Vaccine Associated Feline Sarcoma Task Force Update

Contributors & Contributions to the VAFS Task Force

1998-1999 projects

Update on 1997-1998 Funded Studies

Vaccine Associated Feline Sarcoma Task Force Guidelines

The Vaccine-Associated Feline Sarcoma Task Force (VAFSTF) met on April 5, 1999 at the American Veterinary Medical Association (AVMA) headquarters to award grants to research proposals scored by independent reviewers. The task force also prepared concise guidelines to assist practitioners in diagnosing and managing vaccine-associated sarcomas.

This year is marked by unprecedented financial support for studies investigating the epidemiology, etiology, and treatment of these rare but aggressive tumors. The task force received its first Platinum level donation of $100,000 from Pfizer Animal Health. As of April 1999, various veterinary organizations, individuals, and vaccine manufacturers contributed over $460,000. The task force wishes to thank the following for their generous contributions:

(AAFP = American Association of Feline Practitioners; AAHA = American Animal Hospital Association; AVMA = American Veterinary Medical Association; CFHC = Cornell Feline Health Center; OAHF = Ohio Animal Health Foundation; VCS = Veterinary Cancer Society)

This support has allowed funding of the following six 1998-1999 projects:

Epidemiologic Study of Vaccine-Specific Risk and Vaccination Protocols in the Incidence of Vaccine Associated Sarcomas in Cats. (Principle investigator: P. H. Kass, DVM, PhD). Initially funded for 1998, this study was extended through 1999.

Molecular Biomarkers of Vaccine-Associated Feline Sarcoma: p53 Mutations and Drug Sensitivity. (Principle investigator: S. Kanjilal, PhD)

Papillomavirus, Herpesvirus, and Polyomavirus: Exploring the Etiology of Vaccine-Associated Feline Sarcomas. (Principle Investigator: M. L. Jackson, DVM, PhD)

Evaluation of Mutagenicity of Feline Vaccines (excluding rabies) Using the A_L Assay. (Principle Investigator: S. M. LaRue, DVM, PhD)

The Utility of Contrast-Enhanced Computed Tomography in the Evaluation and Treatment of Cats with Vaccine-Associated Fibrosarcoma. (Principle Investigator: M. C. McEntee, DVM, DACVIM, DAVR)

Towards a Novel Therapy of Vaccine-Associated Feline Sarcomas: Reoviral Oncolysis. (Principle Investigator: J. A. Ellis, DVM, PhD)

In addition, several applicants were invited to develop preliminary data to submit by September 1, 1999 for a second consideration of their proposals.

Update on 1997-1998 Funded Studies

The Task Force also received reports on the studies that were funded in 1997 and 1998.

Epidemiologic Study of Vaccine-Specific Risk and Vaccination Protocols in the Incidence of Vaccine Associated Sarcomas in Cats. (Principle investigator: P. H. Kass, DVM, PhD). Dr. Kass and fellow investigators in a multicenter study are evaluating a number of risk factors, comparing the occurrence in cats with sarcomas to that in cats with basal cell tumors. Veterinary participation in the project has been exemplary; by early May 1999, nearly 2,000 cases and controls have been enrolled in the study.

Molecular Biomarkers of Vaccine-Associated Feline Sarcomas. (Principle Investigator: S. Kanjilal, PhD). The researchers at University of Minnesota have established a comprehensive tissue bank of sarcomas, blood, and normal appearing surgical margins. A number of polymorphisms in the p53 gene have been identified, including in morphologically normal tissues adjacent to sarcomas. Preliminary work on identifying signature mutations and correlations to clinical outcomes has been completed.

Molecular Analysis of Platelet-Derived Growth Factor (PDGF) and the Cellular Protooncogenes sis, fms, and jun in Feline Vaccine-Associated Sarcomas, and Evaluation of the Role of Local Lymphocytes in Tumorigenesis. (Principle investigator: M. J. Hendrick, VMD, DACVP). The researchers at University of Pennsylvania have initiated investigation of tumorigenesis by evaluating the role of local lymphocytes. Preliminary data suggest T-lymphocytes tend to infiltrate the sarcomas, while B-lymphocytes do not. The investigators plan to continue their studies by conducting molecular analysis of growth factors and their receptors.

Growth Factor Expression and Vaccine-Associated Sarcoma Tumorigenicity. (Principal investigator: E. G. MacEwen, VMD). The researchers at the University of Wisconsin-Madison and MD Anderson Cancer Center have established 14 cell lines from vaccine-associated and non-vaccine-associated feline sarcomas, and initiated evaluations of levels of growth factors HGF, IGF, and PDGF, and the response of cell lines to the growth factors. They have also evaluated the tumorigenic potential of several of the cell lines.

Comparable Efficacy of Doxorubicin Versus Stealth Liposomal Doxorubicin in Cats with Vaccine-Associated Sarcomas: A Multicenter Randomized Clinical Trial. (Principle investigator: D. M. Vail, DVM, MS, DACVIM). Vail and colleagues in six sites report that case accrual is ahead of schedule with 74 enrollees at the time of this writing. The stealth form of doxorubicin was found to have a delayed renal toxicity at the dosage of 1.5 mg/kg; studies will continue at the reduced dosage of 1.0 mg/kg.

Treatment of Feline Vaccine-Associated Sarcomas: Comparison of Tumor Response to Radiation Therapy alone with Radiotherapy Plus an Adjuvant Hemoglobin-Based Oxygen Carrier Radiotherapy Sensitizer, and Follow-up Assessment After Surgery and Chemotherapy. (Principle Investigator: A. E. Hohenhaus, DVM, DACVIM). This study was funded late in the cycle, and the number of enrolled cases is as yet insufficient to provide meaningful preliminary data.

The Task Force discussed the diagnosis and treatment of masses with a high index of suspicion for vaccine-associated feline sarcoma, and prepared the following guidelines for practitioners:

Vaccine Associated Feline Sarcoma Task Force Guidelines

Diagnosis and Treatment of Suspected Sarcomas

The following recommendations are based on information available as of April 1999 and are subject to revision as new information becomes available.

Diagnosis

1. Record anatomic location, shape, and size (measured by caliper and recorded in three dimensions) of all masses that occur at the site of an injection.

2. Manage a mass that develops at a previous injection site as if it were malignant until proven otherwise. A lesion should be fully assessed and aggressively treated if it meets any one of the following criteria:

Persists more than 3 months post-injection

Is larger than 2 cm in diameter

Is increasing in size after one month post-injection

3. If a mass meets one or more of the above criteria, we recommend that you perform a diagnostic biopsy prior to surgical excision. A tru-cut needle biopsy or incisional wedge biopsy is preferred for diagnosing lesions. Tru-cut biopsy should be done in such a way that subsequent surgical removal can readily include the entire needle tract. Wedge biopsy should be performed so that subsequent surgery can remove all tissue affected by the biopsy. Fine needle aspiration cytology is considered unreliable for the diagnosis of vaccine associated feline sarcomas (VAFS) and is not recommended.

Management- Masses confirmed as malignant should be handled as listed below:

1. Perform routine thoracic radiographs and pre-operative labwork for any malignant mass.

2. When feasible, histologically confirmed VAFSs should be imaged by computerized tomography (CT) or magnetic resonance imaging (MRI). Soft-tissue sarcomas often spread along fascial planes and may be undetectable visually in early stages of tumor growth. Advanced imaging data is very useful in determining the extent of surgery and/or the size of the radiation field that will be needed to maximize the chances for successful treatment.

3. Consult with an oncologist for current treatment options prior to initiating therapy.

4. Never "shell out" a sarcoma. Incomplete surgical removal of a sarcoma is the most common cause of treatment failure. Employ oncologic surgical techniques to avoid seeding malignant cells. Remove at least a 2-cm margin in all planes, including the deep side. In some instances, this will involve reconstruction of the body wall, removal of bone, or other advanced surgical techniques.

5. Submit the entire excised specimen for histopathology. Mark the excised mass with India ink or suture tags to provide an anatomical reference to facilitate subsequent treatment.

6. Report all histologically confirmed VAFSs to the manufacturer and to U.S. Pharmacopoeia at 12601 Twinbrook Parkway, Rockville, MD 20852, 800-487-7776, FAX 301-816-8532, or www.usp.org/prn.

After a sarcoma has been removed :

1. Recheck by physical examination monthly for the first three months, then at least every 3 months for one year.

2. Perform additional diagnostic procedures as appropriate for the abnormalities detected.