Abstract
Orthovoltage radiation was used to treat odontogenic tumours in three cats following incomplete surgical resection. Cats received a total radiation dose of 48–52 Gy over a period of 26–29 days. Acute toxicities were mild, consisting of hair loss within the radiation field in all cats, and mild mucositis in one cat. All cats had long-term (>35 months) control of their tumour, and two cats are still alive without recurrence of tumour 60 and 39 months, respectively, after completing treatment. Radiation therapy should be considered to be an adjuvant to incomplete surgery in cats with odontogenic neoplasms or epulides.
Anumber of different terms have been used to describe tumours arising from the components of teeth in cats. Some tumours retain the ability to induce reactive proliferation of connective tissue, and thus odontogenic tumours are often described as ‘inductive’ or ‘non-inductive’. Inductive tumours include fibroameloblastoma (adamantinoma), which often have histological remnants of normal odontogenesis where cords of epithelium tend to form ‘cup’-like structures. The most common non-inductive tumour in cats is the calcifying epithelial odontogenic tumour (CEOTs). Other tumour types include ameloblastic fibroma (which is usually encapsulated and, unlike fibroameloblastomas and CEOT, does not invade bone) and odontoma (Gardner 1992). Unfortunately, there is considerable and confusing overlap in the terminology used in veterinary references. However, the majority of odontogenic tumours are not aggressively invasive, so the clinical distinction may not be critical. Epulides, arising from the periodontal ligament, are rare in cats. Metastasis has not been reported from any of these benign tumours.
Inductive fibroameloblastomas (IFA) have almost exclusively been described in cats aged 18 months or less without gender or breed predilection (Dubielzig et al 1979, Mills & Lewis 1981, Dubielzig 1982, Walsh et al 1987, Stebbins et al 1989, Poulet et al 1992, Dernell & Hullinger 1994, Brodey 1996). Cats may be presented because the owner has noticed a mass (Mills & Lewis 1981, Hawkins & Jones 1982) that may grow rapidly or have been present for a long time. The tumours can be quite large (Dernell & Hullinger 1994) and may interfere with prehension of food (Hawkins & Jones 1982). Of 15 cats for which location was provided, the IFA occurred in the maxilla of nine cats and in the mandible of six (Mills & Lewis 1981, Hawkins & Jones 1982, Walsh et al 1987, Stebbins et al 1989, Poulet et al 1992, Dernell & Hullinger 1994), often located around, or cranial to, the canine tooth. Radiographically, lysis of the underlying bone is common and occasionally areas of mineralisation within the tumour may be seen (Dubielzig et al 1979, Mills & Lewis 1981, Hawkins & Jones 1982, Dernell & Hullinger 1994). Teeth may be missing in larger lesions and tumour may invade the nasal cavity (Dubielzig et al 1979).
Calcifying epithelial odontogenic tumours are characterised by their production of amyloid. They have been reported in older domestic short-hair cats with a median age of 9 years. All but one (Ohmachin et al 1996) have been in male cats (Langham et al 1984, Abbott et al 1986, Walsh et al 1987, Stebbins et al 1989, Gardner 1992, Poulet et al 1992, Breuer et al 1994). Reported CEOTs have been between 1 and 3 cm in diameter and six of eight tumours for which location was provided were in the maxilla (Langham et al 1984, Abbott et al 1986, Walsh et al 1987, Gardner 1992, Poulet et al 1992, Breuer et al 1994, Ohmachi et al 1996). Most clinical descriptions indicate that the tumour appears very much like a squamous cell carcinoma (SCC); they are friable, ulcerated and often bleed easily. Interestingly some CEOTs are darkly pigmented (Abbott et al 1986, Walsh et al 1987), making them difficult to distinguish clinically from oral melanoma.
All epulides described in cats have been of the fibromatous or ossifying form. Affected cats have ranged from 5 to 17 years of age (Salisbury et al 1986, Carpenter et al 1987). There is considerable morphological variation in these tumours, ranging from pedunculated to sessile. Epulides may occur in the mandible (Carpenter et al 1987) or the maxilla (Stebbins et al 1989) and are usually less than 1.5 cm in diameter.
Other oral tumours have also been described in older cats which were termed ameloblastic fibroma (Mills & Lewis 1981, Quigley & Leedale 1983, Poulet et al 1992), keratinising ameloblastoma (Stebbins et al 1989), complex odontoma (Walsh et al 1987), odontogenic fibroma and odontogenic fibrosarcoma (Stebbins et al 1989) and odontoblastoma (Quigley & Leedale 1983). These tumours have been reported mostly in older male cats. The histological distinction between these tumours and CEOT or IFA may be clinically artificial. The treatment data for these cats are very similar to those obtained for cats with other odontogenic tumours (Quigley & Leedale 1983, Walsh et al 1987, Stebbins et al 1989, Poulet et al 1992).
With the exception of one cat that received a low dose of radiation, this treatment modality has not been reported for the treatment of odontogenic tumours or epulides in cats. This report documents long-term tumour control in three cats treated with therapeutic doses of radiation therapy for odontogenic tumours.
Results
Case reports
All cats received orthovoltage radiation with a half-value layer of 2.9 mm Cu (cat 1) and 2.12 mm Cu (cats 2 and 3), using a single portal, in 12–13 fractions of 4.0 Gy to the skin surface, given three times a week. A bolus to provide backscatter or lateral scatter was not used in any of the three cats. Anaesthesia was induced and maintained using either ketamine (Ketaset; Fort Dodge, USA) and diazepam (Valium; Roche, USA), or propofol (PropoFlo; Abbott Labs, USA). Duration of anaesthesia for each treatment was between 4 and 7 min.
Cat 1 was a 5-month-old male domestic short-hair cat which was presented with a 2-month history of a rapidly growing mass in the left maxilla and facial deformity with deviation of the nose to the right. Screening blood work (complete blood count and serum chemistry profile) was unremarkable. The mass measured 3.5 × 3.5 × 4cm, and radiographically was an expansile destructive lesion in the maxilla, causing deviation of the nasal septum. Biopsy was consistent with inductive fibroameloblastoma. The tumour was ‘debulked’ and closed with a labial flap, 5 days prior to receiving 52 Gy of radiation therapy to a 5 × 5 cm field that included the surgical site. An abscess at the surgical site was noted after two doses of radiation, antibiotic therapy with amoxicillin/clavulate was instituted and radiation therapy was not interrupted. At the completion of radiation therapy, prednisone was prescribed at a dose of 1 mg/kg for 2 weeks following radiation for mild oral mucositis and serous nasal discharge believed to be due to the acute effects of radiation therapy. An artificial tear solution was used in the left eye until tear production was normal (3 months after radiation therapy). Forty-one months after completion of radiation therapy, the last two left maxillary molars were extracted due to enamel erosion and purulent gingivitis. At this time an early cataract was noted by the attending veterinarian. Sixty months after radiation, the cat had no further progression of the cataract and was still visual from the eye. There was hair coat colour change to the radiation field (white), but the cat was otherwise normal.
Cat 2 was a 15-year-old female spayed domestic shorthair cat which was presented with a painful, bleeding oral tumour on the buccal surface of the left maxilla that had been present for approximately 12 months. The tumour had been debulked using electrocautery 4 months prior to radiation but had not been biopsied and regrew rapidly. Screening bloodwork showed an elevated creatinine of 2.7 mg/dl (normal range=0.6–1.6 mg/dl), but was otherwise unremarkable. The tumour measured 1.5 cm in diameter and was biopsied, but no attempt at resection was made. The biopsy was consistent with a CEOT. Commencing 8 days after biopsy, the cat received 48 Gy of orthovoltage radiation using a 2.5 cm cone centred on the tumour. Subcutaneous fluids (lactated Ringer's solution) were administered daily during anaesthesia and radiation treatment. By the last treatment the tumour had reduced by approximately 30%, but was still present. The tumour continued to shrink, according to the owner and referring veterinarian, but the cat was not presented for follow-up evaluation except to the referring veterinarian. Thirty-five months later the cat was presented to the referring veterinarian with a mass behind the left eye. It was also blind. Euthanasia was performed and necropsy was not permitted.
Cat 3 was an 8-year-old castrated male domestic shorthair cat presented because the owners had noticed a 3-mm ulcerated area on the gingiva above the right maxillary incisors. Screening bloodwork disclosed an elevated creatinine of 2.1 mg/dl with an urinary specific gravity of 1.031. Surgical excision was attempted, but was incomplete histologically Biopsy disclosed a hypercellular to dense connective tissue containing multiple foci of osteodentin material suggestive of an epulis. Commencing 23 days after surgery, the cat received 48 Gy of orthovoltage radiation therapy using a 2-cm bevel cone centred on the surgical site. The cat had no acute radiation toxicities except for hair loss, and 39 months after completing radiation has no evidence of tumour recurrence, no ocular problems and the hair coat has returned to its normal colour after initially regrowing with white pigmentation.
Discussion
Radiation therapy has been very effective for the treatment of odontogenic tumours in dogs. Between 70 and 85% of dogs with acanthomatous epulis treated with radiation therapy showed tumour regression, or had no recurrence after surgery for longer than 1 year (Thrall 1984, Théon et al 1997). Dogs with ameloblastoma (adamantinoma) also had an average of 2-year control following radiation therapy (Langham et al 1977, Dubielzig & Thrall 1982b).
Surgery has been the treatment of choice, particularly for small CEOTs and IFAs. However, localised excision may not be successful due to the high probability of bony invasion. In nine cats with IFA treated surgically, there was no recurrence in five between 6 months and 36 months after surgery (Dubielzig et al 1979, Walsh et al 1987, Poulet et al 1992, Dernell & Hullinger 1994). Local recurrence was seen in the remaining four cats, and in three of these recurrence was seen within 2–6 weeks of surgery (Dubielzig et al 1979, Walsh et al 1987). Recurrence was seen 42 months after surgery in the fourth cat (Poulet et al 1992). Those three cats with early recurrence were treated a second time by surgery either alone or with radiation therapy; one cat had no recurrence 5 years later, while another had a second recurrence 6 months later, but then the tumour remained static for 3.5 years (Walsh et al 1987). A very low dose (15 Gy) of radiation failed to prevent a second recurrence 10 months later in the third cat (Dubielzig et al 1979). The prognosis following surgery for CEOT appears to be cautiously optimistic. In four of the six cats treated surgically, and with adequate follow-up, there was no evidence of disease between 7 months and 2.5 years after surgery (Abbott et al 1986, Walsh et al 1987). Tumour recurrence was seen 13 and 17 months after surgery in the two other cats, respectively (Langham et al 1984, Poulet et al 1992). Radiation therapy is not reported as a treatment modality in cats with CEOT.
In cats the only documented radiation treatment of an odontogenic tumour used what should be considered an inadequate dose (15 Gy), and this failed to control tumour regrowth. The cats in this report received between 48 and 52 Gy of orthovoltage radiation. All three cats had hair loss within the radiation field, but only one of the cats showed evidence of oral mucositis. None of the cats lost weight during treatment and appetite did not appear to be decreased in any cat. None of the cats developed the moist desquamation of skin within the field that is commonly seen in dogs treated with the same dose and schedule of orthovoltage radiation (Frimberger et al 1997). Radiation therapy was well tolerated by the clients and their cats.
The three cats reported here had three different types of oral tumour, and each had long-term control of their neoplasm (35, 39 and 60 months, respectively). Cat 2 developed a ‘tumour behind the eye’ 35 months after radiation and became bilaterally blind. Late tumour recurrence between 1 year and 18 months has been reported for CEOT following surgery (Langham et al 1984, Poulet et al 1992) and this may have been a recurrence of the original tumour; however, the histogenesis must remain speculative as a necropsy was not permitted.
Radiation therapy resulted in long-term tumour control in these cats. This modality should be considered as adjuvant therapy following incomplete surgery for IFA, CEOT and epulis, and could be considered as an alternative to radical surgery for the treatment of these tumours.