Prognosis for presumed feline vaccine-associated sarcoma after excision: 61 cases (1986-1996)

OBJECTIVE: To evaluate time to first recurrence (TFR) and overall survival in cats with presumed vaccine-associated sarcomas (VAS) treated with excision. DESIGN: Retrospective study. ANIMALS: 61 cats with presumed VAS. PROCEDURE: Medical records of cats that received excision as the only initial treatment for presumed VAS were reviewed to evaluate prognosis. Overall survival curves and TFR were determined. RESULTS: Median TFR was 94 days. Median TFR for tumors treated with excision performed at a referral institution (274 days) was significantly longer than that for tumors excised by a referring veterinarian (66 days). Radical first excision yielded significantly longer median TFR (325 days) than did marginal first excision (79 days). Cats with tumors located on the limbs had longer median TFR (325 days) than cats with tumors located in other sites (66 days). Median overall survival time was 576 days. Significant differences in survival times between groups were not detected. Few cats (13.8%) receiving only surgical treatment had long-term (> 2 years) survival. CONCLUSIONS AND CLINICAL RELEVANCE: Radical first excision of presumed VAS is essential for extended TFR. Current recommendations for vaccination of the distal portions of the extremities are appropriate, because this practice permits radical excision of tumors (amputation) that develop at vaccination sites; however, surgery alone is seldom curative.     

Treatment with a combination of doxorubicin, surgery, and radiation versus surgery and radiation alone for cats with vaccine-associated sarcomas: 25 cases (1995-2000)

OBJECTIVE: To compare use of doxorubicin, surgery, and radiation versus surgery and radiation alone for treatment of cats with vaccine-associated sarcoma. DESIGN: Retrospective study. ANIMALS: 25 cats with vaccine-associated sarcomas. PROCEDURE: Time to first recurrence and survival time were compared between the 2 treatment groups. The number of surgeries (1 or > 1) were compared with respect to time to first recurrence and survival time. RESULTS: Median time to first recurrence was 661 days for the group that received doxorubicin, surgery, and radiation. Median time to first recurrence has not yet been attained for the group treated with surgery and radiation alone. Median survival time was 674 days for the group treated with doxorubicin, surgery, and radiation and 842 days for the group treated with surgery and radiation alone. For time to first recurrence and survival time, significant differences were not detected between cats that had 1 surgery and those that had > 1 surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Significant differences between the 2 treatment groups were not detected. The efficacy of doxorubicin in the treatment of vaccine-associated sarcomas is uncertain.     

Evaluation of radiotherapy alone or in combination with doxorubicin chemotherapy for the treatment of cats with incompletely excised soft tissue sarcomas: 71 cases (1989-1999)

OBJECTIVE: To determine whether the addition of doxorubicin chemotherapy affected the outcome of cats with incompletely excised, nonvisceral soft tissue sarcomas undergoing postoperative radiotherapy. DESIGN: Retrospective case series. ANIMALS: 71 cats. PROCEDURES: Medical records were reviewed for clinically relevant data on cats that underwent postoperative radiotherapy for treatment of incompletely excised soft tissue sarcomas with or without concurrent doxorubicin chemotherapy. Radiotherapy was performed on an alternate-day schedule, with a total dose of 58.8 to 63 Gy delivered in 21 fractions. Doxorubicin was administered every 21 days for 3 to 5 cycles. Follow-up information was obtained by means of physical examination or through telephone conversations with refer-ring veterinarians or owners. RESULTS: Median disease-free interval with concurrent radiotherapy and doxorubicin chemotherapy (15.4 months; range, 2.4 to 44.9 months) was significantly longer than median disease-free interval with radiotherapy alone (5.7 months; range, 1.0 to 50.8 months). However, survival time was not significantly different between groups. CONCLUSION AND CLINICAL RELEVANCE: Results suggested that doxorubicin chemotherapy may play a role in extending the disease-free interval in cats undergoing radiotherapy for treatment of incompletely excised soft tissue sarcomas.     

Radiation treatment for incompletely resected soft-tissue sarcomas in dogs

OBJECTIVE: To evaluate efficacy of radiation for treatment of incompletely resected soft-tissue sarcomas in dogs. DESIGN: Prospective serial study. ANIMALS: 48 dogs with soft-tissue sarcomas. PROCEDURE: Tumors were resected to < 3 cm3 prior to radiation. Tumors were treated on alternate days (three 3-Gy fractions/wk) until 21 fractions had been administered. Cobalt 60 radiation was used for all treatments. RESULTS: Five-year survival rate was 76%, and survival rate was not different among tumor types or locations. Four (8%) dogs developed metastases. Eight (17%) dogs had tumor recurrence after radiation. Development of metastases and local recurrence were significantly associated with reduced survival rate. Median survival time in dogs that developed metastases was 250 days. Median disease-free interval for all dogs was 1,082 days. Median time to recurrence was 700 days. Dogs that developed recurrence after a prolonged period responded well to a second surgery. Acute radiation toxicosis was minimal; osteosarcoma developed at the radiation site in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: An excellent long-term survival rate may be achieved by treating soft-tissue sarcomas in dogs with resection followed by radiation. Amputation is not necessary for long-term control of soft-tissue sarcomas in limbs. Development of metastases and recurrence of local tumors after radiation treatment are associated with decreased survival rate. Acute and delayed radiation toxicosis was minimal with the protocol used in this study.     

Surgery alone versus surgery and doxorubicin for the treatment of feline injection-site sarcomas: a report on 69 cases

Sixty-nine cats were treated for injection-site sarcomas at the Veterinary Teaching Hospital of Grugliasco, Turin (Italy). The animals were divided into two subgroups: those subjected to four doxorubicin cycles combined with radical surgical excision 10 days after the second chemotherapy cycle (group A, 49 cats) or those treated with surgery alone (group B, 20 cats). Each cat was monitored for lung metastasis and local recurrence. In group A, 28 cats were alive at the end of the follow-up period. In this group, the recurrence rate was 40.8% while lung metastasis occurred in 12% of cats. In group B, eight animals were alive at the end of the follow-up period, while the rates of recurrence and metastasis were 35% and 10%. Neither the median disease-free interval nor the median overall survival was reached in either group. Moreover, there were no statistically significant differences between the two groups.     

Feline cutaneous hemangiosarcoma: a retrospective study of 18 cases (1998-2003)

Cutaneous hemangiosarcoma (HSA) has been infrequently reported in dogs and cats. Medical records of 18 cats diagnosed with cutaneous HSA were reviewed. Age at the time of diagnosis, breed, sex, tumor location, tumor size, treatment type, survival time, disease-free interval, and cause of death were evaluated. Aggressive surgical excision of the tumor was attempted in 10 cats. A complete surgical excision was achieved in five of the 10 cats. Median survival times were statistically longer in cats that underwent surgery versus cats that did not. Cats with cutaneous HSA treated with aggressive surgical excision of their tumors may have a good long-term prognosis.     

Treatment and outcome of four cats with apocrine gland carcinoma of the anal sac and review of the literature

Anal sac adenocarcinoma is uncommon in cats. We report the outcome of multi-modality therapy in two cats (surgery, definitive radiotherapy and systemic chemotherapy) and surgery alone in two cats. All received surgical excision of the primary tumour followed by radiotherapy and carboplatin chemotherapy in two cases. Both cats that underwent multimodal therapy developed distant metastatic disease and one developed recurrence of the primary tumour. One cat that underwent surgery alone with incomplete margins also developed rapid recurrence. Overall survival times were 89, 161 and 169 days. One cat that had complete surgical excision is still alive without recurrence 425 days postoperatively. Whilst the role of radiation in the local control of this disease is yet to be defined, clearly a more effective systemic therapy is required before such aggressive local treatment can be routinely recommended.     

Periocular cutaneous mast cell tumors in cats: evaluation of surgical excision (33 cases)

Objective  To describe feline periocular cutaneous mast cell tumor (CMCT) clinical features, rates of local tumor recurrence and metastases, and cat survival time following surgical excision.
Animals studied  Thirty-three cats with periocular CMCTs.
Procedures  Medical records of cats diagnosed with periocular CMCTs were reviewed; cats were included if CMCTs were surgically excised and the diagnosis confirmed by histopathology. The appearance, size, location and histopathology findings of CMCTs were recorded. Rates of local recurrence, metastasis, and survival time following surgical excision were collected when available.
Results  All periocular CMCTs were restricted to the eyelids. In addition to surgical excision, three cats were treated with adjunctive therapy (strontium-90 irradiation or cryotherapy) intraoperatively. Local tumor control was achieved in 22/23 cats with a minimum follow-up of 30 days (median follow-up time of 711 days); one cat developed disseminated CMCTs but no local recurrence. Cats with periocular CMCTs had a median survival time of 945 days. Metastatic disease involving peripheral lymph nodes or abdominal viscera was not detected in any cat at any time during the study. All periocular CMCTs were classified as low-grade based on histopathology, and complete excision was achieved in approximately 50% of cases.
Conclusions  Surgical excision of periocular CMCTs in cats is an effective treatment option with rare local recurrence and metastases, even following incomplete surgical excision.     

Feline discrete high‐grade gastrointestinal lymphoma treated with surgical resection and adjuvant CHOP‐based chemotherapy: retrospective study of 20 cases

The aim of this retrospective study was to evaluate the outcome of cats treated with surgical intervention for a discrete intermediate‐/high‐grade gastrointestinal lymphoma prior to CHOP‐based chemotherapy. Variables including sex, breed, haematocrit, white blood cell count, serum albumin concentration, clinical stage of disease, gastrointestinal obstruction and peritonitis were assessed for their effect on survival. Twenty cats met the inclusion criteria with three cats still alive at the time of data analysis. The overall median survival time (MST) was 417 days (range: 12–2962 days). The disease‐free interval (DFI) was 357 days (range: 0–1585 days) with six cats still deemed in remission prior to death. Only clinical stage had a significant effect on both MST and DFI. Cats with discrete intermediate/high‐grade gastrointestinal lymphoma that undergo surgical resection followed by adjuvant CHOP chemotherapy may achieve acceptable overall survival times.     

Combined doxorubicin and cyclophosphamide chemotherapy for nonresectable feline fibrosarcoma

A retrospective evaluation was performed on 12 cats with nonresectable, histopathologically confirmed fibrosarcomas that were treated with doxorubicin and cyclophosphamide chemotherapy. All of the tumors were located in sites potentially used for vaccination. Six cats had a greater than 50% decrease in gross tumor burden. However, the responses were not durable, with a median response duration of 125 days. All cats developed progressive disease. When animals that received other treatments after doxorubicin-based chemotherapy were eliminated from the analysis, median survival time was significantly longer for cats that responded to chemotherapy compared with the median survival time for nonresponders (242 and 83 days, respectively). These findings may serve as a basis for further evaluating the role of chemotherapy in the treatment of vaccine-associated sarcomas.     

CONCOMITANT LIPOSOMAL DOXORUBICIN AND DAILY PALLIATIVE RADIOTHERAPY IN ADVANCED FELINE SOFT TISSUE SARCOMAS

Local recurrence of feline soft tissue sarcomas is common despite aggressive treatment. Liposomal doxorubicin might serve as a depot radiosensitizer if administered concomitantly with daily radiotherapy and thus improve tumor control. In this pilot study, the feasibility of concomitant liposomal radiochemotherapy was evaluated in a palliative setting in 10 cats with advanced soft tissue sarcomas. Cats were treated with median number of 5 (range 5–7) daily fractions of radiotherapy and a median total dose of 20 Gy (range 20–31.5 Gy). One dose of liposomal doxorubicin was administered at the beginning of radiotherapy. Seven cats received further free or liposomal doxorubicin after completion of the liposomal doxorubicin/radiation protocol. Seven of the treated 10 cats (70%) achieved a partial (n=5) or complete (n=2) response with a median response duration of 237 days. The median progression free interval in all 10 cats was 117 days and the median overall survival time was 324 days. Concomitant liposomal radiochemotherapy was tolerated well in nine cats, one cat experienced temporary anorexia. Although the number of patients is too small to make definitive conclusions, results appear promising enough to investigate the role of liposomal doxorubicin as a radiosensitizer further.     

Feline extranodal lymphoma: response to chemotherapy and survival in 110 cats

O bjective : To determine response to treatment, survival and prognostic factors for feline extranodal lymphoma in the UK.
M ethods : Records of cats diagnosed with lymphoma of extranodal sites at seven referral centres were reviewed and information on signalment, tumour location, prior treatment and chemotherapy protocol recorded. Factors influencing response to treatment and survival were assessed.
R esults : One hundred and forty-nine cases met inclusion criteria. Sixty-nine cats had nasal lymphoma, 35 renal, 15 central nervous system, 11 laryngeal and 19 miscellaneous locations. Sixty-six cats received cyclophosphamide, vincristine, prednisolone, 25 Wisconsin-Madison doxorubicin-containing multi-agent protocol, 10 prednisolone alone and nine other combinations. The response rate for the 110 treated cats was 85·5 per cent. Of cyclophosphamide, vincristine, prednisolone treated cats 72·7 per cent achieved complete remission, median survival 239 days. Sixty-four per cent of Wisconsin-Madison treated cats achieved complete remission, median survival 563 days. Cats with nasal lymphoma achieving complete remission had the longest survival (749 days) and cats with central nervous system lymphoma the shortest (70 days). If complete remission was achieved, prior treatment with corticosteroids significantly reduced survival time.
C linical S ignificance : Cats with extranodal lymphoma respond to chemotherapy and achieve survival times comparable to other locations. Corticosteroid pretreatment reduced survival time in cats achieving complete remission.     

Somatic alterations of the p53 tumor suppressor gene in vaccine-associated feline sarcoma

OBJECTIVE: To determine somatic alterations in p53 in vaccine-associated feline sarcoma (VAFS). Animals-27 domestic shorthair cats undergoing first surgical treatment for primary VAFS with no history of chemotherapy or gamma radiation. PROCEDURES: Sequence analysis was performed on the genomic sequence of p53 (between exons 5 through 9) from tumor and blood samples obtained from the cats. Cats were monitored for 3 years and disease-free intervals and survival times calculated. RESULTS: Eight single nucleotide polymorphisms were detected within the genomic sequence of p53, with 20 of 27 cats (74%) having heterozygosity at > or = 1 polymorphic site. Somatic loss of heterozygosity at p53 was detected in the primary tumors of 12 of these 20 (60%) cats. Such allelic deletion was significantly associated with rapid tumor recurrence and reduced overall survival. Point mutations were rare, occurring in 3 of 27 primary tumors. The finding of malignant cells in the surgical margins was significantly associated with disease recurrence, but clear margins (with no detectable malignant cells) were not predictive of positive outcome. CONCLUSIONS AND CLINICAL RELEVANCE: p53 status is an indicator of postsurgical recurrence and overall survival in cats with VAFS. Careful follow-up is important in treating vaccine-site tumors containing allelic deletion of p53, whereas aggressive surgical treatment may be sufficient to control primary vaccination site tumors without the allelic loss.     

PREOPERATIVE RADIOTHERAPY FOR VACCINE ASSOCIATED SARCOMA IN 92 CATS

Medical records for 92 cats with a vaccine associated sarcoma receiving preoperative irradiation, with or without chemotherapy, between December 1985 and September 1998 were reviewed. The purposes were to quantify response to treatment and to attempt identification of factors associated with favorable response. Variables evaluated for a relationship to outcome included signalment, tumor location, presence of gross vs. microscopic tumor, radiation field size, irradiation technique, type of surgical procedure, completeness of excision, and chemotherapy (none, carboplatin alone, and others). Time to first event was calculated for the first day of treatment until local tumor recurrence or metastasis, or the date of euthanasia or death. Median time to first event for all 92 cats was 584 days. Only completeness of surgical excision was related to the time to first event. Median time to first event in cats having complete surgical excision was 986 days compared to 292 days for cats with incomplete excision (P = 0.004). Cats requiring bone removal to effect tumor removal had earlier failure than cats having other types of surgery. There was not a significant relationship between administration of chemotherapy or chemotherapy type and time to first event although outcome in cats receiving carboplatin was better than all other treatment groups. Carboplatin addition to preoperative irradiation appears worthy of further study. Preoperative irradiation is an effective treatment for cats with vaccine associated sarcoma, especially if complete excision can be accomplished following irradiation.     

Marginal excision of low-grade spindle cell sarcoma of canine extremities: 35 dogs (1996-2006)

Objective— To evaluate recurrence rate and disease-free interval (DFI) of dogs with low-grade soft tissue spindle cell sarcoma of the extremities treated by marginal excision.
Study Design— Retrospective study.
Animals— Dogs (n=35) with soft tissue low-grade spindle cell sarcoma.
Methods— Medical records were reviewed and dogs that had marginal surgical resection of low-grade soft tissue spindle cell sarcoma at or distal to elbow and stifle were included.
Results— Histopathologic margins were dirty (12 dogs), clean but close (12), and clean (11). Follow-up after surgery occurred from 210 to 2202 days (minimum, 180 days). Local recurrence and metastatic rates were 10.8% and 0%, respectively. Median DFI and survival time were not reached, because <50% of dogs died of disease-related events. Mean DFI and mean survival time were 697.8 days (95% CI: 559.7–836 days) and 703.5 days (95% CI: 566.6–840.5 days), respectively. There were no significant differences among survival functions stratified by histologic margins.
Conclusion— Marginal surgical excision without adjuvant treatment of low-grade soft tissue spindle cell sarcoma of the extremities results in a low local recurrence rate.
Clinical Relevance— Low-grade spindle cell sarcomas located at or distal to the elbow and stifle joints can be excised without need for wide or radical surgery.     

Prognostic factors for feline mammary tumors

The case records of 100 cats with malignant mammary tumors were reviewed. All cats were staged clinically according to the staging system of the World Health Organization. The following information was obtained from the medical records: age at time of diagnosis, breed, tumor size, date of surgery, type of surgical procedure performed, histologic type of tumor, disease-free interval, survival time, and cause of death. Factors of no prognostic value were age (less than or equal to 10 years vs greater than 10 years) and breed. Tumor size was the most significant prognostic factor (P less than 0.0001). Cats with small tumors (1 cm3 to 8 cm3) had the best prognosis. The type of surgery, conservative vs radical, was significantly (P less than 0.01) related to disease-free interval, but was of no significance in prolonging survival time.     

Evaluation of Adjuvant Doxorubicin-Based Chemotherapy for the Treatment of Feline Mammary Carcinoma

Background: 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.
Hypothesis: Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone.
Animals: Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo).
Methods: 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.
Results: 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).
Conclusions and Clinical Importance: 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.     

Effects of radiotherapy alone and surgery and radiotherapy on survival of dogs with nasal tumours

The case records of 26 dogs with nasal tumours, treated either with radiation alone or surgery and radiation, were compared. One- and two-year actuarial survival rates for 12 dogs treated with radiotherapy were 58 and 13 per cent, respectively, compared to 71 and 38 per cent, respectively, for 14 dogs which were treated with surgery before radiotherapy. Sixty-seven per cent of the dogs treated with radiotherapy had recurrent clinical signs by 52 weeks compared to 36 per cent of the dogs treated with surgery and radiotherapy. The longer disease-free interval of the dogs treated with surgery and radiotherapy was statistically significant. When dogs with sarcomas were compared to those with carcinomas, there was no significant difference in disease-free interval or survival time.     

Liposome-encapsulated doxorubicin (Doxil) and doxorubicin in the treatment of vaccine-associated sarcoma in cats

The purpose of this randomized, multicenter study was to evaluate the toxicity and efficacy of liposome-encapsulated doxorubicin (LED) and doxorubicin (DOX) in the treatment of feline vaccine-associated sarcoma (VAS). Cats were divided according to their disease status into a microscopic arm (no evidence of gross disease) and a macroscopic arm (evidence of gross disease). Each arm was randomized to receive either LED (1-1.5 mg/kg i.v. q3 weeks) or DOX (1 mg/kg i.v. q3 weeks). Thirty-three cats were entered in the macroscopic arm of the study with an overall response rate of 39% (5 complete response and 8 partial response) and a median time to progression of 84 days. Response rates were not different between LED and DOX. Seventy-five cats were entered into the microscopic arm. When compared to a similar historical control population treated with surgery alone, the cats receiving chemotherapy had a prolonged median disease-free interval (388 days versus 93 days). No difference in efficacy was detected between LED and DOX. LED at 1.5 mg/kg induced delayed nephrotoxicosis in 23%, necessitating a decrease in the recommended dosage to 1 mg/kg, and cutaneous toxicosis in 21.7% of treated cats. This study showed that both DOX and LED are efficacious in the treatment of VAS and should be considered in the treatment of this tumor.     

Analysis of prognostic factors associated with injection-site sarcomas in cats: 57 cases (2001-2007)

OBJECTIVE: To identify prognostic factors in cats with injection-site sarcomas (ISSs). DESIGN: Retrospective case series. ANIMALS: 57 cats with ISSs. PROCEDURES: Medical records of cats were reviewed with regard to sex, age, anatomic site of tumor, tumor size, histologic grade, excision of a primary tumor versus excision of a recurrent ISS, use of excision alone versus excision plus adjuvant therapy, local tumor recurrence, and development of distant metastasis to predict overall survival time (ie, time from tumor excision to death). RESULTS: In univariate analyses, local recurrence and development of distant metastasis were significantly associated with survival time in cats. On multivariate analysis, development of distant metastasis remained a significant prognostic factor. Histologic grade was associated with distant metastasis, with cats having grade 3 tumors being significantly more likely to develop metastasis than cats with grade 1 and 2 tumors. Factors associated with local recurrence of ISSs were not identified. CONCLUSIONS AND CLINICAL RELEVANCE: The development of distant metastasis, which may occur later during the course of the disease, was identified as a prognostic factor for overall survival time in cats with ISSs. In addition, cats with histologic grade 3 ISSs should be considered for further interventional studies with chemotherapy to prevent the high rate of distant metastasis.