Most Exciting Advances in Feline Oncology for 2003
World Small Animal Veterinary Association World Congress Proceedings, 2003
Gregory K. Ogilvie, DVM, DACVIM (Internal Medicine & Oncology)
Colorado State University
Ft. Collins, CO, USA

Dramatic advances are occurring in feline oncology in part because this area of specialization is maturing. Gene therapy, new chemotherapeutic agents, new surgical techniques are all being used world wide. Below are just a few examples of advances in our knowledge.

1. What is the incidence, signalment and etiology of feline squamous cell carcinoma?

Squamous-cell carcinomas occur mostly in adult cats especially around the head and neck, and particularly the ears, nose, and eyelids of cats lacking cutaneous pigment. In these locations the tumor is sunlight-induced in the same manner as described for dogs. Siamese cats appear less likely to develop cutaneous squamous-cell carcinoma than other felidae.(a) In a series of 90 cats with nasal planum SCC, 66 cats (73%) had some white skin or hair color.(a)

2. What are the prognostic factors associated with feline squamous cell carcinoma?

Tumor proliferative fraction, as measured by immunohistochemical detection of Proliferating Cell Nuclear Antigen (PCNA) was found to be prognostic for control of nasal planum SCC in cats treated by radiotherapy.(a) In addition, tumor stage was found to be prognostic for tumor control. Cats with smaller tumors (T1) had not reached a median survival (i.e., fewer than half of the cats had tumor recurrence) but the average was 53 months while larger tumors (T3) were controlled for a median of 9 months(a).

3. What is the optimal treatment and related response to therapy for squamous cell carcinoma?

While the synthetic retinoid 13 cis-retinoic acid has not been shown to reverse pre-neoplastic changes for SCC in cats,(a) newer retinoids such as etretinate have not yet been evaluated in this species. In view of the efficacy of etretinate in dogs, it would seem logical that these newer retinoids may also show efficacy for feline preneoplastic squamous-cell carcinoma.

Resection of the pinna for aural SCC is effective in the majority of cats if adequate resection is achieved. Essentially the entire pinna should be removed. However, these tumors may recur locally, as can SCC of the eyelids and nasal planum.

Actinically induced SCC in the cat is very sensitive to radiation therapy. Precancerous plaques and early lesions may be treated with brachytherapy radiation (e.g., strontium-90) at a single high dose. In a group of 25 cats treated with strontium-90, nearly 90% were free of tumor at one year with an average tumor-free period of 34 months.(a)

Local current-field radiation hyperthermia (50oC for 30 seconds) was very effective in causing tumor regression in superficial SCC of cats.(a) Of 19 cats with SCC, 13 (68%) had complete regression. Tumors that did not extend 2 mm or deeper in tissue responded best. Duration of response was observed for only 2 to 6 months.

For more advanced lesions, external-beam teletherapy produces long remissions. It should be remembered, however, that the cat is still susceptible to acquiring new tumors from sunlight exposure, and its behavior should be appropriately modified. Preferably cats should be protected from sunlight exposure during the middle part of the day. Ninety cats with SCC of the nasal planum were treated with orthovoltage-radiation therapy to a dose of 40 Gray in 4-Gray fractions(a). The median control of tumors for these cats was 14 months. However, advanced tumor stage (i.e., larger tumors) affected outcome adversely (see above). Fifteen cats whose tumors recurred were re-irradiated successfully.

Cryotherapy has been recommended as a treatment for SCC of the face in cats. In one study, however, this modality was considerably less effective than either surgery or radiation therapy in achieving local tumor control(a). Eleven of 15 cats had local tumor recurrence within a median of 6 months after cryotherapy. We recently completed a study involving 87 cats with squamous cell carcinomas of the head that were treated with cryotherapy. The median disease free interval was 14 months. Cats that had lesion less than 1 cm in diameter had a much higher probability of having tumors controlled than those with larger tumors. Therefore, we recommend that tumors that are larger than 1 cm in diameter be treated with other procedures other than cryothetherapy.

Photodynamic therapy has been shown to be quite effective in controlling this tumor in cats. In one study, 7 of 11 feline SCCs of the pinna or nasal planum completely resolved using a chloroaluminum sulfonated-phthalocyanine photosensitizer, and 5 of these responses lasted 44 weeks or longer.(a) In another trial using aluminum phthalocyanine tetrasulfonate, long-term (3 to 18 months) responses were seen in 12 of 17 patients.(a) However, toxicities, including 1 fatality, were more prevalent in this study.

Paradoxically, cisplatin was used successfully in a unique collagen-matrix intralesional implant system to treat 118 feline squamous-cell carcinomas(a). In this study, 83% of cats had a > 50% reduction in tumor volume and 64% had complete resolution after 6 treatments. The lack of systemic toxicity seen in these cats was ascribed to the depot nature of the treatments and subsequent slow release of cisplatin. Sterilized sesame oil appears to function as a similar vehicle to collagen matrix, and may be used at a dose of 2 ml of sesame oil to 10 mg cisplatin in 1 ml of saline.(a)

Mitoxantrone chemotherapy rarely brings objective response in feline oral SCC, but could be considered as an option for metastatic skin lesions.(a) When combined with external-beam radiation therapy, mitoxantrone has been shown to control oral SCC for a median of 170 days, which is substantially longer than when either modality is used alone.(a) Three cats with dermal SCC showed partial responses of short duration to bleomycin chemotherapy.(a) Carboplatin is a new cisplatin-like compound that may be of value for treating metastatic squamous cell carcinoma. Alan Theon recently reported that when a carboplatin/sesame seed oil compound was used to treat cats with squamous cell carcinoma, the results were excellent.

4. Specifically define the response to therapy for oral squamous cell carcinoma

In contrast to the situation in dogs, oral SCC in cats is a highly aggressive disease that responds poorly to surgical treatment or to radiation therapy regardless of its location in the mouth.

The longest control and survival rates have been obtained using a combination of radiation therapy and mitoxantrone chemotherapy.(a) The biggest problem for cats that have oral squamous cell carcinomas is that they do not maintain an adequate plane of nutrition. Appetite stimulants and very aromatic foods should be used whenever possible. Care should be taken when feeding baby foods because they often contain onion powder that can cause heinz body anemia. Carboplatin chemotherapy with or without radiation therapy appears to be resulting in good efficacy. The single most important prognostic feature appears to be bone involvement.

5. What is the treatment and associated prognosis of hemangiosarcoma in the cat?

Surgical excision of cutaneous hemangioma usually has a good prognosis, although local recurrence following surgical excision of cutaneous hemangiosarcoma is frequent. Metastasis appears to be rare. It is therefore appropriate to treat this tumor as a soft tissue sarcoma in cats, with aggressive initial surgery as the best therapeutic approach.

6. What are unique aspects of mast cell tumors in cats?

 Mast cell tumor granules do not stain well with Diff Quick type stains unless they are "soaked" in the alcohol for several minutes prior to staining.

 Mast cell tumors tend to metastasize to nodes, liver spleen and bone marrow...rarely to lungs.

 Radiation therapy is extremely effective for controlling local disease.

 Prednisone and vincristine when used as single agents induce a remission (partial or complete) in about 23% of the tumors.

7. What is the optimum treatment and prognosis associated with feline mast cell tumors?

The treatment of choice for cutaneous MCT in cats is surgery; for solitary tumors, a good prognosis can usually be given. Some cats may develop multiple well-differentiated tumors, and these cats may be treated with multiple palliative surgeries or corticosteroids (1 mg/kg prednisone daily). For invasive or incompletely excised MCTs, radiation therapy appears to be a successful adjunct to surgery; however, data regarding tumor control and patient survival are not as well established as for dogs.

Mitoxantrone caused a partial response in a feline mast-cell tumor, but the drug has not been further evaluated for the treatment of this disease.(a)

The treatment of choice for lymphoreticular MCTs in cats is splenectomy; long-term survival occurs in many cats receiving no other therapy. Response to splenectomy seems greater than would be explained by simple tumor mass reduction, as hematologic and other organ involvement apparently resolve. It is possible that splenic suppressor-cell activity may be reduced after splenectomy allowing for some control by the cat's immune system. For this reason the use of postoperative corticosteroids in these cats in controversial.(a)

8. What are the most important prognostic factors for mammary tumors in the cat?

In the last 20 years, little progress has been made in extending the survival time of canine and feline mammary tumor patients. Because stromal invasion is almost always present and metastases are frequently present at the time of surgery, a guarded to poor prognosis should always be given. Sixty-six percent of the cats that have had their tumors surgically excised have a recurrence at the surgical site. Most studies state that the time from tumor detection to the death of the cat is rarely over 12 months. The most significant prognostic factors influencing tumor recurrence and survival for cats with malignant mammary neoplasia are tumor size, the extent of surgery needed to remove the tumors, and histologic grading of the tumors.

MacEwen has shown that tumor size is the most important of these prognostic factors. Following surgery, the median for survival for cats with tumors > 3 cm in diameter is 6 months; for cats with tumors 2 to 3 cm in diameter, the median for survival following surgery is 2 years; and for cats with tumors < 2 cm in diameter, the median for survival after surgery is approximately 3 years. Radical surgery, when compared with regional "lumpectomy", has been shown to reduce local tumor recurrence but not to increase the overall time of survival. Cats with well-differentiated tumors with few mitotic figures per high- power field live longer compared with those with tumors that are not as well-differentiated histopathologically. The one-year survival rate was high in cats with a tumor that did not show lymphatic infiltration. There is a good correlation between the grade of malignancy, method of growth, and prognosis. Patients with pulmonary metastatic disease rarely survive longer than two months.

8. What chemotherapy is effective for the treatment of feline mammary tumors?

Chemotherapy, alone or in combination with surgery, is not as successful for feline mammary tumors as it is for other feline tumors such as lymphoma. Cyclophosphamide has been used alone or in combination with other chemotherapeutic agents and has not consistently helped the feline mammary tumor patient. The combination therapy of doxorubicin and cyclophosphamide has been shown to induce short-term partial and complete responses in 50% of cats with metastatic or nonresectable local disease. This chemotherapeutic protocol has been shown to be toxic in some cats and does not prolong survival. Other drugs that may be used include mitoxantrone and taxol. The role of the later two drugs is still being elucidated, however both have some efficacy in cats with malignant neoplasia. Further studies are necessary to quantify the benefit of adjunctive therapy for mammary neoplasia in cats. Chemotherapy should be used by practitioners that are familiar with the use of these drugs and their side effects.

References

1.  Ogilvie GK, Moore AS. Feline Oncology: A Comprehensive Guide for Compassionate Care. Trenton NJ, Veterinary Learning Systems. 2002. http://www.vetlearn.com

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Gregory K. Ogilvie, DVM, DACVIM (Internal Medicine, Oncology)
Colorado State University
Ft. Collins, CO, USA


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