"Chemotherapy and Feline Sarcomas?" TUMOR TIDBITS, A BIWEEKLY EMAIL NEWSLETTER FROM GULF COAST VETERINARY ONCOLOGY Number 75; October 25, 2002. ======================================================================= THIS WEEK'S TUMOR TIDBIT: CHEMOTHERAPY AND FELINE SARCOMAS? ======================================================================= It appears that daily we learn more and more about how little we understand the problem of vaccine-associated sarcomas that arise in cats. This Tumor Tidbit provides a brief overview (hence a Tidbit) and attempts to conclude whether chemotherapy is indicated in the management of this disorder. WHAT'S KNOWN THUS FAR ABOUT THE CAUSE OR RISKS ABOUT VACCINATIONS IN CATS? >Vaccination can induce sarcoma in cats (primarily fibrosarcoma) at injection sites. The time between vaccination and tumor development can be as short as several months. Specific cause is unknown; but aluminum hydroxide, an adjuvant in many vaccines, has been suggested as a possible cause. The prevalence of fibrosarcoma in cats is low; estimated at 20/100,000 cats. The risk for cats developing fibrosarcoma from a single FeLV or rabies vaccination in the cervical or interscapular region is about 50% higher than that for cats not receiving a vaccine at that site. The risk for cats given 2 vaccinations is approximately 125% higher, and the risk for cats given 3 or 4 vaccinations is approximately 175% higher. WHAT ARE SOME OF THE RECOGNIZED TUMOR TYPES ASSOCIATED WITH VACCINATION AND OTHER DIFFERENTIAL DIAGNOSES? >Vaccine-associated Arthus reaction. Subcutaneous abscess. Fibrosarcoma. Osteosarcoma. Malignant Fibrous Histiocytoma. Malignant Mesenchymoma. Chondrosarcoma. Mast cell neoplasia. Epidermal inclusion cyst. Sebaceous gland adenoma or adenocarcinoma. Apocrine gland adenoma or adenocarcinoma. Pilomatrixoma WHAT ARE SOME COMMON DIAGNOSTIC FINDINGS? >Laboratory results are generally normal. Regional and thoracic radiography are indicated to determine extent of disease and lung metastasis. Cytologic examination of aspirate suggests mesenchymal neoplasia in some patients. Biopsy necessary for definitive diagnosis WHAT ARE THE AVAILABLE TREATMENT APPROACHES? >Wide surgical resection necessary because of invasiveness of this tumor yet completeness may be difficult to impossible in some locations. Radiotherapy indicated if surgical removal is incomplete; preoperative radiotherapy may be warranted to reduce tumor size and allow for completeness of removal. Chemotherapy may provide palliation in patients with nonresectable tumors. No specific chemotherapy regimens have been evaluated. WHAT SHOULD I DO IN PRACTICE AND WHAT DO I TELL THE PET OWNER? >There is no concensus among the veterinary community. A Task Force sponsored by the AVMA is addressing this issue. Some veterinarians consider administering different vaccines at different sites. Owners should be informed of benefits and risks of administering vaccines. Vaccines should be administered in sites amenable to surgical resection (rear limb) in case a neoplasm develops. WHAT'S THE BEST, LATEST, AND MOST RELIABBLE INFORMATION AVAILABLE? >There are four clinical studies that warrant further evaluation, but show promise in the management of VASF in cats: 1] Preoperative radiotherapy for vaccine associated sarcoma in 92 cats. Vet Radiol Ultrasound 2002 Sep-Oct;43(5):473-9. In this study, 92 cats were evaluated using preoperative radiation, with or without carboplatin chemotherapy. The median time to first recurrence for all 92 cats was 584 days. Only completeness of surgical excision was related to the time to first recurrence. Median time 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. 2] Use of surgery and electron beam irradiation, with or without chemotherapy, for treatment of vaccine-associated sarcomas in cats: 78 cases (1996-2000). J Am Vet Med Assoc 2001 Dec 1;219(11):1582-9. In this study of cats treated using a combination of post-operative electron beam radiation and, in some cases, chemotherapy, 32 (41%) cats experienced recurrence, and 9 (12%) cats developed metastases. One- and 2-year survival rates were 86 and 44%, respectively. Median survival time from onset of disease was 730 days (range, 30 to 2,014 days). Median disease-free interval was 405 days (range, 30 to 925 days). Cats that underwent only 1 surgery prior to radiotherapy had a lower recurrence rate than did cats that underwent > 1 surgery and had a significantly longer disease-free interval. Survival time and disease-free interval decreased as time between surgery and the start of radiotherapy increased. Cats that developed metastases had significantly shorter survival times and disease-free intervals than did cats that did not develop metastases. Castrated male cats had a significantly shorter survival time than did spayed female cats. Cats with larger tumors prior to the first surgery had shorter survival times. Twenty-six cats received chemotherapy in addition to surgery and radiotherapy. Whether cats received chemotherapy was not associated with recurrence rate, metastasis rate, or survival time. Results suggest that excision followed by electron beam irradiation may be beneficial for treatment of cats with vaccine-associated sarcomas. Extent of excision prior to radiotherapy did not seem to be associated with recurrence rate. 3] Treatment with a combination of doxorubicin, surgery, and radiation versus surgery and radiation alone for cats with vaccine-associated sarcomas: 25 cases (1995-2000). J Am Vet Med Assoc 2001 Feb 15;218(4):547-50. The objective of this study was to compare use of doxorubicin, surgery, and radiation versus surgery and radiation alone for treatment of cats with vaccine-associated sarcoma. 25 cats with vaccine-associated sarcomas were evaluated from time to first recurrence and survival time between the 2 treatment groups. The number of surgeries (1 or > 1) were compared with respect to time to first recurrence and survival time. 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. Significant differences between the 2 treatment groups were not detected. The efficacy of doxorubicin in the treatment of vaccine-associated sarcomas is uncertain. 4] Combined doxorubicin and cyclophosphamide chemotherapy for nonresectable feline fibrosarcoma. J Am Anim Hosp Assoc 2000 Sep-Oct;36(5):416-21. The 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. WHAT DO WE DO AT GULF COAST? >In our practice, we consider preoperative radiation therapy to be indicated in the management of VASF in cats. Concurrent chemotherapy (carboplatin or adriamycin) is still a judgement call regarding the best intent for reducing the size of the tumor prior to en bloc resection. Again, in our practice, the cat that has "complete" excision following preoperative radiation, with or without chemotherapy, has a good prognosis and we anticipate 80% to remain tumor free and symptom free for 2 years or longer. NEXT WEEK'S TUMOR TIDBIT In next weeks Tumor Tidbit, "How common is Pheochromocytoma and should we treat it?" ======================================================================= We hope this info helps and don't hesitate to call us Gulf Coast Veterinary Oncology! Kevin A. Hahn, DVM, Phd, Diplomate ACVIM (Oncology), drhahn@gcvs.com Janet K. Carreras, VMD, Residency Completed and Certification Examination Passed, ACVIM (Oncology), drcarreras@gcvs.com Glen K. King, DVM, MS, Diplomate ACVR (Radiology & Radiation Therapy), drking@gcvs.com Gulf Coast Veterinary Diagnostic Imaging & Oncology 1111 West Loop South, Suite 150, Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 W: www.gcvs.com