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1.
Death‐associated protein kinase (DAPK) is a serine/threonine kinase and a tumour suppressor gene. Diffuse large B‐cell lymphomas with inactivated DAPK through hypermethylation of a CpG island is known to result in a biologically aggressive phenotype in humans. This retrospective study was carried out to analyse the prognostic significance of DAPK CpG island hypermethylation in canine lymphoma. We hypothesized that DAPK CpG island hypermethylation can be a negative prognostic indicator in dogs with nodal high‐grade B‐cell lymphoma. Forty‐seven dogs with high‐grade B‐cell lymphoma, according to the updated Kiel classification, were evaluated after being treated with a CHOP (vincristine, cyclophosphamide, doxorubicin and prednisolone)‐based chemotherapy protocol. The methylation status of the DAPK CpG island was examined by methylation‐specific PCR. Progression‐free survival (PFS) and overall survival (OS) were compared using the Kaplan‐Meier analysis and log‐rank test. The cox proportional hazard regression model was used to evaluate the effect of multiple variables. Hypermethylation of the DAPK CpG island was detected in 21 of the 47 dogs. The PFS and OS in dogs with the hypermethylation (median: 220 and 266 days, respectively) were significantly shorter than those of dogs without hypermethylation (median: 301 and 412 days, respectively) (PFS, P = .036; OS, P = .007). In the multivariate analysis, hypermethylation of the DAPK CpG island remained an independent prognostic factor in predicting shortened PFS (P = .047) and OS (P = .021) as well as clinical substage b. Overall, hypermethylation of the DAPK CpG island was a negative prognostic factor in canine high‐grade B‐cell lymphoma.  相似文献   

2.
The objective of this multicentre retrospective study was to describe clinical presentation, treatment and outcome and to determine prognostic factors for dogs with presumed primary colorectal lymphoma (PCRL). A total of 31 dogs were included. The predominant features of PCRL were high grade (n = 18) and immunophenotype B (n = 24). Most dogs were substage b (n = 25) with higher prevalence of haematochezia (n = 20). One dog had surgery only. Thirty dogs received chemotherapy; amongst them 13 had surgery or radiotherapy. Progression free survival (PFS) was 1318 days and disease‐related median survival time (MST) was 1845 days. Fourteen dogs were alive at the end of the study with a median follow‐up time of 684 days (3–4678 days). Younger dogs had longer PFS (P = 0.031) and disease‐related MST (P = 0.01). Presence of haematochezia corresponded with longer PFS (P = 0.02). Addition of local treatment to chemotherapy did not significantly improve the outcome (P = 0.584). Canine PCRL has considerably longer PFS and MST than other forms of non‐Hodgkin's lymphoma.  相似文献   

3.
Sixty‐four dogs were treated with single‐agent doxorubicin (DOX) for presumptive cardiac hemangiosarcoma (cHSA). The objective response rate (CR + PR) was 41%, and the biologic response rate (CR + PR + SD), or clinical benefit, was 68%. The median progression‐free survival (PFS) for treated dogs was 66 days. The median survival time (MST) for this group was 116 days and was significantly improved compared to a MST of 12 days for untreated control dogs (P = 0.0001). Biologic response was significantly associated with improved PFS (P < 0.0001) and OS (P < 0.0001). Univariate analysis identified larger tumour size as a variable negatively associated with PFS. The high rate of clinical benefit and improved MST suggest that DOX has activity in canine cHSA.  相似文献   

4.
Oral fibrosarcoma (FSA) is a common oral tumour in dogs, and historically reported survival times after surgical excision range from 7.0 to 12.2 months with local recurrence rates of 32-57%. The purpose of this retrospective study was to report outcome in a cohort of dogs with oral FSA treated with surgical excision with or without adjuvant radiation therapy. Twenty-nine dogs with a histological diagnosis of FSA arising from the oral cavity that underwent surgical resection of their oral FSA were included in this study. Twenty-one dogs were treated with surgical excision alone and eight dogs with both surgery and radiation therapy. The median progression-free interval was >653 days. The median survival time was 743 days. The 1- and 2-year survival rates were 87.7 and 57.8%, respectively. Seven (24.1%) dogs developed local recurrence. Seven dogs (24.1%) developed metastasis.  相似文献   

5.
Ki67 can discriminate between high‐ and low‐grade canine lymphomas, but its prognostic role in specific subtypes of the neoplasm is unknown. We assessed the prognostic significance of Ki67% (percentage of Ki67‐positive cells), evaluated by flow cytometry, in 40 dogs with high‐grade B‐cell lymphoma, treated with a modified Wisconsin–Madison protocol (UW‐25). The following variables were investigated for association with lymphoma specific survival (LSS) and relapse free interval (RFI): Ki67%, breed, sex, age, stage, substage, complete remission (CR). By multivariate analysis, Ki67% (P = 0.009) and achievement of CR (P = 0.001) were independent prognostic factors for LSS. Dogs with intermediate Ki67% (20.1–40%) presented longer LSS and RFI (median = 866 and 428 days, respectively) than dogs with low (median = 42 days, P < 0.001; median = 159 days, P = 0.014) or high (median = 173 days, P = 0.038; median = 100 days, P = 0.126) values. Determination of Ki67 is a prognostic tool that improves the clinical usefulness of flow cytometric analysis in canine high‐grade B‐cell lymphoma.  相似文献   

6.
High‐grade canine mast cell tumours (HG‐MCT) have a high rate of locoregional relapse. In this study, dogs with HG‐MCT treated with radiation therapy (RT) were retrospectively evaluated to determine the benefit associated with treating the locoregional lymph nodes (LNs). Forty‐two dogs were included. Variables assessed for association with overall survival (OS) and progression‐free survival (PFS) included WHO stage, tumour location and size, LN irradiation (prophylactic, therapeutic or none), LN treatment (yes or no), LN status at RT (metastatic or nonmetastatic) and RT intent (definitive vs palliative). Lower‐stage disease at irradiation was significantly associated with prolonged median PFS (425 vs 125 days for stage 0 vs 1‐4), and OS (615 vs 314 days for stage 0 vs 1‐4). Having any LN treatment and definitive RT were both significantly associated with prolonged OS. In order to evaluate the role of LN irradiation, dogs were divided into subgroups: (a) stage 0 at irradiation with no LN treatment (n = 14), (b) stage 0 at irradiation with prophylactic LN irradiation (n = 6), (c) stage 0 at irradiation but previously stage 2 (n = 5) and (d) stage >0 at irradiation (n = 17). Prophylactic LN irradiation significantly prolonged PFS (>2381 vs 197 days; group B vs A). Interestingly, dogs that were stage 2 and had LN treatment (C) had prolonged OS vs dogs with negative LNs and no LN treatment (A) (1908 vs 284 days; P = .012). This study confirms that prophylactic and therapeutic LN irradiation in dogs with HG‐MCT is beneficial and improves outcome.  相似文献   

7.
This study evaluated the prognosis factors of age, tumour size, anatomic location, histological grade and proliferating cell nuclear antigen (PCNA) expression in 13 dogs with oral squamous cell carcinoma (OSCC) with bone invasion and without signs of lymph node or distant metastasis. All animals were treated with radical excision performed with at least 1 cm margin, based on computed tomography images. In the 2‐year follow‐up, median disease‐free survival was 138 days for dogs with grade 3 tumours and was not reached for those with grade 2 tumours. Grade 3 tumours and PCNA labelling index ≥65% were related with a shorter disease‐free survival time and consequently poor prognosis (p = 0.003 and p = 0.034, respectively). Mean PCNA labelling index was significantly higher in recurrent cases (p = 0.011). Histological grade and PCNA expression may be important prognosis factors in canine OSCC.  相似文献   

8.
Canine oral melanoma is the first malignancy of the oral cavity in dogs and is characterized by a local invasiveness and a high metastatic propensity. A better knowledge of genetic alterations is expected to improve management of this tumour. Copy number alterations are known characteristics of mucosal melanomas both in dogs and humans. The goal of this study was to explore the prognostic value of somatic focal amplifications on chromosomes (Canis Familiaris [CFA]) 10 and 30 in canine oral melanoma. The cohort included 73 dogs with oral melanoma confirmed by histology, removed surgically without adjuvant therapy and with a minimal follow‐up of 6 months. Epidemiological, clinical and histological data were collected and quantitative‐PCR were performed on formalin‐fixed paraffin‐embedded (FFPE) samples to identify specific focal amplifications. The 73 dogs included in the study had a median survival time of 220 days. Focal amplifications on CFA 10 and 30 were recurrent (49.3% and 50.7% of cases, respectively) and CFA 30 amplification was significantly associated with the amelanotic phenotype (P = .046) and high mitotic index (MI; P = .0039). CFA 30 amplification was also linked to poor prognosis (P = .0005). Other negative prognostic factors included gingiva location (P = .003), lymphadenomegaly (P = .026), tumour ulceration at diagnosis (P = .003), MI superior to 6 mitoses over 10 fields (P = .001) and amelanotic tumour (P = .029). In multivariate analyses using Cox proportional hazards regression, CFA 30 amplification (Hazard ratio [HR] = 2.08; P = .011), tumour location (HR = 2.20; P = .005) and histological pigmentation (HR = 1.87; P = .036) were significantly associated with shorter survival time. Focal amplification of CFA 30 is linked to an aggressive subset and constitutes a new prognostic factor.  相似文献   

9.
Background: Feline oral squamous cell carcinoma (SCC) carries a very poor prognosis with traditional treatments. Hypothesis/Objectives: To examine the effectiveness of adding carboplatin to a previously published accelerated radiation protocol in the treatments of oral SCC in cats. Animals: Thirty‐one cases of oral SCC in cats. Tumor sites included lingual (n = 9), mandible (n = 10), maxilla (n = 7), tonsil (n = 4), and cheek (n = 1). Methods: Prospective trial using a planned radiation protocol consisting of 14 fractions of 3.5 Gy given within a 9‐day period with the addition of carboplatin given at 90–100 mg/m2 on day 1 and day 4.5. Treatments were twice daily with a 6‐hour delay between treatments. All cats presenting with oral SCC without evidence of distant metastasis were eligible. Results: Median survival for all cats was 163 days (range 53–770 days) with a mean of 319 ± 53 days with significant predictors of survival being site (P= .004) and whether there was a complete response at 30 days (P= .001). Cats with tumors of tonsil origin or cheek responded best to therapy and were long‐term survivors with a mean survival of 724 days and the median had not been reached because of continued survival of 4 cats. Conclusions and Clinical Importance: This protocol offers an aggressive yet tolerable treatment of oral SCC in cats that might offer improved survival as compared with previously reported treatments. The long‐term survival of cats with tonsillar SCC has not been reported previously.  相似文献   

10.
Systemic mastocytosis is a rare phenomenon, with limited information regarding prognostic features and effective treatment of canine patients with this disease. The objective of this study is to determine the impact of certain features and treatments on dogs with systemic mastocytosis. The medical records of 40 dogs from 4 northeastern US veterinary hospitals, with evidence of systemic mast cell disease, were evaluated retrospectively. Variables analysed with relation to overall survival and prognostic significance included treatment protocol used, substage, presence of a cutaneous or visceral tumour, presence of multiple cutaneous Mast cell tumours, grade of the primary tumour and metastatic site(s). Dogs with metastatic disease confined to distant lymph nodes lived longer than those with circulating mast cells in the blood (P = .001), and those with metastatic disease evident in more than 2 sites had a worse prognosis than those with disease in a single location (P = .005). Additionally, administration of chemotherapeutic agents led to increased survival over prednisone therapy alone (P = .008), with the combination of lomustine, vinblastine and prednisone prolonging survival over the tyrosine kinase inhibitor, toceranib phosphate (P = .002). Presence of mast cells in the blood and/or evidence of disease in more than 2 sites indicate widespread dissemination suggesting their use as negative prognostic features. Furthermore, a chemotherapy protocol including combination lomustine and vinblastine therapy may be more effective than toceranib phosphate for the treatment of dogs with disseminated mast cell disease. Overall, patients with systemic mastocytosis have a grave prognosis and more effective treatment options are needed.  相似文献   

11.
The majority of the known prognostic factors in dogs with lymphoma have been evaluated before treatment commences or at the time of diagnosis. Prognostic factors evaluated during the initial phase of treatment are less described but may provide important clinical information. In this retrospective study, 82 canine lymphoma patients were categorized according to the weight change between diagnosis and after 5 weeks of chemotherapy. Dogs that gained greater than 5% or lost greater than 5% of initial body weight were categorized as increased‐ or decreased‐weight groups, respectively. Those in which weight changed less than 5% were categorized as the maintained‐weight group. The median progression‐free survival (PFS) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 226, 256 and 129 days, respectively. The decreased‐weight group had significantly shorter PFS than the increased and maintained groups (P = .023, P = .003, respectively). The median survival time (ST) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 320, 339 and 222 days, respectively. There was no significant difference in ST among the three groups (P = .128). In Cox‐regression results, weight change group and initial body weight were significant risk factors associated to PFS (P = .007, P = .001, respectively) while only patient's initial body weight was a significant risk factor to ST (P = .013). In conclusion, evaluation of initial body weight and weight changes over time can provide valuable information regarding PFS and ST in dogs with multicentric lymphoma.  相似文献   

12.
Surgical Excision of Soft Tissue Fibrosarcomas in Cats   总被引：2，自引：1，他引：1  
Objective — The purpose of this study was to determine the tumor-free interval and survival times of cats who had one (group 1) or more (group 2) surgeries, or surgery and radiation therapy (RTH) (group 3) for treatment of soft tissue fibrosarcomas (FSA).
Study Design — Retrospective study.
Animals or Sample Population — 45 client-owned cats.
Methods — Medical records of cats with soft tissue FSA were examined. Vaccination and feline leukemia virus (FeLV) status, age, sex, breed, tumor location, number of surgeries, completeness of excision, and histopathological grade were evaluated to correlate with tumor-free interval and survival periods.
Results — Overall median tumor-free interval and survival times were 10 and 11.5 (range, 1 to 40) months. Median tumor-free interval and survival times were more than 16 months each in group 1, more than 5 and 13 months in group 2, and 4.5 and 9 months in group 3. Age, sex, breed, vaccination or FeLV status, tumor location, or histopathological grade did not affect median tumor-free interval or survival times ( P <.05). Cats with complete excisions had significantly longer median tumor-free interval (>16 versus 4 months) and survival time (>16 versus 9 months) than those with incomplete excisions ( P =.008). Radiation therapy did not seem to extend tumor-free interval and survival times ( P =.013). However, most group 3 cats had incomplete surgical excisions, resulting in recurrent or progressive disease.
Conclusions — Complete surgical excision of FSA in cats is possible and can be curative.
Clinical Relevance — Aggressive surgical excision with wide margins appears to contribute to extended tumor-free interval and survival times in cats with soft tissue FSA. Controlled prospective studies are needed to determine the efficacy of RTH in treatment.  相似文献   

13.
Masitinib mesylate is a tyrosine kinase inhibitor approved for the treatment of gross, non‐metastatic grade II and III canine mast cell tumours (MCTs). This study evaluated the use of masitinib as a frontline and rescue agent for metastatic and non‐metastatic canine MCTs. Identification of toxicities and prognostic factors in these dogs was of secondary interest. Twenty‐six dogs were included in this study. The overall response rate to masitinib was 50%. The median survival time for dogs that responded to masitinib was 630 days versus 137 days for dogs that did not respond (P = 0.0033). Toxicity was recorded in 61.5% of treated dogs, but the majority of adverse events were mild and self‐limiting. Response to masitinib, not tumour grade, stage or location, was the most significant prognostic factor for survival in dogs with MCTs.  相似文献   

14.
Pretreatment D‐dimer levels have been reported to predict survival in several types of malignancies in human patients. The objective of this study was to evaluate the prognostic value of pretreatment D‐dimer level in dogs with intermediate to high‐grade non‐Hodgkin lymphoma (NHL). In a prospective, randomized, double‐blind study of F14512 vs etoposide phosphate, we assessed the prognostic value of pretreatment plasma D‐dimer level in 48 client‐owned dogs diagnosed with intermediate to high‐grade NHL. The correlation between pretreatment plasma D‐dimer level and various clinical features, progression‐free survival (PFS) and overall survival (OS) was analysed. The median value of pretreatment plasma D‐dimer level was 0.4 μg/mL (range: 0.1‐14.3 μg/mL). High pretreatment plasma D‐dimer level (>0.5 μg/mL) was detected in 44% (21/48) of dogs. High D‐dimer levels were not correlated with naive vs relapsed lymphoma, clinical stage, substage, immunophenotype or treatment group. D‐dimer levels >0.5 μg/mL were significantly associated with inferior median PFS (54 vs 104 days, P = .011) and OS (93 vs 169 days, P = .003). In the multivariate analysis, high D‐dimer levels remained an independent predictor for worse PFS (HR: 3.21, 95% CI: 1.57‐6.56, P = .001) and OS (HR: 3.87, 95% CI: 1.88‐7.98; P < .001). This study suggests that pretreatment plasma D‐dimer level can serve as a predictor of prognosis in dogs with intermediate to high‐grade NHL. Further studies are warranted to confirm these findings.  相似文献   

15.
Sarcomas comprise approximately one‐third of canine intranasal tumors, however few veterinary studies have described survival times of dogs with histologic subtypes of sarcomas separately from other intranasal tumors. One objective of this study was to describe median survival times for dogs treated with radiation therapy for intranasal sarcomas. A second objective was to compare survival times for dogs treated with three radiation therapy protocols: daily‐fractionated radiation therapy; Monday, Wednesday, and Friday fractionated radiation therapy; and palliative radiation therapy. Medical records were retrospectively reviewed for dogs that had been treated with radiation therapy for confirmed intranasal sarcoma. A total of 86 dogs met inclusion criteria. Overall median survival time for included dogs was 444 days. Median survival time for dogs with chondrosarcoma (n = 42) was 463 days, fibrosarcoma (n = 12) 379 days, osteosarcoma (n = 6) 624 days, and undifferentiated sarcoma (n = 22) 344 days. Dogs treated with daily‐fractionated radiation therapy protocols; Monday, Wednesday and Friday fractionated radiation therapy protocols; and palliative radiation therapy protocols had median survival times of 641, 347, and 305 days, respectively. A significant difference in survival time was found for dogs receiving curative intent radiation therapy vs. palliative radiation therapy (P = 0.032). A significant difference in survival time was also found for dogs receiving daily‐fractionated radiation therapy vs. Monday, Wednesday and Friday fractionated radiation therapy (P = 0.0134). Findings from this study support the use of curative intent radiation therapy for dogs with intranasal sarcoma. Future prospective, randomized trials are needed for confirmation of treatment benefits.  相似文献   

16.
Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B‐cell lymphoma treated with either a COP‐type (35%) or CHOP‐type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression‐free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty‐eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1‐year survival rate was 38% and the 2‐year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP‐type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy.  相似文献   

17.
Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma.  相似文献   

18.
Squamous cell carcinoma (SCC) accounts for approximately 10% of all feline tumors. The purpose of this retrospective study was to describe outcomes for a group of cats with oral SCC that were treated with palliative radiation therapy. Fifty‐four cats met the inclusion criteria of nonresectable, oral SCC treated with coarse fractionated megavoltage (MeV) radiation therapy. Radiation therapy for all cats was delivered with a 6 MeV linear accelerator. Total radiation doses of 24 Gray to 40 Gray were administered in three to four fractions, once‐per‐week over 4 to 5 weeks. Concurrent chemotherapy protocols varied and were administered at the discretion of the clinician and client. Forty‐nine patients completed the planned treatment protocols. Overall mean and median survival times for cats completing the planned treatment protocols were 127 and 92 days (n = 49). Mean and median survival times of cats receiving palliative radiation therapy alone were 157 and 113 days (n = 12). Mean and median survival times of patients receiving both radiation therapy and chemotherapy were 116 and 80 days (n = 37). Patients with sublingual tumors had a median survival time of 135 days (n = 15), compared to mandibular tumors that had a median survival time of 80 days (n = 26). For the majority of patients that completed the planned treatment protocol (65%), owners reported a subjectively improved quality of life. Findings from this uncontrolled study supported the use of palliative radiation therapy for cats with nonresectable oral squamous cell carcinoma.  相似文献   

19.
This retrospective study identified prognostic factors associated with survival; and compared survival data in 94 canine mammary carcinoma (MCA) dogs treated with surgery (n = 58), or surgery and adjunct chemotherapy (n = 36), and a subset of dogs with poor prognostic factors. On multivariate analysis independent predictors of median survival time (MST) were clinical stage, lymphatic invasion (LI; present 179 days; none 1098 days), ulceration (present 118 days; none 443 days) and surgical margins (incomplete 70 days; complete 872 days). Complete surgical margins were associated with MST in dogs with stages 1–3 MCA (incomplete 68 days; complete 1098 days) and dogs with LI (incomplete 70 days; complete 347 days). There was no statistically significant improvement in MST in dogs with advanced disease (stage 4 or LI) treated with adjunctive chemotherapy (chemotherapy 228 days; none 194 days); although five dogs with complete surgical margins that received mitoxantrone and carboplatin had a mean survival of 1139 days.  相似文献   

20.
Background: Activation of the KIT receptor tyrosine kinase is associated with the development of canine mast cell tumors (MCT). Hypothesis/Objective: To evaluate the efficacy of masitinib, a potent and selective inhibitor of KIT, in the treatment of canine MCT. Animals: Two hundred and two client‐owned dogs with nonmetastatic recurrent or nonresectable grade II or III MCT. Methods: Double‐blind, randomized, placebo‐controlled phase III clinical trial. Dogs were administered masitinib (12.5 mg/kg/d PO) or a placebo. Time‐to‐tumor progression (TTP), overall survival, objective response at 6 months, and toxicity were assessed. Resulsts: Masitinib increased overall TTP compared with placebo from 75 to 118 days (P= .038). This effect was more pronounced when masitinib was used as first‐line therapy, with an increase in the median TTP from 75 to 253 days (P= .001) and regardless of whether the tumors expressed mutant (83 versus not reached [P= .009]) or wild‐type KIT (66 versus 253 [P= .008]). Masitinib was generally well tolerated, with mild (grade I) or moderate (grade II) diarrhea or vomiting as the most common adverse events. Conclusions and Clinical Importance: Masitinib is safe and effective at delaying tumor progression in dogs presenting with recurrent or nonresectable grade II or III nonmetastatic MCT.  相似文献   

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