<p>Kaplan Meier estimates comparing vaccinated Group 2 to unvaccinated control Group 3 for ... more <p>Kaplan Meier estimates comparing vaccinated Group 2 to unvaccinated control Group 3 for (A) TTP (p = 0.34) and (B) LSS (p = 0.18).</p
As the official journal of the Veterinary Cancer Society, Veterinary and Comparative Oncology is ... more As the official journal of the Veterinary Cancer Society, Veterinary and Comparative Oncology is pleased to include these abstracts from the Annual Conference and we hope you find them informative and useful. These abstracts have not been subjected to peer review or editorial revision, however, and it would be prudent for the reader to exercise caution in the interpretation and application of the data presented.
<p>Kaplan Meier estimates comparing intent-to-treat Group 1 to unvaccinated control Group 3... more <p>Kaplan Meier estimates comparing intent-to-treat Group 1 to unvaccinated control Group 3 for (A) time-to-progression (TTP) (p = 0.16) and (B) lymphoma-specific survival (LSS) (p = 0.37).</p
<p>PBMCs were obtained from dogs at the time of diagnosis (pre) and 3 weeks post vaccinatio... more <p>PBMCs were obtained from dogs at the time of diagnosis (pre) and 3 weeks post vaccination (post) and antigen-specific immune responses directed against (A) CDV-HA and (B) lymph node tumor antigens were determined by IFN-γ ELISPOT. *p<0.1, **p<0.05.</p
<p>Kaplan Meier estimates for lymphoma-specific survival (LSS) of relapsed dogs who receive... more <p>Kaplan Meier estimates for lymphoma-specific survival (LSS) of relapsed dogs who received salvage therapy, demonstrating statistically significant differences between vaccinated Group 2 to unvaccinated control Group 3 (p = 0.038).</p
The purpose of this study was to evaluate the absolute lymphocyte and lymphoblast count in pretre... more The purpose of this study was to evaluate the absolute lymphocyte and lymphoblast count in pretreatment complete blood counts (CBCs) from dogs with lymphoma with the suspicion that non-lymphopenic animals likely had circulating lymphoblasts. Fifty-six dogs diagnosed with lymphoma were prospectively enrolled if they had no previous treatment (including glucocorticoids) and if they had intention-to-treat with a CHOP based protocol. All dogs had pre-treatment CBCs with review by a board-certified clinical pathologist. One hundred lymphoid cells were counted and the percentage lymphoblasts recorded. The mean absolute lymphocyte count was 2690/µL and mean absolute lymphoblast count was 1350/µL. Twenty-six dogs were lymphopenic ( 100/µL) was significantly correlated with a lymphocyte count over 1000/µL (p<0.001). The sensitivity and specificity, of a lymphocyte count over 1000/µL predicting the presence of circulating lymphoblasts, are 0.73 and 0.77 respectively. These results indicate...
The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (O... more The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (OSA) with other breeds to determine whether Rottweilers experienced a more aggressive form of the disease. Two hundred and fi fty-eight dogs were evaluated (102 clinical and 156 necropsy cases). In the necropsy population, Rottweilers had a younger mean age at death (7.3 versus 9 years, P = 0.006). There were no signifi cant differences between Rottweilers and other breeds in age at diagnosis, median disease-free interval or survival time. However, Rottweilers were more likely to have metastasis to the brain (7 versus 0%, P = 0.03). These results suggest that OSA in Rottweilers may have a different biological behaviour, but this study did not confi rm that these differences were associated with a worse outcome . Doberman Pinscher, German Shepherd, Golden Retriever, Great Dane, Irish Setter, Rottweiler and Saint Bernard. 2,5,10 -13 Standard treatment recommendations for canine OSA include surgery (amputation or limb-sparing procedures) followed by chemotherapy. 12 -17 Despite treatment, most dogs still die of metastatic disease within 1 -2 years of diagnosis. 12,13,15,17 -21 Current chemotherapy protocols include the chemotherapeutic agents
A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemen... more 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. recognized that a subset of patients would go into durable remissions (i.e. be cured); however, despite a high initial response rate (higher than 80% in most protocols), the majority of dogs would relapse and succumb to their lymphoma. Only 20-25% of the cases would be alive for 2 years or longer. The high response rates to relatively low dose-intense protocols indicate that canine lymphomas are uniquely chemotherapy sensitive tumours, and also suggest that further improvements, both in terms of remission rates and survival times, may be made through dose intensification. Results from human oncology trials, however, have been mixed; some studies have documented clinically significant improvements in outcome in patients treated with such doseintense/dose-dense protocols, whereas others have resulted in only marginal or no improvements in remission and survival durations. 21 -26 The inconsistent results from dose intensification may in part be due to the presence of cancer stem cells, a distinct
Introduction: The Patnaik grading system for canine cutaneous MCT is currently one of the best de... more Introduction: The Patnaik grading system for canine cutaneous MCT is currently one of the best determinants of prognosis; however, clinical outcome does not always correlate with histologic grade. The development of molecular markers offers a potential advantage and may complement subjective grading. The primary purpose of this study was to correlate histologic grading to Ki67/PCNA/AgNOR/c-Kit scores.
Cell-based active immunotherapy for cancer is a promising novel strategy, with the first dendriti... more Cell-based active immunotherapy for cancer is a promising novel strategy, with the first dendritic cell (DC) vaccine achieving regulatory approval for clinical use last year. Manufacturing remains arduous, especially for DC vaccines, and the prospect of using cell-based immunotherapy in the adjuvant setting or in combination with chemotherapy remains largely untested. Here, we used a comparative oncology approach to test the safety and potential efficacy of tumor RNA-loaded, CD40activated B cells in privately owned dogs presenting with non-Hodgkin's lymphoma (NHL), a clinical scenario that represents not only a major problem in veterinary medicine but also a bona fide spontaneous animal model for the human condition. When administered to NHL dogs in remission after induction chemotherapy, CD40-B cells electroporated ex vivo with autologous tumor RNA safely stimulated immunity in vivo. Although chemotherapy plus CD40-B vaccination did not improve time-to-progression or lymphoma-specific survival compared to dogs treated with chemotherapy alone, vaccination potentiated the effects of salvage therapy and improved the rate of durable second remissions as well as subsequent lymphoma-specific survival following salvage therapy. Several of these relapsed dogs are now long-term survivors and free of disease for more than a year. Overall, these clinical and immunological results suggest that cell-based CD40 cancer vaccination is safe and synergizes with chemotherapy to improve clinical outcome in canine NHL. More broadly, our findings underscore the unique value of clinical investigations in tumor-bearing companion animals.
The purpose of this study was to evaluate the efficacy and toxicity of a single-agent, dose-inten... more The purpose of this study was to evaluate the efficacy and toxicity of a single-agent, dose-intensified doxorubicin protocol in canine hemangiosarcoma (HSA). Canine HSA is a highly malignant tumor, and most affected dogs die within 6 months of diagnosis. Doxorubicin is the most, and possibly the only, effective chemotherapeutic drug for this malignancy, but it provides only moderate improvement in survival. On the basis of previous studies reporting similar survival in dogs treated with doxorubicin as a single agent and doxorubicin-based combination chemotherapy and the concept of summation dose intensity, a dose-intensified single-agent doxorubicin protocol was initiated. Twenty dogs with HSA were recruited to participate in this study. Workup and staging were performed according to standard practice. Chemotherapy was initiated within 3 weeks of surgery. Doxorubicin was scheduled to be administered at 30 mg/m2 i.v. every 2 weeks for a total of 5 treatments. The dogs were monitored for toxicity and signs of recurrence during and at regular intervals after chemotherapy. The protocol was tolerated well. No dogs were hospitalized because of adverse effects or developed clinical signs consistent with doxorubicin-induced cardiomyopathy. There was a significant difference in survival in dogs with stage I and I1 HSA compared with dogs with stage III HSA. with median survival times of 257, 210, and 107 days, respectively. These results are slightly better than the historical control with respect to toxicity and efficacy but are not statistically different from what is achieved with standard treatments. There was no association between dose intensity and outcome.
Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a f... more Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a few months of diagnosis. Most dogs present with signs from tumor rupture, resulting in hemoabdomen and intra-abdominal dissemination. The abdomen is also the main site of disease recurrence. Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. Fourteen dogs with splenic HSA. A prospective, unmasked, uncontrolled clinical trial. After staging of disease status and splenectomy, pegylated liposomal encapsulated doxorubicin was administered intraperitoneally (1 mg/kg body weight) every 3 weeks for 4 cycles. All dogs were monitored for recurrence of HSA. Samples of plasma and abdominal fluid were collected for measurement of doxorubicin concentration and pharmacokinetic analysis. Nonlinear mixed-effect modeling was used to describe the pharmacokinetics of liposomal doxorubicin administered IP. All 14 dogs died, 12 because of HSA and 2 from other causes. Postmortem examination was performed on 12 dogs. All 12 dogs died because of HSA-related causes and had hepatic metastases and hemoabdomen. The IP-treated dogs had fewer serosal, mesenteric, and omental metastases than historical controls treated with systemic doxorubicin. Results of the postmortem examination and pharmacokinetic analysis confirmed that IP delivery of doxorubicin resulted in an effective drug concentration with a clearance comparable with that after i.v. delivery. IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.
Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the... more Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate the effect of this strategy. Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone. Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo). Retrospective cohort study. Clinical data were collected and compared to identify differences between groups. Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were evaluated. Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx + Chemo groups were 372 and 676 days, respectively (P= .15) and median survival times (ST) were 1,406 and 848 days, respectively (P= .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P= .03). This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may benefit from adjuvant chemotherapy.
The etiopathogenesis of feline mammary carcinoma is not well understood. Although putative, risk ... more The etiopathogenesis of feline mammary carcinoma is not well understood. Although putative, risk factors include breed, reproductive status, and regular exposure to progestins. An association between age at ovarihysterectomy (OHE) and mammary carcinoma development has not been established. Therefore, a case-control study was performed to determine the effects of OHE age, breed, progestin exposure, and parity on feline mammary carcinoma development. Cases were female cats diagnosed with mammary carcinoma by histological examination of mammary tissue. Controls were female cats not diagnosed with mammary tumors selected from the same biopsy service population. Controls were frequency matched to cases by age and year of diagnosis. Questionnaires were sent to veterinarians for 308 cases and 400 controls. The overall questionnaire response rate was 58%. Intact cats were significantly overrepresented (odds ratio [OR] 2.7, confidence interval [CI] = 1.4-5.3, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) in the mammary carcinoma population. Cats spayed prior to 6 months of age had a 91% reduction in the risk of mammary carcinoma development compared with intact cats (OR 0.9, CI = 0.03-0.24). Those spayed prior to 1 year had an 86% reduction in risk (OR 0.14, CI = 0.06-0.34). Parity did not affect feline mammary carcinoma development, and too few cats had progestin exposure to determine association with mammary carcinoma. Results indicate that cats spayed before 1 year of age are at significantly decreased risk of feline mammary carcinoma development.
There is little information regarding mammary tumors in male cats. The purpose of this study was ... more There is little information regarding mammary tumors in male cats. The purpose of this study was to characterize the clinical characteristics of mammary carcinoma in male cats, compare this malignancy to the disease in female cats, and identify prognostic factors. Thirty-nine male cats with mammary carcinoma were identified. One pathologist reviewed the biopsies from all cats, and complete follow-up information regarding outcome was available for 27 cats. Information collected included signalment, age at neutering, history of progestin therapy, age at tumor diagnosis, size of tumor, type of surgery (lumpectomy, simple mastectomy, or radical mastectomy), results of clinical staging, adjunctive therapies, time to local recurrence, survival, and cause of death. The mean age at tumor diagnosis (12.8 years) was slightly older than that reported in female cats. The incidence of local tumor recurrence in 9 of 20 (45%) cats was similar to that reported in females. A history of progestin therapy was present in 8 of 22 (36%) cats for which this information was known. The median time to local recurrence was 310 days (range 127-1,363 days), and overall median survival was 344 days (range 14-2,135 days). Tumor size and lymphatic invasion were identified as negative prognostic factors. This study indicates that mammary carcinoma in the male cat has many similarities to the disease in females, with an aggressive clinical course in most cats.
Cell-based vaccination strategies to induce functional tumorspecific T cells in cancer patients h... more Cell-based vaccination strategies to induce functional tumorspecific T cells in cancer patients have focused on using autologous dendritic cells. An alternative approach is to use RNA-loaded CD40 activated B cells (CD40-B) that are highly efficient antigen-presenting cells capable of priming naive T cells, boosting memory T-cell responses and breaking tolerance to tumor antigens. The use of tumor RNA as the antigenic payload allows for gene transfer without viruses or vectors and permits major histocompatibility complex (MHC)independent, multiple-antigen targeting. Here, we use CD40L transfected K562 cells to generate functional CD40-B cells from the peripheral blood of humans and dogs. Testing of RNA-loaded CD40-B cells in dogs allows not only for its development in veterinary medicine but also for determination of its safety and efficacy in a large animal model of spontaneous cancer prior to initiation of human clinical trials. We found that CD40-B cells from healthy humans, healthy dogs and tumor-bearing dogs express increased levels of immune molecules such as MHC and CCR7. Moreover, RNAloaded CD40-B cells induce functional, antigen-specific T cells from healthy dogs and dogs with lymphoma. These findings pave the way for immunotherapy trials using tumor RNA-loaded CD40-B cells to stimulate antitumor immunity in a large animal model of spontaneous neoplasia. Gene Therapy (2008) 15, 955-965;
... hyperplasia (n= 9), and hemangioma (n= 2). Malignant lesions included anaplastic sarcoma (n=3... more ... hyperplasia (n= 9), and hemangioma (n= 2). Malignant lesions included anaplastic sarcoma (n=3 ... There are a few small case series providing evidence of efficacy for radiotherapy of ... were isolated from twenty cancer-bearing dogs receiving either single-agent doxorubicin or the ...
<p>Kaplan Meier estimates comparing vaccinated Group 2 to unvaccinated control Group 3 for ... more <p>Kaplan Meier estimates comparing vaccinated Group 2 to unvaccinated control Group 3 for (A) TTP (p = 0.34) and (B) LSS (p = 0.18).</p
As the official journal of the Veterinary Cancer Society, Veterinary and Comparative Oncology is ... more As the official journal of the Veterinary Cancer Society, Veterinary and Comparative Oncology is pleased to include these abstracts from the Annual Conference and we hope you find them informative and useful. These abstracts have not been subjected to peer review or editorial revision, however, and it would be prudent for the reader to exercise caution in the interpretation and application of the data presented.
<p>Kaplan Meier estimates comparing intent-to-treat Group 1 to unvaccinated control Group 3... more <p>Kaplan Meier estimates comparing intent-to-treat Group 1 to unvaccinated control Group 3 for (A) time-to-progression (TTP) (p = 0.16) and (B) lymphoma-specific survival (LSS) (p = 0.37).</p
<p>PBMCs were obtained from dogs at the time of diagnosis (pre) and 3 weeks post vaccinatio... more <p>PBMCs were obtained from dogs at the time of diagnosis (pre) and 3 weeks post vaccination (post) and antigen-specific immune responses directed against (A) CDV-HA and (B) lymph node tumor antigens were determined by IFN-γ ELISPOT. *p<0.1, **p<0.05.</p
<p>Kaplan Meier estimates for lymphoma-specific survival (LSS) of relapsed dogs who receive... more <p>Kaplan Meier estimates for lymphoma-specific survival (LSS) of relapsed dogs who received salvage therapy, demonstrating statistically significant differences between vaccinated Group 2 to unvaccinated control Group 3 (p = 0.038).</p
The purpose of this study was to evaluate the absolute lymphocyte and lymphoblast count in pretre... more The purpose of this study was to evaluate the absolute lymphocyte and lymphoblast count in pretreatment complete blood counts (CBCs) from dogs with lymphoma with the suspicion that non-lymphopenic animals likely had circulating lymphoblasts. Fifty-six dogs diagnosed with lymphoma were prospectively enrolled if they had no previous treatment (including glucocorticoids) and if they had intention-to-treat with a CHOP based protocol. All dogs had pre-treatment CBCs with review by a board-certified clinical pathologist. One hundred lymphoid cells were counted and the percentage lymphoblasts recorded. The mean absolute lymphocyte count was 2690/µL and mean absolute lymphoblast count was 1350/µL. Twenty-six dogs were lymphopenic ( 100/µL) was significantly correlated with a lymphocyte count over 1000/µL (p<0.001). The sensitivity and specificity, of a lymphocyte count over 1000/µL predicting the presence of circulating lymphoblasts, are 0.73 and 0.77 respectively. These results indicate...
The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (O... more The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (OSA) with other breeds to determine whether Rottweilers experienced a more aggressive form of the disease. Two hundred and fi fty-eight dogs were evaluated (102 clinical and 156 necropsy cases). In the necropsy population, Rottweilers had a younger mean age at death (7.3 versus 9 years, P = 0.006). There were no signifi cant differences between Rottweilers and other breeds in age at diagnosis, median disease-free interval or survival time. However, Rottweilers were more likely to have metastasis to the brain (7 versus 0%, P = 0.03). These results suggest that OSA in Rottweilers may have a different biological behaviour, but this study did not confi rm that these differences were associated with a worse outcome . Doberman Pinscher, German Shepherd, Golden Retriever, Great Dane, Irish Setter, Rottweiler and Saint Bernard. 2,5,10 -13 Standard treatment recommendations for canine OSA include surgery (amputation or limb-sparing procedures) followed by chemotherapy. 12 -17 Despite treatment, most dogs still die of metastatic disease within 1 -2 years of diagnosis. 12,13,15,17 -21 Current chemotherapy protocols include the chemotherapeutic agents
A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemen... more 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. recognized that a subset of patients would go into durable remissions (i.e. be cured); however, despite a high initial response rate (higher than 80% in most protocols), the majority of dogs would relapse and succumb to their lymphoma. Only 20-25% of the cases would be alive for 2 years or longer. The high response rates to relatively low dose-intense protocols indicate that canine lymphomas are uniquely chemotherapy sensitive tumours, and also suggest that further improvements, both in terms of remission rates and survival times, may be made through dose intensification. Results from human oncology trials, however, have been mixed; some studies have documented clinically significant improvements in outcome in patients treated with such doseintense/dose-dense protocols, whereas others have resulted in only marginal or no improvements in remission and survival durations. 21 -26 The inconsistent results from dose intensification may in part be due to the presence of cancer stem cells, a distinct
Introduction: The Patnaik grading system for canine cutaneous MCT is currently one of the best de... more Introduction: The Patnaik grading system for canine cutaneous MCT is currently one of the best determinants of prognosis; however, clinical outcome does not always correlate with histologic grade. The development of molecular markers offers a potential advantage and may complement subjective grading. The primary purpose of this study was to correlate histologic grading to Ki67/PCNA/AgNOR/c-Kit scores.
Cell-based active immunotherapy for cancer is a promising novel strategy, with the first dendriti... more Cell-based active immunotherapy for cancer is a promising novel strategy, with the first dendritic cell (DC) vaccine achieving regulatory approval for clinical use last year. Manufacturing remains arduous, especially for DC vaccines, and the prospect of using cell-based immunotherapy in the adjuvant setting or in combination with chemotherapy remains largely untested. Here, we used a comparative oncology approach to test the safety and potential efficacy of tumor RNA-loaded, CD40activated B cells in privately owned dogs presenting with non-Hodgkin's lymphoma (NHL), a clinical scenario that represents not only a major problem in veterinary medicine but also a bona fide spontaneous animal model for the human condition. When administered to NHL dogs in remission after induction chemotherapy, CD40-B cells electroporated ex vivo with autologous tumor RNA safely stimulated immunity in vivo. Although chemotherapy plus CD40-B vaccination did not improve time-to-progression or lymphoma-specific survival compared to dogs treated with chemotherapy alone, vaccination potentiated the effects of salvage therapy and improved the rate of durable second remissions as well as subsequent lymphoma-specific survival following salvage therapy. Several of these relapsed dogs are now long-term survivors and free of disease for more than a year. Overall, these clinical and immunological results suggest that cell-based CD40 cancer vaccination is safe and synergizes with chemotherapy to improve clinical outcome in canine NHL. More broadly, our findings underscore the unique value of clinical investigations in tumor-bearing companion animals.
The purpose of this study was to evaluate the efficacy and toxicity of a single-agent, dose-inten... more The purpose of this study was to evaluate the efficacy and toxicity of a single-agent, dose-intensified doxorubicin protocol in canine hemangiosarcoma (HSA). Canine HSA is a highly malignant tumor, and most affected dogs die within 6 months of diagnosis. Doxorubicin is the most, and possibly the only, effective chemotherapeutic drug for this malignancy, but it provides only moderate improvement in survival. On the basis of previous studies reporting similar survival in dogs treated with doxorubicin as a single agent and doxorubicin-based combination chemotherapy and the concept of summation dose intensity, a dose-intensified single-agent doxorubicin protocol was initiated. Twenty dogs with HSA were recruited to participate in this study. Workup and staging were performed according to standard practice. Chemotherapy was initiated within 3 weeks of surgery. Doxorubicin was scheduled to be administered at 30 mg/m2 i.v. every 2 weeks for a total of 5 treatments. The dogs were monitored for toxicity and signs of recurrence during and at regular intervals after chemotherapy. The protocol was tolerated well. No dogs were hospitalized because of adverse effects or developed clinical signs consistent with doxorubicin-induced cardiomyopathy. There was a significant difference in survival in dogs with stage I and I1 HSA compared with dogs with stage III HSA. with median survival times of 257, 210, and 107 days, respectively. These results are slightly better than the historical control with respect to toxicity and efficacy but are not statistically different from what is achieved with standard treatments. There was no association between dose intensity and outcome.
Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a f... more Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a few months of diagnosis. Most dogs present with signs from tumor rupture, resulting in hemoabdomen and intra-abdominal dissemination. The abdomen is also the main site of disease recurrence. Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. Fourteen dogs with splenic HSA. A prospective, unmasked, uncontrolled clinical trial. After staging of disease status and splenectomy, pegylated liposomal encapsulated doxorubicin was administered intraperitoneally (1 mg/kg body weight) every 3 weeks for 4 cycles. All dogs were monitored for recurrence of HSA. Samples of plasma and abdominal fluid were collected for measurement of doxorubicin concentration and pharmacokinetic analysis. Nonlinear mixed-effect modeling was used to describe the pharmacokinetics of liposomal doxorubicin administered IP. All 14 dogs died, 12 because of HSA and 2 from other causes. Postmortem examination was performed on 12 dogs. All 12 dogs died because of HSA-related causes and had hepatic metastases and hemoabdomen. The IP-treated dogs had fewer serosal, mesenteric, and omental metastases than historical controls treated with systemic doxorubicin. Results of the postmortem examination and pharmacokinetic analysis confirmed that IP delivery of doxorubicin resulted in an effective drug concentration with a clearance comparable with that after i.v. delivery. IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.
Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the... more Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate the effect of this strategy. Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone. Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo). Retrospective cohort study. Clinical data were collected and compared to identify differences between groups. Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were evaluated. Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx + Chemo groups were 372 and 676 days, respectively (P= .15) and median survival times (ST) were 1,406 and 848 days, respectively (P= .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P= .03). This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may benefit from adjuvant chemotherapy.
The etiopathogenesis of feline mammary carcinoma is not well understood. Although putative, risk ... more The etiopathogenesis of feline mammary carcinoma is not well understood. Although putative, risk factors include breed, reproductive status, and regular exposure to progestins. An association between age at ovarihysterectomy (OHE) and mammary carcinoma development has not been established. Therefore, a case-control study was performed to determine the effects of OHE age, breed, progestin exposure, and parity on feline mammary carcinoma development. Cases were female cats diagnosed with mammary carcinoma by histological examination of mammary tissue. Controls were female cats not diagnosed with mammary tumors selected from the same biopsy service population. Controls were frequency matched to cases by age and year of diagnosis. Questionnaires were sent to veterinarians for 308 cases and 400 controls. The overall questionnaire response rate was 58%. Intact cats were significantly overrepresented (odds ratio [OR] 2.7, confidence interval [CI] = 1.4-5.3, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) in the mammary carcinoma population. Cats spayed prior to 6 months of age had a 91% reduction in the risk of mammary carcinoma development compared with intact cats (OR 0.9, CI = 0.03-0.24). Those spayed prior to 1 year had an 86% reduction in risk (OR 0.14, CI = 0.06-0.34). Parity did not affect feline mammary carcinoma development, and too few cats had progestin exposure to determine association with mammary carcinoma. Results indicate that cats spayed before 1 year of age are at significantly decreased risk of feline mammary carcinoma development.
There is little information regarding mammary tumors in male cats. The purpose of this study was ... more There is little information regarding mammary tumors in male cats. The purpose of this study was to characterize the clinical characteristics of mammary carcinoma in male cats, compare this malignancy to the disease in female cats, and identify prognostic factors. Thirty-nine male cats with mammary carcinoma were identified. One pathologist reviewed the biopsies from all cats, and complete follow-up information regarding outcome was available for 27 cats. Information collected included signalment, age at neutering, history of progestin therapy, age at tumor diagnosis, size of tumor, type of surgery (lumpectomy, simple mastectomy, or radical mastectomy), results of clinical staging, adjunctive therapies, time to local recurrence, survival, and cause of death. The mean age at tumor diagnosis (12.8 years) was slightly older than that reported in female cats. The incidence of local tumor recurrence in 9 of 20 (45%) cats was similar to that reported in females. A history of progestin therapy was present in 8 of 22 (36%) cats for which this information was known. The median time to local recurrence was 310 days (range 127-1,363 days), and overall median survival was 344 days (range 14-2,135 days). Tumor size and lymphatic invasion were identified as negative prognostic factors. This study indicates that mammary carcinoma in the male cat has many similarities to the disease in females, with an aggressive clinical course in most cats.
Cell-based vaccination strategies to induce functional tumorspecific T cells in cancer patients h... more Cell-based vaccination strategies to induce functional tumorspecific T cells in cancer patients have focused on using autologous dendritic cells. An alternative approach is to use RNA-loaded CD40 activated B cells (CD40-B) that are highly efficient antigen-presenting cells capable of priming naive T cells, boosting memory T-cell responses and breaking tolerance to tumor antigens. The use of tumor RNA as the antigenic payload allows for gene transfer without viruses or vectors and permits major histocompatibility complex (MHC)independent, multiple-antigen targeting. Here, we use CD40L transfected K562 cells to generate functional CD40-B cells from the peripheral blood of humans and dogs. Testing of RNA-loaded CD40-B cells in dogs allows not only for its development in veterinary medicine but also for determination of its safety and efficacy in a large animal model of spontaneous cancer prior to initiation of human clinical trials. We found that CD40-B cells from healthy humans, healthy dogs and tumor-bearing dogs express increased levels of immune molecules such as MHC and CCR7. Moreover, RNAloaded CD40-B cells induce functional, antigen-specific T cells from healthy dogs and dogs with lymphoma. These findings pave the way for immunotherapy trials using tumor RNA-loaded CD40-B cells to stimulate antitumor immunity in a large animal model of spontaneous neoplasia. Gene Therapy (2008) 15, 955-965;
... hyperplasia (n= 9), and hemangioma (n= 2). Malignant lesions included anaplastic sarcoma (n=3... more ... hyperplasia (n= 9), and hemangioma (n= 2). Malignant lesions included anaplastic sarcoma (n=3 ... There are a few small case series providing evidence of efficacy for radiotherapy of ... were isolated from twenty cancer-bearing dogs receiving either single-agent doxorubicin or the ...
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Papers by Beth Overley