Michael S. Kent, MAS, DVM, DACVIM (Oncology), DACVR (Radiation Oncology)
Side effects of radiotherapy can be broken down in to acute and late effects. Acute effects most commonly occur part way through therapy and often resolve several weeks after therapy is finished. They most commonly are treated symptomatically and while they can impact quality of life they are generally self-limiting. Late effects on the other hand are side effects that occur months to years later and are generally more serious in nature and often life threatening.
Acute effects on the brain can include edema and often patients are placed on prednisone (0.5mg/kg PO q24 hrs) to help with this during therapy. Treatment is generally continued for several weeks after therapy with a slow taper. If a patient does have deteriorating neurological signs then mannitol treatment may help (1gm/kg IV). Brain necrosis is reported side effect of radiation therapy that is more likely to occur with higher dose per fraction protocols.1 Once there is brain necrosis treatment is generally not effective. Second tumors are also a risk of radiotherapy.
Whenever the eyes are included in a radiation field the vast majority of patients will develop acute and late effects. The most common acute side effects seen include conjunctivitis, keratoconjunctivitis sicca (KCS), corneal ulceration, and anterior uveitis. Late effects include KCS retinal hemorrhage and cataract formation.2 Cataract formation is a common late effect if the lens is included I the radiation field and will generally occur with one year. In general treatment is the same as if the condition were not caused by radiation. It is important to manage these side effects aggressively or loss of the eye can result. As these are common sequelae patients should be monitored regularly, particularly for tear production.
The most common side effect from irradiating the mouth is mucositis. This is inflammation of the mucosal surfaces. Mucositis will often start by the second week of therapy in patients receiving full course radiotherapy. It ranges from mild erythema mimicking a thermal food burn to having a fibrinous exudate, to severe ulceration. As this can be painful analgesics should be strongly considered. NSAIDS or tramadol can be very effective in treating this. Antibiotic therapy with amoxicillin clavulanic acid, metronidazole or clindamycin should also be started once mucositis starts to avoid and treat secondary infection. Oral rinses with lidocaine based mouth flushes are also commercially available, or compounded at a local pharmacy. They generally contain viscous lidocaine, diphenhydramine and Maalox.
Before beginning a course of radiation dental cleaning and any needed tooth extractions should be done. This will decrease the chance of bad late effects secondary to dental disease and bone necrosis (see below).
If the lung has to be included in a radiation field then radiation pneumonitis may be seen as an acute effect.3 This is generally seen 2-3 months after radiation and can be seen on radiographs. Cough may be seen in patients with radiation pneumonitis, but they can also be asymptomatic so it is important to monitor patients for this if lung has been included in the radiation field. Treatment with anti-inflammatory doses of prednisone (0.5 mg/kg PO q 12-24hrs) may help relieve clinical signs and reduce inflammation. Left untreated this may progress to fibrosis, which is not easily treated, and may require lung lobectomy.
Skin effects of treatment are some of the most concerning for owners. Acute effects of the skin are often seen toward the end of therapy in patients receiving full course radiotherapy. They actually reach their height about 7-10 days after radiotherapy has finished and take several weeks in total to resolve. The initial signs seen include a mild erythema of the skin which usually starts about half way through therapy and slowly progresses. The reaction then often progresses to dry desquamation, which is characterized by scaling of the skin. As the reaction progresses further we then see moist desquamation with edema and a fibrinous exudates forming. In severe cases ulceration secondary to necrosis is possible. Generally light skinned animals start their reaction earlier in the course of therapy than dark skinned animals. Cats are more likely to have dry desquamation and dogs are more likely to develop moist desquamation as their most severe reaction.
Skin reactions tend to be worse in areas of skin folds and where the skin is more susceptible to becoming moist such as ear canals and feet. If the ear canal is to be included in the radiation field then the ears should be cleaned regularly with saline and any underlying infections treated. On the feet dogs will often lose their pads, which can be painful. We often recommend that dogs wear booties to help protect their pads. During the worst of the reaction we will often bandage the affected foot using non-adherent type bandage material. It can take several months for the pads to grow back.
Discomfort and pruritus is usually associated with these acute skin effects. Prednisone can be used to help reduce inflammation (0.5mg/kg). Tramadol (2-4mg/kg PO TID-QID) can be used as effective analgesic as well. In severe cases fentanyl patches can be used.
It is important to keep the radiation area clean during treatment and the immediate post radiotherapy period in order to help avoid infection. Further we place dogs on a prophylactic course of antibiotics (cefpodoxime proxetil or cephalexin) starting half way through therapy and continuing at least until the two-week recheck. In cases of severe moist desquamation silver sulfadiazine creams can be used. Aloe vera gel can also be used in dry and moist desquamation.
Generally we do not recommend bandaging the radiation area if at all possible. Bandaging can cause further trauma to the tissue. The patients themselves can exacerbate the skin effects by either licking or scratching at the wound. E-collars or T-shirts, depending on the location, can be quite effective in helping to prevent this and are often required for several weeks.
If treating a skin or subcutaneous lesion, the hair in the field is shaved at the start of therapy, which will help not only with patient positioning, but also wound management later. Loss of hair or epilation will occur commonly in radiation fields. This is especially true with higher doses used in definitive protocols but also can be seen in some cases treated with palliative courses. Depending on the patient and the severity of their reaction, most dogs and almost all cats will grow their hair back in the radiation field. It will generally grow back in thinner and either grey or white in color. It can take up to 6 months after finishing radiation therapy to see hair growth. Owners should be warned to protect the area from excessive sun exposure as this can lead to sunburn. The area can be covered or if possible a pediatric sunscreen can be applied to the area.
Osteoradionecrosis is the death of bone in a site of radiation therapy. It is a late effect and can either be spontaneous or secondary to trauma because of a limited ability to repair the damage after it is irradiated. The main causes are hypocellularity of the tissue, hypoxia due to decreased blood supply. In people this most commonly occurs in the oral cavity. Treatment is difficult and requires surgical removal of the non-viable bone and closure of the overlying mucosa. In severe cases fracture is possible as well which will be difficult to repair or if on an extremity may require bone grafts and plating or amputation. It is important to differentiate this from tumor recurrence as they may look similar on radiographs.
Risk of Second Tumor Formation
Radiation is an effective carcinogen. Since it is a DNA damaging agent it is possible for it to either deactivate a tumor suppressor gene or activate an oncogene. There are no histologic differences between spontaneously occurring and radiation induced tumors. A tumor is classified as a radiation induced tumor if it meets the following criteria: The patient was previously irradiated in the area where the new tumor arose, the tumor is of a different histology than the original tumor (to distinguish it from local recurrence) and there is a latency period of at least five years. As these criteria were developed for humans the latency period may be too long for our patients. In people, the use of orthovoltage is associated with an increased risk of developing a radiation-induced tumor. This is due to the increased absorption of dose to bone.
The risk of developing a radiation induced sarcoma is 0.035-0.2% in people. The incidence has not been well documented in veterinary medicine and may be lower as our patients may not live long enough to develop a radiation induced tumor. Most commonly, radiation induced tumors are sarcomas with fibrosarcomas and osteosarcomas being the most common types in dogs. There are several case reports and series documenting suspected radiation induced tumors in dogs.4,5 In humans there is also an increased risk for developing leukemias and brain tumors after receiving radiotherapy.
Patients with radiation-induced tumors should be staged and treated as any other patient with that type of cancer.
1. Brearley MJ, Jeffery ND, Phillips SM, et al. J Vet Intern Med 1999;13:408-412.
2. Roberts SM, Lavach JD, Severin GA, et al. J Am Vet Med Assoc 1987;190:43-47.
3. McEntee MC, Page RL, Cline JM, et al. Vet Radiol Ultrasound 1992;33:190-197.
4. McEntee MC, Page RL, Theon A, et al. Vet Radiol Ultrasound 2004;45:357-361.
5. Dickinson PJ, McEntee MC, Lipsitz D, et al. Vet Radiol Ultrasound 2001;42:463-470.