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1.
Dose intense CHOP protocols have been shown to improve outcome for people with non‐Hodgkin's lymphoma, but evaluation of dose intense CHOP protocols for canine lymphoma is currently limited. The hypothesis of this retrospective study was that a 15‐week dose intense CHOP protocol would have shorter treatment duration with similar efficacy to other doxorubicin‐based multidrug protocols. Thirty‐one client owned dogs with multicentric lymphoma were treated with a 15‐week CHOP chemotherapy protocol with an overall response rate of 100% and a median progression‐free interval (PFI) of 140 days [95% confidence interval (CI) 91–335 days]. Dogs that had two or more treatment delays had significantly prolonged PFI and overall survival in multivariate analysis. Dose intensity did not correlate with patient outcome. Dogs experiencing multiple treatment delays secondary to adverse events may receive their individual maximally tolerated dose while dogs with no adverse events may be underdosed. Future studies should focus on individual patient dose optimization.  相似文献   

2.
The goals of this retrospective study were to determine the patient characteristics of dogs with high‐grade primary mediastinal lymphoma and to determine outcome and associated prognostic factors. A total of 42 dogs were identified, in which 36 received treatment and had follow‐up information available. The most common clinical signs included lethargy, anorexia and polyuria/polydipsia. Hypercalcemia and pleural effusion were common findings at diagnosis. The phenotype was almost exclusively T‐cell, most often in association with lymphoblastic cytomorphology as defined by the World Health Organization (WHO) lymphoma classification scheme. The overall progression‐free survival (PFS) and overall survival (OS) were 133 and 183 days, respectively. Treatment with a CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) protocol was associated with an improved PFS (144 days) and OS (194 days) when compared with dogs that received other medical therapies (P = .005 and P = .002, respectively); the absence of pleural effusion at diagnosis was associated with an increased OS but not PFS. These results suggest that while the prognosis for dogs with mediastinal lymphoma is poor, survival may be improved with treatment using a CHOP‐based protocol.  相似文献   

3.
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   

4.
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   

5.
Numerous factors are known to affect the prognosis of dogs with chemotherapy‐treated lymphomas. However, prognostic factors for dogs with specific subtypes of lymphoma are less clearly defined. The objective of this study was to identify prognostic factors for dogs receiving CHOP‐based chemotherapy for primary nodal diffuse large B‐cell lymphoma (DLBCL). Medical records of dogs treated for DLBCL at the Purdue Veterinary Teaching Hospital (PUVTH) from 2006 to 2016 were reviewed. Factors potentially related to prognosis were analysed using multivariable statistical methods. Ninety‐eight dogs were included in the study. Best overall response to chemotherapy was complete remission in 80 dogs (81.6%) and partial remission in 18 dogs (18.4%). Median progression‐free survival (PFS) for the entire population was 252 days (range 19‐1068). Factors significantly associated with achieving partial (rather than complete) remission following CHOP included presence of thrombocytopenia at diagnosis (OR 6.88; 95% CI 1.98‐23.93; P = .002), baseline serum globulin concentration (OR 2.63; 95% CI 1.03‐6.75; P = .044), and age at diagnosis (OR 1.36; 95% CI 1.08‐1.71; P = .009). Factors significantly associated with PFS in the lowest quartile (≤93 days) included presence of thrombocytopenia at diagnosis (OR 8.72; 95% CI 1.54‐49.33; P = .014), age at diagnosis (OR 1.47; 95% CI 1.12‐1.94; P = .005), and baseline neutrophil count (OR 1.18; 95% CI 1.02‐1.37; P = .025). Presence of thrombocytopenia, greater age, higher neutrophil count, and higher serum globulin concentration all may be associated with a particularly poor outcome in dogs receiving CHOP‐based chemotherapy for DLBCL.  相似文献   

6.
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   

7.
Canine B‐cell lymphoma is a clinically heterogenous disease; however, it is generally treated as a single disease entity. The purpose of this clinical trial was to prospectively evaluate naïve canine B‐cell lymphoma patients using histopathology, flow cytometry (FC) and a standardized chemotherapy protocol to better define subsets of this disease that may respond differently to treatment. Sixty‐four dogs with naïve multicentric B‐cell lymphoma were treated with a standardized 19‐week CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy protocol. Most of the dogs (84.3%) were diagnosed with diffuse large B‐cell lymphoma (DLBCL), followed by nodal marginal zone (7.8%), small B‐cell (4.7%), Burkitt‐like (1.6%) and follicular lymphoma (1.6%). FC confirmed the diagnosis of B‐cell lymphoma in all cases. There were no clear phenotyping differences between the subtypes of B‐cell lymphoma detectable by our FC panel. The histologic subtypes in this study exhibited a range of forward scatter values on flow cytometry, but all of the DLBCL cases were higher than a value of 469, while the only cases with a lower forward scatter value were follicular lymphoma and diffuse small B‐cell lymphoma. Dogs with DLBCL had a significantly better objective response rate to the CHOP protocol (96.3%) than the non‐DLBCL subtypes (70%, P = .024). The median progression‐free survival time for patients with DLBCL (233 days) was significantly longer than that of all other histopathologic subgroups combined (163 days, P = .0005).  相似文献   

8.
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   

9.
Twenty‐nine dogs were treated with linac‐based stereotactic radiation therapy (SRT) for non‐lymphomatous nasal tumours. Only dogs with a follow‐up time >365 days were included in this retrospective analysis. No dogs had evidence of distant metastasis at diagnosis. Treatment was planned and a total of 30 Gy in 3 daily 10 Gy fractions was delivered using intensity‐modulation, cone‐beam CT‐based image guidance and a robotic treatment couch. Clinical signs improved in all cases. Nineteen dogs had CT scans 3‐4 months post‐SRT and all had partial or complete tumour response. Minimal acute toxicities were detected. Clinically significant late toxicities included oronasal or nasocutaneous fistulas (N = 3) and biopsy‐confirmed fungal rhinitis with no evidence of tumour progression (N = 2). The median progression‐free survival (PFS) was 354 days, with 49% and 39% progression‐free at 1 and 2 years post‐SRT, respectively. The median survival time (ST) was 586 days, with 69% and 22% alive 1 and 2 years post‐SRT, respectively. Neither the clinical parameters evaluated (modified Adams’ stage, histopathology, presence of intracranial extension of the tumour) nor dosimetric data were predictive for PFS or ST. This SRT protocol appears to be well tolerated, and PFI and ST are comparable or superior to those reported in other definitive‐intent radiotherapy protocols.  相似文献   

10.
The aim of the study was to report the outcome of treatment of 97 dogs with lymphoma that received a multi‐agent chemotherapy protocol containing epirubicin as the primary anthracycline. Seventy‐five dogs received a 25‐week protocol with no maintenance phase whilst 22 dogs received a maintenance phase. Complete response rate was 96% and time to first relapse (TTR) and overall survival (OS) time for all dogs were 216 and 342 days, respectively. Dogs with T‐cell lymphoma and those classified as WHO substage b had significantly poorer OS times and TTR. The protocol was well tolerated with toxicity similar to doxorubicin‐containing protocols. Epirubicin as part of a multi‐agent protocol is safe and effective in the treatment of canine multicentric lymphoma. There is a high initial response rate and an overall median survival time that is similar to other published doxorubicin‐containing protocols.  相似文献   

11.
Safety and efficacy of a protocol of alternating 1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea (CCNU; 70 mg m?2) and vinblastine (3.5 mg m?2), and prednisone (1–2 mg kg?1; CVP) in dogs with mast cell tumours (MCT) were evaluated. A total of 17 dogs had nonresectable MCTs and 35 received CVP as adjunctive treatment to locoregional control of metastatic MCTs or grade III MCTs. Neutropenia with fever occurred in 8% of dogs after treatment with vinblastine and in 2% after treatment with CCNU. Persistent elevation of serum alanine transaminase, suggestive of hepatotoxicity, occurred in 9% of the dogs. Response rate in dogs with nonresectable MCTs was 65%; five achieved a complete response (median, 141 days) and six achieved a partial response (median, 66 days). Overall median progression‐free survival (PFS) time in dogs treated in the adjuvant setting was 489 days. Dogs with grade III MCTs had shorter PFS compared with dogs with metastatic grade II MCTs (190 days versus 954 days; P < 0.001). Phase III studies are needed to provide reliable information about the comparative efficacy of this protocol.  相似文献   

12.
The standard of care treatment for canine lymphoma is multi‐agent chemotherapy containing prednisolone, cyclophosphamide, vincristine and an anthracycline such as doxorubicin (CHOP) or epirubicin (CEOP). Lomustine, vincristine, procarbazine, and prednisone (LOPP) has been evaluated as a rescue, with encouraging results; however, resistance to vincristine is likely in patients relapsing on CHOP/CEOP, and this agent may enhance LOPP toxicity without improving efficacy. The aim of this study was to evaluate responses to a modified‐LOPP protocol that does not include vincristine (LPP) and is administered on a 21‐day cycle. Medical records of dogs with high‐grade multicentric lymphoma from 2012 to 2017 were reviewed. Dogs with relapsed lymphoma that received LPP as a rescue protocol were enrolled. Response, time from initiation to discontinuation (TTD) and toxicity of LPP were assessed. Forty‐one dogs were included. Twenty‐five dogs (61%) responded to LPP including 12 complete responses (CR) and 13 partial responses (PR). Responders had a significantly longer TTD (P < .001) compared to non‐responders with 84 days for CR and 58 days for PR. Neutropenia was documented in 20 dogs (57%): 12 grade I to II, 8 grade III to IV. Thrombocytopenia was infrequent (20%): 5 grade I to II, 2 grade III to IV. Twelve dogs developed gastrointestinal toxicity (30%): 10 grade I to II and 2 grade III. Nineteen dogs had elevated ALT (59%): 9 grade I to II, 10 grade III to IV. Treatment was discontinued due to toxicity in 8 dogs (19%). The LPP protocol shows acceptable efficacy and toxicity‐profile and minimizes in‐hospital procedures.  相似文献   

13.

Background

KIT inhibitors, such as toceranib (TOC), and vinblastine (VBL) have not been prospectively compared in the treatment of macroscopic mast cell tumors (MCTs). Also, it is unknown whether VBL or TOC is superior for treating MCT without c‐kit mutations.

Hypothesis/Objectives

To determine the value of KIT genotyping and localization in treatment decisions for dogs with macroscopic MCT. We hypothesized that c‐kit mutated MCT would have a better response to TOC than VBL.

Animals

Eighty‐eight client‐owned dogs with macroscopic MCT.

Methods

Prospective, randomized trial. Dogs were randomized to TOC (2.75 mg/kg EOD) or VBL (2.5 mg/m2 weekly × 4 then EOW) by KIT localization and c‐kit mutation status using an adaptive randomization scheme.

Results

Sixty dogs were allocated to TOC and 28 to VBL. Of the dogs receiving TOC, 20% had c‐kit mutations, compared to 30% receiving VBL (P = 0.74). Overall response rates were 46% (TOC) and 30% (VBL) (odds ratio = 1.56 [0.62–3.92]; P = 0.28). Median progression‐free survival (PFS) for dogs receiving VBL was 78 days (7–1,521) and for TOC 95.5 (14–990); hazard ratio (HR) = 1.34 [0.72–2.50]; P = 0.36. Median overall survival (OS) was 241.5 days (10–1,521) for the VBL group and 159 (20–990) for the TOC group; HR = 0.80 ([0.45–1.41]; P = 0.44).

Conclusions and Clinical Importance

Neither PFS nor OS was significantly different between treatment groups. As the proportion of dogs with c‐kit mutations was not different between treatment groups in this population of dogs, c‐kit mutation status did not predict treatment response.  相似文献   

14.
Published studies on the use of stereotactic radiotherapy for dogs with pituitary tumors are limited. This retrospective observational study describes results of stereotactic radiotherapy for 45 dogs with imaging‐diagnosed pituitary tumors. All dogs were treated at a single hospital during the period of December 2009–2015. The stereotactic radiotherapy was delivered in one 15 Gray (Gy) fraction or in three 8 Gy fractions. At the time of analysis, 41 dogs were deceased. Four were alive and censored from all survival analyses; one dog received 8 Gy every other day and was removed from protocol analyses. The median overall survival from first treatment was 311 days (95% confidence interval 226–410 days [range 1–2134 days]). Thirty‐two dogs received 15 Gy (median overall survival 311 days; 95% confidence interval [range 221–427 days]), and 12 received 24 Gy on three consecutive days (median overall survival 245 days, 95% confidence interval [range 2–626 days]). Twenty‐nine dogs had hyperadrenocorticism (median overall survival 245 days), while 16 had nonfunctional masses (median overall survival 626 days). Clinical improvement was reported in 37/45 cases. Presumptive signs of acute adverse effects within 4 months of stereotactic radiotherapy were noted in 10/45, and most had improvement spontaneously or with steroids. Late effects versus tumor progression were not discernable, but posttreatment blindness (2), hypernatremia (2), and progressive neurological signs (31) were reported. There was no statistical difference in median overall survival for different protocols. Patients with nonfunctional masses had longer median overall survival than those with hyperadrenocorticism (P = 0.0003). Survival outcomes with stereotactic radiotherapy were shorter than those previously reported with definitive radiation, especially for dogs with hyperadrenocorticism.  相似文献   

15.
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   

16.
The objective of this retrospective study was to report the outcome of treatment of canine oral fibrosarcomas (FSA) in relation to median survival and progression‐free survival (PFS), and to report whether grade was prognostic in relation to median survival. Sixty‐five dogs with oral FSA presented to the WSU VTH between June 1998 and March 2010. Significant predictors of median survival were location (P = 0.0099), tumour size or oral stage (P = 0.0312), type of surgery (P = 0.0182), margins (P = 0.0329) and grade (P = 0.0251). Significant predictors of PFS were location (P = 0.0177), and radiation protocol (P = 0.0343). A combination of surgery and radiation was the strongest predictor of prolonged median survival (P = 0.0183) and PFS (P = 0.0263) at 505 and 301 days, respectively. Treatment of canine oral FSA with a combination of surgery and radiation therapy provided the longest median survivals.  相似文献   

17.
A dose‐intensified/dose‐dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub‐stage b (58.5%). The median time to progression (TTP) and lymphoma‐specific survival were 219 and 323 days, respectively. These results are similar to previous less dose‐intense protocols. Sub‐stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma‐specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.  相似文献   

18.
19.
No standard of care is currently recognized for treatment of canine prostatic carcinoma (PC). This retrospective study assesses outcome following definitive‐intent, intensity‐modulated radiation therapy (RT) in dogs with PC. Medical records review was performed, including 18 patients from four institutions undergoing definitive‐intent intensity‐modulated radiotherapy to treat PC. Diagnosis was incidental in 7/18 (39%) patients. Five dogs (28%) had evidence of metastasis to loco‐regional lymph nodes at diagnosis. Seventeen patients received concurrent non‐steroidal anti‐inflammatory drugs; 15/18 (83%) patients received maximally‐tolerated dose (MTD) chemotherapy, with variable drugs and protocols employed. Total prescribed radiation dose ranged from 48 to 54 Gy (median 50 Gy) delivered as daily doses of 2.5‐2.8 Gy. One patient was euthanized prior to completing radiotherapy. Acute toxicity was observed in nine patients; Grade 1‐2 diarrhoea was the most common toxicity observed. Suspected late toxicity (urethral stricture, ureteral stricture and hindlimb oedema) was observed in three patients. Median event‐free survival (EFS) following RT was 220 days, and median overall survival was 563 days. Local progression occurred in seven patients at a median of 241 days. Median overall survival was significantly longer in incidentally diagnosed dogs (581 vs 220 days in symptomatic dogs, P = .042). EFS was significantly longer in patients treated with MTD chemotherapy (241 vs 25 days, P < .001), and significantly shorter in patients presenting with evidence of metastatic disease (109 days) vs those without (388 days, P = .008). These findings suggest that definitive‐intent radiotherapy is a valuable treatment option for local control of canine PC with moderate risk of toxicity.  相似文献   

20.
Dogs with multicentric T-cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T-cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty-three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P=0.01).  相似文献   

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