Feline squamous cell carcinoma

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Among the most common malignant cancers of cats, and the most common head and neck cancer, feline squamous cell carcinoma (SCC) has a wide range of survival expectations and treatments. The neoplasm tends not to produce distant metastases, but is highly invasive, and, especially in the mouth cavity, can interfere with quality of life. It can occur on the nose and is much more treatable there than in the mouth.

Early diagnosis is key. A biopsy is necessary. If there is a clinical suspicion during the surgical biopsy that SCC is likely, it can be extremely useful to get a CT scan while under the same anesthesia. This is likely to be needed for radiation treatment planning, but having CT images from the same time as the biopsy is not simply "documenting the lesion", but is useful in other aspects of continuing treatment.

Etiology

Canned food (RR = 3.6; P =.014), and independently specifically tuna intake (RR = 4.7; P =.004), as well as exposure to flea collars (RR = 5.3; P =.002) increased the risk of SCC, but without P53 overexpression. This study found environmental tobacco smoke to be a lower risk factor (P = .11). [1] P53 gene overexpression has been reported in cats exposed to environmental tobacco smoke. [2]

Pathology

The World Health Organization has defined a staging system for feline tumors of epidermal origin:[3]

  • T
    • T0: no evidence of tumor
    • Tis: tumor in situ
    • T1: tumor < 2 cm in diameter
    • T2: 2-5 cm in diameter or minimally invasive
    • T3: Tumor > 5 cm in diameter or invading subcutis
    • T4: Invading fascia, muscle or bone
  • N
    • N0: Absence of lymph node metastasis
    • N1: Presence of lymph node metastasis
  • M
    • M0: Absence of distant metastasis
    • M1: Presence of distant metastasis

Treatment

Detected very early, the tumor may be removable by surgery, but, in most cases, it is inoperable yet the surgery allows a definitive histopathological diagnosis.

Assuming the owner authorizes active treatment, the first steps are radiation or radiation coupled with chemotherapy, followed by additional cycles of chemotherapy and possibly additional radiation. The owner's decision can be difficult; some cats will not respond at all to what may be quite expensive therapy, but others may have significant life extension with good quality of life.

Radiation

Basic palliative radiotherapy uses multiple doses, commonly over four weeks. Protocols that have been used monday-wednesday-friday schedule, [4] hypofractionated radiotherapy [5] and accelerated radiotherapy protocols.[6] "A hypofractionated protocol has lower financial costs, greater convenience and fewer anesthesia procedures needed...Although hypofractionation has advantages, including greater convenience and lower cost, it allows tumor repopulation."[7] A small study (i.e., 9 cats) of an accelerated protocol has been described, which used twice-daily treatments for 7 of 9 days. The authors observe SCC is relatively resistant to radiation, the reasons for which may include:

  1. Hypoxic cells within the tumor, which are less sensitive to radiation than well-oxygenated cells
  2. Repopulation during extended course of radiation; it was reported that tumors can double in 5 days,[8]

Antineoplastic agents

Bleomycin and carboplatin are the most common adjuvant and palliative antineoplastic agents. As with any cancer chemotherapy, the challenge is managing the toxicity. Weekly complete blood counts are a standard of care, as, of course, the owner's observations about the cat's activity and moods.

Bleomycin is given as a weekly subcutaneous injection. There are guidelines for maximum lifetime dosage, but they may be exceeded based on the condition and response of the cat. It is less myelosuppressive than carboplatin, but pulmonary fibrosis is a feared side effect.

Carboplatin is administered intravenously every 3 to 4 weeks. Its use is off-label and the dose is still being optimized. [9] In general, a new treatment is not started until the leukocyte, and especially neutrophil, counts return to normal.

Combined chemotherapy has been explored in early trials, and, while theoretically promising, is not yet within the standard of care. [10] Mitoxantrone may be administered with bleomycin or as a sole drug.

Role of NSAIDs

Some of the tumors express cyclooxygenase-2, so a selective NSAID, such as meloxicam, offers both pain relief and the potential to reduce the inflammation of a tumor. Unfortunately, these agents also can cause life-threatening gastrointestinal bleeding. Misoprostol has not been useful as a prophylactic drug, as its overall effects on prostaglandins cause severe side effects. It is not standard practice to administer them with a prophylactic proton pump inhibitor or histamine H2 antagonist.

Experimental treatments

There is substantial research in protocols using specialized radiotherapy, (e.g., plesiotherapy) which have substantially extended life. Plesiotherapy is the short-duration external application of a radiation source, as opposed to brachiotherapy that implants the source, has showed some promise. In a study of 90strontium with 16 cats who had SCC of the nose, 11 had complete response (i.e., no visible tumor for 6-8 weeks), 2 cats with partial response, and 2 cats with partial response who were withdrawn from the study. Survival ranged from 134 to 2043 days (median 652). This method does not penetrate deeply and is less likely to help highly invasive tumors.[11]

Various studies have used electric stimulation, hyperthermia and hyperbaric oxygen as a supplement to chemotherapy or radiotherapy.[12] Photosensitization and photodynamic therapy is being explored.

Quality of life

The tumor itself may not be painful; the concern, especially in oral cancers, is that it interferes with eating or breathing.

Scrupulous mouth and wound cleaning help. If your'e very lucky and have a cat that was trained to a toothbrush, this may help. Otherwise, cotton balls, makeup sponges, or quilted cotton makeup pads, wetted with 3% hydrogen peroxide, can help. Dab, don't rub, and some scabs will break loose.

The cat may suffer pain after manipulation of the tumor for examinations or oral medication, or perhaps by trauma (e.g., while eating). Pain management is a challenge in cats, due to their intolerance of many opioid analgesics. Gabapentin can provide baseline pain relief. Buprenorphine, orally, in the buccal cavity, or subcutaneously is useful for breakthrough pain.

As with a wide variety of cancers, cachexia is common even if there is no mechanical problem with eating.

Complications

Especially when radiation or carboplatin are in use, the patient's defenses to infection are reduced. The tumor itself can predispose to infection.

References

  1. Bertone ER, Snyder LA, Moore AS (2003), "(abstract) Environmental and lifestyle risk factors for oral squamous cell carcinoma in domestic cats", J Vet Intern Med 17 (4): 557-562
  2. L. A. Snyder, E. R. Bertone, R. M. Jakowski, M. S. Dooner. J. Jennings-Ritchie, A. S. Moore, "p53 Expression and Environmental Tobacco Smoke Exposure in Feline Oral Squamous Cell Carcinoma", Veterinary Pathology 41 (3): 209-214, DOI:10.1354/vp.41-3-209
  3. Owen LN. TNM Classification of Tumors in Domestic Animals. World Health Organization, 1980
  4. The´on AP, Madewell BR, Shearn V, Moulton JE. Prognostic factors associated with radiotherapy of squamous cell carcinoma of the nasal plane in cats. J Am Vet Med Assoc 1995; 7: 991e6
  5. Kinzel S, Hein S, Koch J. Hypofractionated radiation therapy for the treatment of malignant melanoma and squamous cell carcinoma in dogs and dats [abstract]. Berl Munch Tierarztl Wochenschr 2003; 3e4: 134e8.
  6. Melzer K, Guscetti F, Bley CR, Sumova A, Roos M, Kaser- Hotz B. Ki67 reactivity in nasal and periocular squamous cell carcinomas in cats treated with electron beam radiation therapy. J Vet Intern Med 2006; 20: 676e81.
  7. Simone CS Cunha et al. (2010), Radiation therapy for feline cutaneous squamous cell carcinoma using a hypofractionated protocol, DOI::10.1016/j.jfms.2009.10.005, at 306-313
  8. JL Fidel, RK Sellon, RK Houston, BA Wheeler (23 August 2007), "A Nine-Day Accelerated Radiation Protocol for Feline Squamous Cell Carcinoma", Veterinary Radiology & Ultrasound 48 (5): 482-485
  9. Kisseberth WC, Vail DM, Yaissle J, Jeglum KA, Couto CG, Ward H, Khanna C, Obradovich JE (2008), "Phase I clinical evaluation of carboplatin in tumor-bearing cats: a Veterinary Cooperative Oncology Group study.", J Vet Intern Med 22 (1): 83-8
  10. Martinez-Ruzafa I, Dominguez PA, Dervisis NG, Sarbu L, Newman RG, Cadile CD, Kitchell BE (2009 May-Jun), "(Abstract) Tolerability of gemcitabine and carboplatin doublet therapy in cats with carcinomas.", J Vet Intern Med 23 (3): 570-7
  11. Mark Goodfellow et al. (June 2006), "A retrospective study of 90Strontium plesiotherapy for feline squamous cell carcinoma of the nasal planum", Journal of Feline Medicine & Surgery 8 (3): 169-176, DOI:10.1016/j.jfms.2005.12.003
  12. Enrico P. Spugnini et al., "(Abstract) Electrochemotherapy for the treatment of squamous cell carcinoma in cats: A preliminary report", The Veterinary Journal 179 (1): 117-120, DOI:10.1016/j.tvjl.2007.08.011