While fibrosarcomas predominated at the vaccine sites, other sarcomas were seen, including osteosarcomas, malignant fibrous histiocytomas, rhabdomyosarcomas and chondrosarcomas. These sarcomas displayed more aggressive biologic behavior when compared to sarcomas found in non-vaccinated areas. Further study revealed that these sarcomas were occurring in younger cats, were larger in size and had a low metastatic but high local reoccurrence rate. No association with breed, sex or neuter status was noted in these cases.

The recognition of VAFS as a separate clinical entity prompted much attention and study. Kass et al. were the first to study the disease from an epidemiological stand-point. Kass confirmed that indeed there was an increased incidence of soft tissue sarcomas (STS) associated with some vaccines and that these tumors were occurring in the interscapular and femoral regions of vaccinated cats. There was a statistically significant correlation between FeLV and rabies vaccinations and tumor formation within 1 year of treatment. He calculated a 5.5 and a 2 fold increased risk with FeLV and RV, respectively, in the formation of tumors. Kass calculated the association between number of vaccinations given simultaneously in one location with tumor occurrence. He found that there was a 50% increase when one vaccine was administered, 127% increase with 2 vaccines and a 175% increase with 3 or 4 vaccinations given to the same area at the same time.

Histologically, the tumors shared several characteristics. They all had the inflammatory process already described with the associated macrophages and lymphocytes. They also displayed increased cellular pleomorphism, mitotic figures, and local invasion as compared to sarcomas not related to vaccines. The VAFS also usually involved the subcutis while the NVAFS involved the dermis. The SQ location in the interscapular and thigh areas and presence of the characteristic inflammatory lesions are pathognomonic for VAFS.

The incidence of new cases of VAFS range from 1-10/10,000 vaccines administered. Tumors can occur from less than one month to more than 10 years after vaccination. In one study, the average latent period before tumor incidence was 26 months. The average age of the affected animals was 8 years old as compared to the average age of 11 years in cats with non-vaccine associated sarcomas. The VAFS are, on average, larger at diagnosis than NVAFS tumors. The mean size of VAFS tumors was 3-5cm as compared to 1-3cm that occur in the NVAFS. The VAFS tumors are also much more aggressive than NVAFS, with a recurrence rate of 62-70% after surgical resection. These tumors have a relatively low metastatic rate of 10-25%.

Treating these tumors is difficult as they are very locally aggressive. The best therapy is an aggressive and radical first surgery. It is recommended that suspicious masses be biopsied first to facilitate surgical treatment planning. Granulomas can be removed with minimal resection. Confirmed VAFS should be removed with well planned and aggressive surgery. If surgery is non-curative, with each subsequent surgery, the time to disease recurrence shortens. A study by Hershey et al focused on the average TFR (time to first recurrence) comparing first operation at a general veterinarian with first surgery performed by a surgical specialist. The difference between TFR was highly significant, with general surgeons producing 66 days to TFR vs. 274 days when surgery was performed by a specialist. The study also compared the TFR when a marginal first excision, a wide first excision and a radical first excision was used as the initial surgical intervention. The results were 66 days vs. 419 days vs. 325 days, respectively. The differences between wide and radical excisions was not statistically significant. Tumors involving the limbs had a longer TFR when compared to those involving the interscapular/trunk area. Overall, the median survival time for the cats in this study was 576 days, even with multiple treatment attempts.

Using radiation therapy (RTH) as a single modality to treat VAFS does not seem to have much promise. In a 1999 paper by Hendrick et al, median tumor-free intervals and survival times were compared when only surgery or RTH were used as treatment tools. The results were 16 months/>24 months vs. 4.5 months/9 months, respectively. However, the combination RTH with surgery is the current recommended therapy. Completeness of the surgical excision is the most critical factor in an animal's disease free interval. A 1998 study from North Carolina State University evaluated 33 cats that received 48 Gy RTH 2-4 weeks before surgery. The overall disease free interval was 398 days and survival time was 600 days. The only factor that significantly influenced treatment success or failure was if the surgical margins were free of tumor cells. In this study, neither the number of surgical attempts nor the tumor volume seemed to influence tumor control or survival.

These tumors are not very chemotherapy sensitive, but drugs have been used as a part of a combined modality treatment with some success. Most commonly, doxorubicin, cyclophosphamide, mitoxantrone and carboplatin were used. One study felt that a combination of doxorubicin and cyclophosphamide decreased the tumor size and caused regression of metastatic lesions.

VAFS is a disease process that is still poorly understood. Aluminum adjuvant alone is not the cause, since both aluminum containing and aluminum free adjuvants have been implicated in tumor development. Ellis et al have shown that this disease is not retrovirus-linked. What predisposes 1 to 10 of 10,000 vaccinated cats to develop these terribly aggressive and usually fatal tumors? Is there a genetic predisposition? A tumor suppressor gene inactivation? An apoptotic gene modification? Are there differences in immune status? Are there differences in the reactions to the inflammation? Does the severity of inflammation make a difference? Obviously, the many unanswered questions will require the concentrated efforts of many scientists and clinicians to ultimately resolve and prevent this disease process.

The goals of this case series were to examine medical records of cats that have been treated for vaccine associated feline sarcomas at the University of Illinois Veterinary Cancer Care Clinic (U of I VCCC) to compare responses with those seen at other referral institutions. The variables that we considered are: 1) the median survival time for our patients; 2) the median disease-free interval; 3) age at onset; 4) duration of the mass prior to diagnosis; 5) impact of total dose of RTH on disease-free interval (DFI) and survival.

Inclusion criteria were cats that had all, or part of their treatment at the U of IVCCC. The biopsy diagnosis of VAFS or presence of a soft tissue sarcoma either interscapularly or in the femoral region was adequate for consideration in our case series. Information was gathered from our records and from telephone contact with the owners or referring veterinarians on a retrospective data collection form developed by Dr. Dennis Macy of Colorado State University. If the cat received definitive therapy at another institution, i.e. RTH by linear accelerator, the case was excluded from this case series. The results were evaluated by Kaplan-Meier statistical methods to determine survival curves. If cats were still alive at the time of analysis or were lost to follow-up for any reason, they were censored for survival data.

Thirty cases fit the inclusion criteria for this case series. All of the animals but two were domestic short-hair cats; the exceptions were a Persian and a Siamese. There were seventeen male neutered cats, twelve female spayed and one female intact cat that ranged from 3 years old to 16 years old at presentation. The median age at presentation was 9.5 years and the mean age was 9.1 years. The median/mean survival time for all of the cats in the series was 53/81weeks (range 1 week to 260 weeks). For the cats below the median age, the median survival time was 88 weeks, the mean, 94 weeks (range 20 weeks to 260 weeks). The cats above the average age, the median survival time was 50 weeks, the mean, 56 weeks (range 1 week to 153 weeks). The median disease-free interval (DFI) for all of the cats in our series was 16 weeks with a mean of 45.5 weeks (range 1 week to 208 weeks).

The duration of the mass until a diagnosis was confirmed ranged from 1 week up to 20 weeks; 4 weeks was the median and 5.6 weeks was the mean time. When a mass was present for <= 4 weeks (n = 21 cats) vs. >4 weeks (n = 8 cats), the differences between the survival times was statistically significant. When the mass was present <=4 weeks, the median survival time for those cats was 105 weeks with a mean of 98.7 weeks (range 6 weeks to 260 weeks). When the mass was present >4 weeks, the median/mean survival time was 32/34.7 weeks (range 1 week to 53 weeks), respectively.

For twelve of the cats, the area of the vaccination was known. Seventeen cases could not be specifically linked to a particular vaccination. In the group of cats for which the vaccination site was known, 3 had received a rabies vaccine at the site, 1 had received a feline leukemia virus vaccine at the site, 5 had received both rabies and FVRCP at the site and 3 received rabies, FeLV and FVRCP vaccines in the same area concurrently.

Twenty-two of the cats had received some treatment attempt before referral to the U of I. Ten of the cats had an excisional biopsy performed, 6 underwent conservative surgeries and 6 had wide excision with at least 1 cm margins. Of the 22 pre-treated cats, 15 had one pre-treatment, 4 cats were treated twice, one cat was treated 3 times and one cat treated 4 times before referral to the U of I for further therapy.