Feline high-grade and large granular lymphocyte alimentary lymphomas treated with COP- or CHOP-based chemotherapy: A multi-centric retrospective study of 57 cases.

Specific data regarding outcome of cats with high-grade and large granular lymphocyte alimentary lymphoma (HGAL and LGL, respectively) treated with multi-agent chemotherapy are scarce. The aims of this multi-centric, retrospective study were to describe the outcome of cats with HGAL and LGL treated with COP- or CHOP-based chemotherapy and to identify potential prognostic factors. Cats with a cytological or histological diagnosis of HGAL or LGL lymphoma treated with COP- or CHOP-based protocol as first-line chemotherapy were included. Data regarding diagnosis, staging, treatment and follow-up were collected. Fifty-seven cats treated with CHOP (n = 37) or COP (n = 20) protocols were included. Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 20%, 22%, 36% and 22% of cats, respectively, for an overall response rate of 42%. Median progression-free interval (PFI) was 148 days and overall median survival time (OST) was 131 days. Cats achieving CR, PR or SD showed significantly longer PFI (p < .01) and OST (p < .015) compared with cats with PD. Other positive prognostic factors in multi-variate analysis were rescue treatment (p < .001) and absence of lymph node involvement (p < .03). Negative prognostic factors were diffuse infiltration of the gastrointestinal tract (p = .035) and infiltration of a non-haematopoietic organ (p < .01).

Outcome of dogs treated with chemotherapy for mesothelioma: A retrospective clinical study on 40 cases and a literature review.

Mesothelioma is an uncommon cancer in dogs for which there is no established standard of care. Chemotherapy is often suggested despite no definitive proof of efficacy. The aim of this study was to evaluate the impact of chemotherapy on survival of dogs with mesothelioma. A retrospective multicentric study was carried out. To be included, dogs needed to present an evocative clinical evolution and a morphological diagnosis of mesothelioma. Exclusion of other cause of effusion and complete clinical follow-up were also required. Fourty dogs were included, 27 received chemotherapy (group 1) and 13 did not (group 2). Groups were heterogeneous regarding the proportion of animals undergoing surgery as part of their treatment (16 in group 1, 2 in group 2; p = .016) and homogeneous otherwise. Univariate analysis showed that dogs from group 1 survived significantly longer than dogs from group 2 (MST: 366 vs. 74 days; p < .001). Complete resolution of effusion after the first chemotherapy administration positively correlated with survival in group 1 (MST: 415 vs. 160 days; p < .01). All other variable tested had no significant impact on survival in univariate analysis, but dogs undergoing surgery and dogs having serous membranes' modification at medical imaging tended to survive longer. Multivariate analysis confirmed that chemotherapy was the sole variable independently associated with survival in our study (odds ratio 5.57-6.12; p < .01).

Toward Neuro-Oncologic Clinical Trials of High-Dose-Rate Synchrotron Microbeam Radiation Therapy: First Treatment of a Spontaneous Canine Brain Tumor.

PURPOSE: The high potential of microbeam radiation therapy (MRT) in improving tumor control while reducing side effects has been shown by numerous preclinical studies. MRT offers a widened therapeutic window by using the periodical spatial fractionation of synchrotron generated x-rays into an array of intense parallel microbeams. MRT now enters a clinical transfer phase. As proof of principle and cornerstone for the safe clinical transfer of MRT, we conducted a "first in dog" trial under clinical conditions. In this report, we evaluated whether a 3-dimensional conformal MRT can be safely delivered as exclusive radiosurgical treatment in animal patients METHODS AND MATERIALS: We irradiated a 17.5-kg French bulldog for a spontaneous brain tumor (glioma suspected on magnetic resonance imaging) with conformal high-dose-rate microbeam arrays (50-µm-wide microbeams, replicated with a pitch of 400 µm) of synchrotron-generated x-rays. The dose prescription adjusted a minimal cumulated valley dose of 2.8 Gy to the plnning target volume (PTV) (cinical target volume (CTV)+ 1 mm). Thus, each beam delivered 20 to 25 Gy to the target as peak doses, and ∼1 Gy as valley doses RESULTS: The treatment was successfully delivered. Clinical follow-up over 3 months showed a significant improvement of the dog's quality of life: the symptoms disappeared. Magnetic resonance imaging, performed 3 months after irradiation, revealed reduction in tumor size (-87.4%) and mass effect with normalization of the left lateral ventricle. CONCLUSIONS: To our knowledge, this neuro-oncologic veterinary trial is the first 3-dimensional conformal synchrotron x-ray MRT treatment of a spontaneous intracranial tumor in a large animal. It is an essential last step toward the clinical transfer of MRT in the near future to demonstrate the feasibility and safety of treating deep-seated tumors using synchrotron-generated microbeams.

Are severe adverse events commonly observed in dogs during cancer chemotherapy? A retrospective study on 155 dogs.

Overall prevalence of severe adverse events (sAE) has been poorly studied in veterinary medicine and peer-reviewed studies mostly focused on a single protocol, making it difficult to have a general overview. The aim of this retrospective study was to assess the frequency and risk factors of sAE secondary to various protocols of chemotherapy in dogs. Medical records of 155 dogs receiving chemotherapy between January 2013 and December 2018 were reviewed. Adverse events (AE) were graded according to Veterinary Comparative Oncology Group-common terminology criteria for AE (VCOG-CTCAE) grading system. Statistical analyses were performed to determine whether demographic, cancer type and chemotherapy protocol were associated with development of sAE and their consequences. AE were reported at least once in 124 (80%) dogs and sAE were observed in 50 (32.3%) dogs. Among them, 23 (14.8%) had gastro-intestinal and 31 (20.0%) had myelotoxic events. sAE led to hospitalisation in 37 (23.9%) dogs, to chemotherapy arrest in 12 (7.7%) dogs and to euthanasia or death in 9 (5.8%) dogs. Haematopoietic tumours were statistically associated with a higher frequency of sAE (p = .004), gastrointestinal sAE (p = .009) and hospitalisation (p = .004). A body weight over 10 kg was associated with less haematological sAE (p < .001). The use of a multi-agent protocol was highlighted as a risk factor for sAE (p = .038) and haematological sAE (p < .001). sAE following chemotherapy and leading to hospitalisation, chemo arrest or death were relatively common. A special attention during chemotherapy follow-up should be given to small dogs and those receiving multi-agent protocol or treated for haematopoietic tumours.

Proof-of-concept study: Evaluation of plasma and urinary electrolytes as markers of response to L-asparaginase therapy in dogs with high-grade lymphoma.

Response to chemotherapy is one of the most important prognostic factors in dogs with lymphoma. The objective of this feasibility study was to evaluate if clinical responses to a specific cytotoxic agent (L-asparaginase) could be anticipated by measuring analyte concentrations in plasma and urine concentrations of lymphoma-bearing dogs. We hypothesized that potassium and phosphate concentrations in plasma and urine would be higher in dogs that completely responded to therapy. Plasma and urine samples of dogs with lymphoma were obtained before 12 and 24 hours after intramuscular L-asparaginase injections. Peripheral lymph node volumes were evaluated according to the Veterinary Cooperative Oncology Group standardized criteria. Plasma and urine electrolyte, calcium, phosphate, creatinine, urea, total protein, and albumin concentrations were measured, and the fractional excretions of each electrolyte were calculated. Statistical analyses compared complete vs partial responders using a linear regression model. Contrast analyses were also performed to differentiate the mean of each group, with adjustments made with the Benjamini-Hochberg procedure. Fourteen dogs were included, eight with complete responses, and six with partial responses. Plasma phosphate concentrations were significantly higher at 12 hours (P = .0003) and 24 hours (P = .009) after complete responses to therapy. This study demonstrates the potential use of plasma and urine analyte monitoring after chemotherapy induction. Plasma phosphate measurements represent a potential indicator of early responses to L-asparaginase therapy. Larger population studies are warranted to confirm these preliminary results.

A DNA telomerase vaccine for canine cancer immunotherapy.

Telomerase reverse transcriptase (TERT) is highly expressed in more than 90% of canine cancer cells and low to absent in normal cells. Given that immune tolerance to telomerase is easily broken both naturally and experimentally, telomerase is an attractive tumor associated antigen for cancer immunotherapy. Indeed, therapeutic trials using human telomerase peptides have been performed. We have developed an immunogenic yet catalytically inactive human telomerase DNA construct that is in clinical trials with patients presenting solid tumors. Paralleling this human construct, we have developed a canine telomerase DNA vaccine, called pDUV5. When administered intradermally to mice combined with electrogene transfer, pDUV5 induced canine TERT specific cytotoxic T-cells as measured by IFN-γ ELISpot assay. Intradermal vaccination of healthy dogs with 400 µg of pDUV5 generated strong, broad and long lasting TERT specific cellular immune responses. In vitro immunization with cTERT peptides revealed the maintenance of cTERT specific T-cells in PBMCs from tumor bearing dogs showing that this repertoire was not depleted. This study highlights the potential of pDUV5 as a cancer vaccine and supports its evaluation for the treatment of spontaneous canine tumors.

Non-ocular melanomas in cats: a retrospective study of 30 cases.

Objectives The aim of the study was to describe the clinical outcome of 30 cats with non-ocular melanomas and to evaluate the association between clinical or pathological parameters and overall survival time. Methods The database of the animal histopathological laboratory of the National Veterinary School of Nantes (Oniris, Nantes, France) was retrospectively searched to identify cases of feline non-ocular melanomas between December 2009 and April 2014. For each case, clinical data, including signalment, location of the primary tumour, staging, treatment and outcome, were collected from the medical records or via interviews with referring veterinarians. Histological and immunohistochemical evaluation included mitotic index, cytonuclear atypias, junctional activity, Melan A and S100 immunostaining, and surgical margins. Univariate analysis to test the prognostic value of the different variables was performed by the Kaplan-Meier product limit method using the log-rank test of significance. Results Thirty cats were included in the study. Eleven had a cutaneous non-auricular melanoma, six had a tumour located on the pinna and 13 had a tumour in the oral cavity. Cats with auricular melanomas were significantly younger than cats with tumours in other locations. Location and presence of clinical signs were not of prognostic significance, but the achromic phenotype was significantly associated with a poorer prognosis. Twenty cats were treated with surgery and survived significantly longer than cats that received only medical treatment or that did not receive any treatment. According to our data, mitotic index, cytonuclear atypias, junctional activity, Melan A or S100 expression, and surgical margins were not associated with survival. Conclusions and relevance We show for the first time, in a large series, that the auricular form of melanoma affected significantly younger cats than other extraocular forms. Most feline non-ocular melanomas are malignant and achromic tumours are associated with a poorer prognosis. According to this study, surgery should be considered as a priority.