Radiotherapy

During radiotherapy radioactive or ionizing beams are aimed at the tumour, resulting in damage of quickly dividing cells (such as cancer cells) within the irradiated region. The objective of radiotherapy is to destroy tumour cells while further sparing healthy peripheral tissues. The sensitivity of cells to ionizing rays generally depends on three factors: (1) cellular oxygenation (the more perfused/rich in oxygen the tumour is, the better the radiation therapy works), (2) the phase of the cell cycle at the time of irradiation (cells are more sensitive to damage when dividing) and (3) the cell’s capacity to repair damage (cancer cells are less able to repair DNA lesions than healthy cells). That is why the cancerous tissues need to be irradiated multiple times.

The therapeutic principle of radiotherapy is to divide the total radiation amount in several doses (fractions). This splitting of the dose leads to a better tumour response, while preserving the functionality of the healthy tissues for repair.

Fractionation

Generally speaking, the greater the number of fractions, the higher the total dose administered can be, while reducing the risk of delayed side effects. This type of protocol is preferred for curative treatments (= treatment with the goal to cure the patient). Depending on the animal's situation, the radiotherapist can opt for conventional fractionation, hyperfractionation or hypofractionation:

  1. Conventional and hyperfractionation: this is a treatment schedule characterized by lower doses at each treatment session and more treatment sessions vs hypofractionation. There’s a higher risk of side effects on adjacent tissues in the short term, but a lower risk in the long term. In veterinary medicine doses are administered in 12 to 16 sessions (conventional fractionation) or 18 to 20 sessions (hyperfractionation) with 3 to 5 sessions per week over 3 to 4 weeks. Depending on the animal’s case, a different approach may be chosen. For example, for more aggressive tumours, a higher dose can be given via conventional fractionation, whereas when specific organs are at risk or it concerns a young animal, a lower dose per session could be more appropriate (hyperfractionation).
  2. Hypofractionation: this treatment schedule is characterized by higher doses at each treatment session and fewer treatment sessions vs hyperfractionation. There’s a lower risk of side effects in the short term, but a higher risk in the long term. It is mainly done in patients with metastases (palliative treatment) or when excision surgery is not possible. The doses are administered in 2 to 5 sessions with 1 session per week over 1 to 4 weeks.
Radiotherapy use

Radiotherapy can be used as a sole treatment option or in combination with other treatment modalities.

  1. As a sole treatment: radiotherapy can be used to treat various radiosensitive lesions at superficial and deeper locations. With the latest technology and highly precise planning techniques now available in several centres, there are an increasing number of applications for radiotherapy as a sole treatment - i.e. without surgery (such as head/neck tumours (in the mouth, nose and thyroid glands), central nervous system tumours (in the brain and spinal cord), heart base tumours, adrenal gland tumours, bladder and prostate tumours, ...).
  2. As a complementary treatment: radiotherapy can be used together with/instead of chemotherapy, or following surgery. If radiotherapy is administered before surgery, the tumour will be more oxygenated and therefore more responsive to radiotherapy. Furthermore, when the tumour region has been irradiated before surgery, this reduces the risk of tumour spread as a potential consequence of surgical manipulations. However, it’s not always possible or useful to irradiate before surgery. Potential disadvantages include wound healing complications and delay of the surgical procedure. Radiotherapy can also be administered during surgery, to irradiate possible remaining cancer cells. This means that the tumour bed is irradiated before suturing the skin. This technique is increasingly used in human medicine; it makes it possible to destroy a part of the cancer cells which might have remained after tumour excision. Furthermore, this technique could have a local immunomodulatory effect, activating the immune system against the cancer cells.

Radiotherapy leads to shrinking or in the best case to complete destruction of the tumour. Some tumour types, such as lymphoma, are very sensitive to radiotherapy and can disappear in a few days, whereas most tumour types respond within 4 to 12 weeks to radiotherapy.

Types of radiation therapy

Radiotherapy with curative intent is typically administered over 3 to 4 weeks with 3 to 5 sessions per week (average of 12-20 treatment sessions). Palliative radiotherapy is mainly used to enhance quality of life, reduce pain and keep the hospitalization period as short as possible. E.g. for the treatment of tumours that cannot be surgically removed, when multiple anaesthesia sessions are impossible or in case of metastases. Because the patient needs to be perfectly still, the animal is sedated during the treatment session. The treatment session itself usually takes only a few minutes.

There are 3 main types of radiotherapy: Ortho/megavoltage radiotherapy, brachy- or Curietherapy, and metabolic radiotherapy

Ortho/megavoltage radiotherapy (external radiation)
For external radiation, machines produce X-rays that penetrate the tissues.
Orthovoltage (low energy X-rays produced by X-ray tubes):
A single beam provides the dose, whereas for megavoltage multiple beams are used. Orthovoltage is very suitable for surfaces or tumours located in the skin or mucous membranes (= at small depth). Orthovoltage radiotherapy can be used during surgery (intra-operative radiotherapy), e.g. in case of relapse of an aggressive tumour or when sufficient surgical margins are difficult to obtain. The surgical zone is irradiated after tumour removal, but before suture. This way, potentially remaining cancer cells are irradiated which reduces the chances of relapse as irradiation decreases the production of growth factors and stimulates the immune system to fight cancer cells. Irradiation of the surgical site can reduce or even prevent further post-operative radiotherapy sessions (particularly of interest for animals for whom the number of anaesthesia’s should remain limited, such as a dog with heart failure, or when repeated transportation is not possible).
Megavoltage (high energy X-rays or electrons produced by linear accelerators):

The beams penetrate the tissues more deeply than is the case with orthovoltage. With megavoltage, a lower percentage of the dose is delivered to the skin resulting in less possible skin damage. Megavoltage is suited for both superficial and deeper lesions. Of note, the units emitting megavoltage beams are mounted on an arm that can rotate 360° around the animal, which allows multiple angles via which the tumour can be irradiated. Megavoltage allows a dose distribution adapted to the tumour’s shape, whereas orthovoltage allows less flexibility for the dose distribution.

For tumours located deeply or in an anatomically complex location, a scan needs to be made that charts the tumour’s precise location and size. These scanner images are then used to create a radiation administration plan. Linear accelerators can come with various planning techniques (3D CRT, IMRT/VMAT, SRT) that allow a precise modelling of the tumour (not all linear accelerators have these technique capabilities). This means that based on the obtained model of the tumour, an even more precise irradiation of the tumour is possible and it allows a better sparing of surrounding healthy tissue. All planning techniques require a precise positioning of the animal: the animal must be positioned for the imaging in a way that can be closely replicated on a day-to-day basis for treatment.

  • 3D CRT and IMRT: for both planning techniques, the tumour and normal organs are outlined via the CT scans in 3D and multiple beams are positioned around the patient to deliver the radiation. Intensity-modulated radiation therapy (IMRT) allows greater finetuning of the radiation dose than 3D Conformal Radiation Therapy (3D CRT) (in ten to 25 treatment sessions). With IMRT, the radiaton beams are divided into a grid-like pattern, separating the one big beam into many smaller 'beamlets'. These beamlets help to protect the healthy tissues. Subsequently, IMRT techniques are significantly more complex than 3D CRT and require the close collaboration and expertise of an appropriately-trained multidisciplinary team (which could consist of radiation oncologists, radiologists, qualified radiotherapy technicians and medical physicists). For both planning techniques, the tumour does not necessarily need to have clear boundaries.
  • SRT: Stereotactic radiotherapy (SRT) relies on a similar planning technique as IMRT/VMAT but uses much tighter margins around the target. It irradiates the tumour from many different angles around the body. The beams meet at the tumour. This means the tumour receives a high dose of radiation (in one to five treatment sessions) and the tissues around it receive a much lower dose. SRT is only used to treat well-defined tumours and not microscopic disease. From a practical standpoint, SRT minimizes the number of anaesthesia episodes required in older and sometimes debilitated dogs and is generally more convenient for the dog owner.

The veterinary radiotherapy specialist will decide which treatment is best for your dog, based on their tumour's size and extent, the type of tumour and location.

Brachy- or Curietherapy
The source of radiation (radioactive needles or seeds) is placed inside or next to the tumour by the surgeon. This way, the radiation source will mainly irradiate the tumour tissue and affect the surrounding healthy tissue as little as possible. Because these needles or seeds irradiate over a very limited distance (the level of radiation is negligible at a distance of 5 mm from the needle), this type of radiotherapy is very well suited for irradiation of hollow tissues (nasal cavity, urethra, colon, etc.) and for locations close to important structures such as the eye, the lungs or the intestines. Because of the reduced radiation on healthy tissue, the side effects are reduced as well. This type of radiotherapy usually requires a hospitalization of a few days, depending on the used administration method. The procedure depends on the tumour to be treated, the kind of implant and the dosage of radiation. The implants are placed under local anaesthesia or general sedation. This type of radiotherapy is used separately or complementary to surgery and/or external radiation.
Metabolic radiotherapy
This therapy consists of irradiating a tissue via a radioactive molecule. In veterinary medicine, it is mostly used for thyroid tumours, as most thyroid tumours capture iodine molecules. For radioactive iodine radiotherapy, this characteristic is exploited by administering radioactively charged iodine molecules (I-131). The radioactive iodine accumulates in the thyroid (tumour). As the radioactive compound decays, radiation is released and local irradiation of the thyroid cancer cells occurs. The treatment requires a hospitalization of 7-21 days (the duration of the hospitalization varies between countries) because the radioactive Iodine is excreted via urine and feces and may be harmful to people and other animals that are in contact with the dog.
Tumour types sensitive to radiotherapy

Tumour types generally sensitive to radiation include:

  • brain tumours (meningioma, schwannoma, choroid plexus tumour, astrocytoma, glioma, pituitary macroadenoma and adenocarcinoma)
  • nasal tumours (mainly lymphoma, carcinoma)
  • oral tumours (acanthomatous epulis, squamous cell carcinoma, melanoma)
  • tumours on the limbs/body (small soft tissue sarcoma, lymphoma, mast cell tumour, ceruminous gland tumour, thyroid carcinoma, bladder tumour, prostate tumour, perianal adenoma, anal sac adenocarcinoma).

Radiation is also used as palliative therapy for osteosarcoma, as it has a very efficient painkilling effect.

Side effects radiation therapy

Side effects of radiotherapy can appear fast (acute) or can be delayed. The risks and benefits for the individual patient should discussed with the radiooncologist before treatment.

Acute effects

Acute effects are mainly seen in quickly replicating tissue: bone marrow, epidermis, cells of the gastro-intestinal tract, mucous membranes (inflammation) and cancer cells. The total administered dose, the intensity of the dose, the amount and location of treated tissue are all factors that influence the side effects on healthy tissue. These acute effects will appear during radiotherapy with a curative intent, but they subside as time passes and appropriate care is given. Inflammation of the mucous membranes generally occurs within 7 to 10 days after the start of the treatment, inflammation of the skin within 12 to 14 days.

  • After irradiation of the oral cavity, acute effects can consist of inflammation of the mucosae, which can manifest itself through tenderness of the mouth and thickened saliva. This resolves within two weeks after the end of the treatment. Redness of the irradiated skin can occur, along with (temporary) hair loss, dry and moist desquamation and/or swelling of the lips.
  • After irradiation of the nasal cavity, the acute effects can be similar to those above, but as the eye is closer to the irradiation zone, inflammation of the eyelids and mucosae can occur, as well as dry eye (lower production of quality of tear fluid).
  • After irradiation of the brain, acute effects can consist of inflammation in the back of the oral cavity, the eye and ear. A mild to moderate exacerbation of the neurological signs is often transient (occurs 3-16 weeks after the treatment), but it can take a while for the symptoms to resolve.
  • After irradiation of the trunk or extremities temporary hair loss can occur, change in the colour of the hair and/or skin, dry or moist desquamation (accompanied by pain and itching) within 3-5 weeks after the start of the treatment.
  • After irradiation of the bone, inflammation of the skin can occur, as well as an increased risk of fracture. Because bone tumours weaken the bone and the radiotherapy has a painkilling effect, the dog may us the affected paw more and because of this, there’s an increased weight-bearing which heightens the risk of fracture.
  • After irradiation of the abdomen, inflammation of the mucosae can occur. E.g. inflammation of the intestines can lead to diarrhoea.
  • Irradiation of the thorax is often used for relief of respiratory distress. Effects of irradiation can include coughing and fast irregular heart beating.
Late effects

Late effects are mainly seen in tissues that replicate slowly (such as the brain, the spinal cord, the muscle, the bone, the kidney and the lung). Because the damage is often irreversible, this limits the total dose of radiation that can be administered. To calculate the most efficient dose, a CT-scan is almost always necessary before the start of the irradiation.

  • After irradiation of the oral cavity, late effects can consist of production of fragile bone (uncommon), dryness of the mouth due to dysfunction of the salivary glands, fistula between the nasal and oral cavity.
  • After irradiation of the nasal cavity, cataract and eye damage can occur.
  • After irradiation of the brain, 6 months to years after irradiation, depending on the dose, volume and fractions administered, degradation of the irradiated brain region can occur.
  • Effects of thorax irradiation can include heart failure.
Where is veterinary radiotherapy available? (non-exhaustive list)

Radiation with megavoltage radiotherapy is offered at

Radiation with orthovoltage radiotherapy is possible at

Radiation with brachy- or curietherapy is possible at

Radiation with metabolic radiotherapy (I131) for thyroid tumours is possible at

References
  1. Aurélia Klajer. Tout ce que vous avez toujours voulu savoir sur la Radiothérapie sans jamais oser le demander. Webinar Vet Academy, October 4th 2023.
  2. Pierre Boyé and Jérôme Benoit. Place de la radiothérapie dans la stratégie thérapeutique anticancéreuse chez le chien et le chat. Le Point Vétérinaire, Octobre 2016 / N° 369.
  3. Cancer Research UK. Stereotactic radiotherapy. https://www.cancerresearchuk.org/about-cancer/treatment/radiotherapy/external/types/stereotactic-body-radiotherapy-sbrt - accessed November 2023.
  4. Dierenkliniek Randstad, http://www.dierenkliniekrandstad.be/medische-info/oncologie/behandelingsmogelijkheden/behandelingsmogelijkheden - accessed May 2019.
  5. LaRue SM, Gordon IK. Radiation Therapy. Withrow and MacEwen's Small Animal Clinical Oncology, 5th edition, Chapter 12 (p 180-195).
  6. LaRue SM, Gordon IK. Radiation Therapy. Withrow and MacEwen's Small Animal Clinical Oncology, 6th edition, Chapter 13 (p 213-225).
  7. UPMC Hillman Cacer Center. 3D Conformal Radiation Therapy. https://hillman.upmc.com/cancer-care/radiation-oncology/treatment/external-beam/3d-conformal - accessed November 2023.