Barbara Kaser-Hotz, Dr.med.vet., Dr. habil., DACVR (Radiology and Radiation Oncology), DECVDI
The management of carcinomas plays an important role in veterinary medicine. The biologic behavior differs from species to location of the tumor. Interestingly, squamous cell carcinoma of the nasal planum in a cat is treated with good success and high cure rates, whereas the same histology, and same size tumor at the base of the tongue is thought to be almost untreatable.
As treatment option, surgery is used to achieve local tumor control. Radiation can be administered as a sole treatment option when surgery is not possible or in an adjuvant setting before or after surgery. The fractionation protocol appears critical in these tumors. Combining radiation with chemotherapy is common practice in advanced head and neck tumors in humans. There is currently increased evidence that this might also be true for the aggressive squamous cell carcinomas in cats.
Head and Neck Cancer in Humans
Squamous cell carcinoma in humans is common and thought to be induced by smoking, heavy alcohol use etc. Patients can be cured with aggressive treatment. Typically, radiation follows surgical removal of the tumor and in many instances, radiation is combined with cisplatin. Large controlled clinical trials have been done, exploiting fraction size, overall treatment time and response of normal tissue, and it seems useful to learn from these trials also for the management of animal patients. It is now well known that the doubling time of oral squamous cell carcinomas in people is in average 4 days. Therefore, killing of cells has to be achieved by rapidly applying the radiation dose, an option called accelerated radiation therapy. However, side effects will increase dramatically, when the same dose is given over a shorter period of time. Therefore, the dose per day is divided into two or three fractions, and this method is referred to hyperfractionated radiation. In humans, the EORTC 22791 trial showed an increase of local tumor control from 40 to 59% at 5 years; this is a tremendous advantage by simply altering the fractionation protocol, and dramatically points out the importance of a simple factor such as "treatment time". As many of these tumors experience acute and chronic hypoxia, further improvement was achieved by adding nicotinamide and carbogen breathing to overcome hypoxia. Further, a strong synergy with radiation was shown when EGFR receptor dimerization and tyrosine kinase phosphorylation were blocked using targeted therapy. There is enough evidence in veterinary medicine that the same parameters may play a role, and therefore, the therapeutic concepts could be adapted further also in veterinary medicine
Carcinomas in Cats
Squamous cell carcinoma of the nose and eyelid has been treated with radiation and the results are favorable. A twice per day fractionation protocol was developed empirically for cats, applying the dose within originally 4 days, and now commonly in 5 days. It is important to keep the time between the two fractions 6 hours apart in order to allow repair of sublethal damage to normal tissue. Cats and their owners appreciate the short hospitalization time. One main drawback is anemia, which is often preexisting and is further aggravated by the multiple anesthesias. Hypoxic cells are less radioresponsive and biologically more aggressive.
Oral carcinomas in cats are much more difficult to manage and even so, metastatic potential is not high, cats are lost shortly after diagnosis, usually due to local failure. Even when surgery, radiation and low dose chemotherapy were combined in cats with tumors of the tongue and pharynx, median survival was 3 months. The prognosis appears better when tumors are located in the mandible and mandibulectomy combined with aggressive radiation therapy resulted in longer survival.
Another promising approach was the use of radiosensitizing agents, such a gemcitabine or etanidazole in combination with radiation. Chemotherapy alone does not appear to be effective, as well as large doses of radiation are inappropriate.
Further combined studies, including targeted therapy, chemo-radiation, with hyperfractionated therapy, need to be exploited to hopefully improve tumor control and survival.
Oral Carcinomas in Dogs
Unlike the cats, oral carcinomas in the dog are curable in many situations. Surgery is the treatment of choice in completely resectable tumors. Local tumor control was better with smaller tumors. Radiation therapy is effective in controlling these tumors, either in an adjuvant setting or a sole treatment modality. Rostral tumor location has been the most important prognostic factor. Piroxicam may induce tumor response, but is usually short lasting. Better results are reached when Piroxicam is combined with cisplatin or carboplatin. Cisplatin appears to be more effective but has more side effects (renal).
Carcinomas of the Nose in Dogs
Unlike in the cat, nasal planum carcinoma in the dog is not responsive to radiation. Due to severe side effects, the rapid application of the total dose is not easily done in dogs. As of today, cure can only be achieved with aggressive surgery. Carcinomas of the nasal passages are treated routinely with radiation therapy. Best results are reached when a) carcinomas are well differentiated and b) when the tumor is small and located unilaterally and not invading the brain, and c) high doses can be given to the tumor by conforming the dose to the tumor making use of modern treatment planning systems.
Carcinomas in Other Locations
With improved radiation techniques, it becomes possible also in veterinary medicine, to create a treatment plan for carcinomas in other body locations, such as transitional carcinomas of the urethra, pulmonary carcinomas, prostatic carcinoma etc. The best results are expected to be seen, when surgery, radiation and medical therapy are combined. The timing of the individual treatment modality however is a challenge and needs to be further defined. In human medicine, there is evidence in head and neck cancer, that preoperative radiation therapy is advantageous in bulky disease, and chemotherapy is followed after the gross tumor mass is removed surgically.
RT: Dose given in a week.
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