomide with or without hypofractionated radiation therapy on clinical outcome in dogs with inflammatory mammary carcinoma.

In dogs, inflammatory mammary carcinoma is a clinicopathological entity characterized by rapid progression and aggressive behavior from onset of disease. Reported median survival time is short, with no effective treatment options. The aims of this prospective, noncontrolled clinical trial were to investigate outcome variables and safety profile of toceranib, thalidomide and piroxicam with or without hypofractionated radiation therapy in dogs with measurable histologically confirmed inflammatory mammary carcinoma that underwent a complete staging. Eighteen dogs were enrolled: 14 received medical treatment, and 4 were treated with hypofractionated radiation therapy and medical therapy. Overall, median time to progression was 34 days and median survival time was 109 days. In dogs treated with medical therapy, overall response rate was 21%, and clinical benefit rate (CBR) was 64%; median time to progression was 28 days and median survival time was 59 days. In dogs receiving medical therapy and undergoing radiation therapy, overall response rate and clinical benefit rate were 100%, with significantly longer time to progression (156 days) and survival time (180 days). Overall, treatment was well tolerated, with mild gastrointestinal and dermatological adverse events. Although the optimal treatment to this disease remains uncertain, the current approach consisting of systemic anti-angiogenic drugs with or without hypofractionated radiation therapy, provided clinical benefit in a significant proportion of dogs and should, therefore, be further explored.

The use of low-dose metronomic chemotherapy in dogs-insight into a modern cancer field.

The era of chemotherapy, which started in the middle of the last century, has been ruled by the routine use of dose-intense protocols, based on the "maximum-tolerated dose" concept. By promoting a balance between patient's quality of life and the goal of rapidly killing as many tumour cells as possible, these protocols still play a prominent role in veterinary oncology. However, with the opening of a new millennium, metronomic chemotherapy (MC) started to be considered a possible alternative to traditional dose-intense chemotherapy. Characterized by a long-term daily administration of lower doses of cytotoxic drugs, this new modality stands out for its unique combination of effects, namely on neovascularization, immune response and tumour dormancy. This article reviews the rationale for treatment with MC, its mechanism of action and the main studies conducted in veterinary medicine, and discusses the key challenges yet to be solved.

Utility of flow cytometry in canine primary cutaneous and matched nodal mast cell tumor.

Mast cell tumors (MCT) are among the most frequent tumors in dogs, but studies regarding canine mast cell immunophenotype are lacking. The aim of this study was to assess the feasibility of flow cytometric analysis of MCTs, to describe canine MCTs immunophenotype(s), and to evaluate the ability of flow cytometry to detect mast cells in lymph node aspirates. Thirty-four primary canine MCTs and 12 draining lymph nodes were evaluated regarding the expression of CD117, IgE, CD11b, CD18, CD44, CD34, CD25 and CD45. Distinct populations attributable to mast cells and eosinophils were recognized based on light scatters and CD117 positivity. Common antigens (CD18, CD45, CD44) and CD117 were detected in all cases; positivity for IgE and CD11b was found in 28 (82%) and 23 (68%) cases respectively, while CD34 and CD25 were occasionally expressed. A single multicolor tube (IgE/CD117/CD11b/CD21/CD5) allowed the identification of mast cells in lymph nodes, showing a high correlation with cytology in quantifying mast cells infiltration. In conclusion, flow cytometric analysis can be applied to characterize canine MCTs and can be used to detect the presence of mast cells in lymph nodes. The immunophenotype abnormalities observed may be useful to confirm the neoplastic nature of such mast cells but the diagnostic usefulness of atypical antigen expression remains to be clarified.

Effects of pre-analytical variables on flow cytometric diagnosis of canine lymphoma: A retrospective study (2009-2015).

Flow cytometry (FC) is increasingly being used for immunophenotyping and staging of canine lymphoma. The aim of this retrospective study was to assess pre-analytical variables that might influence the diagnostic utility of FC of lymph node (LN) fine needle aspirate (FNA) specimens from dogs with lymphoproliferative diseases. The study included 987 cases with LN FNA specimens sent for immunophenotyping that were submitted to a diagnostic laboratory in Italy from 2009 to 2015. Cases were grouped into 'diagnostic' and 'non-diagnostic'. Pre-analytical factors analysed by univariate and multivariate analyses were animal-related factors (breed, age, sex, size), operator-related factors (year, season, shipping method, submitting veterinarian) and sample-related factors (type of sample material, cellular concentration, cytological smears, artefacts). The submitting veterinarian, sample material, sample cellularity and artefacts affected the likelihood of having a diagnostic sample. The availability of specimens from different sites and of cytological smears increased the odds of obtaining a diagnostic result. Major artefacts affecting diagnostic utility included poor cellularity and the presence of dead cells. Flow cytometry on LN FNA samples yielded conclusive results in more than 90% of cases with adequate sample quality and sampling conditions.

Canine nodal marginal zone lymphoma: Descriptive insight into the biological behaviour.

Canine nodal marginal zone lymphoma (nMZL) is classified as an indolent lymphoma. Such lymphomas are typified by low mitotic rate and slow clinical progression. While the clinical behaviour of canine splenic MZL has been described, characterized by an indolent course and a good prognosis following splenectomy, there are no studies specifically describing nMZL. The aim of this study was to describe the clinical features of and outcome for canine nMZL. Dogs with histologically confirmed nMZL undergoing a complete staging work-up (including blood analysis, flow cytometry [FC] on lymph node [LN], peripheral blood and bone marrow, imaging, histology and immunohistochemistry on a surgically removed peripheral LN) were retrospectively enrolled. Treatment consisted of chemotherapy or chemo-immunotherapy. Endpoints were response rate (RR), time to progression (TTP) and lymphoma-specific survival (LSS). A total of 35 cases were enrolled. At diagnosis, all dogs showed generalized lymphadenopathy. One-third was systemically unwell. All dogs had stage V disease; one-third also had extranodal involvement. The LN population was mainly composed of medium-sized CD21+ cells with scant resident normal lymphocytes. Histology revealed diffuse LN involvement, referring to "late-stage" MZL. Median TTP and LSS were 149 and 259 days, respectively. Increased LDH activity and substage b were significantly associated with a shorter LSS. Dogs with nMZL may show generalized lymphadenopathy and an advanced disease stage. Overall, the outcome is poor, despite the "indolent" designation. The best treatment option still needs to be defined.

Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous mast cell tumours: A prospective study.

BACKGROUND: Distant metastases in dogs with cutaneous mast cell tumors (cMCT) are rare and incurable. The aims of this prospective study were to clarify the clinico-pathological features of stage IV cMCTs and to identify possible prognostic factors for progression-free interval (PFI) and survival time (ST). MATERIAL AND METHODS: Dogs were eligible for recruitment if they had a previously untreated, histologically confirmed cMCT and if they underwent complete staging demonstrating stage IV disease. Dogs were uniformly followed-up, whereas treatment was not standardized and included no therapy, surgery, radiation therapy, chemotherapy, tyrosine-kinase inhibitors or a combination of these. RESULTS: 45 dogs with stage IV cMCT were enrolled. All dogs had distant metastatic disease, and 41 (91.1%) dogs had also metastasis in the regional lymph node. Histopathological grade and mutational status greatly varied among dogs. Median ST was 110 days. Notably, PFI and ST were independent of well-known prognostic factors, including anatomic site, histological grade, and mutational status. Conversely, tumor diameter >3 cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis. CONCLUSION: Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3 cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT.

Comparison between May-Grünwald-Giemsa and rapid cytological stains in fine-needle aspirates of canine mast cell tumour: Diagnostic and prognostic implications.

Mast cell tumours (MCTs) are often diagnosed by cytology based on the identification of purple intracytoplasmic granules with methanolic Romanowsky stains, including May-Grünwald-Giemsa (MGG). In clinical practice, aqueous rapid stains (RS) are commonly used, but mast cell granules may not stain properly. Aim of this prospective study was to investigate the frequency of MCT hypogranularity with RS and its potential implications in tumour identification, cytological grading assessment and recognition of nodal metastatic disease. Cytological preparations of canine primary MCTs and metastatic lymph nodes with subsequent histopathological confirmation were included. For each case, good-quality smears were stained with both MGG and RS and comparatively assessed. Eleven of 60 (18.3%) primary MCTs were hypogranular with RS; 9 of them were histologically high-grade tumours and in 3 cases (5%) a definitive MCT diagnosis could not be made. Accuracy in cytological grading assessment (85%) did not differ between RS and MGG. Thirteen of 28 (46.4%) metastatic lymph nodes were hypogranular with RS and 3 independent observers failed to identify nodal MCT metastases in 7% to 18% of RS-stained smears. This study confirms that, in limited cases, RS can be ineffective in staining MCT granules, particularly in high-grade tumours, thus making diagnosis more dependent on experience and quality of preparations. In dubious cases, methanolic stains should be applied. The use of RS is discouraged for the search of nodal metastases, as the identification of isolated mast cells can be more challenging.

Survival analysis of dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide, piroxicam and thalidomide.

Unresectable or metastatic (advanced) primary pulmonary carcinoma (PPC) represents a therapeutic challenge where surgery may be contraindicated and the therapeutic role of maximum-tolerated dose (MTD) chemotherapy remains uncertain. This study was undertaken to explore the impact of metronomic chemotherapy (MC) in dogs with advanced PPC. Previously untreated dogs with advanced (T3 or N1 or M1) PPC, with complete staging work-up and follow-up data, receiving MC (comprising low-dose cyclophosphamide, piroxicam and thalidomide), surgery, MTD chemotherapy or no oncologic treatment were eligible for inclusion. For all patients, time to progression (TTP) and survival time (ST) were evaluated. Quality-of-life (QoL) was only evaluated in patients receiving MC. To assess QoL, owners of dogs receiving MC were asked to complete a questionnaire before and during treatment. Ninety-one dogs were included: 25 received MC, 36 were treated with surgery, 11 with MTD chemotherapy and 19 received no treatment. QoL was improved in dogs receiving MC. Median TTP was significantly longer in patients receiving MC (172 days) than patients undergoing surgery (87 days), receiving MTD chemotherapy (22 days), or no oncologic treatment (20 days). Median ST was similarly longer in patients receiving MC (139 days) than those undergoing surgery (92 days), MTD chemotherapy (61 days) and no oncologic treatment (60 days). In dogs with advanced PPC, MC achieved a measurable clinical benefit without significant risk or toxicity. This makes MC a potential alternative to other recognized management approaches.

The impact of extirpation of non-palpable/normal-sized regional lymph nodes on staging of canine cutaneous mast cell tumours: A multicentric retrospective study.

Metastasis to regional lymph nodes (RLNs) in dogs with cutaneous mast cell tumour (cMCT) has been correlated with shortened survival time and higher risk of spread to distant sites. In the present study, extirpation of non-palpable or normal-sized RLNs was included in the surgical management of cMCT in dogs. Correlations between histological nodal status (HN0-3) and tumour variables were analysed. Ninety-three dogs with single cMCT without distant metastasis that underwent wide surgical excision of the primary tumour and extirpation of non-palpable or normal-sized RLN were included. The association between HN (HN0 vs HN > 0; HN0-1 vs HN2-3) and tumour variables (site, longest diameter, ulceration, 3-tier and 2-tier histological grades) was analysed by a generalized linear model with multinomial error. Then, 33 (35.5%) RLNs were HN0, 14 (15%) were HN1, 26 (28%) were HN2 and 20 (21.5%) were HN3. The presence of positive (HN > 0) RLN was significantly associated with cMCT larger than 3 cm. No other association was statistically significant. Non-palpable/normal-sized RLN in dogs with cMCT can harbour histologically detectable metastatic disease in nearly half of the cases. Extirpation of the RLN should always perfomed to obtain a correct staging of the disease, even in the absence of clinical suspicion of metastasis. Further studies should evaluate the possible therapeutical effect of the tumour burden reduction obtained by exrtipartion of a positive RLN.

Feline large granular lymphocyte lymphoma: An Italian Society of Veterinary Oncology (SIONCOV) retrospective study.

Feline large granular lymphocyte (LGL) lymphoma is an uncommon subtype of lymphoma characterized by a grave prognosis and scarce response to chemotherapy. There are limited reports on clinico-pathological and prognostic factors. One-hundred and 9 cats with newly diagnosed LGL lymphoma that underwent initial staging (including hematology, serum biochemistry, thoracic radiographs and abdominal ultrasound), and followed-up were retrospectively evaluated. LGL lymphoma was localized within the gastrointestinal tract with or without extra-intestinal involvement in 91.7% of the cases, and at extra-gastrointestinal sites in 8.3%. Symptoms were frequent. Anemia (31.2%) and neutrophilia (26.6%) were commonly observed, and 14 (12.8%) cats had neoplastic circulating cells. Frequent biochemistry abnormalities included elevated ALT (39.4%) and hypoalbuminemia (28.4%). Twenty (54.1%) of 37 cats had elevated serum LDH. Treatment varied among cats, and included surgery (11%), chemotherapy (23%), corticosteroids (38.5%) and no treatment (27.5%). Median time to progression (MTTP) was 5 days, and median survival time (MST) 21 days. MST was significantly shorter in the case of substage b, circulating neoplastic cells, lack of chemotherapy administration, and lack of treatment response. A small subset of cats (7.3%) survived more than 6 months, suggesting that a more favorable clinical course can be found among LGL lymphoma patients.

Unusual dermatological toxicity of hydroxyurea in two dogs with spontaneously occurring tumours.

Hydroxyurea is a chemotherapeutic agent used to treat hypereosinophilic syndrome, mast cell tumours and many myeloproliferative disorders. It is usually well tolerated; however, reported side effects include myelosuppression and gastrointestinal complications as well as cutaneous toxicity, in very rare cases. We report the unusual appearance of onychomadesis involving several claws on all feet in two canine patients receiving long-term hydroxyurea treatment. The healing of nail lesions required cessation of treatment in one dog and dose reduction in the second animal, supporting a strict relationship between onychopathy and administration of hydroxyurea. The aim of this case report is to increase clinical awareness of dermatological toxicity associated with long-term administration of hydroxyurea.

Comparison of doxorubicin-cyclophosphamide with doxorubicin-dacarbazine for the adjuvant treatment of canine hemangiosarcoma.

Canine hemangiosarcoma (HSA) is a neoplasm of vascular endothelial origin that has an aggressive biological behaviour, with less than 10% of dogs alive at 12-months postdiagnosis. Treatment of choice consists of surgery followed by adjuvant doxorubicin-based chemotherapy. We prospectively compared adjuvant doxorubicin and dacarbazine (ADTIC) to a traditional doxorubicin and cyclophosphamide (AC) treatment, aiming at determining safety and assessing whether this regimen prolongs survival and time to metastasis (TTM). Twenty-seven dogs were enrolled; following staging work-up, 18 were treated with AC and 9 with ADTIC. Median TTM and survival time were longer for dogs treated with ADTIC compared with those receiving AC (>550 versus 112 days, P = 0.021 and >550 versus 142 days, P = 0.011, respectively). Both protocols were well tolerated, without need for dose reduction or increased interval between treatments. A protocol consisting of combined doxorubicin and dacarbazine is safe in dogs with HSA and prolongs TTM and survival time.

A retrospective analysis of chemotherapy switch suggests improved outcome in surgically removed, biologically aggressive canine haemangiosarcoma.

Haemangiosarcoma (HSA) has an aggressive biological behaviour and carries a poor prognosis, with less than 10% of treated dogs surviving longer than 1 year. In this retrospective study a varied metronomic chemotherapy (MC) regimen preceded by adjuvant doxorubicin-based maximum-tolerated dose chemotherapy (MTDC) was compared with MTDC, in terms of efficacy [time to metastasis, (TTM) and survival time (ST)] and safety in dogs with biologically aggressive HSA. Dogs were eligible if they had no metastasis after MTDC and received either no further chemotherapy or MC maintenance. Twelve dogs received MTDC, and 10 received MC thereafter. Median TTM and ST were significantly longer for dogs receiving MTDC-MC (not reached versus 150 days, P = 0.028; and not reached versus 168 days, P = 0.030, respectively). Treatment was well tolerated. MTDC followed by MC is safe and suggests improved TTM and ST in dogs with surgically removed, biologically aggressive HSA that are treated in the microscopic setting.