90Sr THERAPY FOR ORAL SQUAMOUS CELL CARCINOMA IN TWO CATS

KOICHI NAGATA, KIMBERLY A. SELTING, CRISTI R. COOK, METTA RENSCHLER, JIMMY C. LATTIMER

Two cats with a superficial oral squamous cell carcinoma responded favorably to treatment using a 90Sr probe.

From one to six fields were applied per tumor, depending on tumor size. The surface dose per treatment ranged

from 75 to 150Gy and the total surface dose ranged from 200 to 500Gy. Adverse effects were minimal. The

cats survived 7 months and 5 years 9 months from the time of diagnosis. These data indicate that with careful

patient selection 90Sr may be useful for the treatment of feline oral squamous cell carcinoma in some patients.

r 2010 Veterinary Radiology & Ultrasound, Vol. 52, No. 1, 2011, pp 114–117.

Key words: cats, oral squamous cell carcinoma, strontium.

Introduction

ORAL CAVITY TUMORS represent 10% of tumors diag-

nosed in cats, and approximately 90% of oral tumors

in cats are malignant.1 The most common feline oral tumor

is squamous cell carcinoma. Although sunlight increases

the risk of feline cutaneous squamous cell carcinoma, the

etiology of feline oral squamous cell carcinoma is un-

known.2 There was a twofold increase in squamous cell

carcinoma in cats exposed to environmental tobacco

smoke in one study.3

Squamous cell carcinoma occurs most frequently in older

cats, with a mean age of 10.3 years.1 The most common

clinical finding in cats with oral squamous cell carcinoma is

a mass or facial asymmetry, followed by ptyalism, anorexia,

sneezing, nasal discharge, pawing at the mouth, changes in

eating habits, oral hypersensitivity, loose teeth, dysphagia,

weight loss, and halitosis .4,5 Common physical examina-

tion findings include mucosal ulceration, necrosis, and

severe suppurative inflammation.1 Treatment is challenging

because most oral squamous cell carcinomas are invasive at

the time of diagnosis. Most cats die of local disease, and

death due to metastasis is unusual. Median survival of cats

treated with mandibulectomy and radiation therapy was 14

months.6 Median survival with single modality treatment

was 3 months, whereas some improvement was achieved

using various combinations of surgery, radiation, and/or

chemotherapy.5,7–11 However, in general, the prognosis for

cats with oral squamous cell carcinoma is guarded to poor

regardless of type of treatment.

Plesiotherapy, which involves the direct application of a

radiation source to a tumor, is effective for shallow lesions

because the radiation dose drops off significantly below

depths of 2mm.12–14 Strontium-90 (90Sr) has been used for

plesiotherapy, 90Sr in secular equilibrium with its daughter

product Yttrium-90, emits b rays with endpoint energies

0.546 and 2.27MeV, respectively. The half-life of 90Sr is be

between 27.7 and 28.4 years. For plesiotherapy, the 90Sr

source is attached to the end of a rod in a sealed reservoir,

then positioned over the tumor. The use of 90Sr applicators

has been described for feline squamous cell carcinoma of

the nasal planum, canine limbal tumors, feline mast cell

tumors, and uropygial tumors of birds.14–20 Complete re-

sponse rates of 73% and 90% have been reported for

squamous cell carcinoma of the nasal planum in cats

treated with 90Sr.14,15 Side effects are generally mild and

infrequent, however, when limbal melanoma was treated in

combination with surgery, 50% acute side effects, such as

corneal scarring, corneal neovascularization, conjunctivitis,

and keratopathy, and 20% late side effects, such as deep

sclera thinning and focal scleromalacia, were seen.15,18,19

We hypothesized that 90Sr might be feasible for treating

small oral squamous cell carcinoma in cats.

Herein, we describe the response to 90Sr treatment

for two cats with oral squamous cell carcinoma. The ap-

plicator� had a circular active diameter of approximately

8mm.

Case History Descriptions

Cat 1

A 11-year-old domestic longhair cat had bilateral ulcer-

ated hard palate squamous cell carcinoma without bone

involvement. The right lesion was 1 cm long and had a

cavity within the ulceration. The left lesion, which was

smoother and more superficial, measured 0.25 cm by 0.5 cm.90Sr radiation therapy was performed using 100Gy per field.

There was some field overlap. The dose rate at this time

was 8032 cGy/min. Two treatments were given, 1 weekAddress correspondence and reprint requests to Koichi Nagata, at the

above address. E-mail: knagat@hotmail.comReceived April 6, 2010; accepted for publication June 22, 2010.doi: 10.1111/j.1740-8261.2010.01731.x

From the Department of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211.

�RA-2A Medical Applicator, Tracerlab Inc., Waltham, MA, USA

114

apart. The larger right lesion worsened slightly and the

smaller left lesion improved between treatments. Two

weeks later no evidence of tumor progression was noted

grossly or in CT images and a third treatment was

performed using four fields, to deliver 75Gy to the tumor

surface per field. A fourth treatment was performed 1 week

later and consisted of a single field; 75Gy was administered

per field to the tumor surface. Approximately 7 weeks after

the fourth 90Sr treatment, a 1-cm-diameter mass was found

on the left caudal mandible. Areas of mandibular lysis and

proliferation were apparent radiographically. The hard

palate lesions had resolved completely.

The mandibular lesion was also diagnosed as squamous

cell carcinoma. A left mandibulectomy was performed.

Mitoxantrone and piroxicam treatments were initiated

30 days after surgery. Mitoxantrone treatments were

repeated every 3 weeks for four cycles and piroxicam was

given daily. Piroxicam was changed subsequently to a

Monday, Wednesday, and Friday schedule due to devel-

opment of mild azotemia. At 21 months after the first 90Sr

treatment, the owner noted a red lesion on the right hard

palate. The lesion, which was considered an in-field recur-

rence, was given a fifth 90Sr treatment, which corresponded

to 150Gy per field at the surface. At this time, the total

surface dose to the palate lesions from all 90Sr treatments

was estimated to be 500Gy.

Ten days after the fifth treatment the lesion was smaller

but at 2 months the lesion was larger. Cytologically, nor-

mal keratinocytes were identified so the lesion was treated

as mucositis. One month later, the lesion was slightly larger

and much redder and measured 1mm thick in CT images.

The lesion was presumed to be a radiation related side

effect, and the owner continued to treat the lesion sup-

portively. The palate lesion resolved in 2 months.

Two and a half years later, approximately 4.5 years from

the initial diagnosis of squamous cell carcinoma, the cat

experienced dramatic weight loss and piroxicam was dis-

continued. Renal insufficiency caused by piroxicam was

suspected and daily fluid administration was initiated. Five

years and 9 months following the initial diagnosis, the cat

sustained a spinal injury and underwent euthanasia. A

postmortem examination was not performed.

Cat 2

A 12-year-old mixed breed cat had a sublingual ulcer-

ated mass in the frenulum, which measured approximately

1.5�0.7 cm laterally and 0.6 cm thick. The mass, which did

not invade the tongue or intermandibular space, was di-

agnosed histologically as a squamous cell carcinoma.

Strontium treatment was performed approximately 3

weeks later. The 90Sr probe was applied to six sites with

the administration of approximately 100Gy per site. Some

overlap existed to treat the entire tumor. The dose rate of

the applicator at this time was about 8374 cGy/min. In-

creased drooling was noted approximately 1 week later,

and lasted approximately 2 weeks. The lesion almost com-

pletely regressed within 1 month of treatment. The tumor

was lighter in color than the surrounding tissues but was

smooth and intact. The response to initial treatment lasted

at least 6 weeks. The second treatment was performed ap-

proximately 7 weeks after the first and consisted of appli-

cation of three sites on the frenulum. Approximately

100Gy was administered per site. About 2 months later,

the cat began to hypersalivate. Tumor recurrence was

noted at the dorsal aspect of the previously affected area,

along the dorsal frenulum and ventral aspect of the tongue.

No further treatment was administered. About 6 weeks

later the tumor was larger and would hemorrhage after

eating. The cat was euthanized 40 days later and a nec-

ropsy was not performed.

Discussion

A total of three squamous cell carcinomas in two cats

responded favorably to 90Sr therapy. The tumors in cat 1

were controlled longer than the tumor in cat 2. This may be

due to the more superficial nature of the tumors in cat 1,

the higher total dose, or differences in radiation sensitivity

between tumors. Survival from the time of diagnosis, 5

years 9 months in cat 1, and 7 months in cat 2, are longer

than the 3-month survival time of most cats with oral

squamous cell carcinoma treated with a single modality.5,7–11

Because 90Sr has only superficial penetration, small, early

detected lesions are more likely to respond.

Side effects associated with 90Sr in these cats were mild

and the therapy was generally well tolerated. Cat 1 devel-

oped a superficial erythematous lesion with thickness and

ulceration, which was characterized by normal keratin-

ocytes on cytology. This may be a late side effect. The cat

did not seem affected clinically by this lesion.

Interestingly, cat 1 developed three squamous cell car-

cinomas in different locations in the mouth. This may be

explained by field cancerization, a theory first proposed in

1953 when analysing histologically abnormal tissue sur-

rounding oral squamous cell carcinoma .21 Since then, the

term field cancerization has been used to describe the

phenomenon by which an entire field of tissue develops

malignant or premalignant change in response to a car-

cinogen. Organ systems in which field cancerization has

been described are: head and neck, lung, esophagus, vulva,

cervix, colon, breast, bladder, and skin.22–31It is possible

that grooming and ingestion or inhalation of environmen-

tal carcinogens may have resulted in field cancerization in

the cat 1.

The number of cats in this study is small, and the cats

were not evaluated in a standard way nor were they mon-

itored uniformly. Also, the dose and number of treatments

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differed between the cats. Modalities other than strontium

were also used in one cat; for example, mitoxantrone and

piroxicam.

The radiation dose used in human patients with head

and neck squamous cell carcinoma ranges from 60–72Gy,

typically in 1.5–2Gy fractions.32,33 An accelerated radia-

tion protocol for feline oral squamous cell carcinoma (n¼ 9

cats), using 14 fractions of 3.5Gy in 9 days, resulted in

median overall survival of 3 months.34 The optimal dose of90Sr for treatment of feline oral squamous cell carcinoma is

unknown. The surface dose per treatment ranged from

75Gy to 150Gy, which corresponds at 2mm depth to ap-

proximately 22 and 44Gy, respectively.14 The total surface

dose ranged from 200 to 500Gy This dose was determined

arbitrarily based on a typical human stereotactic radiosur-

gery protocol for the treatment of vestibular schwannomas,

which involves 12–16Gy per treatment.35 Currently, our

goal is to deliver 150Gy at the surface per treatment (or

44Gy at the depth of 2mm), which is based on doses used

for treatment of feline nasal planum squamous cell carci-

noma, which were 128Gy at the surface15 and 50Gy at

2mm depth.14

Both cats reported here responded favorably to 90Sr

therapy. Because of the unique properties of 90Sr, which

includes rapid dose falloff with depth, and because of the

invasive nature of feline oral squamous cell carcinoma, 90Sr

is rarely considered for cats with this disease. However, the

cats described in this report illustrate that 90Sr may be a

useful alternative for small superficial lesions o3mm in

thickness without bone involvement.

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