Pub Date : 2024-09-01Epub Date: 2024-06-18DOI: 10.1111/vco.12990
Chiara Catalucci, Marco Luigi Bianchi, Elisabetta Treggiari, Marta Pieri, Katja Ruess, Paola Valenti
Multiagent chemotherapy is considered the most effective treatment for canine high-grade lymphoma; however, due to cost and time requirements, single-agent protocols have also been described. The aim of our study was to evaluate the outcome and prognostic factors of dogs affected by multicentric lymphoma treated with lomustine and prednisolone as first-line treatment. Cases of medium-large-cell multicentric lymphoma treated with lomustine and prednisolone were included in the study. Response to therapy, time to progression (TTP), median disease-free interval (MDFI) and median survival time (MST) were retrospectively described. Thirty cases were included. Eleven (36.67%) were T cell, 11 (36.67%) were B cell and 8 (26.66%) had unknown immunophenotype. The overall response rate (RR) was 87%, with 15 patients achieving CR (50%) and 11 patients PR (37%). The median TTP, MDFI and MST were 42, 63 and 90 days, respectively. The only factor significantly associated with MDFI and MST was the stage. Dogs with multicentric lymphoma treated with lomustine and prednisolone have lower RR, TTP, MDFI and MST compared with dogs receiving multiagent protocols. Based on the short-lasting response, this study confirms that this protocol might have minimal utility beyond palliation.
{"title":"Use of Lomustine and Prednisolone as First-Line Treatment in Canine Multicentric Lymphoma.","authors":"Chiara Catalucci, Marco Luigi Bianchi, Elisabetta Treggiari, Marta Pieri, Katja Ruess, Paola Valenti","doi":"10.1111/vco.12990","DOIUrl":"10.1111/vco.12990","url":null,"abstract":"<p><p>Multiagent chemotherapy is considered the most effective treatment for canine high-grade lymphoma; however, due to cost and time requirements, single-agent protocols have also been described. The aim of our study was to evaluate the outcome and prognostic factors of dogs affected by multicentric lymphoma treated with lomustine and prednisolone as first-line treatment. Cases of medium-large-cell multicentric lymphoma treated with lomustine and prednisolone were included in the study. Response to therapy, time to progression (TTP), median disease-free interval (MDFI) and median survival time (MST) were retrospectively described. Thirty cases were included. Eleven (36.67%) were T cell, 11 (36.67%) were B cell and 8 (26.66%) had unknown immunophenotype. The overall response rate (RR) was 87%, with 15 patients achieving CR (50%) and 11 patients PR (37%). The median TTP, MDFI and MST were 42, 63 and 90 days, respectively. The only factor significantly associated with MDFI and MST was the stage. Dogs with multicentric lymphoma treated with lomustine and prednisolone have lower RR, TTP, MDFI and MST compared with dogs receiving multiagent protocols. Based on the short-lasting response, this study confirms that this protocol might have minimal utility beyond palliation.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-16DOI: 10.1111/vco.12981
Kathryn E Cronise, Jonathan Coy, Steven Dow, Marlene L Hauck, Daniel P Regan
Immune checkpoint inhibitor therapy can provide significant clinical benefit in patients with certain cancer types including melanoma; however, objective responses are only observed for a subset of patients. Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and, compared with cutaneous melanoma, is significantly less responsive to immune checkpoint inhibitors. Spontaneous canine tumours have emerged as valuable models to inform human cancer studies. In contrast to human melanoma, most canine melanomas are mucosal-an incidence that may be leveraged to better understand the subtype in humans. However, a more comprehensive understanding of the immune landscape of the canine disease is required. Here, we quantify tumour infiltrative T and myeloid cells in canine mucosal (n = 13) and cutaneous (n = 5) melanomas using immunohistochemical analysis of CD3 and MAC387 expression, respectively. Gene expression analysis using the Canine IO NanoString panel was also performed to identify genes and pathways associated with immune cell infiltration. T and myeloid cell densities were variable with geometric means of 158.7 cells/mm2 and 166.7 cells/mm2, respectively. Elevated T cell infiltration was associated with increased expression of cytolytic genes as well as genes encoding the coinhibitory checkpoint molecules PD-1, CTLA-4, TIM-3 and TIGIT; whereas increased myeloid cell infiltration was associated with elevated expression of protumourigenic cytokines. These data provide a basic characterization of the tumour microenvironment of canine malignant melanoma and suggest that, like human melanoma, inherent variability in anti-tumour T cell responses exists and that a subset of canine melanomas may respond better to immunomodulation.
免疫检查点抑制剂疗法可为包括黑色素瘤在内的某些癌症类型患者带来显著的临床获益;然而,只有一部分患者能观察到客观反应。粘膜黑色素瘤是一种罕见的黑色素瘤亚型,预后较差,与皮肤黑色素瘤相比,对免疫检查点抑制剂的反应明显较弱。自发性犬肿瘤已成为人类癌症研究的重要参考模型。与人类黑色素瘤不同的是,犬黑色素瘤大多为粘膜瘤--这种发病率可用于更好地了解人类黑色素瘤的亚型。然而,我们需要更全面地了解犬类疾病的免疫状况。在这里,我们分别使用 CD3 和 MAC387 表达的免疫组化分析方法对犬粘膜(13 例)和皮肤(5 例)黑色素瘤中的肿瘤浸润性 T 细胞和髓细胞进行了量化。还使用犬 IO NanoString 面板进行了基因表达分析,以确定与免疫细胞浸润相关的基因和通路。T 细胞和骨髓细胞密度各不相同,几何平均数分别为 158.7 个细胞/mm2 和 166.7 个细胞/mm2。T细胞浸润的增加与细胞溶解基因以及共同抑制检查点分子PD-1、CTLA-4、TIM-3和TIGIT的编码基因的表达增加有关;而髓样细胞浸润的增加与原发肿瘤细胞因子的表达增加有关。这些数据提供了犬恶性黑色素瘤肿瘤微环境的基本特征,并表明与人类黑色素瘤一样,抗肿瘤 T 细胞反应也存在固有的变异性,而且犬黑色素瘤亚群可能对免疫调节反应更好。
{"title":"Immunohistochemical and transcriptomic characterization of T and myeloid cell infiltrates in canine malignant melanoma.","authors":"Kathryn E Cronise, Jonathan Coy, Steven Dow, Marlene L Hauck, Daniel P Regan","doi":"10.1111/vco.12981","DOIUrl":"10.1111/vco.12981","url":null,"abstract":"<p><p>Immune checkpoint inhibitor therapy can provide significant clinical benefit in patients with certain cancer types including melanoma; however, objective responses are only observed for a subset of patients. Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and, compared with cutaneous melanoma, is significantly less responsive to immune checkpoint inhibitors. Spontaneous canine tumours have emerged as valuable models to inform human cancer studies. In contrast to human melanoma, most canine melanomas are mucosal-an incidence that may be leveraged to better understand the subtype in humans. However, a more comprehensive understanding of the immune landscape of the canine disease is required. Here, we quantify tumour infiltrative T and myeloid cells in canine mucosal (n = 13) and cutaneous (n = 5) melanomas using immunohistochemical analysis of CD3 and MAC387 expression, respectively. Gene expression analysis using the Canine IO NanoString panel was also performed to identify genes and pathways associated with immune cell infiltration. T and myeloid cell densities were variable with geometric means of 158.7 cells/mm<sup>2</sup> and 166.7 cells/mm<sup>2</sup>, respectively. Elevated T cell infiltration was associated with increased expression of cytolytic genes as well as genes encoding the coinhibitory checkpoint molecules PD-1, CTLA-4, TIM-3 and TIGIT; whereas increased myeloid cell infiltration was associated with elevated expression of protumourigenic cytokines. These data provide a basic characterization of the tumour microenvironment of canine malignant melanoma and suggest that, like human melanoma, inherent variability in anti-tumour T cell responses exists and that a subset of canine melanomas may respond better to immunomodulation.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-04DOI: 10.1111/vco.12982
Victor Nowosh, Alexcia Camila Braun, Anna Paula Carreta Ruano, Ludmilla Thomé Domingos Chinén, Cristina de Oliveira Massoco
Liquid biopsy for circulating tumour cell (CTC) detection is generally unexplored in veterinary medicine. Dogs with highly aggressive and heterogeneous tumours, such as oral malignant melanoma (OMM), could benefit from studies involving size-based isolation methods for CTCs, as they do not depend on specific antibodies. This pilot study aimed to detect CTCs from canine OMM using Isolation by Size of Epithelial Tumor Cells (ISET), a microfiltration methodology, followed by immunocytochemistry (ICC) with Melan-A, PNL2, and S100 antibodies. Ten canine patients diagnosed by histopathology and confirmed as OMM by immunohistochemistry were enrolled, their prognostic data was assessed, and blood samples were collected for CTC analysis. Results have shown the detection of intact cells in 9/10 patients. ICC has shown 3/9 Melan-A-positive, 3/9 PNL2-positive, and 8/9 S100-positive patients, confirming the importance of opting for a multimarker assay. A significant number of negative-stained CTCs were found, suggesting their high heterogeneity in circulation. Microemboli stained with either PNL2 or S100 were found in a patient with a high isolated cell count and advanced clinical stage. Preliminary statistical analysis shows a significant difference in CTC count between patients with and without lymph node metastasis (p < .05), which may correlate with tumour metastatic potential. However, we recommend further studies with more extensive sampling to confirm this result. This pilot study is the first report of intact CTC detection in canine OMM and the first application of ISET in veterinary medicine, opening new possibilities for liquid biopsy studies in canine OMM and other tumours.
{"title":"Pilot study to evaluate isolation by size of circulating tumour cells in canine oral melanoma.","authors":"Victor Nowosh, Alexcia Camila Braun, Anna Paula Carreta Ruano, Ludmilla Thomé Domingos Chinén, Cristina de Oliveira Massoco","doi":"10.1111/vco.12982","DOIUrl":"10.1111/vco.12982","url":null,"abstract":"<p><p>Liquid biopsy for circulating tumour cell (CTC) detection is generally unexplored in veterinary medicine. Dogs with highly aggressive and heterogeneous tumours, such as oral malignant melanoma (OMM), could benefit from studies involving size-based isolation methods for CTCs, as they do not depend on specific antibodies. This pilot study aimed to detect CTCs from canine OMM using Isolation by Size of Epithelial Tumor Cells (ISET), a microfiltration methodology, followed by immunocytochemistry (ICC) with Melan-A, PNL2, and S100 antibodies. Ten canine patients diagnosed by histopathology and confirmed as OMM by immunohistochemistry were enrolled, their prognostic data was assessed, and blood samples were collected for CTC analysis. Results have shown the detection of intact cells in 9/10 patients. ICC has shown 3/9 Melan-A-positive, 3/9 PNL2-positive, and 8/9 S100-positive patients, confirming the importance of opting for a multimarker assay. A significant number of negative-stained CTCs were found, suggesting their high heterogeneity in circulation. Microemboli stained with either PNL2 or S100 were found in a patient with a high isolated cell count and advanced clinical stage. Preliminary statistical analysis shows a significant difference in CTC count between patients with and without lymph node metastasis (p < .05), which may correlate with tumour metastatic potential. However, we recommend further studies with more extensive sampling to confirm this result. This pilot study is the first report of intact CTC detection in canine OMM and the first application of ISET in veterinary medicine, opening new possibilities for liquid biopsy studies in canine OMM and other tumours.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-11DOI: 10.1111/vco.12987
Joana Rodrigues-Jesus, Ana Canadas-Sousa, Pedro Oliveira, Ana Catarina Figueira, Carla Marrinhas, Gonçalo N Petrucci, Hugo Gregório, Flora Tinoco, Andrea Goulart, Helena Felga, Hugo Vilhena, Patrícia Dias-Pereira
Inflammation is a frequent finding in feline mammary neoplasms. Recent research suggests that the presence and location of tumour-associated immune cells might play a significant role in the clinical outcome of feline mammary carcinomas. The present study aimed to characterise the overall inflammatory infiltrates in healthy, hyperplastic/dysplastic, benign and malignant lesions of the feline mammary gland, and to evaluate its association with clinicopathological features. Perilesional and intralesional inflammatory foci were evaluated in 307 lesions from 185 queens, and categorised according to its distribution and intensity. The presence, location and density of tertiary lymphoid structures were also assessed. A control group included 24 queens without mammary changes. The presence of intralesional and perilesional inflammatory infiltrate was observed in a majority of the lesions (80.8% and 90.2%, respectively), but differed according to the type of mammary lesion, being more remarkable in malignant neoplasms. Only scarce individual cells were observed in 28.1% of the normal mammary glands. Data analysis revealed statistically significant associations (p < 0.05) between the presence of a more prominent intralesional and perilesional inflammatory reaction and several clinicopathological features associated with worse prognosis, including clinical stage, tumour size, mitotic count, lymphovascular invasion and lymph node metastasis. Furthermore, tertiary lymphoid structures were significantly more frequent in tumours with an infiltrative growth and lymph node metastasis. According to our results, the inflammatory reaction present in different types of feline mammary lesions is associated with the development of more aggressive tumours.
{"title":"Distribution of Inflammatory Infiltrate in Feline Mammary Lesions: Relationship With Clinicopathological Features.","authors":"Joana Rodrigues-Jesus, Ana Canadas-Sousa, Pedro Oliveira, Ana Catarina Figueira, Carla Marrinhas, Gonçalo N Petrucci, Hugo Gregório, Flora Tinoco, Andrea Goulart, Helena Felga, Hugo Vilhena, Patrícia Dias-Pereira","doi":"10.1111/vco.12987","DOIUrl":"10.1111/vco.12987","url":null,"abstract":"<p><p>Inflammation is a frequent finding in feline mammary neoplasms. Recent research suggests that the presence and location of tumour-associated immune cells might play a significant role in the clinical outcome of feline mammary carcinomas. The present study aimed to characterise the overall inflammatory infiltrates in healthy, hyperplastic/dysplastic, benign and malignant lesions of the feline mammary gland, and to evaluate its association with clinicopathological features. Perilesional and intralesional inflammatory foci were evaluated in 307 lesions from 185 queens, and categorised according to its distribution and intensity. The presence, location and density of tertiary lymphoid structures were also assessed. A control group included 24 queens without mammary changes. The presence of intralesional and perilesional inflammatory infiltrate was observed in a majority of the lesions (80.8% and 90.2%, respectively), but differed according to the type of mammary lesion, being more remarkable in malignant neoplasms. Only scarce individual cells were observed in 28.1% of the normal mammary glands. Data analysis revealed statistically significant associations (p < 0.05) between the presence of a more prominent intralesional and perilesional inflammatory reaction and several clinicopathological features associated with worse prognosis, including clinical stage, tumour size, mitotic count, lymphovascular invasion and lymph node metastasis. Furthermore, tertiary lymphoid structures were significantly more frequent in tumours with an infiltrative growth and lymph node metastasis. According to our results, the inflammatory reaction present in different types of feline mammary lesions is associated with the development of more aggressive tumours.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-12DOI: 10.1111/vco.12988
Suzanne Agnes Erich, Erik Teske
The precise cause of HS/DCS is still unknown. The relatively low incidence in humans urges for an animal model with a high incidence to accelerate knowledge about genetics and optimal treatment of HS/DCS. Namely, until now, the therapies targeting genetic variants are still more experimental and sparsely used, while consensus is missing. In addition, the literature about variants and possible mutation-targeted therapies in humans and dogs consists mainly of case reports scattered throughout the literature. Therefore, an overview is provided of all currently known genetic variants in humans and dogs with HS/DCS and its subtypes, their possible mutation-targeted therapies, their efficacy, and a contemplation about the future. Several genetic variants have already been discovered in HS/DCS, of which many are shared between canine and human HS/DCS, but unique variants exist as well. Unfortunately, none of these already found variants seem to be specifically causal for HS/DCS, and the puzzle of its landscape of genetic variation is far from complete. The use of mutation-targeted therapies, including MAPK-/MEK-inhibitors and the future use of PTPN11-, CDK4/6- and PD-1-inhibitors, seems to be promising for these specific variants, but clearly, clinical trials are needed to determine optimal inhibitors and standardised protocols for all variants. It can be concluded that molecular analysis for variants and subsequent mutation-targeted therapy are an essential addition to cancer diagnostics and therapy. A joint effort of humans and dogs in research is urgently needed and will undoubtedly increase knowledge and survival of this devastating disease in dogs and humans.
{"title":"One Health: Therapies Targeting Genetic Variants in Human and Canine Histiocytic and Dendritic Cell Sarcomas.","authors":"Suzanne Agnes Erich, Erik Teske","doi":"10.1111/vco.12988","DOIUrl":"10.1111/vco.12988","url":null,"abstract":"<p><p>The precise cause of HS/DCS is still unknown. The relatively low incidence in humans urges for an animal model with a high incidence to accelerate knowledge about genetics and optimal treatment of HS/DCS. Namely, until now, the therapies targeting genetic variants are still more experimental and sparsely used, while consensus is missing. In addition, the literature about variants and possible mutation-targeted therapies in humans and dogs consists mainly of case reports scattered throughout the literature. Therefore, an overview is provided of all currently known genetic variants in humans and dogs with HS/DCS and its subtypes, their possible mutation-targeted therapies, their efficacy, and a contemplation about the future. Several genetic variants have already been discovered in HS/DCS, of which many are shared between canine and human HS/DCS, but unique variants exist as well. Unfortunately, none of these already found variants seem to be specifically causal for HS/DCS, and the puzzle of its landscape of genetic variation is far from complete. The use of mutation-targeted therapies, including MAPK-/MEK-inhibitors and the future use of PTPN11-, CDK4/6- and PD-1-inhibitors, seems to be promising for these specific variants, but clearly, clinical trials are needed to determine optimal inhibitors and standardised protocols for all variants. It can be concluded that molecular analysis for variants and subsequent mutation-targeted therapy are an essential addition to cancer diagnostics and therapy. A joint effort of humans and dogs in research is urgently needed and will undoubtedly increase knowledge and survival of this devastating disease in dogs and humans.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-18DOI: 10.1111/vco.12989
Marilia Takada, Keita Kitagawa, Yongzhen Zhang, Jürgen B Bulitta, Steven Moirano, Abigail Jones, Jennifer Borgen, Ashley Onsager, Tuddow Thaiwong, David M Vail
MAPK has been reported as a key oncogenic pathway for canine histiocytic sarcoma, which can be pharmacologically targeted with trametinib, a small inhibitor of MEK1/2. Preliminary data showed promising antitumor activity in in vitro and in vivo models and represented a proof of concept to translate the findings from bench to bedside. In this phase I, dose escalating study using a 3 + 3 cohort design, trametinib was evaluated in 18 dogs with cancer. Adverse events were graded according to VCOG-CTCAE v2. Blood samples and tumour biopsies were collected for pharmacokinetic and pharmacodynamic assessment. Trametinib was well tolerated with a maximum tolerated dose of 0.5 mg/m2/day, PO. Dose-limiting toxicities included systemic hypertension, proteinuria, lethargy and elevated ALP, and were all Grade 3. The drug exposures increased more than linearly with dose since the elimination of trametinib was saturable. At a dose of 500 μg Q24h (0.5 mg/m2/day in a 30 kg dog), approximately 70% of dogs had an average steady-state concentration of 10 ng/mL, achieved after approximately 2 weeks. This threshold was associated with clinical efficacy in humans. Target engagement was not observed in biospecimens collected on Days 0 and 7. In conclusion, trametinib was considered safe in dogs with cancer, and the dose of 0.5 mg/m2/day was the recommended dose for phase II studies.
{"title":"Population Pharmacokinetics, Pharmacodynamics and Safety Properties of Trametinib in Dogs With Cancer: A Phase I Dose Escalating Clinical Trial.","authors":"Marilia Takada, Keita Kitagawa, Yongzhen Zhang, Jürgen B Bulitta, Steven Moirano, Abigail Jones, Jennifer Borgen, Ashley Onsager, Tuddow Thaiwong, David M Vail","doi":"10.1111/vco.12989","DOIUrl":"10.1111/vco.12989","url":null,"abstract":"<p><p>MAPK has been reported as a key oncogenic pathway for canine histiocytic sarcoma, which can be pharmacologically targeted with trametinib, a small inhibitor of MEK1/2. Preliminary data showed promising antitumor activity in in vitro and in vivo models and represented a proof of concept to translate the findings from bench to bedside. In this phase I, dose escalating study using a 3 + 3 cohort design, trametinib was evaluated in 18 dogs with cancer. Adverse events were graded according to VCOG-CTCAE v2. Blood samples and tumour biopsies were collected for pharmacokinetic and pharmacodynamic assessment. Trametinib was well tolerated with a maximum tolerated dose of 0.5 mg/m<sup>2</sup>/day, PO. Dose-limiting toxicities included systemic hypertension, proteinuria, lethargy and elevated ALP, and were all Grade 3. The drug exposures increased more than linearly with dose since the elimination of trametinib was saturable. At a dose of 500 μg Q24h (0.5 mg/m<sup>2</sup>/day in a 30 kg dog), approximately 70% of dogs had an average steady-state concentration of 10 ng/mL, achieved after approximately 2 weeks. This threshold was associated with clinical efficacy in humans. Target engagement was not observed in biospecimens collected on Days 0 and 7. In conclusion, trametinib was considered safe in dogs with cancer, and the dose of 0.5 mg/m<sup>2</sup>/day was the recommended dose for phase II studies.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-12DOI: 10.1111/vco.12980
Sofia Chichorro Ramos, Patrícia Dias-Pereira, Ana Lúcia Luís, Michael MacFarlane, Andreia Alexandra Santos
Electrochemotherapy (ECT) is a treatment modality that combines the electroporation of cell membranes with chemotherapy to facilitate the transport of non-permeant molecules into cells. Several canine and feline studies have shown promising results, suggesting that ECT can be a valid adjuvant or alternative treatment option for some tumours. The objective of this paper is to provide a bibliographic review of the principles and applications of ECT in veterinary medicine and to compare to its use in human medicine.
{"title":"Electrochemotherapy in dogs and cats-A review.","authors":"Sofia Chichorro Ramos, Patrícia Dias-Pereira, Ana Lúcia Luís, Michael MacFarlane, Andreia Alexandra Santos","doi":"10.1111/vco.12980","DOIUrl":"10.1111/vco.12980","url":null,"abstract":"<p><p>Electrochemotherapy (ECT) is a treatment modality that combines the electroporation of cell membranes with chemotherapy to facilitate the transport of non-permeant molecules into cells. Several canine and feline studies have shown promising results, suggesting that ECT can be a valid adjuvant or alternative treatment option for some tumours. The objective of this paper is to provide a bibliographic review of the principles and applications of ECT in veterinary medicine and to compare to its use in human medicine.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-15DOI: 10.1111/vco.12995
Nicolas Diop, David Sayag, Grégoire Bernardo Marques, Gabriel Chamel, Thomas Chavalle, Jean-Bapiste Eon, Franck Floch, Mathilde Lajoinie, Frédérique Ponce, Laura E Barrett
Electrochemotherapy (ECT) with intravenous (IV) and/or intratumoral (IT) bleomycin has shown considerable efficacy in the treatment of non-resectable feline cutaneous squamous cell carcinoma (cSCC), boasting response rates of up to 95%, but other chemotherapy protocols have not yet been investigated. The objective of this prospective multicentre study was to compare the overall response rate (ORR) and progression-free interval (PFI) between cats with cSCC treated with ECT using IT and IV carboplatin (IV + IT), IV carboplatin (IV) or IV bleomycin (IV). A total of 44 cats with unresectable cSCC across three centres were enrolled and treated with ECT using carboplatin IV + IT (n = 10), carboplatin IV (n = 11) or bleomycin IV (n = 23). Treatment response according to RECIST criteria was recorded at 2 and 4 weeks post-treatment, and patients were followed until disease progression and/or death. All three groups were comparable regarding age, sex, weight, and lesion size. Adverse events were generally mild, localised and similar between groups. ORRs were 90.0% (carboplatin IV + IT), 90.9% (carboplatin IV) and 95.6% (bleomycin IV) and were not significantly different (p = 0.79). Median PFI was not reached for carboplatin IV + IT or carboplatin IV and was 566 days for bleomycin IV, with no significant difference between the three groups (p = 0.81). This study suggests that ECT using IV or IV + IT carboplatin is a reasonable alternative therapeutic option for managing cSCC, and further studies are warranted to compare outcomes between treatment protocols.
{"title":"Comparison of Three Chemotherapy Protocols With Electrochemotherapy for the Treatment of Feline Cutaneous Squamous Cell Carcinoma.","authors":"Nicolas Diop, David Sayag, Grégoire Bernardo Marques, Gabriel Chamel, Thomas Chavalle, Jean-Bapiste Eon, Franck Floch, Mathilde Lajoinie, Frédérique Ponce, Laura E Barrett","doi":"10.1111/vco.12995","DOIUrl":"10.1111/vco.12995","url":null,"abstract":"<p><p>Electrochemotherapy (ECT) with intravenous (IV) and/or intratumoral (IT) bleomycin has shown considerable efficacy in the treatment of non-resectable feline cutaneous squamous cell carcinoma (cSCC), boasting response rates of up to 95%, but other chemotherapy protocols have not yet been investigated. The objective of this prospective multicentre study was to compare the overall response rate (ORR) and progression-free interval (PFI) between cats with cSCC treated with ECT using IT and IV carboplatin (IV + IT), IV carboplatin (IV) or IV bleomycin (IV). A total of 44 cats with unresectable cSCC across three centres were enrolled and treated with ECT using carboplatin IV + IT (n = 10), carboplatin IV (n = 11) or bleomycin IV (n = 23). Treatment response according to RECIST criteria was recorded at 2 and 4 weeks post-treatment, and patients were followed until disease progression and/or death. All three groups were comparable regarding age, sex, weight, and lesion size. Adverse events were generally mild, localised and similar between groups. ORRs were 90.0% (carboplatin IV + IT), 90.9% (carboplatin IV) and 95.6% (bleomycin IV) and were not significantly different (p = 0.79). Median PFI was not reached for carboplatin IV + IT or carboplatin IV and was 566 days for bleomycin IV, with no significant difference between the three groups (p = 0.81). This study suggests that ECT using IV or IV + IT carboplatin is a reasonable alternative therapeutic option for managing cSCC, and further studies are warranted to compare outcomes between treatment protocols.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-04-28DOI: 10.1111/vco.12977
Eliza R Richartz, Brittany A Hodgkiss, Noah C Black-Ocken, Rebecca A Fuentes, Jayme S Looper, Sita S Withers
YouTube is the third most popular app in the world and continues to grow each year while it reaches over 2 billion users a month. A variety of veterinary topics are addressed on YouTube but to date there have been no studies analysing misinformation of various canine cancer topics on YouTube or social media. This study described the characteristics of 99 unique videos and used the validated DISCERN quality criteria for consumer health information and the Patient Education Materials Assessment Tool (PEMAT) to characterize their usefulness. The overall median DISCERN quality score was 3 (out of 5), the median PEMAT understandability score was 72%, and 61% of videos contained little to no misinformation. 53% of videos were created by veterinarians and this subset had significantly higher PEMAT understandability and DISCERN quality scores compared with client-created content (p = .0228 and p ≤ .0001, respectively). Videos with little to no misinformation had statistically significant higher DISCERN quality scores (3 vs. 2, p = .0001). There was no statistical significance between misinformation levels and video length, PEMAT understandability, thumbs up/view, or views/mo. These data reveal similar rates of misinformation in videos on canine cancer compared to that reported for various human cancer topics. This study highlights the need for veterinarians to guide clients to more reliable and understandable information regarding their pet's health.
{"title":"Characterization of the dissemination of canine cancer misinformation on YouTube.","authors":"Eliza R Richartz, Brittany A Hodgkiss, Noah C Black-Ocken, Rebecca A Fuentes, Jayme S Looper, Sita S Withers","doi":"10.1111/vco.12977","DOIUrl":"10.1111/vco.12977","url":null,"abstract":"<p><p>YouTube is the third most popular app in the world and continues to grow each year while it reaches over 2 billion users a month. A variety of veterinary topics are addressed on YouTube but to date there have been no studies analysing misinformation of various canine cancer topics on YouTube or social media. This study described the characteristics of 99 unique videos and used the validated DISCERN quality criteria for consumer health information and the Patient Education Materials Assessment Tool (PEMAT) to characterize their usefulness. The overall median DISCERN quality score was 3 (out of 5), the median PEMAT understandability score was 72%, and 61% of videos contained little to no misinformation. 53% of videos were created by veterinarians and this subset had significantly higher PEMAT understandability and DISCERN quality scores compared with client-created content (p = .0228 and p ≤ .0001, respectively). Videos with little to no misinformation had statistically significant higher DISCERN quality scores (3 vs. 2, p = .0001). There was no statistical significance between misinformation levels and video length, PEMAT understandability, thumbs up/view, or views/mo. These data reveal similar rates of misinformation in videos on canine cancer compared to that reported for various human cancer topics. This study highlights the need for veterinarians to guide clients to more reliable and understandable information regarding their pet's health.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-18DOI: 10.1111/vco.12991
Tracy L Gieger, Leanne Magestro, Jillian Walz, Hiroto Yoshikawa, Michael W Nolan
Although canine pituitary masses (PM) are increasingly treated with stereotactic radiotherapy (SRT), historical literature supports superior outcomes with conventional full-course fractionated radiation therapy (FRT). A multi-institutional retrospective study was performed, including dogs with PM treated from 2016 to 2022 with SRT (total dose 30 or 35 Gy in 5 daily fractions) or FRT (total dose 50-54 Gy in 19-20 daily fractions). The influence of potential prognostic/predictive factors was assessed, including pituitary: brain height, pituitary: brain volume, sex, age and endocrine status (functional [F] vs. nonfunctional [NF] PM). Forty-four dogs with PM were included (26 F, 14 NF, 4 unknown). All patients completed protocols as scheduled (SRT = 27, FRT = 17) and two dogs had suspected Grade 1 acute neurotoxicity. During the first 6 months after RT, 5/27 (19%) dogs treated with SRT (4 F, 1 NF) and 3/17 (18%) dogs treated with FRT (all F) died or were euthanised because of progressive neurologic signs. The overall median survival time was 608 days (95% CI, 375-840 days). Young age at the time of treatment was significant for survival (p = 0.0288); the overall median survival time was 753 days for dogs <9 years of age (95% CI, 614-892 days) and 445 days for dogs ≥9 years of age (95% CI, 183-707 days). Survival time was not associated with treatment type or any other factor assessed herein. A prospective study using standardised protocols would further validate the results of the present study and potentially elucidate the predictors of early death.
{"title":"Outcomes of Stereotactic Radiation Therapy Versus Fractionated Radiation Therapy in 44 Dogs With Pituitary Masses: A Multi-Institutional Retrospective Study (2016-2022).","authors":"Tracy L Gieger, Leanne Magestro, Jillian Walz, Hiroto Yoshikawa, Michael W Nolan","doi":"10.1111/vco.12991","DOIUrl":"10.1111/vco.12991","url":null,"abstract":"<p><p>Although canine pituitary masses (PM) are increasingly treated with stereotactic radiotherapy (SRT), historical literature supports superior outcomes with conventional full-course fractionated radiation therapy (FRT). A multi-institutional retrospective study was performed, including dogs with PM treated from 2016 to 2022 with SRT (total dose 30 or 35 Gy in 5 daily fractions) or FRT (total dose 50-54 Gy in 19-20 daily fractions). The influence of potential prognostic/predictive factors was assessed, including pituitary: brain height, pituitary: brain volume, sex, age and endocrine status (functional [F] vs. nonfunctional [NF] PM). Forty-four dogs with PM were included (26 F, 14 NF, 4 unknown). All patients completed protocols as scheduled (SRT = 27, FRT = 17) and two dogs had suspected Grade 1 acute neurotoxicity. During the first 6 months after RT, 5/27 (19%) dogs treated with SRT (4 F, 1 NF) and 3/17 (18%) dogs treated with FRT (all F) died or were euthanised because of progressive neurologic signs. The overall median survival time was 608 days (95% CI, 375-840 days). Young age at the time of treatment was significant for survival (p = 0.0288); the overall median survival time was 753 days for dogs <9 years of age (95% CI, 614-892 days) and 445 days for dogs ≥9 years of age (95% CI, 183-707 days). Survival time was not associated with treatment type or any other factor assessed herein. A prospective study using standardised protocols would further validate the results of the present study and potentially elucidate the predictors of early death.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}