Radiotherapy in dogs and cats: price, indications, side effects

Radiotherapy for dogs and cats

Radiotherapy is a therapeutic procedure that uses ionizing radiation to kill cells, and is often part of the treatment of various types of cancer. Application oncological radiotherapy supplements surgical and systemic procedures (chemotherapy, immunotherapy) in the treatment and control of neoplasms.

Although some tumors are treated with only one of these treatments, many cancers, both malignant and benign, are best treated with a combination of these treatments. The recommendations for radiotherapy depend, among other things, on the type of tumor and its location. It should be noted that Radiotherapy is not a universal option for all types of cancer. It should only be used when the benefits of treatment outweigh the potential costs. Each type of cancer is always tested to determine the most effective combination of treatments (surgery, chemotherapy and / or radiation therapy). Based on these studies, the veterinarian makes recommendations for the optimal treatment of a specific tumor in a given animal.

• What is radiotherapy?
• Irradiation methods
  • Radiation from a distance with external beams - teleradiotherapy
  • Irradiation from the inside - brachytherapy (introducing the radiation source inside the patient's body)
  • Systemic radiotherapy
• What is the radiation dose?
• How is radiation delivered?
• What is radiotherapy in veterinary used for?
  • Cancer radiotherapy
• Types of techniques and types of planning in radiotherapy
  • Conventional radiation therapy (CFRT)
  • Intensity Modulated Radiation Therapy (IMRT)
  • Three-dimensional conformal radiotherapy (3D-CRT)
  • Stereotactic radiation (SRT)
  • Dynamic adaptive radiotherapy (DART) or planned adaptive therapy
  • Image Guided Radiotherapy (IGRT)
• How does radiation therapy work in dogs and cats?
• Imaging
  • Treatment planning
  • Preparation and delivery of radiation
• Types of cancer treated with radiation therapy
  • Soft tissue sarcomas
  • Post-injection sarcoma in cats
  • Mast cell tumor in dogs
  • Nose tumors
  • Oral tumors
  • Melanoma
  • Oral fibrosarcoma
  • Squamous cell oysters
  • Squamous cell carcinoma
  • Tumors of the brain, pituitary gland and spinal cord
  • Brain Tumors
  • Pituitary tumors
  • Spinal cord tumors
  • Other tumors
  • Histiocytic sarcoma (HS)
  • Osteosarcoma (osteosarcoma)
  • Anal adenocarcinoma and anal gland adenocarcinoma
  • Tumors of the genitourinary system
  • Thyroid tumors
  • Thymoma
  • Lymphoma
• Adverse Effects of Radiotherapy in Dog and Cat
  • Types of radiation effects
  • Overview of the side effects of radiation
• How to prevent the negative effects of radiation therapy?
• Frequently asked questions about radiation therapy in animals
  • How effective is radiation therapy in dogs and cats?
  • What are the benefits of radiation therapy?
  • Does radiation therapy hurt?
  • Is the pet's isolation required after radiation therapy??
  • How much does radiation therapy cost for a dog and a cat?
  • Can radiotherapy in a dog or cat be performed in Poland??

What is radiotherapy?

In its simplest terms, radiotherapy involves exposing the tumor to a high-energy beam of x-rays multiple times for several days or weeks. Radiation works by damaging tiny proteins and DNA molecules, preventing replication and killing cells. Additionally - as a result of the ionization of tissues, highly reactive free hydroxyl radicals are formed, which secondarily damage the DNA. The idea is to eliminate cancer cells so that they can no longer divide and spread. However, since the radiation is not selective, it affects both normal and cancer cells. The main goal of radiotherapy is therefore to reach as many cancer cells as possible while avoiding damage to the normal surrounding tissue. This is the so-called maximizing the tumor effect and minimizing the effect of normal tissue. For this reason, radiation therapy is used as a series of many small doses administered at intervals of time. Often times, the tumor cannot be destroyed, but can be reduced in size so that surgery can be performed to remove the tumor. Radiotherapy is also used to reduce the clinical symptoms associated with cancer (e.g. bleeding, pain) and thus enable the animal to maintain a good quality of life.

Irradiation methods

The discovery and application of therapeutic radiation dates back to the end of the 19th century. Radiation therapy uses electromagnetic or molecular radiation and delivers beams of photons, electrons, or waves to damage the cell's DNA.

Various methods of irradiation are used to destroy cancer cells and at the same time save healthy tissue.

Radiation from a distance with external beams - teleradiotherapy

Machines that deliver radiation at a distance include ortovoltaic apparatuses and megavolt cameras. Ortovoltaic energy comes from an apparatus similar to the one used to produce diagnostic x-rays (X-rays) for humans and animals, but the energy is much higher. The radiation beams generated by these devices have limited penetration and are used to irradiate superficial tissues. As energy is absorbed more by some normal tissues than others, there are side effects on tissues such as bone and skin when treating cancer. For this reason, this procedure is not as widely used as megavoltage. Megavolt radiation comes from cobalt and linear accelerators. The advantage of this type of radiation is the ability to penetrate deep into the tissue and heal all parts of the tumor.

Irradiation from the inside - brachytherapy (introducing the radiation source inside the patient's body)

Brachytherapy consists in the temporary or permanent introduction of radioactive sources into the tumor. This type of treatment has been used in veterinary medicine, but apart from treating horses, it is not widely used today.

Systemic radiotherapy

The patient is administered radioactive isotopes (e.g. iodine 131 is used to treat hyperthyroidism in cats).

What is the radiation dose?

The radiation dose is the amount of energy absorbed per unit of mass. The dose unit is 1 Gray (1Gy = 1J / 1kg).
In order to destroy cancerous tissue, it should be irradiated with an appropriate dose of radiation. The point is that it should be a dose that will ensure the highest possible probability of destroying the tumor, while at the same time damaging the healthy surrounding tissue as little as possible. Such a dose can be administered in many ways - once or in the so-called. fractions or partial doses.

Many different radiotherapy protocols have been described for use in veterinary oncology. The main differences between them are the amount of radiation per dose and the frequency with which the doses are administered. There are several fractionation schemes:

• conventional fractionation - that is, irradiation takes place once a day with a specific dose of radiation 5 times a week,
• hypofractionation - that is, irradiation with high fractional doses, but in a smaller number,
• hyperfractionation - irradiation with two or three smaller fractional doses during the day instead of one.

How is radiation delivered?

Depending on the desired depth of treatment, radiation therapy can be delivered by photons or electrons. Radiation works by interacting between photons or electrons and the target tissue (tumor). Tumors can differ in their sensitivity to radiation; some tumors (e.g. mast cell tumor or lymphoma) are more sensitive to radiotherapy than others, so the dose recommended for treating them may be lower. On the other hand, radio-resistant tumors (e.g. melanoma) will require a much larger dose to treat them.

Different types of radiation therapy are used in human and veterinary patients:

• Photons are able to penetrate deep into the body, saving the skin at the same time.
• Electrons can penetrate even a few centimeters deep into the skin, which makes this type of therapy effective in the treatment of superficial tumors.
• Protons can store their energy with a very high precision and are most often used for tumors in pediatric patients, tumors of the skull or spine; they are not used in veterinary medicine.

Photons and electrons are most commonly used in veterinary medicine.

Due to the energy of the radiation beam, radiotherapy is divided into:

• Megavolt radiotherapy which uses high energy radiation (> 1 MV). The devices used to generate this type of energy are:
  • cobalt bombs (1.25MeV) containing the isotope of cobalt Co60 (no longer used in human and animal radiotherapy in Europe),
  • linear accelerators (4-25 MeV),
  • tomotherapy devices, thanks to which spiral irradiation with high doses is possible, taking into account the anatomical relations and the position of the patient (used in the USA),
  • cyberknife - small linear accelerator,
  • gamma knife - uses cobalt radiation contained in many capsules (used to treat people).
• Orvoltage radiation therapy. It uses X-ray machines with low-energy 100-500kV radiation beams.

Most radiotherapy treatments are performed using photons, where the source of the high energy X-ray beams are linear accelerators. They allow the radiation dose to be delivered even to the deepest tumors of the largest patients. The most commonly used beams are 4 to 8 Megavolts (MV). One of the main advantages of the MV linear accelerator is the ability to conserve skin, however this can be a disadvantage when treating superficial skin tumors as they may not receive the required dose. Thanks to modern, highly specialized machines, dosing precision of 2 to 3% can be achieved. To achieve this, e.g. multi-leaf collimator, providing complex beam shaping that enables precise radiation delivery to the tumor and spares normal tissue. Dynamic wedges are another way to conserve normal tissue by adjusting the beam and dose delivered to the desired location. They change the angle of the isodose curve with respect to the beam axis at a given depth.

Orvolute machines capable of delivering low-energy external beam radiation are less versatile than linear accelerators and cobalt Co60 machines that produce megavoltage radiation. In addition, the electron beam capabilities of linear accelerators allow for more targeted treatment of smaller patients.

What is radiotherapy in veterinary used for?

Cancer radiotherapy

Spontaneous malignancies are common in dogs and quite common in cats. Surgical treatment is currently one of the most commonly used forms of therapy, but the disease is often very advanced before the animal goes to the doctor. In dogs and cats, tumors grow rapidly and can kill an animal within weeks. Unfortunately - when noticed by a veterinarian, such changes are often inoperable. After incomplete surgical removal, the tumor recurs and spreads very quickly.

The aim of radiotherapy is the so-called. "Local control ". Radiation is used to control the tumor by limiting or even stopping tumor growth in a specific part of the body. Unfortunately, not all cancers are suitable for radiotherapy because of their type or location. Irradiation - like surgery - is locoregional and cannot be used to treat systemic neoplastic diseases. If the cancer has already spread, radiation therapy is also not recommended as a stand alone treatment. However, for most tumors that are confined to a specific location in the body, radiation therapy is a way to aggressively attack an inoperable tumor.

Since radiation therapy is almost always a local therapy, irradiated tumors also need to be relatively localized. The particularly sensitive types of cancer are:

• mast cell tumors,
• squamous cell carcinoma of the mouth of a dog or cat,
• meningioma,
• thyroid tumors,
• sometimes histiocytic sarcoma.

Tumors of the white blood cells (lymphoma, plasmacytoma) are also sensitive to radiotherapy. However, they usually respond to chemotherapy, and because they are often multifocal, chemotherapy is usually more appropriate. Depending on the type of tumor, its location, clinical condition of the patient, prognosis and wishes of the owner, radiotherapy may be radical or palliative.

Traditional radiotherapy is used when the goal is long-term cancer control. However, there are often situations where such long-term cancer control is not possible and radiation therapy is used to keep patients comfortable.

Radiation therapy with intention to cure / radical / curative

Radical radiation therapy is delivered with high total doses of radiation therefore side effects are inevitable but are accepted as an inevitable part of treatment. Radical therapy can be a treatment for:

• final (with the intention to cure) - when surgery is not considered or in the case of recurrence of the disease after prior surgical excision of the tumor;
• neoadjuvant - radiation therapy is given before the final surgery to reduce the size of the tumor;
• adjuvant (complementary) - after treatment with other methods in the case of suspected or confirmed presence of microscopic disease. Often times, a combination of surgery and radiation therapy has many more benefits than either method alone. This applies in particular to sarcomas (spindle cell sarcoma, hemangiopericytoma, soft tissue sarcoma) and mast cell tumors.

Cure radiotherapy is most commonly used in the postoperative period to treat incompletely resected soft tissue sarcomas and mast cell tumors when the chances of recovery are high and the prognosis is good. Treatment of tumors in the early stages, without metastases, may result in a good effect or even complete recovery.

Palliative radiotherapy

Palliative radiotherapy is used to alleviate the clinical symptoms and discomfort of many types of cancer that cannot be treated with other techniques, such as surgery. The essence of palliative therapy is to alleviate pain and maintain a good quality of life for cancer patients, not to extend the survival time or cure the cancer. For these reasons, it does not require high doses of radiotherapy, and the delivered dose is sufficient to control the clinical symptoms that are burdensome for the patient.

Palliative radiotherapy is used to treat brain tumors, nasal tumors, oral melanomas, some inoperable soft tissue sarcomas, and to relieve pain in primary bone tumors (osteosarcoma) - that is, in situations where other treatments would be less effective or impossible.

The dosing protocol for palliative radiotherapy involves the delivery of higher doses per fraction, typically once a week for 3 to 4 doses, however other regimens exist which include, but are not limited to: daily dosing for 5 consecutive days, dosing times daily for 2 consecutive days or 2 times a week for 2 weeks.

Pending response to treatment and in the time between treatments, palliative radiotherapy may be repeated, however with later protocols the risk of delayed side effects may increase.

The most common use of palliative radiotherapy:

• Relieving pain from tumors that originate in the bone or are invading bone, such as osteosarcoma and bone metastases.
  • Most patients experience moderate to significant improvement in pain-related clinical symptoms. Such benefits may last from several weeks to several months depending on the patient's individual characteristics. Clinical improvement may occur within a few days of the first dose; sometimes, however, it may take several weeks after the last dose of treatment before the pain symptoms begin to subside.
• Relief of pain and other clinical symptoms associated with nasal tumors such as epistaxis.
  • In one study in 56 dogs treated with the four fractions a week, 73% had complete relief from nosebleeds and 27% had partial relief from epistaxis.
  • Another study showed 100% responses in 38 dogs, with a median duration of response of 10 months and median overall survival of 10 months.
  • In 48 other dogs treated with different fractionation regimens, the overall response rate was 91.6%, 66% completely resolved clinical signs and the median duration of response was 4 months.
  • In two other studies in 12 and 56 dogs with 4 weekly doses, median survival was 14.5 months and 7 months, respectively, with a 95% response.
• Palliative radiotherapy has been used for thyroid tumors for which no surgery or final therapy has been performed.
  • A study in 13 dogs with invasive thyroid cancer treated with palliative radiotherapy for 4 treatments once a week showed that all dogs had either a reduction in primary tumor size or cessation of tumor growth with a median survival time of 22 months.
• Other types of cancer reported to benefit from palliative radiotherapy include: oral tumors, anal sinus tumors, sarcomas with severe disease, prostate tumors, retroperitoneal angiosarcoma, and lymphoma.

Radiotherapy of "mild " diseases

Radiation (used at doses lower than those needed to treat cancer) has a potent local anti-inflammatory effect through a variety of mechanisms including direct toxicity to inflammatory cells and alteration of cell adhesion and cytokine expression. In human medicine, the use of radiotherapy to treat benign diseases is controversial mainly because of the fear of radiation-induced cancers. There are medical conditions in veterinary medicine for which low-dose anti-inflammatory radiation may be considered. They are e.g.:

• osteoarthritis,
• granulomatous meningitis,
• acral lick dermatitis,
• refractory inflammatory bowel disease and / or pancreatitis,
• chronic rhinitis,
• treatment-resistant stomatitis in cats.

Types of techniques and types of planning in radiotherapy

The possibility of radiation therapy is becoming more and more available in veterinary facilities around the world. With advances in imaging diagnostics and computerized treatment planning, oncology radiotherapy has made great strides in establishing state-of-the-art treatment plans. They include:

• The use of computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) for both tumor imaging and radiation treatment planning.
• The combination of newer imaging methods allowed for treatment planning using three-dimensional conformal radiotherapy (3D-CRT).
• Newer technologies are used in many veterinary oncology facilities, including:
  • inverse-treatment planning,
  • intensity-modulated radiotherapy (IMRT),
  • Stereotactic Radiotherapy (SRT),
  • dynamic adaptive radiotherapy (DART) or planned adaptive technology
  • and image-guided radiotherapy (IGRT).

There are several radiation protocols in veterinary medicine:

Conventional radiation therapy (CFRT)

It uses radiation to reduce or destroy tumors, including those that cannot be safely or completely removed by surgery alone. Also as a palliative therapy to relieve pain. It can be used in conjunction with chemotherapy after surgery or as a sole treatment. Usually used in 15-21 treatment sessions for 3-4 weeks.

Intensity Modulated Radiation Therapy (IMRT)

It is an advanced form of high-precision radiotherapy, which is based on the regulation of the intensity of the radiation beams throughout the treatment field using a multi-leaf collimator system moving to - and from the beams. Collimators are computer-controlled devices that use up to 120 movable "leaves " in order to adjust the radiation beam to the shape of the tumor at any angle, while protecting as much as possible the adjacent healthy tissue. These devices make it possible to change the dose of radiation within a single beam. The radiation dose intensity is increased near the tumor, while the radiation in the adjacent normal tissue is reduced or completely eliminated.

IMRT is based on the "everything but " approach. Defining and avoiding critical structures is crucial, and less so the precise determination of target organs. IMRT thus improves the adaptability to the concave shapes of the tumor, for example when the tumor is wrapped around a sensitive structure (such as the spinal cord), a major organ or a blood vessel. This results in fewer side effects. In humans, IMRT is especially important in the treatment of head and neck cancer, as well as prostate and rectal cancer. Intensity-controlled radiation therapy is rarely used in veterinary medicine, but has been reported in the treatment of nasal tumors where the dose delivered to the tumor is limited by the tolerance of the surrounding critical structures - eyes and brain - so the dose cannot be safely increased without aggravating serious complications.

In IMRT, radiation is delivered in low doses over several treatments to reduce or completely destroy tumors. The usual treatment regimen is Monday to Friday and lasts for 2-3 weeks, although this may vary depending on the type of tumor and the individual animal. For palliative radiotherapy, where the aim is to relieve pain rather than reduce or destroy the tumor, IMRT may be given 1-2 times a week as needed for several weeks.

Three-dimensional conformal radiotherapy (3D-CRT)

It is a sophisticated type of external beam treatment planning. Computers calculate a three-dimensional virtual model of the tumor volume. The information from this virtual model is then used to plan radiation therapy. During 3D-CRT, multiple radiation beams adjust to the size and shape of the tumor, limiting exposure to nearby tissues and organs. 3D-CRT is designed to provide a high dose of radiation in a selected area while limiting side effects on healthy tissues. However, this form of radiation delivery does not include IMRT.

Stereotactic radiation (SRT)

It is the most advanced form of radiotherapy. It is sometimes also referred to as stereotactic radiosurgery (SRS) or stereotactic radiation therapy (SRT).

• SRS - only one very high dose dose is given (e.g. 25 Gy)
• SRT - 2-5 high dose fractions are administered (e.g. 10 Gy) in quick succession.

SRT uses finely collimated beams of radiation aimed precisely at the target and is usually delivered in 1-5 carefully planned doses (compared to 15-30 sessions of conventional radiation therapy). The goal is to deliver a very high dose to a small area with minimal doses of radiation therapy to the surrounding tissues. As each session requires anesthesia and is usually an outpatient visit, this is a significant improvement in patient safety, the ability of families to provide treatment to the animal, and quality of life. While side effects are still possible, the protocol is much shorter. There is a major difference in stereotaxic radiation compared to fractionated radiation as normal tissue sparing is done by avoiding normal tissue structures rather than by delivering smaller doses of fractions during radiotherapy (fractionation).

SRS / SRT provides radiation with greater precision than previous forms of radiation therapy, meaning you can increase tumor destruction while reducing exposure of the rest of the body to radiation. Since most of the side effects associated with radiation therapy result from the inevitable damage to the healthy tissue surrounding the tumor, such precision reduces the likelihood and severity of side effects. In addition to significantly reducing side effects, SRT / SRS allows the treatment of some cancers previously considered "incurable" due to their delicate location in the body (brain, spine, lungs, etc.). This therapy is usually given with the intention of curing the cancer, not just relieving its symptoms.

Stereotactic radiosurgery (SRS) is a very precise method of delivering radiation. It was designed to treat functional brain disorders, but is now indicated in the treatment of tumors, vascular lesions and pain syndromes, including the brain and spine. Treatment can be with a linear particle accelerator or with a gamma knife. In veterinary medicine, this type of irradiation is used very rarely, because still very few veterinary centers have the technology necessary to offer this type of treatment.

Dynamic adaptive radiotherapy (DART) or planned adaptive therapy

This technology makes it possible to quickly make daily changes to the radiation therapy plan while the patient is being treated. It is needed when there are drastic changes in the tumor during therapy and its aim is to minimize exposure of normal tissue to irradiation.

Image Guided Radiotherapy (IGRT)

It allows you to accurately perform radiotherapy using imaging before and during treatment. It uses the patient's images during therapy to determine the accuracy of the settings and checks for any movements during the treatment. As a result, it is possible to use smaller safety margins in treatment planning, and corrections can be made in real time before the procedure is performed. By verifying the actual location of the target tumor, it is more likely to deliver the dose needed to treat the disease and to avoid inadvertent dosing to adjacent critical structures. Image-guided radiotherapy can also be used to modify changes in tumor size and shape, therefore IGRT is the basis for dynamic adaptive radiotherapy.

This is especially true in IMRT where steep dose gradients are used.

• Strontium plesiotherapy, a therapy in which large doses of radiation is delivered by a small probe to a very small and defined area, may be used for some types of cancer (such as nasal squamous cell carcinoma in cats).
• Other forms of radiation therapy, such as active iodine for thyroid cancer and samarium for bone tumors, are used as brachytherapy. They are radioactive substances that target specific diseased tissue in the body. This minimizes radiation to normal tissues and maximizes radiation to tumor tissue. Samar (tradename Quadramet) was developed at the University of Missouri and is used to reduce pain associated with primary bone cancer (osteosarcoma) or bone metastases in dogs. In humans, it is used to treat breast and prostate cancer that has spread to the bones.

How does radiation therapy work in dogs and cats?

The radiotherapy process consists of three main steps:

Imaging

Before starting radiotherapy, a computerized tomography scan is usually performed to determine the extent and exact margins of the tumor. As a result, the appropriate dose of radiation can be delivered in a focused manner, which minimizes damage to the surrounding tissues. Thanks to the CT scan, it is possible to identify the area to be treated. At this stage, it is crucial to immobilize the patient, as the established position will be repeated throughout the course of radiotherapy. Therefore, general anesthesia of the animal is necessary, and the desired and reproducible body position is achieved with the use of pillows, anti-chew blocks, dental molds, vacuum mattresses, gutters, thermoplastic covers, etc.

After obtaining images from computed tomography, three volumes are determined:

• Total tumor volume (GTV) which represents the actual size of the tumor. Sometimes, if the primary tumor has previously been surgically removed, the GTV cannot be determined.
• The clinical target volume (CTV) defines the tumor together with the margin of microscopic disease around it. Thanks to this size, it is possible to select the appropriate size of the bundles and their distribution.
• Planning target volume (PTV). It includes CTV along with a margin that takes into account possible variability in tumor position (e.g. as a result of differences in the daily position and movements of internal organs).

Treatment planning

Treatment planning takes into account GTV, CTV, PTV, treatment volume, irradiated volume and organs at risk. In the first stage of treatment planning, isodose distribution is created by collecting all information about the location of the tumor. The CT or MR images are then fed into treatment planning software, followed by the creation of patient contours, especially body contours, CTV, and critical structures (brain, eyes, spinal cord, etc.). After creating a 3D model of the tumor, the software is used to determine the strength and shape of the radiation beam or beams that are needed to best penetrate the entire tumor while sparing surrounding healthy tissues as much as possible. Such conformational planning allows to minimize the radiation dose to healthy tissue while maximizing the radiation dose to the tumor. In addition, by dividing each dose into multiple beams reaching the patient from different directions, the amount of radiation for any tissue is reduced. Sometimes (e.g. in the case of superficial tumors) computed tomography is not performed, and the tumor can be planned "manually " based on physical measurements and radiographs. After the plan is executed, it is sent to the linear accelerator.

Preparation and delivery of radiation

Once the exact boundaries of the treatment area have been determined, the hair will be shaved at this boundary. Sometimes this area is marked with a marker or tattoo to ensure that that specific area is treated repeatedly

Correct positioning of the patient is of key importance. Unlike human radiotherapy, animals will not lie still for 5 minutes without sedation or general anesthesia. Although the actual treatments are relatively short, all veterinary patients must be anesthetized. Patients wear an intravenous catheter, receive fluids during anesthesia and are monitored. Although most animals tend to be older, brief episodes of anesthesia are generally well tolerated.

Radiotherapy focuses the X-ray beam on the area to be treated. A linear accelerator directs a beam of radiation towards the tumor and some normal tissues around it. The equipment is in many respects similar to the equipment used to take standard X-rays, except that the energy of the radiation beam is much higher and the exposure times are much longer.

Usually, the administration of radiation is divided into many small fractions. This allows normal tissue to regenerate between doses and minimizes the risk of delayed side effects. The planned total amount of radiation is divided into several - several small fractions and administered at appropriate time intervals (depending on the treatment protocol). This schedule helps protect normal tissue by spreading the total radiation dose.
Radiotherapy is performed in a series of treatments over many weeks. Depending on the type of cancer and the purpose of treatment, it may last from 1 week to 2 months. The total radiation dose used and the number of treatments will depend on many factors including the size and location of the tumor (i.e. which normal tissues will be in the treated area), the overall health of the animal, and the type of tumor.

A single radiation therapy session lasts an average of 5-20 minutes. The first day is usually the longest due to the initial setup time, but most radiotherapy sessions will not exceed 30 minutes. Sometimes CT or MRI images are used in a computerized treatment planning system to more accurately target the tumor and avoid critical normal structures near the tumor.

After each irradiation, the patient wakes up and is released home, usually on the same day (for out-of-hospital patients).

Radiotherapy varies from animal to animal. Your doctor will work out the best treatment plan for your individual case. Treatments are performed by a radiotherapist and a trained team of doctors and veterinary technicians.

Radiotherapy is a very flexible form of treatment, and no two treatment plans are exactly the same. In general, two categories of treatment can be distinguished: definitive and palliative radiotherapy.

• Final radiotherapy. Such protocols are used in cases where there is a possibility of recovery and / or long-term survival.
  • Examples of tumors treated with terminal therapy include tumors that are insufficiently or narrowly dissected, such as mast cell tumors and sarcomas (soft tissue sarcomas and injection sarcomas), nasal tumors, and pituitary tumors.
  • These regimens provide a lower dose, but more treatments are required - usually 16-19 treatments in total (total treatment time is around 3.5 weeks). This is to reduce the risk of long-term effects on adjacent normal tissues that cannot be avoided during treatment.

Types of cancer treated with radiation therapy

Potentially all tumors can be treated with radiation therapy, but not all tumors respond the same to radiation. Treatment will depend on the location and type of the tumor, its expected behavior, prognosis, health, and other factors.

There are several types of cancer that can be treated with radiation therapy alone, however, it is most commonly used to destroy or limit the growth of leftover cancer cells (i.e. microscopic disease) after surgical removal of the tumor. Radiation therapy can also be used to reduce the size of very large tumors before surgery, making surgery easier to perform.

Radiation is most commonly used for mast cell tumors, soft tissue sarcomas, carcinomas, nasal tumors, and to reduce pain associated with bone cancer. The use of radiation therapy significantly improves the life expectancy and quality of life for most patients. Early side effects are tolerated by most animals and pain and inflammation are actively controlled with appropriate medications.

Cancers often referred to radiation therapy include:

• skin tumors and soft tissue tumors of the limbs and trunk (soft tissue sarcomas, mast cell tumors, carcinomas, melanomas),
• bone tumors (limbs, skull, spine and pelvis),
• joint tumors,
• nose and mouth tumors (sarcomas, carcinomas, melanomas, odontogenic tumors, lymphomas, tonsil and tongue tumors),
• cancers of the larynx, pharynx and trachea,
• brain tumors / spinal cord tumors,
• periocular and facial tumors,
• ear tumors,
• thyroid tumors,
• perianal sinus adenocarcinomas,
• anus / rectum tumor,
• tumors of the bladder, prostate and urethra,
• tumors of the base of the heart and mediastinum (thymoma, chemodectoma, ectopic thyroid gland, lymphoma, less often others),
• inoperable lung tumors and other chest tumors,
• inoperable tumors of the abdomen / pelvis.

Soft tissue sarcomas

Soft tissue sarcomas are a group of tumors that originate from mesenchymal cells. They are similar in biological behavior and account for approximately 15-20% of all skin and subcutaneous tumors in dogs. These sarcomas can arise anywhere from an anatomical site, but the frequency of metastasis is low to moderate (15-41%), depending on the degree of malignancy. Their aggressive local behavior is characteristic, therefore local tumor control is the most important issue in their treatment (especially in low- and medium-grade tumors). The group of soft tissue sarcomas includes:

• hemangiopericytoma,
• fibrosarcoma,
• neurofibrosarcoma,
• myxosarcoma,
• nerve sheath tumors.

The treatment of choice is total surgical excision with a surgical margin of 2 cm to 3 cm laterally and one plane of the deep fascia. However, because soft tissue sarcomas very often arise in areas where skin availability is limited (e.g. distal parts of the limbs), often the tumor is not completely removed and additional therapy is indicated, e.g. radiotherapy. Radiation can be used before or after surgery.

• Neoadjuvant radiotherapy (before surgery) is not widely used due to the low sensitivity of macroscopic soft tissue sarcomas to radiation.
• Adjuvant (adjuvant) radiotherapy in the case of incompletely removed tumors may be used in the form of definitive or palliative treatment.

According to the research carried out:

• In soft tissue sarcomas not completely resected and not subjected to radiotherapy, the frequency of local recurrences is 17-40%. For comparison, in one study with soft tissue sarcomas treated with surgery and radiotherapy, the local recurrence rate was 16%, and the 5-year survival rate was 78%.
• In a study of 35 dogs with soft tissue sarcoma treated according to the final protocol, a daily dose of 3Gy to 4.2 Gy per fraction was used in the Monday-Friday schedule for a total dose of 42 Gy to 57 Gy. The overall median survival was 1,851 days and the median time to relapse was greater than 798 days.
• In another study in 48 dogs with soft tissue sarcomas treated with the Mon-Wed-Fri 3Gy / fraction / 21fraction regimen for a total dose of 63Gy, the five-year survival rate was 76%, the median disease-free period for all dogs was 1,082 days, and the median duration was to relapse was 700 days.
• In contrast to these, another study in 56 dogs with soft tissue sarcoma treated postoperatively with hypofractionated radiotherapy on a weekly schedule for 4 weeks ranging from 8 Gy to 9 Gy / fraction up to a total dose of 32 Gy to 36 Gy documented disease-free intervals: annual - 82%, two-year - 74%, three-year - 70% and five-year - 65%.
• It should be mentioned that marginally resected low-grade soft tissue sarcoma can do very well without additional therapy.

Post-injection sarcoma in cats

Injection sarcomas of cats (Feline injection site sarcomas - FISS) are aggressive, high-grade tumors that are believed to arise at the injection site. They are characterized by local infiltrating growth and therefore cause considerable therapeutic difficulties. In the case of post-injection sarcomas in cats, they often relapse after surgery or even radiation therapy alone. Therefore, these tumors pose a challenge to local control, and treatment is often frustrating. The most effective therapeutic approach is to combine surgical resection with radiation therapy. However, even after complete tumor resection with full histological margin and full treatment with fractionated radiotherapy, the local recurrence rate is 28-45%. Median survival time associated with combination therapy (surgery + radiotherapy) has been reported to range from 600 to 1,300 days.

• In a study in 92 cats with ISS using pre-operative radiotherapy with 16 3Gy fractions / fraction per day for a total dose of 48Gy, the median time to first event (this is the time from day 1 of treatment to local recurrence or metastatic disease), for all cats was 584 days.
• Importantly, only the completeness of the surgical resection was related to the time to the first event. The median time to first event in cats after total surgical resection was 986 days, compared with 292 in incomplete resection cats.
• This study showed that preoperative irradiation is an effective treatment for cats with ISS, especially if complete excision can be obtained after radiation therapy.

Mast cell tumor in dogs

Mast cell tumor (MCT) is a common canine and feline cancer that poses a considerable therapeutic challenge and may benefit from radiotherapy. MCT is the most common skin cancer in dogs, accounting for approximately 21% of all skin tumors in this species. For most cutaneous MCTs, surgical removal of the tumor is the treatment of choice. However, locally recurrent, diffuse or inoperable mastocytomas require additional treatment.

• Neoadjuvant radiotherapy may be recommended when the tumor is too large to be surgically excised or is in a very unfavorable location. However, this type of therapy is not widely used due to the complication of accelerating the release of histamine by cancerous mast cells. High doses of prednisolone prior to radiotherapy are used to reduce the risk of mast cell degranulation prior to radiotherapy. Its administration may also facilitate the surgical resection of many diffuse MCTs.
• Adjuvant radiotherapy after tumor resection or cytoreductive surgery is the most commonly used. Many studies document good long-term results for dogs with MCTs treated post-operatively with radiation therapy.

In a study involving 35 dogs with inoperable MCTs on the head or limbs of grade 1 to 3, patients were treated with prednisolone 40 mg / m2 daily for 10-14 days prior to hypofractionated radiotherapy which was performed weekly 8 Gy / fraction to the total dose. 32 Gy.

• Overall response rate: 88.5%;
• median progression free period: 1,031 days with annual and biennial rates of 60% and 52% respectively.
• Interestingly, the location, not the degree of malignancy of the tumor, had an impact on survival - dogs with tumors on the limbs survived longer than dogs with tumors on the head.

Hypofractionated radiotherapy in combination with toceranib and prednisolone was prospectively evaluated in 17 dogs with inoperable MCTs. Dogs were treated with four fractions of 6 Gy / fraction once a week for a total dose of 24 Gy or three fractions of 8 Gy / fraction once a week for a total dose of 24 Gy.

• The overall response rate was 76.4% with 58.8% of the dogs achieving a complete response and 17.6% a partial response;
• the median progression-free period was 316 days.

In a study of 19 dogs with cutaneous MCTs and regional lymph node metastases treated with cytoreductive surgery, prior to final radiotherapy including a Monday-Friday regimen from 3 Gy / fraction to a total dose of 48 Gy to 57 Gy, median disease-free survival was 1,240 days.

In a study of 37 dogs with incompletely resected Grade 2 mast cell tumors treated with radiotherapy, tumor control was achieved over 90% after 1 and 2 years.

In another study of 57 dogs with incompletely resected mast cell tumors, the median disease-free period was 32.7 months.

Nose tumors

Nose tumors account for approx. 1% of all tumors in dogs. Most (80%) are malignant tumors (epithelial, mesenchymal, or round cell tumors) and have poor long-term prognosis. Although the risk of distant metastasis is minimal, the most important problem with intranasal tumors is that they are locally invasive and difficult to surgically excise. If the tumor is not treated, it is recommended that the animal be euthanized within several months of diagnosis. This is due to the progression of the cancer and the inability to control the bothersome symptoms such as sneezing, nosebleeds and pain.

The primary treatment for nasal tumors in dogs and cats is radiation therapy, especially since most cancers respond to radiation. Palliative or curative radiotherapy can substantially improve patients' quality of life.

• Ultimate radiotherapy is associated with long-term (moderate to severe) side effects, such as e.g. keratitis. Such consequences are often unacceptable to pet owners, especially if recovery is unattainable and the long-term prognosis is poor. However, a study in 16 dogs with various nasal tumors revealed that dogs treated with definitive radiotherapy (16-18 x3 Gy per day fraction for a total dose of 48 Gy to 54 Gy) and then surgically removed had no long-term side effects, and the average duration of the survival was 457 days.
• Palliative radiotherapy is used to relieve the patient's clinical symptoms (improve airflow and stop epistaxis). Reports in the literature regarding the use of radiotherapy in dogs with nasal tumors differ in the fractionation schedule, dose per fraction and total dose delivered. The median survival time ranged from 7 to 11 months.

In a study of 65 cats with various nasal tumors treated with radiation therapy, clinical signs improved in 86.2% of cats after radiation therapy. Acute complications such as increased sneezing, nasal and / or ocular discharge were observed in more than half of irradiated cats (58.5%) but were manageable and acceptable. The most common late side effect (20.5%) was cataract. The median duration of overall survival and PFS was 432 days and 229 days, respectively. There was no significant difference in overall survival in cats with nasal lymphoma compared to cats with other cancers.

Oral tumors

The most common oral cancers in dogs are:

• malignant melanoma of the oral cavity (oral malignant melanoma OMM),
• fibrosarcoma,
• squamous cell carcinoma SCC,
• squamous cell enamel.

In cats, squamous cell carcinoma predominates. Due to their location and often the high degree of advancement of the disease when they are noticed, these neoplasms pose a great therapeutic challenge. Most of them are locally invasive and require aggressive surgery with wide margins. The complex anatomy of the oral cavity makes it very difficult to perform a complete tumor removal procedure. In order to improve local control, it is recommended to combine surgery with radiotherapy. Most canine oral tumors (epiglomas, melanoma, fibrosarcoma, and squamous cell carcinoma) respond to radiation therapy. Feline SCCs were shown to be poorly responsive to radiation therapy under various fractionation regimens.

Melanoma

Melanoma in dogs is an extremely aggressive neoplasm with a high degree of local invasiveness and high metastatic potential. Local control is achieved by surgery and / or adjunctive radiation therapy. However, even with local disease under control, the relapse rate is high: 70% of dogs will relapse within three to four months after surgical resection. The metastatic tendency is also high: 59% to 74% in the regional lymph nodes, 60% - 65% in the lungs.

Hypofractionated radiation protocols have been used in the primary treatment of melanoma in animals. Several studies have found response rates greater than 80% with doses ranging from 8Gy to 9Gy per fact. However, the overall median survival time ranged only from 5 to 7.9 months due to metastatic disease. One of 3 radiotherapy protocols was used in a retrospective study in 140 dogs with melanoma. Median time to first event for all dogs was 5 months and median survival was 7 months. There were no differences in response, time to first event, and survival between the three irradiation protocols.

Oral fibrosarcoma

Oral fibrosarcoma is a mesenchymal tumor, composed of spindle cells or fibroblasts. The best local control is achieved by combining a surgical approach with complementary radiotherapy. In a retrospective analysis of 65 dogs with oral fibrosarcoma, this approach resulted in a median survival of 505 days and a progression-free survival of 301 days.

Squamous cell oysters

Squamous cell adenomas (epulides) are benign odontogenic tumors of the mouth that can be successfully treated with extensive surgical resection. They often attack the underlying bone, so the surgical incision must be wide, encompassing the surrounding soft tissues and the underlying bone. However, in some cases surgery is not possible due to the location and / or size of the tumor (which requires extensive reconstruction of the mandible or maxilla) or microscopic disease may remain after surgical resection. In such situations, supportive therapy may be effective radiotherapy. In a prospective clinical study involving 47 dogs with squamous cell tumors, dogs were treated with 12.4 Gy / fraction 3 times per week for a total dose of 48 Gy. 3-year progression-free survival was 80%.

Squamous cell carcinoma

Squamous cell carcinoma is the most common oral cancer in cats. These tumors are locally invasive and due to their local dilatation, surgery alone is not cured. Response to radiation therapy is usually poor, with relatively short survival times. Different retrospective studies describe different treatment protocols, but the number of cats in each study is small. Described protocols (6Gy / fraction twice a week; 8Gy / fraction on days 0.7, 21; 4.2 Gy / fraction given in the Monday-Wednesday-Friday schedule; 3.5Gy / fraction twice a day) and their use in Radiotherapy combined with surgery or as monotherapy resulted in different survival times of 42.5 days, 116 days, 163 days, 174 days and 14 months. Unfortunately, most cats die prematurely as a result of local disease.

Tumors of the brain, pituitary gland and spinal cord

Brain Tumors

Intracranial tumors are particularly frustrating and difficult to treat due to their location and the lack of histopathological diagnosis in the vast majority of cases. These tumors are often benign, slowly expanding lesions that locally compress healthy brain tissue. Complete surgical excision is almost always impossible without causing extensive damage to the surrounding healthy brain tissue. Palliative treatment with prednisolone does not give good results. Despite the fact that most treatments are based solely on imaging diagnostics, fractionated radiation therapy is a very useful treatment option, either alone or as a surgical aid. Various studies on different hypofractionated radiotherapy protocols for canine brain tumors have shown that the median survival time ranges from approximately 300 to 700 days.

Pituitary tumors

Due to the different structure of the pituitary gland in dogs and cats and more difficult surgical access compared to humans, treatment of pituitary tumors in veterinary medicine with radiotherapy was the treatment of choice. Radiotherapy of pituitary tumors in dogs associated with hyperadrenocorticism has shown an improvement in neurological status and may help control hormone secretion.

A number of studies have been carried out using different fractionation regimens to treat pituitary mac tumors in dogs. Survival times achieved through these protocols range from 147 days to over 1,400 days.

Radiotherapy is also an effective treatment for pituitary tumors in cats, leading to extended survival and control of both tumor and paraneoplastic symptoms. Pituitary tumors in cats associated with acromegaly, hyperadrenocorticism and insulin-resistant diabetes have shown a marked improvement in the control of hormonal disorders.

In a study of 5 cats with pituitary tumors (4 adenomas and 1 carcinoma), radiation therapy was administered at a total dose of 39 Gy prescribed in 12 fractions from 3.5 Gy to 4 Gy per fraction delivered on a Monday-Wednesday-Friday schedule. Survival times were 5.5, 8, 15, 18, and 25 months.

In a study of 12 cats with pituitary tumors administered 5 weekly fractions to a total fraction of 37Gy, the median overall survival was 72.6 weeks.

Spinal cord tumors

Limited information is available on the treatment of spinal cord tumors in dogs and cats. Treating meningiomas with surgery and radiotherapy can have a good or excellent prognosis. On the other hand, in the case of spinal cord nephroblastoma, surgery and radiation therapy can be effective in improving the survival rate of dogs.

Other tumors

Histiocytic sarcoma (HS)

Canine histiocytic sarcoma is an aggressive round cell tumor that comes in two forms:

• located,
• disseminated.

The localized form most often affects joints, skin, subcutaneous tissue, and bones or tissues around them. This form is amenable to topical treatments, but more than 90% of these dogs will develop distant metastases.

Radiotherapy may be used as a palliative treatment to relieve symptoms such as lameness associated with the primary tumor. In a study of 37 dogs with HS, radiation therapy significantly improved survival. The median survival time for dogs treated with radiation was 182 days compared with 60 days for dogs not treated with radiation. The combination of lomustine and radiotherapy resulted in a median survival time of 208 days compared to 68 days for untreated dogs.

Osteosarcoma (osteosarcoma)

Osteosarcoma is the most common primary bone tumor in dogs (85% of all primary bone tumors), with approximately 75% affecting limb bones. These tumors are relatively common in large breeds of dogs. Common symptoms for canine osteogenic sarcomas are severe pain and rapid loss of condition. The prognosis is poor due to the aggressive behavior and high metastatic potential of this tumor. The treatment of choice is limb amputation with adjuvant carboplatin chemotherapy, but even with such combination therapy, early metastases to the lungs are not infrequent.

Radiotherapy is mainly used as a palliative treatment when amputation is not possible in patients with osteosarcoma of the limbs as an effective method of temporarily controlling pain. Various approaches to palliative radiotherapy for the treatment of canine osteosarcoma have been described, with overall response rates ranging from 74% to 92%, median duration of response intervals from 73 to 130 days, and median survival from 122 to 313 days. In most of the reported studies, clinical improvement is seen in approximately 50% of dogs.

Anal adenocarcinoma and anal gland adenocarcinoma

Anal gland adenomas in dogs are very common. Most often they are treated surgically due to the primary disease and lymph node involvement. Some of these tumors will regress after treatment with stylboestrol, but often such tumor control is only temporary. Surgical excision of these tumors involves deep cuts in a highly vascularized area and is often complicated by significant bleeding and postoperative infection with chronic discharge from the perianal sinuses. Therefore, it is not uncommon for the tumor to be completely excised and eventually the appearance of metastases in the lymph nodes.

Adenocarcinomas can respond fairly well to radiation therapy, which however is only a satisfactory treatment for such a condition. Radiation is used to control local recurrences and treat regional lymph nodes. Survival times reported as 544 days with radiotherapy, surgery, and chemotherapy for anal sinus adenocarcinoma. When treating this region, protocols are usually longer to reduce the risk of late side effects.

In 2016, 2 studies were conducted assessing hypofractionated radiotherapy in the treatment of advanced disease in patients with anal gland adenocarcinoma, and both reported good rates of symptom relief and a median duration of local follow-up for 9-11 months.

Tumors of the genitourinary system

Cancer of the prostate and bladder has long been considered poorly responsive to radiation. In 2004, in a pilot study that evaluated hypofractionated radiation (6 fractions x 5.75 Gy) in combination with piroxicam and mitoxantrone, it showed a 90% clinical improvement rate and a median survival time of 11 months. The belief that radiation has a weak effect on these cancers was confirmed due to the fact that the effects were not better than the results obtained with chemotherapy and piroxicam alone. However, a 2012 study of full IMRT treatment (20 fractions 2.7-2.85 Gy) showed a median event-free survival of 11 months and a median overall survival of 22 months, which would be a significant improvement over previous studies. The side effects were mild and the treatment was well tolerated.

Thyroid tumors

Invasive thyroid tumors may be risky for surgical removal and may recur due to the inability to remove the tumor completely. While displaceable or encysted thyroid tumors are excellent candidates for surgery, radiation therapy is indicated for invasive tumors or as an adjunct to an incomplete or narrow excision. The reported median progression-free survival is> 2 years.

Thymoma

Thymomas are sporadic in dogs, cats and rabbits and are often difficult to treat surgically. In cats and rabbits, the median survival time was 2 years after radiotherapy.

Lymphoma

Lymphoma is extremely sensitive to radiation and reacts very quickly. Radiation is very useful for localized lymphomas such as the tissues of the nose, brain and spine, head tissue, mediastinum, mandible, maxilla and subcutaneous tissue.

Reports show a response rate in cats greater than 80% and median complete remission of 114 weeks. In one study, abdominal radiotherapy as salvage therapy (after unsuccessful chemotherapy) for feline gastrointestinal lymphoma had a 90% response rate with a median survival after 7 months of irradiation. Radiotherapy has also been used to treat cutaneous and mucocutaneous lymphomas in dogs with prolonged remission times. The role of radiation in multicentric lymphoma in dogs is unclear.

• Canine angiosarcoma is often treated with surgery and / or chemotherapy. However, radiotherapy can be an effective palliative treatment for angiosarcoma, especially in subcutaneous and retroperitoneal sites, with a response rate of 70%. Unfortunately, all angiosarcomas have a high metastatic potential and often metastasize distant within months.
• Infiltrative lipomas are an unusual disease - they are characterized by frequent local recurrences, but generally do not pose a risk of metastasis. One study investigating radiotherapy for these tumors showed an 80% progression-free survival 3 years after irradiation. Radiation is beneficial for macroscopic and narrowly dissected infiltrating lipomas.
• Other tumors for which the role of radiotherapy is not yet defined but appears to have moderate to high tumor response and control rates include extramedullary plasmacytomas and heart tumors (chemodectomas).

Adverse Effects of Radiotherapy in Dog and Cat

Adverse effects of radiation therapy

Radiation can be an effective treatment for tumors in pets. Many cancers do not tolerate radiation well, so it appears to preferentially damage cancer cells. However, as with any type of cancer therapy, there are some risks and side effects associated with the treatment. Some damage inevitably happens to non-cancerous cells and there are often changes to the skin after radiation therapy that make it look older in the treated area, making it more susceptible to later injury. Normal, healthy tissues can tolerate some amount of damage from radiation. As a rule, they are not serious, and due to the fact that radiotherapy is a regional treatment, most side effects are almost always limited to the treated area.

• Some of the side effects of radiation therapy are considered tolerable:
  • Hair loss is common in the treatment area. Hair loss may persist for a while, but many patients experience regrowth.
  • The color of regrown hair may also change and the skin may lose its elasticity and discolor in the treated area. However, these are all cosmetic effects that the patient is not aware of.
• Other, more worrying side effects of radiation therapy:
  • Many animals develop sunburn-like inflammatory skin lesions which may last up to 2 weeks in severe cases. It happens immediately after surgery in about 5% of cases. This "radiation dermatitis" can cause your pet to scratch or rub, but it is important to prevent it from doing so. Animals typically experience such severe side effects for 3-4 weeks.
  • Patients may experience nausea and vomiting, and develop diarrhea as a result of radiotherapy. This usually only happens when large parts of the abdomen are irradiated. Months or years after radiotherapy, you may experience late side effects. Chronic side effects, when they occur, develop gradually and include, among others.in.:
    • development of non-healing wounds (5%),
    • pathological fractures (1%),
    • and even new tumors at the site of irradiation (
• The side effects of radiotherapy depend on the course of the radiotherapy used, the location and size of the area to be treated, and their severity may vary from patient to patient. Each radiotherapy protocol is considered individually for each animal being treated, and the tumor response to treatment is carefully monitored by an oncologist both during and after treatment.

Types of radiation effects

There are two main categories of radiation effects: acute (early) nipples and late effects.

Acute Effects

• They occur in tissues where cells divide rapidly, such as the epithelial lining (skin, oral and nasal mucosa, gastrointestinal tract).
• They usually occur during or within weeks of treatment due to the death of rapidly dividing cells and associated inflammation.
• They occur to some extent in all patients undergoing radiation therapy, but are usually transient, last for 1-2 weeks, and begin to heal within 2-3 weeks after stopping treatment. In some cases, it may take up to 1-3 months for complete recovery.
• The acute side effects depend on the tumor, its location, and surrounding tissues that may be affected by the radiation. If the tumor is deep under the skin, the dose of radiation to the skin will be low, but if the tumor is on the surface, the skin will receive a higher dose of radiation, which increases the risk of side effects.
• The acute effects of radiotherapy - most often inflammatory - may be unpleasant for the patient, but if they are uncomplicated, they usually disappear within 3-4 weeks after stopping treatment.
• Possible acute side effects:
  • Skin: redness, exudative dermatitis.
    • If the treated area includes skin and is shaved, hair may take longer to grow back and may change color. When hair grows back, it often has a different color and texture, usually white or gray.
    • Most patients lose their hair during and after treatment and usually grow back within about 6 months.
    • Skin changes can resemble sunburn. Redness, irritation and ulceration of the treated area may occur, which is called wet peeling. In dogs, the skin becomes red, thick, moist, and scaly. In cats, the skin rarely becomes wet, but the skin may turn red and flaky.
  • Eye: conjunctivitis, keratitis.
    • If the eye is treated, side effects such as blepharitis, conjunctivitis and keratitis are possible.
    • The reduced tear flow makes the eye susceptible to corneal ulceration.
    • Cataracts and damage to the retina, which can lead to blindness, are also possible.
  • Oral cavity: inflammation of the mucosa.
    • If the oral cavity is treated, radiation can lead to mucositis, which is manifested by excessive salivation, bad breath (halitosis) and / or the formation of plaques or ulcers. As a consequence, this may result in the occurrence of secondary infections.
    • If the digestive tract is in the radiation field, diarrhea can also be observed.
  • Bones: missing.

Chronic effects

• Late side effects of radiation occur in tissues where cells divide slowly and infrequently, such as nerve tissue (brain and spinal cord), heart, and bones.
• Late side effects of radiation appear months or years after treatment (most often more than 6 months after the end of treatment) as a result of fibrosis and vascular changes. Cells try to divide but die from DNA damage instead. For these reasons, late side effects do not usually heal and can cause serious problems.
• The delayed effects can be serious or even life-threatening, and are generally permanent - they do not disappear once they occur.
• As with acute effects, they depend on the tumor and surrounding tissues that have been exposed to radiation.
• The risk of late effects from radiation is dose limiting as it is greater at higher doses per fraction. The radiation dose administered is adapted to the treated area, so the risk of serious late effects is less than 5% (1% for brain and spinal cord). However, the risk increases with higher radiation doses. This is what happens, for example. in the case of hypofractionated protocols in palliative therapy or stereotaxic protocols. Protocols using lower doses per fraction have a lower risk of late effects, thus allowing higher total doses to be delivered, leading to better tumor control.
  • Possible late side effects:
    • skin: hyperkeratosis, pigmentation,
    • eye: cataract, dry eye,
    • oral cavity: bone necrosis (rare),
    • bones: bone necrosis, secondary tumors (even many years after treatment).

Irradiation-induced tumors in veterinary medicine are extremely rare. In patients who live for years after treatment, it is possible for a tumor to regrow after irradiation, but to be considered a radiation-induced tumor, it must be in (or very close to) the irradiation field being treated, does not relapse of the treated tumor, and is present. at least 6 months after radiation, but usually longer.

These side effects are permanent but can sometimes be treated with surgery.

Overview of the side effects of radiation

Skin

Under normal conditions, skin cells mature and peel off. However, the stem cells present in the basal layer of the epidermis are constantly dividing to replace these dead skin cells. Radiation causes the death of rapidly dividing basal keratinocytes, which disrupts the skin renewal process and damages the skin barrier.

If an animal has a tumor or a surgical scar containing cancer cells that are on or just below the skin's surface, radiation effects on the skin will arise if the patient is treated with a full fractionated protocol.

Acute Effects

• Acute radiation dermatitis.
  • Transient hyperemia and erythema may occur in the irradiated area within a few hours after radiotherapy due to local dilation of the capillaries. Usually, this is not accompanied by any discomfort. After about 2-4 weeks of treatment, a so-called. dry exfoliation, i.e. painless exfoliation of the upper layers of the skin. Subsequently, ulceration of the skin surface occurs, turning into the so-called. into moist exfoliation (i.e. moist exudative dermatitis). Damp exfoliation is generally painful and patients are prone to secondary infection of the affected areas. The activation of local inflammatory pathways and degranulation of mast cells also contribute to the intensification of the inflammatory process and discomfort. Damp exfoliation is irritating to the pet and most patients try to lick and / or scratch the area. Avoid self-injury with an Elizabethan collar as this reduces the risk of delayed healing and infection. The increased risk of severe dermatitis is considered to be in areas with skin folds (facial folds in brachycephalic breeds), the pads, the skin around the eyes and the perineum.
  • Treatment. For the treatment or prevention of acute radiation dermatitis, each facility typically develops its own protocols. Management should be based on the severity and location of the dermatitis in each patient:
    • Elizabethan collars are recommended at the first sign of dermatitis to prevent self-harm. Self-injury to the irradiation sites can cause serious complications due to delayed healing and secondary infection.
    • As a rule, it is not recommended to treat patients with mild dermatitis limited to hyperemia and dry exfoliation. Patients with itching are often prescribed diphenhydramine.
    • Patients with wet / wet dermatitis are prescribed painkillers such as non-steroidal anti-inflammatory drugs, gabapentin, and amantadine. Parenteral treatment, e.g. sticking a fentanyl patch.
    • The affected areas should be shaved and cleaned at the first sign of moist dermatitis, and your doctor may also recommend topical application of the ointment. It is rather not recommended to apply ointments containing petroleum jelly to the skin. Animals tend to lick the ointment, which may intensify the early effects.
    • Patients with dermatitis around the eyes or face are recommended to use triple antibiotic or erythromycin eye ointment daily.
    • Systemic antibiotics such as cephalosporins or amoxicillin with clavulanic acid are used to prevent or treat secondary infection in patients with moderate to severe dermatitis.
    • Dressings on wounds are usually not recommended as radiation dermatitis is often exudative.
    • The skin reactions may worsen after the end of radiotherapy and be most serious after stopping treatment. The skin will heal in 2-4 weeks after worst effects have occurred, if there are no other complications (e.g. infection, steroid use and some systemic diseases).
    • Cats are generally more resistant to radiation from the skin. Most cats experience hair loss and dry flaking, which can be itchy.

Late side effects of radiation

• In most patients, chronic changes after irradiation are only cosmetic and do not cause discomfort.
• Loss of hair. Hair follicles and skin appendage glands are sensitive to radiation even at fairly low doses. Most people who receive radiation to tumors on or near the skin experience hair loss, which may be temporary or permanent. The coat usually grows back within 3-6 months, but this can vary with the seasonal hair growth of particular breeds of dogs and cats.
• Hair may grow back in a different color or texture. Often the hair that grows back is white or gray (leukotrichia).
• The skin may remain thinner or thicker than normal and the skin pigment may be darker or lighter than before radiotherapy (hyper- or hypopigmentation).
• Chronic skin lesions are poorly described in animals. These can include fibrosis, ulceration, and lymphedema. Increased expression of growth factor β (TGF-β) and other inflammatory cytokines causes fibrosis, endothelial damage and - in severe cases - skin atrophy and necrosis. Treatment of radiation induced fibrosis may be based on the oral administration of pentoxifylline.
• Surgical correction or even amputation may be necessary in patients with chronic wounds.

Lymphedema

If irradiation is carried out around the entire circumference of the limb, there may be swelling and edema in the limb distal from the radiation field. Radiation causes damage to the lymphatic vessels, fluid accumulation and swelling. This occurs in a small percentage of patients and may occur weeks to months after surgery. Treatment of lymphedema involves physical therapy and the use of painkillers.

mouth

Adverse radiation effects in the oral cavity can occur in patients with tumors located in the maxilla or mandible, in the hard or soft palate, and in patients with tumors in the nasal cavity, and sometimes in some patients with brain tumors or cranial tumors.

Inflammation of the oral mucosa. The mucosa may become red and swollen and its surface may ulcerate and form a yellow-gray plaque. Saliva may feel 'sticky' and thicker than normal and salivation is often abundant. Often there is a bad smell in the mouth (halitosis).

Poor appetite

Due to the discomfort of mucositis, patients may refuse to eat sufficient food. People undergoing radiation therapy report a decrease in the sharpness of taste, and this is likely to be also present in veterinary patients, especially if the tongue is in the radiation field. As commercial high-salt foods can cleanse irritants, it is advisable to introduce soft, cooked food such as. boiled chicken breast, turkey and rice or baby food (onion and garlic not included). Some patients prefer gruel-like food, while others respond better to small meatball-shaped pieces that can be swallowed whole. The animal should be encouraged to eat by hand-feeding or by heating the food. If your pet is unable to eat or drink while receiving radiation therapy, it may be necessary to insert a temporary tube into the esophagus or stomach. Consultation with a veterinary nutritionist may also be appropriate, especially if special or home diets are desired.

nasal cavity

Most animals with a tumor within the nasal cavity have nasal discharge before the start of radiation therapy. The amount of discharge may increase with or even with treatment and may be clear to white or slightly yellow in color, and sometimes it may also contain some blood. Such a "runny nose" usually resolves within 2-4 weeks after the end of radiotherapy, but because the tumor has caused damage to normal structures, it may not completely heal. In addition, the defense mechanisms of the nasal cavity will never be fully functional again due to the tissue tearing apart by the tumor and radiation damage to the normal mucosa. Therefore, even months or years after treatment, patients are more prone to bacterial or, less commonly, fungal infections of the nasal cavity (chronic rhinitis).
If there is an increase in secretion or a change in color (especially yellow or greenish), see your veterinarian as antibiotics or further investigation may be needed. Sneezing, retrograde sneezing, coughing, or labored breathing usually resolve after radiation therapy, but in some patients or with certain types of cancer, these clinical signs may never fully resolve.

Esophagus and trachea

Esophageal and tracheal side effects may occur in animals with a tumor located on the neck or chest.

• The most common acute side effects of radiation are tracheitis or esophagitis. This can manifest as a dry cough, decreased appetite, vomiting, regurgitation after eating, and / or excessive or painful swallowing. You may also notice excessive salivation and visible discomfort when swallowing.
• Late side effects are rare and include scar formation within these organs. While the trachea has rigid rings that hold its shape, the esophagus does not have any "scaffolding" and scar tissue can constrict the lumen of this organ. This results in difficult swallowing of solid food or - in severe cases - even prevents it. This scar tissue formation occurs for many months or years after therapy. If acute esophageal side effects are severe, perforation may occur in the esophageal wall. There is a life-threatening situation.

Eyes

Even though you make every effort to avoid eye irradiation, one or both eyes may be in the radiation field when treating tumors in the nose, mouth, or brain.

• Conjunctivitis and keratitis. The superficial layers of the eyeball and conjunctiva may become irritated, reddened and inflamed.
• KCS. The tear glands are also sensitive to radiation and can reduce or stop producing tears, causing a condition called dry keratoconjunctivitis (KCS) or "dry eye". This may or may not be permanent depending on the animal's sensitivity to radiation and may start as early as 2 weeks after treatment or as late as 6 weeks. It is necessary to treat the eye with artificial tears to keep the cornea moist, otherwise it will be damaged.
• Cataract. The lenses of the eye are also sensitive to radiation. An eye that is in the irradiation field may develop cataracts 6-12 months after radiotherapy. The patient may retain some vision or may lose sight of this eye altogether due to cataracts. Many blind animals can learn to adapt to their environment and maintain a good quality of life. However, if blindness affects the animal's quality of life, cataract surgery can correct blindness in most patients.

Ears

When treating tumors of the brain or skull, one or both ears may be in the radiation field.

• Inflammation of the ear canal. The epithelial lining of the ear canal is just as irritated as the skin, and the ear canals can become red or ulcerated. You may notice discharge from the ear.
• Some owners report that their pets do not hear well after radiation therapy. The exact cause of hearing loss is not well understood. This can be the result of permanent damage to the fine hairs in the ear canal, or a build-up of shed skin cells and secretions.
• Some animals have chronic ear problems (scratching or rubbing the ears) after radiation therapy.
• Rarely, a patient develops a head tilt or imbalance due to changes in the inner ear. This can be a temporary or, rarely, permanent problem.
• In order to minimize irritation of the ear canal, ear drops recommended by your veterinarian may be administered.

The brain and spinal cord

Small areas of the brain can end up in the radiation field when treating tumors in the nose or mouth. Radiation very rarely causes neurological abnormalities in such patients. If they do occur, it is usually more than 6 months after radiotherapy. Patients being treated for brain tumors are more likely to experience side effects in the brain:

• Acute effects may occur immediately after treatment or up to two weeks after irradiation.
  • It is most commonly associated with anesthesia during radiation therapy, as some anesthetic drugs can increase intracranial pressure, leading to neurological side effects.
  • Radiation can also cause inflammation of the normal brain tissue surrounding the tumor, which can lead to a variety of neurological disorders: from mild dementia and photosensitivity to seizures and unresponsive in severe cases.
  • There is a slight risk of death in the short term, usually in animals with very large tumors or those that were already very debilitated before treatment was started.
• Acute delayed effects occur in approximately 10-30% of patients receiving radiation therapy for brain tumors and can occur 2-6 months after radiation therapy.
  • Presumably they are associated with edema and inflammation of the brain and spinal cord secondary to radiation and / or death of cancer cells. This may manifest as a sharp worsening of neurological symptoms. These changes are usually temporary, but it may take months for you to recover.
  • Recurrence in the post-irradiation period is unlikely but possible in aggressive brain tumors.
• Late side effects on the brain and spinal cord are rarely seen up to 6 months after stopping treatment, but can occur many years later. Late effects on the brain can be very serious or life-threatening as the vast majority of brain cells do not divide in adults, and damaged or killed neurons are essentially not replaceable.
  • Depending on the part of the spinal cord treated, the patient may have reduced ability to move the fore and hind limbs and may even become completely paralyzed.
  • If the side effects are related to the brain, the animal may have decreased consciousness, altered posture or behavior, seizures, or other neurological symptoms.
  • Some patients treated for brain tumors improve dramatically with radiation therapy, however some animals may deteriorate with treatment.

Lungs

If the tumor undergoing radiation therapy is located on the wall or in the chest cavity, some of the lungs may be exposed to radiation. The lungs are very sensitive to radiation damage. Lung damage occurs in two phases:

• In the first phase, 2-6 months after the procedure, pneumonia occurs.
  • Most animals show no symptoms, however, the radiological features of pneumonia can be seen on a chest X-ray.
  • Some patients experience a cough and / or difficulty breathing.
  • Pneumonia is usually temporary and can be treated with medication if needed.
• The second phase of damage is associated with scarring of the lung tissue (fibrosis). Even very small doses of radiation can lead to lung fibrosis of approx. 9-12 months after radiotherapy, causing loss of normal organ function.

Colon and bladder

In the case of radiotherapy of tumors in the pelvic area, part of the colon, rectum and bladder may be in the radiation field.

• Colitis may develop at the end of the second week of treatment and may persist for 2-4 weeks after stopping treatment.
  • Colitis is usually accompanied by diarrhea which may contain mucus and / or small amounts of fresh blood. It is possible for the animal to pass a small amount of faeces more frequently. Some patients have long-term intermittent colitis.
  • Diarrhea observed immediately after starting radiotherapy (within 1-3 days) is not related to radiation but rather to the stress of hospitalization. Such colitis is treated with oral medications in most cases and may resolve with therapy. If anxiety and stress persist, diarrhea may not be completely relieved by the end of therapy.
• Inflammation of the bladder and can be present at the same time as colitis. Commonly observed symptoms include straining to urinate, blood in the urine or an increased need to urinate.
• Late side effects are rare but can occur many months after irradiation and are associated with scar tissue formation.
  • If a scar forms around your colon, it can narrow it, making it difficult to pass stools.
  • Narrowing of the urinary tract can result in prolonged effort to urinate. If the scar is completely blocking the flow of urine, it is a life-threatening situation.
  • Formation of fistulas (holes in the walls of the colon, rectum, or urethra) secondary to radiation is extremely rare, but if they do occur, life-threatening.

How to prevent the negative effects of radiation therapy?

The effect of radiation therapy on both the tumor and healthy tissue depends on several factors, including:

• Fractionation. The principle of fractionation is to divide the total dose into several smaller doses over several days or weeks, which maximizes the effect of radiotherapy on the tumor but minimizes side effects on healthy tissue.
• Total time of the procedure. Normal tissue toxicity depends on the total time over which the dose is administered and the size of the fraction. Dividing the total dose into smaller and frequent fractions reduces the risk of side effects and allows you to increase the total dose per area compared to one high dose treatment.
• Irradiation volume. It is very important in dose setting and treatment planning. The smaller the volume to be irradiated, the higher the total dose that can be tolerated by this irradiated field.
• Technique of radiation therapy. New radiotherapy techniques enable precise dose delivery and preserve healthy tissue, reducing potential side effects. They can also increase the dose, which can improve tumor control and result in increased cure rates.
• Patient and biological factors. It is always recommended to approach the patient individually when planning radiotherapy, taking into account both his clinical condition, test results and tumor advancement assessment as well as the expected behavior of histologically specific types of tumors.

Tissues differ in their response to radiation therapy, and some organs are more sensitive to radiation than others. The most sensitive organs are the eyes, kidneys and spinal cord, therefore the dose of radiation directed at these organs is kept to a minimum. The lungs, liver, thyroid gland, ovaries and testes are also sensitive and have minimal normal tissue tolerance, so radiotherapy is rarely performed, especially in veterinary medicine.

One of the secondary effects of radiation is its effect on normal, healthy tissue, which can kill rapidly dividing healthy cells such as skin cells and intestinal mucosa. If the treatment is well planned (that is, the radiation dose is higher for the tumor compared to the surrounding healthy tissue), the tumor can be successfully treated and eradicated. Since all radiotherapy treatments are recommended within the limits of normal tissue tolerance, any reduction in the dose of radiotherapy may result in insufficient tumor control.

It is very important to prevent the adverse effects of radiation therapy, especially in patients who are likely to survive long term. Preventive measures include restricting patient movement during surgery by using positioning devices and creating irradiation plans that target the neoplastic tissue, while avoiding normal tissue as much as possible.

Frequently asked questions about radiation therapy in animals

How effective is radiation therapy in dogs and cats?

Much higher doses of radiation are used in humans to heal the patient. When a cancer is diagnosed in an animal, it is very rarely that the goal of treatment is complete recovery. In dogs and cats, lower doses are used to prolong a good quality of life (rather than a cure) with as little suffering as possible for the patient. In this way, veterinarians usually try to maximize the amount of time a pet can live while enjoying a good quality of life. Palliative radiation therapy is one way to prolong your pet's life in comfort. Its purpose is not to eliminate the tumor (although it does occasionally), but to reduce the negative impact it has on the body of your dog or cat. When tumors grow, they are often painful and can physically interfere with the proper functioning of certain parts of the body (e.g. the passage of faeces through the colon) and may bleed, drastically reducing the animal's quality of life. Palliative radiation therapy can eliminate or at least reduce all of these symptoms for a period of time.
Radiotherapy is rarely the first option for treating a tumor. Where possible, complete removal by surgery or chemotherapy is preferred. However, for tumors that are unsuitable for surgery, radiation therapy provides a highly effective and life-prolonging treatment.

What are the benefits of radiation therapy?

In some cases, radiation therapy may be the final treatment for cancer. However, even if a cure is not possible, radiation therapy can provide some relief. The most important benefits of radiotherapy are:

• destruction of tumors in inaccessible places,
• reducing the size of the tumor,
• pain relief, reduction of pressure or bleeding,
• improving the animal's quality of life,
• an important component of a broader spectrum of treatments, which may include chemotherapy or surgery.

Does radiation therapy hurt?

Radiotherapy is painless and has very few side effects in low doses. The most common side effects are related to the treated area. Swelling, skin damage, and / or hair loss may occur. In addition, some animals may appear tired or less active during radiation therapy.

Is the pet's isolation required after radiation therapy??

Often, owners are concerned that an animal that has received radiation therapy may need to be isolated after treatment because of the risk of radiation affecting other people or pets. This is not the case with this type of radiation. When the instrument is turned off, the radiation beam does not exist and does not pose a threat to anyone or anything else.

How much does radiation therapy cost for a dog and a cat?

It is very difficult to make accurate estimates of an animal's cancer treatment. The radiotherapy procedure itself is expensive, but it also entails costs, such as:

• consultation with a doctor dealing with veterinary oncology,
• performing or repeating tests (e.g. computed tomography),
• possible need for surgery and / or chemotherapy,
• travel costs to a reference center,
• accommodation costs,
• another.

The cost of radiotherapy itself can vary considerably depending on whether its goal is palliative or definitive treatment, and can be several thousand zlotys. All treatment plans are unique for each patient, and the exact pricing is usually presented only after an oncological consultation.

Can radiotherapy in a dog or cat be performed in Poland??

There are relatively few specialized centers that have the necessary equipment and knowledge to conduct radiotherapy in animals. The two main centers in Poland offering this type of treatment are:

• RTWet - Polish Center of Veterinary Radiotherapy (Miedniewice),
• Vetspec - Small Animal Health Center (Groblice).

Summary

Radiotherapy is an increasingly used method in veterinary medicine. It is no longer a "secret" treatment that is available only in research facilities and is increasingly included in treatment protocols used in animals with cancer. The most important facts about the use of radiation therapy in animals are below:

• Radiotherapy, like surgery, is a regional treatment. Therefore, it does not apply to the treatment of extensive or generalized diseases.
• Radiotherapy can be regarded as the primary treatment for all malignant tumors in pets when there is any doubt about the possibility of complete surgical removal.
• Radiotherapy can be used in neo - and / or adjuvant treatment along with surgery and chemotherapy.
• It can be radical (curative) or palliative.
  • Radical treatment is aimed at healing the tumor to the point of remission, therefore side effects are inevitable.
  • Palliative treatment aims to relieve clinical symptoms and ensure a good quality of life with minimal side effects.
• The effect of radiotherapy depends on the fractionation protocol, total treatment time, irradiation volume, and patient factors.
• Radiotherapy must be properly planned to ensure an adequate minimum dose.
• Radiotherapy is generally well tolerated with minimal to moderate side effects in normal tissues depending on the selected fractionation regimen.
• Increasingly, newer radiotherapy techniques are used in veterinary medicine to allow precise dose delivery and preservation of normal tissue, thus reducing the risk of potential side effects.
• Common cancers treated with radiation therapy include brain tumors, nasal tumors, mast cell tumors, soft tissue sarcomas, oral tumors, and osteosarcomas.
• After making the decision about radiation therapy, you should institute immediate treatment. Even a delay of several days can decide about success or failure.
• Standard dose regimens used in human radiation therapy are usually not practical for animals that require general anesthesia for treatment. Many animals are old and in poor condition and multiple general anesthesia is contraindicated. Therefore, treatment is carried out with one, two or three large doses.
• Various parameters and variables are assessed to determine whether radiotherapy may be of benefit to an individual patient. The following factors are taken into account: expected result, tumor reactivity, tumor location, presence of microscopic versus macroscopic disease, hardware capabilities and software availability, and whether concomitant or post-radiotherapy treatment is planned.

Each year, more than 10 million dogs and cats will be diagnosed with a malignant tumor. Remember that cancer is a disease and does not always have to be a death sentence right away. Still developing cancer treatment techniques enable us to control tumors more and give us the weapon to fight against previously incurable diseases. Today, we can do more than ever, especially if the tumor is in a delicate anatomical location, such as. brain, spinal cord or internal organ. The use of radiotherapy is therefore worth considering when all other treatment methods are insufficient.

What is radiotherapy?

Radiotherapy is a therapeutic procedure that uses ionizing radiation to kill cells, and is often part of the treatment of various types of cancer.

Can radiotherapy be performed in Poland??

Yes, there are currently two facilities in Poland that offer this type of treatment.

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