Corrigendum: Melanoma of the dog and cat: consensus and guidelines.

[This corrects the article DOI: 10.3389/fvets.2024.1359426.].

Melanoma of the dog and cat: consensus and guidelines.

Melanoma of the dog and cat poses a clinical challenge to veterinary practitioners across the globe. As knowledge evolves, so too do clinical practices. However, there remain uncertainties and controversies. There is value for the veterinary community at large in the generation of a contemporary wide-ranging guideline document. The aim of this project was therefore to assimilate the available published knowledge into a single accessible referenced resource and to provide expert clinical guidance to support professional colleagues as they navigate current melanoma challenges and controversies. Melanocytic tumors are common in dogs but rare in cats. The history and clinical signs relate to the anatomic site of the melanoma. Oral and subungual malignant melanomas are the most common malignant types in dogs. While many melanocytic tumors are heavily pigmented, making diagnosis relatively straightforward, melanin pigmentation is variable. A validated clinical stage scheme has been defined for canine oral melanoma. For all other locations and for feline melanoma, TNM-based staging applies. Certain histological characteristics have been shown to bear prognostic significance and can thus prove instructive in clinical decision making. Surgical resection using wide margins is currently the mainstay of therapy for the local control of melanomas, regardless of primary location. Radiotherapy forms an integral part of the management of canine oral melanomas, both as a primary and an adjuvant therapy. Adjuvant immunotherapy or chemotherapy is offered to patients at high risk of developing distant metastasis. Location is the major prognostic factor, although it is not completely predictive of local invasiveness and metastatic potential. There are no specific guidelines regarding referral considerations for dogs with melanoma, as this is likely based on a multitude of factors. The ultimate goal is to provide the best options for patients to extend quality of life and survival, either within the primary care or referral hospital setting.

New Therapies in Veterinary Oncology.

The expanding number of specialized oncology therapeutics available in veterinary oncology can make staying updated on the most recent advances challenging. This article summarizes the mechanism of action, available supporting data, and clinical use of three key veterinary cancer/supportive care therapeutics: Laverdia-CA1, Canalevia-CA1, and Stelfonta. This information will help guide clinical use within your practice and can be incorporated into discussions with clients regarding the newest available options for their dogs with cancer.

Randomised trial evaluating chemotherapy alone or chemotherapy and a novel monoclonal antibody for canine T-cell lymphoma: A multicentre US study.

Background: Canine peripheral nodal T-cell lymphoma is considered chemotherapy resistant and carries a relatively poor prognosis. Prospective evaluations reporting the impact of chemotherapy on progression-free survival (PFS) and overall survival time for dogs with T-cell lymphoma are lacking. This study examined the impact of L-CHOP (L-asparaginase, doxorubicin, cyclophosphamide, vincristine, prednisone) chemotherapy or L-CHOP in combination with AT-005, a US Department of Agriculture-licensed caninised monoclonal antibody, on PFS and response rates in dogs with clinical intermediate- and high-grade peripheral nodal T-cell lymphoma. Methods: A prospective, randomised, placebo-controlled, investigator- and owner-blinded, multicentre study was completed. All dogs received a 19-week L-CHOP chemotherapy protocol with randomisation (1:1) into placebo or AT-005 groups. Response was evaluated via the Veterinary Cooperative Oncology Group criteria for canine lymphoma. Results: Forty-nine dogs were enrolled (25 received placebo and 24 received AT-005). Most demographic factors were similar between the two groups, with the exception that more dogs with stage IV and V disease were treated with AT-005 (34% vs. 8%; p = 0.03). Median PFS was 103 days (95% confidence interval [CI], 56-118) in the placebo group versus 64 days (95% CI, 36-118) in the AT-005 group. The overall response rate (ORR) for all dogs was 98% (48 of 49); complete response rate in the placebo group (64%) was not different from the AT-005 group (67%). Conclusions: To the best of the authors' knowledge, this is the first prospective study to document that treatment with L-CHOP chemotherapy, with or without AT-005, may result in a high ORR, but relatively brief PFS in dogs with clinical intermediate- and high-grade T-cell lymphoma.

Diagnosis and histopathologic prognostication of canine melanocytic neoplasms: A consensus of the Oncology-Pathology Working Group.

One of the primary objectives of the Oncology Pathology Working Group (OPWG) is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for veterinary oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for the diagnosis of, and histopathologic prognostication for, canine cutaneous and oral/lip melanocytic neoplasms, suggest guidelines for reporting, provide recommendations for clinical interpretation, and discuss future directions. This document represents the opinions of the working group and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists, American College of Veterinary Internal Medicine or the Veterinary Cancer Society.

Multicenter, randomized, double-blinded, placebo-controlled study of rabacfosadine in dogs with lymphoma.

BACKGROUND: Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs. HYPOTHESIS/OBJECTIVES: To determine the efficacy and safety of RAB in dogs with lymphoma. ANIMALS: One hundred and fifty-eight client-owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019. METHODS: Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression-free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected. RESULTS: The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P < .0001, HR 6.265 [95% CI 3.947-9.945]). The BORR for RAB-treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo-treated dogs (P < .0001). One month after the last treatment, 37 RAB-treated dogs (33%) were progression free compared with no placebo-treated dogs (P < .0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB-treated (20%) and 5 placebo-treated dogs (13%). CONCLUSIONS AND CLINICAL IMPORTANCE: Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo.

Outcome in dogs with curative-intent treatment of localized primary pulmonary histiocytic sarcoma.

Primary pulmonary histiocytic sarcoma (PHS) is a rare form of dendritic cell or macrophage neoplasia originating within the pulmonary parenchyma. There is limited literature describing prognosis in dogs with PHS receiving curative-intent treatment consisting of surgical excision and adjuvant chemotherapy. The primary objective of this study was to report outcomes in dogs with localized PHS treated with standardized local and systemic therapy. A secondary objective was to identify prognostic factors in this population. A multi-institutional retrospective study was performed and medical records including all surgical and histopathologic reports were retrospectively reviewed. For inclusion, dogs were required to have confirmed localized PHS and they must have undergone curative-intent surgery with resection of all gross primary tumour and enlarged tracheobronchial lymph nodes; additionally, they must have received curative-intent treatment with adjuvant single-agent CCNU chemotherapy. Twenty-seven dogs from six veterinary teaching hospitals and five private practices treated from 2008-2019 were included. The overall median survival time was 432 days. Higher CCNU dose was demonstrated to have a negative impact on survival on univariate, but not multivariable, analysis. Factors that were not found to be associated with survival on univariate analysis included body weight, breed, clinical signs at the time of diagnosis, hypoalbuminaemia, tumour size, lung lobe affected, lymph node metastasis, surgical margins and CCNU dose reductions. This study supports a favourable prognosis for dogs diagnosed with localized PHS treated with curative-intent surgery in addition to adjuvant CCNU chemotherapy and suggests that multimodal treatment may be advisable to attempt to prolong survival.

Value, Limitations, and Recommendations for Grading of Canine Cutaneous Mast Cell Tumors: A Consensus of the Oncology-Pathology Working Group.

One of the primary objectives of the Oncology Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects and provide guidelines for oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for grading of canine cutaneous mast cell tumors, suggest guidelines for reporting, and provide recommendations for its clinical interpretation. The article mainly focuses on histologic grading, but relevant information on mitotic count and cytological grading are also discussed. This document represents the opinions of the working group and the authors but does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society.

Clinical outcomes of dogs with transitional cell carcinoma receiving medical therapy, with and without partial cystectomy.

The objective of this retrospective study was to evaluate the effects of surgery on outcome for dogs with naturally occurring urinary bladder transitional cell carcinoma. Forty-seven dogs met the inclusion criteria. Thirty-one dogs (Group A) were treated with partial cystectomy and adjunctive medical therapy and 16 dogs (Group B) were treated with medical therapy alone. Overall survival was greater in dogs treated with partial cystectomy and adjunctive medical therapy (498 days for Group A versus 335 days for Group B, hazard ratio 2.5; 95% confidence interval: 1.1 to 5.7; P = 0.026). Progression-free survival was not different between groups (85 days for Group A versus 83 days for Group B; P = 0.663). No prognostic factors were identified for progression-free survival. Due to the many cases in Group A that were lost to follow-up, time-to-event survival analysis was performed. No significant difference in overall survival was noted, and no prognostic factors were identified in the time-to-event analysis. Prospective, randomized studies are needed to determine the role of partial cystectomy in the treatment of transitional cell carcinoma.

Résultats cliniques des chiens atteints d'un carcinome à cellules transitionnelles recevant un traitement médical, avec et sans cystectomie partielle. L'objectif de cette étude rétrospective était d'évaluer les effets de la chirurgie sur les résultats chez des chiens atteints d'un carcinome à cellules transitionnelles de la vessie d'origine naturelle. Quarante-sept chiens répondaient aux critères d'inclusion. Trente et un chiens (Groupe A) ont été traités par cystectomie partielle et traitement médical d'appoint et 16 chiens (Groupe B) ont été traités par thérapie médicale seule. La survie globale était plus élevée chez les chiens traités par cystectomie partielle et traitement médical d'appoint (498 jours pour le Groupe A contre 335 jours pour le Groupe B, rapport de risque de 2,5; intervalle de confiance à 95 % : 1,1 à 5,7; P = 0,026). La survie sans progression n'était pas différente entre les groupes (85 jours pour le Groupe A contre 83 jours pour le Groupe B; P = 0,663). Aucun facteur pronostique n'a été identifié pour la survie sans progression. En raison des nombreux cas dans le Groupe A qui ont été perdus de vue lors du suivi, une analyse du temps de survie a été realisée. Aucune différence significative dans la survie globale n'a été notée et aucun facteur pronostique n'a été identifié dans l'analyse du temps de survive. Des études prospectives randomisées sont nécessaires pour déterminer le rôle de la cystectomie partielle dans le traitement du carcinome à cellules transitionnelles.(Traduit par Dr Serge Messier).

Safety evaluation of the canine osteosarcoma vaccine, live Listeria vector.

Canine osteosarcoma (OSA) is an aggressive bone tumour in dogs. Standard-of-care treatment typically results in relatively short survival times; thus, alternative treatments are needed to confer a survival advantage. It has been shown that OSA is an immunogenic tumour, suggesting that immune modulation may result in superior outcomes. A cryopreserved, Listeria-based OSA vaccine was recently developed and an initial study in dogs reported prolonged survival for patients receiving the vaccine in conjunction with standard-of-care. The goal of the current observational study was to report on the safety of the lyophilized formulation of this vaccine (the canine OSA vaccine, live Listeria vector [COV-LLV]) in a group of dogs previously diagnosed with OSA. Forty-nine (49) dogs received the COV-LLV and were included for analysis. Adverse events (AEs) noted during and after vaccinations were recorded. The AEs observed were typically mild and self-limiting, with nausea, lethargy and fever being most common. Four dogs (8%) cultured positive for Listeria (three infections including an amputation site abscess, septic stifle joint and bacterial cystitis; and one dog whose lungs cultured Listeria-positive on necropsy within 24 hours of COV-LLV administration). These cases join the previously reported Listeria-positive thoracic abscess that developed in a canine following use of COV-LLV. Although uncommon, it is important to realize this clinically significant AE is possible in patients treated with live therapeutic Listeria vaccines. As Listeria is zoonotic, caution is required not only for the patient receiving the vaccine, but also for the health care workers and family caring for the patient.

Rabacfosadine for naïve canine intermediate to large cell lymphoma: Efficacy and adverse event profile across three prospective clinical trials.

While current lymphoma therapies induce remission in most dogs, drug-resistant relapse is common, creating a need for novel agents. Rabacfosadine (RAB), a double prodrug of the acyclic nucleotide phosphonate 9-(2-phosphonylmethoxyethel) guanine (PMEG), preferentially targets lymphoma cells with reduced systemic toxicity compared with PMEG. Previous studies evaluating RAB administered every 21 days have suggested efficacy in both naïve and relapsed subjects; however, no large studies of RAB as a single agent have been reported in previously untreated dogs with intermediate to large cell lymphoma. The purpose of this study was to evaluate the safety and efficacy of RAB in dogs with previously untreated (excluding corticosteroids) lymphoma. Sixty-three dogs received up to five RAB treatments every 21 days (16 at 0.82 mg/kg and 47 at 1.0 mg/kg) as a 30 minutes intravenous infusion, with (n = 23) or without (n = 40) concurrent corticosteroids. Response assessment and adverse event (Ae) evaluation were performed every 21 days via Veterinary Cooperative Oncology Group (VCOG) criteria. The overall response rate was 87% (52% CR, 35% PR). The overall median progression free interval was 122 days (199 for CR, 89 for PR and 153 days for all responders). T-cell immunophenotype and corticosteroid pre-treatment were predictive of inferior outcomes on multivariate analysis. AEs were most commonly of gastrointestinal origin (hyporexia/diarrhoea) and generally resolved with supportive treatment and/or dosage adjustment. Three dogs experienced VCOG-CTCAE grade 5 delayed pulmonary fibrosis. In conclusion, RAB administered every 3 weeks is generally well tolerated and demonstrates substantial antitumour activity in dogs with previously untreated intermediate to large cell lymphoma.

Concurrent use of rabacfosadine and L-asparaginase for relapsed or refractory multicentric lymphoma in dogs.

BACKGROUND: Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L-asparaginase (L-ASP) has not been studied. HYPOTHESIS/OBJECTIVES: To evaluate the safety and efficacy of L-ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma. ANIMALS: Fifty-two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin-based chemotherapy protocol. METHODS: Open-label, multicenter, prospective single-arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L-asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB. RESULTS: The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression-free survival time (MPFS) was 63 days (range 5-428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44-428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L-ASP were negative prognostic factors on multivariate analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent RAB/L-ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed.

Prognostic and predictive significance of KIT protein expression and c-kit gene mutation in canine cutaneous mast cell tumours: A consensus of the Oncology-Pathology Working Group.

One of the primary objectives of the Oncology-Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for oncologic pathology. Consensus is established through critical review of peer-reviewed literature relevant to a subgroup's particular focus. Subsequent acceptance and approval of the document by the OPWG membership at large establishes consensus. The intent of this publication is to help educate practitioners and pathologists on the value of diagnostics related to the KIT receptor tyrosine kinase for canine cutaneous mast cell tumours and to provide a guide for the use of these tests in veterinary medicine. This document represents the opinions of the OPWG and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society.

Pilot study comparing serum chemotherapy levels after intra-arterial and intravenous administration in dogs with naturally occurring urinary tract tumors.

The proposed advantages of intra-arterial chemotherapy (IAC) are based on the premises of local dose escalation to the tumor and reduced availability of systemic drugs. There is a lack of objective pharmacokinetic data to confirm the advantage of IAC in dogs with naturally occurring urogenital tumors. The objective of this study was to determine if IAC administration in urogenital tumors would result in decreased systemic drug exposure when compared to intravenous routes. Twenty-two dogs with naturally occurring urogenital tumors were enrolled in this prospective case-controlled study. Mitoxantrone, doxorubicin, or carboplatin were administered by IAC and intravenous routes [intravenous awake (intravenous chemotherapy - IVC) and under general anesthesia (IVGAC)] 3 weeks apart. Serum assays were used to determine the extent of systemic drug exposure. Dose-normalized peak systemic serum concentration (Cmax) and area under the serum drug concentration-time curve (AUC) were used to quantify systemic exposure. A total of 26 mitoxantrone treatments were administered to 10 dogs. While there was no significant difference in Cmax, the AUC was significantly lower after IAC compared with IVGAC. Ten doxorubicin treatments were administered to 5 dogs. There were no significant differences in Cmax or AUC. A total of 14 carboplatin treatments were administered to 7 dogs. The Cmax was significantly lower for IAC compared to IVC, while the AUC values were equivocal. This study demonstrates certain lower serum values may be achieved after IAC delivery of carboplatin and mitoxantrone. These chemotherapy agents may have a preferred pharmacological profile for regional chemotherapy delivery in dogs with urogenital tumors.

Les avantages proposés de la chimiothérapie intra-artérielle (CIA) sont basés sur les prémisses d'une escalade de la dose locale à la tumeur et d'une disponibilité réduite des drogues systémiques. Il y a un manque de données pharmacocinétiques objectives pour confirmer l'avantage de l'administration de CIA chez les chiens avec des tumeurs urogénitales se produisant naturellement. L'objectif de la présente étude était de déterminer si l'administration de CIA lors de tumeurs urogénitales résulterait en une diminution de l'exposition systémique aux drogues lorsque comparé aux voies intraveineuses. Vingt-deux chiens avec des tumeurs urogénitales d'occurrence naturelle participèrent à cette étude cas-témoin prospective. De la mitoxantrone, de la doxorubicine, ou de la carboplatine furent administrées par CIA et voies intraveineuses [intraveineuse éveillée (chimiothérapie intraveineuse ­ CIV) et sous anesthésie générale (CIVAG)] à 3 sem d'intervalle. Des analyses du sérum furent utilisées afin de déterminer l'étendue de l'exposition systémique aux drogues. Le pic de la concentration sérique systémique normalisé pour la dose (Cmax) et la surface sous la courbe de la concentration sérique de la drogue-temps (SSC) furent utilisés pour quantifier l'exposition systémique. Un total de 26 traitements à la mitoxantrone fut administré à 10 chiens. Bien qu'il n'y ait pas de différence significative dans le Cmax, la SSC était significativement plus basse après la CIA comparativement à la CIVAG. Dix traitements de doxorubicine furent administrés à cinq chiens. Il n'y avait pas de différence significative dans le Cmax ou ls SSC. Un total de 14 traitements de carboplatine fut administré à sept chiens. Le Cmax était significativement plus bas pour la CIA comparativement à la CIV, alors que les valeurs de SSC étaient équivoques. Cette étude démontre que certaines valeurs sériques plus faibles peuvent être obtenues après CIA avec la carboplatine et la mitoxantrone. Ces agents de chimiothérapie pourraient avoir un profil pharmacologique préférentiel pour livraison régionale de chimiothérapie chez les chiens avec des tumeurs urogénitales.(Traduit par Docteur Serge Messier).

Histiocytic Sarcoma and Hemangiosarcoma Update.

Histiocytic sarcoma (HS) and hemangiosarcoma (HSA) are uncommon and aggressive neoplasms that develop much more frequently in dogs than in cats. Breed-specific predispositions have been identified for both cancers. The development of novel diagnostics is underway and may aid in earlier diagnosis. Therapeutic approaches to HS and HSA depend on the stage of disease and may include surgery, radiation therapy, and chemotherapy. Such interventions improve outcome; however, aside from a small number of clinical circumstances, both diseases are considered largely incurable. Continued efforts toward the identification of driver mutations and subsequent druggable targets may lead to improvements in long-term prognosis.

Biomechanical Considerations in Foot and Ankle Circular External Fixation: Maintenance of Wire Tension.

Initial tensioning of the forefoot wires to 130 kg followed by simultaneous tensioning of the calcaneal wires to 90 kg and using the rigid double-row foot plate closed anteriorly via threaded rods produce maximum preservation of the initial wire tension during foot circular external fixation.

Outcome and Prognostic Indicators in Cats Undergoing Splenectomy for Splenic Mast Cell Tumors.

This was a multi-institutional retrospective study evaluating the outcome and clinical parameters associated with the postoperative prognosis of 36 cats with splenic mast cell tumors treated with splenectomy. Clinical parameters reviewed included signalment, clinical history, results of staging tests, surgical variables, administration of blood products, presence of metastasis, postoperative complications, administration of chemotherapy postoperatively, chemotherapy protocol, and response to chemotherapy. Overall median survival time was 390 days (range, 2-1737 days). Administration of a blood product (P < .0001), metastasis to a regional lymph node (P = .022), and evidence of either concurrent or historical neoplasia (P = .037) were negatively associated with survival. Response to chemotherapy (P = .0008) was associated with an improved median survival time. Larger-scale prospective studies evaluating different chemotherapy protocols are required to elucidate the discrepancy between lack of survival benefit with administration of chemotherapy and improvement in survival time with positive response to chemotherapy.

Maintenance therapy with toceranib following doxorubicin-based chemotherapy for canine splenic hemangiosarcoma.

BACKGROUND: Spenic hemangiosarcoma (HSA) in dogs treated with surgery alone is associated with short survival times, and the addition of doxorubicin (DOX) chemotherapy only modestly improves outcome. The purpose of this study was to evaluate the impact of toceranib administration on progression free survival in dogs with stage I or II HSA following splenectomy and single agent DOX chemotherapy. We hypothesized that dogs with splenic HSA treated with adjuvant DOX followed by toceranib would have prolonged disease-free interval (DFI) and overall survival time (OS) when compared to historical dogs treated with DOX-based chemotherapy alone. RESULTS: Dogs with stage I or II splenic HSA were administered 5 cycles of single-agent DOX every 2 weeks beginning within 14 days of splenectomy. Dogs were restaged 2 weeks after completing DOX, and those without evidence of metastatic disease began toceranib therapy at 3.25 mg/kg every other day. Forty-three dogs were enrolled in this clinical trial. Seven dogs had evidence of metastatic disease either before or at re-staging, and an additional 3 dogs were found to have metastatic disease within 1 week of toceranib administration. Therefore 31 dogs went on to receive toceranib following completion of doxorubicin treatment. Twenty-five dogs that received toceranib developed metastatic disease. The median disease free interval for all dogs enrolled in this study (n = 43) was 138 days, and the median disease free interval for those dogs that went on to receive toceranib (n = 31) was 161 days. The median survival time for all dogs enrolled in this study was 169 days, and the median survival time for those dogs that went on to receive toceranib was 172 days. CONCLUSIONS: The use of toceranib following DOX chemotherapy does not improve either disease free interval or overall survival in dogs with stage I or II HSA.