Radiotherapy in Horses (Equis) | Vetlexicon
equis - Articles

Radiotherapy

ISSN 2398-2977


Synonym(s): Radiation, brachytherapy

Introduction

  • Ionizing radiations used for therapeutic purposes in veterinary medicine include:
    • Beta radiation (high energy electrons).
    • Gamma radiation (electromagnetic radiation).
    • Applied by brachytherapy or more rarely in horses by teletherapy.
    • Currently teletherapy is not used to any extent in equine medicine but few reports of individual cases support value of procedure.
See Radiotherapy: radiation sources table.
  • Exposure to ionizing radiation kills cells by producing secondary charged particles and free radicals in the nucleus.
  • These cause different types of DNA damage and prevent successful mitosis.
  • Radiation damages both normal and tumor cells, but normal cells are better able to repair radiation damage, and can usually repair and function normally, whereas tumor cells will die in response to appropriate doses of ionizing radiation.
  • Other structures may be involved in the response of tissue radiation, such as proteins and lipids in the cell membrane, and radiation may also lead to exposure of the immune system to abnormal epitopes, encouraging a pro-inflammatory, tumor-specific immune response, contributing to tumor regression.
  • Different cells have different sensitivity to radiation, mostly because of differences in the rate of cell division; cells that are actively dividing will be damaged by much lower doses of radiation than those required to destroy a well-differentiated cell.
  • Early unwanted effects of radiation can be seen within a few weeks of the completion of a treatment course, and may include skin erythema, desquamation of the skin, and depigmentation.
  • Late unwanted effects may be seen many months or years after radiotherapy, such as fibrosis, bone necrosis, and (in periocular locations) cataract formation

Uses

  • Ionizing radiation of tumor masses.

Advantages

  • Very effective.
  • Slow effects (easier to prevent excessive regional cytotoxic effects).
  • Good cosmetic effects.
  • More effective in fast dividing cells.

Disadvantages

  • Operator exposure (occupational hazard).
  • Cost.
  • Availability.
  • Logistics.
  • Non-discriminatory (normal cells are also affected) can have serious effects on rapid dividing cells such as bone marrow and testicular cells during treatments for slower growing masses (such as keratinocytes or fibroblasts) where treatment is given local to these, although shielding and careful planning minimizes these effects.
  • Administrative: long inventory and accountability.

Technical problems

  • Radiation regulations and Health and Safety at Work considerations Radiography: radiation safety.
  • Licensing requirements for both method and facility for procedure.
  • Training of staff used.

Alternative techniques

  • Chemotherapy.
  • Surgery/cryosurgery.
  • Immune methods relying on immunological recognition of neoplastic tissues.

Time required

Preparation

  • Considerable planning is required to ensure effective use while minimizing unwanted effects and operator hazards

Decision taking

Criteria for choosing test

  • Safety.
  • Efficacy.
  • Patient compliance.
  • Cost effectiveness.

Risk assessment

  • Very high operator risk with inappropriate use of radiation.
  • Zero significant risk for patient.

Requirements

Personnel

Veterinarian expertise

  • High level of qualification with special licensing of operator and facilities required.

Anesthetist expertise

  • Most brachytherapy techniques can be successfully performed under standing sedation.
  • General anesthesia is required for teletherapy techniques.
  • Some interstitial radiation methods require general anesthesia Anesthesia: general - overview.
  • Ophthalmic procedures may require a relatively 'deep' level of general anesthesia.

Nursing expertise

  • Specialist nurses required during assistance.

Other involvement

  • Radiographer with experience is helpful.

Materials required

Minimum equipment

Ideal equipment

  • Full radiation protection clothing, capable of gamma radiation control, ie heavy lead apron and gloves in addition to barriers.
  • Teletherapy requires specific building requirements for appropriate shielding.

Minimum consumables

Other requirements

  • Special licensing requirements.

Preparation

Pre-medication

Dietary preparation

  • Nil specifically.

Site preparation

  • Careful surgical clip and scrub of implantation sites.
  • Careful cleansing if topical brachytherapy is to be applied.

Other preparation

  • Full careful planning is essential in all cases.
  • All equipment to be set out before start to minimize exposure.
  • Careful log entries need to be made in a notebook, especially with implants. Information entered should include, where appropriate:
    • Specifics about the patient.
    • Physical characteristics about the neoplastic mass.
    • Calculated dose to be delivered.
    • Duration of exposure.
    • Date of removal.

Restraint

Technique

Approach

Step 1 - Restraint

Step 2 - Therapy

  • Apply by implantation (Iridium-192/Gold-198).
  • Topical plaque application does not require general anesthesia and is safe using intact plaque (plesiotherapy).
  • Apply via radiation catheters and a remote afterloader (high dose rate brachytherapy technique).

Step 3 - Recovery

  • Full radiation isolation if implants used.
  • No isolation require if high dose rate brachytherapy, plesiotherapy or teletherapy are performed.

Core procedure

Step 1 - Teletherapy  

  • Teletherapy applied by beam of radiation directed from continuous or pulsed source, usually via a linear accelerator.
  • 'Tele' is derived from the Greek for long, and the term teletherapy is used to describe a technique where the radiation source is at some distance from the tumor.
  • Performed far less frequently in equine medicine, mainly for logistic and capital cost reasons.
  • General anesthesia is essential Anesthesia: general - overview.
  • Extremely high energy alpha, beta or gamma radiation produced in a beam form (usually using a linear accelerator) directed from the source towards the tumor tissue.  Multiple beams can be applied to provide a therapeutic dose in an internal locus without significant damage to surrounding tissues (requires computer controls and a stationary patient).
  • Relative penetration of various radiations limits effect and applications but multiple beams can be used to create a radiation hot-spot which with careful positioning can be very finely defined.  Such a technique may be used to apply fractionated doses simultaneously, ie single beams not being of sufficient power to damage tissues through which they pass but focusing at a central point where the combined power is sufficient to cause ionization of the target DNA.
  • Larger doses can be given and more extensive tumor cells can be destroyed in this way.  Single beam applications usually require multiple fractionated doses and in most cases this would require repeated general anesthesia making the procedure considerably more difficult.
  • Modern linear accelerator are becoming ever more sophisticated, allowing targeting of the tumor from several different directions to minimize the exposure of normal tissues between the machine and the tumor, therefore providing an effective tumor treatment whilst minimizing side-effects.
  • Currently in any case, limited to use on distal limbs and the head. Not generally considered suitable for periocular lesions because there is no effective way to shield the eye from such high energy radiation.
  • Careful imaging, planning and positioning of the patient is essential.

Step 2 - Brachytherapy

  • Brachytherapy is derived from the Greek 'brachy' meaning short, and refers to radiotherapy where the radioactive source is in direct contact with the tumor.
  • Brachytherapy also applies to radiation materials which are introduced into the bloodstream with delivery to a target organ where it is deposited and accumulates in sufficient quantity to cause ionization of cells: 
    • This technique is seldom used in horses but has become increasingly valuable as monoclonal antibodies are developed so that the radioactive labeled antibody has a specific target cell type to which it adheres.
    • Process is elegant in concept but has inherent limitations.
  • Most frequent methods include sources of beta and gamma radiation implanted into the tumor mass.

Interstitial brachytherapy

  • Radioactive implant inserted into tissues and left in situ until required dose has been delivered, eg iridium-192, gold-198.
  • Gamma radiation continuously emitted through the target tissue and the relative emissions and lengths of source can be adjusted.
  • Radiation is applied in fractionated doses calculated to deliver the required lethal overall dose - more important for beta radiation than for gamma radiation.
  • technique used primarily for treatment of superficial tumors situated in areas which are not amenable to surgery, or which have recurred after previous treatment attempts by other methods.
Iridium-192 - low dose rate
  • Wires or seeds are implanted into the tumor, where they are left for a specified time and removed when the prescribed radiation dose has been achieved.
  • Sources are expensive and require specialized facilities for stabling and care over the period of treatment, which may be up to 10 days or more. The horse must be kept isolated during this time as the implants remain radioactive and therefore a health and safety concern for personnel.
  • Half-life is 72 days.
  • Treatment over 10 days usually provides 10,000 rads (sufficient for fibroblast tumors such as sarcoid Sarcoid and fibrosarcoma Skin: fibroma / fibrosarcoma).
  • Relatively safe during implantation procedure, although some level of operator exposure is inevitable during implantation and removal.
  • Sources must be removed after required duration.
  • Implants can become displaced and lost, which necessitates exposure of personnel to potentially quite high doses of radiation whilst attempting to locate the implants, and if the implants are consumed by the horse it may be some time before they are located in its feces and the horse can be discharged from isolation.
  • Implants are very expensive and availability of this treatment is low.
Iridium-192 - high dose rate
  • Uses a specialized remote afterloader, treatment times extremely short (typically 2-6 min), and there is no operator exposure.
  • The horse is not 'radioactive' following treatment, and can be treated as normal with no requirement for isolation.
  • Periocular lesions can be successfully treated under standing sedation in specially designed stocks.
  • Radiation catheters are implanted into the tumor, imaged, and a treatment plan is created. The catheters are connected to a remote afterloader which drives the high dose rate iridium-192 source from a shielded safe into the catheters for treatment according the to the predefined plan.
  • During treatment, the horse is monitored via CCTV from an adjacent shielded radiation bunker; there is no exposure of personnel to the radiation.
  • Results are similar to those with low dose rate techniques; this is an extremely effective method of delivering radiotherapy.
  • High cost of treatment.
  • Limited availability: very few centers across the world can offer this treatment due to the high cost of facilities and extensive training required.
Gold-198
  • Half-life is 48 h.
  • Very high activity at time of implantation - significant operator safety risks.
  • No need to remove sources after 96 h of radiation isolation.

Electronic brachytherapy

  • A technique involving electronic brachytherapy has been used to treat 3 types of superficial tumor.
  • This uses a miniature x-ray source to deliver radiation, rather than a radioactive isotope and can be given via a cone applicator or an interstitial technique.
  • Multiple general anesthetics are required for safe treatment, success rates are unknown, and exposure of the anesthetist to a low level of radiation is inevitable, despite shielding with lead gowns, gloves, goggles and lead shield.
  • Cost is similar to high dose rate brachytherapy and the disadvantages and unproven nature of the treatment are concerns.
  • Very limited availability.

Superficial brachytherapy (plesiotherapy)

  • Radiation sources applied directly onto the mass, eg strontium-90 plaque.
Strontium-90 plaques
  • Much easier/safer to handle but require fractionation and therefore repeated potential operator exposure.
  • Has a better effect on very superficial tumors than iridium-192.
  • Only suitable for very superficial tumors: 60% of the radiation dose is absorbed in the first 1 mm of tissue.
  • Treatment limited to very superficial corneoscleral, conjunctival or eyelid lesions, with the possibility of treating very small lesions in other locations.
  • Corneoscleral and conjunctival lesions require general anesthesia for accurate positioning of the probe; lesions in some periocular and other locations may be treatable under heavy standing sedation, depending on the horse's temperament.
  • With appropriate simple shielding methods, operator exposure is negligible.
Ruthenium plaques
  • Can be sutured to cover mass, eg on conjunctiva or sclera.
  • Short half-life and safe shielded backing makes procedure safer.
  • Extremely expensive.

Aftercare

Immediate Aftercare

Monitoring

  • Regular check to ensure safe/stable implant when implants are left in situ.
  • Radiation monitoring equipment required with full warning indicators when implants are left in situ.

Fluid requirements

  • Daily water/feed.

General Care

  • During low dose rate interstitial brachytherapy treatment no human contact is permitted all procedures to be remotely controlled.
  • Repeated sedations in topical and high dose rate brachytherapy treatment protocols may encourage intestinal impactions.
  • Diet adjusted to minimize risks.

Analgesia

Antimicrobial therapy

  • Nil usually required.
  • Radiation also kills bacteria.

Other medication

  • Nil usually.

Wound Protection

  • Cover implants if on limbs or other vulnerable regions.

Special precautions

  • Slow effects are the norm:
    • Ionizing radiation results in DNA alterations and so cell replication does not occur.
    • Tumor regression depends on tumor cell type and rate of growth/lifespan.
    • Bone/fibrous tissue tumors may respond slowly.
    • Squamous cell carcinoma Skin: neoplasia - squamous cell carcinoma responds faster because of higher cell turnover and shorter lifespan of cells.

Long term Aftercare

Follow up

  • Owners should be warned that although the effects are usually good and the cosmetic effects are often remarkable, the full effects may not be apparent until 6-12 months after treatment.
  • During follow-up period may be several periods when swelling and infection develop:
    • Local immunocompromise is expected.
    • Necrosis of cells results in local abscess formation (often alarming but to be expected).
    • Treat using basic principles of control of infection and bathing to debride necrotic tissue.

Outcomes

Complications

  • Local abscessation.
  • Slow healing.
  • Alterations in hair color (usually white - leukotrichia) and skin color (leukoderma) Skin: color dilution.
  • Skin at site often thinner than normal and liable to trauma and actinic dermatitis (sunburn Skin: sunburn 01Skin: sunburn 02).

Reasons for treatment failure

  • Inadequate dose.
  • Inappropriate treatment method chosen.
  • Failure to make correct overall assessment of the tumor itself.

Prognosis

  • Excellent where correct doses and methods are used and the whole tumor can be radiated.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Bradley W M, Schlipp D & Khatibzadeh S M (2015) Electronic brachytherapy used for the successful treatment of three different types of equine tumours. Equine Vet Educ 29 (6), 293–298 WileyOnline.
  • Burks B S, Leonard J M, Orsini J A & Trombetta M (2009) Interstitial brachytherapy in the management of haemangiosarcoma of the rostrum of the horse: case report and review of the literature. Equine Vet Educ 21 (9), 487-493 VetMedResource.
  • Byam-Cook, Henson F M & Slater J D (2006) Treatment of periocular and non-ocular sarcoids in 18 horses by interstitial brachytherapy with iridium-92. Vet Rec 159 (11), 337-341 PubMed.
  • Henson F M D & Dobson J M (2004) Use of radiation therapy in the treatment of equine neoplasia. Equine Vet Educ 16 (6), 315-318 VetMedResource.
  • Knottenbelt D C & Kelly D F (2000) The diagnosis and treatment of periorbital sarcoid in the horse: 445 cases from 1974-1999. Vet Ophthal 3 (2), 73-82 PubMed.
  • Theon A (1998) Radiation therapy in the horse. Vet Clin N Am Equine Prac 14 (3), 673-688 PubMed.
  • Knottenbelt D C, Edwards S E R & Daniel E A (1995) The diagnosis and treatment of the equine sarcoid. In Pract 17 (3), 123-129 VetMedResource.
  • Blackwood L & Dobson J M (1994) Radiotherapy in the horse. Equine Vet Educ 6 (2), 95-99 VetMedResource.
  • Theon A P & Pascoe J R (1994) Iridium-192 interstitial brachytherapy for equine periocular tumours: treatment results and prognostic factors in 115 horses. Equine Vet J 27 (2), 117-121 PubMed.
  • Walker M A, Adams W et al (1991) Iridium-192 brachytherapy for equine sarcoid, one and two year remission rates. Vet Radiol 32 (4), 206-208 VetMedResource.
  • Walker M A, Goble D & Geiser D (1986) Two-year non-recurrence rates for equine ocular and periorbital squamous cell carcinoma following radiotherapy. Vet Radiol 27 (5), 146-148 VetMedResource.
  • Turrel J M & Koblik P D (1983) Techniques of afterloading iridium-192 interstitial brachytherapy in veterinary medicine. Vet Radiol 24 (6), 278-283 VetMedResource.
  • Frauenfelder H C, Blevins W E & Page E H (1982) 90Sr for treatment of periocular squamous cell carcinoma in the horse. J Am Vet Med Assoc 180 (3), 307-309 VetMedResource.
  • Baker J R & Leyland A (1975) Histological survey of tumours of the horse with particular reference to those of the skin. Vet Rec 96, 419-422 PubMed.

Other sources of information

  • Knottenbelt D C, Patterson-Kane J C & Snalune K L (2015) Clinical Equine Oncology. Elsevier, UK.
  • Scott D W (2003) Dermatologic Therapy. In: Equine Dermatology. W B Saunders, USA. pp 187-188.