The purpose of this presentation is to provide a general overview of radiation therapy in veterinary medicine and will provide a brief overview of basic physics and biology of external beam radiation. We will also discuss the evolution of radiation therapy and how it has impacted our ability to treat cancers that were previously deemed untreatable. We will discuss indications for referral, reviewing commonly treated tumor types and evidence-based outcomes that support the use of stereotactic radiation in veterinary medicine. Finally, we will define the role of the veterinary technician in implementing radiation therapy in veterinary practice.

• Outline:
• Case report—Lexi
• What is radiation?
• Physics
• Biology
• The evolution of radiation therapy
• Indications for referral
• Implementing SRS in veterinary practice
• Where YOU come in
• What is Radiation?
• Electromagnetic energy
• Light waves, radio waves, microwaves…
• X-Rays!
• Types of radiation
• Electromagnetic
• X-Rays
• Produced in an x-ray machine or linear accelerator
• This will be the focus of our discussion
• γ-Rays
• Emitted from radioactive elements
• Cobalt units
• I-131
• Particulate
• Electrons, Protons, Heavy charged particles
• X-Rays
• Electromagnetic energy
• Encountered every day
• The x-rays pass through the subject
• Absorbed—Biological effects in tissue
• Transmitted—Captured by film or scattered
• Patients are not radioactive
• Radiation is not excreted in any form after the imaging or treatment is performed
• Diagnostic:
• Low energy (kV)
• Differential absorption in tissue
• Bone absorbs more than soft tissue, fat, lung
• Film absorbs the x-rays that were not absorbed by the patient—shades of gray seen on film
• Therapeutic
• High energy (MV)
• Absorbed evenly across all tissues
• Biologic effects in tissue/cells—DNA damage
• What is Radiation Therapy? The Biology:
• X-rays damage DNA of cells
• Cells die when attempting to replicate/multiply
• Interference with replication—grow inhibition
• Non-invasive, pain-free therapy
• Localized treatment
• Response to DNA damage
• Repair
• Many mechanisms
• "Normal" cells have intact DNA repair mechanisms—repair is more likely in healthy tissue
• Cell death
• Cancer cells have faulty DNA repair mechanisms
• Cancer cells are more likely to die when DNA is damaged
• Mitotic death (mitosis = cell division)
• Cell dies when attempting to copy its DNA and divide
• Apoptotic cell death
• Occurs in particular cell types
• Lymphocytes
• Vascular endothelial cells
• Tumor response and cell kinetics
• Kinetics = rate of a reaction
• Here, we are referring to what happens to a tumor after radiation as an implication of the tumor’s cellular kinetics (rate of growth)
• Tumor cells die when they are trying to divide/multiply
• Rapidly growing tumors should die/shrink rapidly
• Slowly growing tumors should die/shrink slowly/gradually
• What owners need to know:
• Most tumors will not shrink overnight
• Prepare for a marathon, not a sprint
• Normal tissue response and cell kinetics
• Same is true for normal tissues!
• Tissues that turn over quickly—show side effects early/shortly after treatment
• Acute radiation effects
• Tissues that turn over slowly—show side effects months/years after treatment
• Late radiation effects
• Acutely responding tissues
• Rapid rate of cell turnover
• Show side effects days–weeks after treatment
• Recovery time is usually quick and complete
• Skin, mucosa, GI tract, hematopoietic system
• Late responding tissues
• Slow rate of cell turnover
• Show side effects months–years after treatment
• Recovery, if it occurs, is slow and often not complete
• Late radiation effects are dose limiting
• CNS (brain, spinal cord), bone, lung, kidney, lens
• Acute radiation effects
• Timeline:
• Time from radiation – side effect = time for a stem cell to become a mature/functional cell
• Skin = 10–14 days
• Mucosa = 7–10 days
• GI = 5–7 days
• Timeline for recovery = similar
• What?
• The surface of your skin will slough tomorrow—damage here is not important
• The stem cell layer of your skin will "rise" to the surface in 10–14 days—damage here is important!
• And the damage will show up when those stem cells reach the surface = 10–14 days post-treatment for skin
• Late radiation effects
• Pathogenesis less clear than acute effects
• Fibrosis, necrosis, vascular changes
• "Failed" healing
• Generally considered irreversible—dose limiting
• 5% risk considered acceptable
• Incidence with SRS comparable to CFRT/IMRT
• Severity may be worse
• "5% feels like 100% if it happens to your pet"
• Radiation Therapy—The Evolution
• Clinical Setup/"Point-and-Shoot" Radiation Therapy
• Intensity Modulated Radiation Therapy (IMRT)
• Stereotactic Radiosurgery (SRS, SRT, SBRT, SABR)
• Volumetric Modulated Arc Therapy (VMAT, RapidArc®)
• Radiation Therapy—CFRT
• Conventionally Fractionated Radiation Therapy (CFRT)
• Widely available
• 15–21 treatments ("fractions") and anesthetic events
• Standard of care for incompletely excised tumors
• Mast cell tumors, soft tissue sarcomas, AGASACA
• Healthy tissue will repair over time, but dose per fraction must remain low to avoid severe toxicity = spare normal tissues by fractionation
• Targeting tumors: Multi-leaf collimator—Static
• Allows better conformity to decrease normal tissue damage
• Radiation Therapy—IMRT
• Intensity Modulated Radiation Therapy (IMRT)
• Dynamic multi-leaf collimator—non-uniform fluence
• Multiple beams—steep dose gradient
• Inverse treatment planning
• Patient-specific, CT-based identification of tumor target and organs at risk
• Requires accurate, precise and highly reproducible patient positioning
• 15–20 fractions
• What is Stereotactic Radiosurgery (SRS)?
• More Precision
• We can treat tumors in locations previously thought "untreatable"
• Lung, liver, kidney, prostate, adrenal gland, heart base, etc…
• Fewer Treatments
• Treatments given in 1–3 consecutive days (instead of 15–20)
• Fewer anesthetic events and trips to the hospital
• Fewer Side Effects
• Radiation side effects happen when healthy tissue is exposed to radiation—more precision means those side effects are greatly reduced
• Indications for Referral
• Cancer Treatment Options
• Chemotherapy
• Surgery
• Radiation
• Immunotherapy
• Palliative care
• Radiation Therapy
• Local therapy
• Consider when surgery not feasible or is unlikely to achieve clean margins
• Can result in side effects to healthy tissues
• Indications for referral:
• When there is residual microscopic disease
• Post-surgery dirty margins (mast cell tumor, soft tissue sarcoma)
• Conventionally fractionated radiation is standard of care to minimize risk for tumor regrowth
• Bulky disease, where a good surgical option does not exist
• Location
• Ability to achieve clean margins
• High morbidity
• Advanced stage disease
• Palliative radiation addresses local/clinical disease
• Implementing SRS in Veterinary Practice
• PetCure Preliminary Data
• Patients with incomplete datasets not included in this analysis
• Censored =
• Alive
• Lost to follow-up
• Death from unrelated cause
• All analysis NCSS v11.0
• Study power suboptimal in many cases
• Tumors commonly treated with radiation therapy—Canine Nasal Tumors
• Current literature:
• MST no treatment = 95 days
• MST surgery = 3–6 months
• MST CFRT/IMRT = 11–19.7 months
• Stage 4 (cribriform lysis) = 6.7 months
• MST SRS literature = 12–20 months
• PetCure Median Survival Estimates:
• Carcinoma = 634 days (132 cases, 80 censored)
• 21 months
• Chondrosarcoma = 710 days (19 cases, 15 censored)
• 23.6 months
• Squamous cell carcinoma = 273 days (17 cases, 7 censored)
• 9 months
• Tumors commonly treated with radiation therapy—CNS*
• Canine brain tumors—presumed meningioma
• MST no treatment = 2–3 months
• MST surgery + CFRT = 11–19 months
• SRS literature = 18 months (Griffin, CSU 2014)
• Meningiomas only
• PetCure Median Survival Estimates:
• Glioma = 622 days (30 cases, 20 censored)
• 20.7 months
• Previously reported with CFRT = 8–10 months
• Meningioma = 647 days (117 cases, 85 censored)
• 21.5 months
• Median survival estimate = 20.7 months
• Previously reported with CFRT = 8–10 months
• Tumors commonly treated with radiation therapy—Osteosarcoma
• Canine OSA
  • MST palliative care only (pain meds) = 1–3 months
  • MST amputation alone = 3–6 months
  • MST amputation + chemotherapy = ∼1 year (8–12 months)
  • SRS experience =
    • Bisphosphonate therapy prior to treatment
    • Chemotherapy indicated following SRS
    • MST = ∼12–15 months
• Tumors commonly treated with radiation therapy—Oral Tumors
• Oral tumors
• Prognosis dependent on histotype
• Local control generally good (>12–18 months)
• Call before performing dental procedures!
• Tumors commonly treated with radiation therapy—Canine soft tissue sarcoma*
• SRS
• 43 total cases, 38 censored
• 19–1624 days
• 75% Quantile estimate: 944 days (31 months)
• All had gross disease
• No systemic therapy in this group
• Tumors confined to the skin/subQ
• Tumors commonly treated with radiation therapy—Canine soft tissue sarcoma—Clinical Trial*
• Nanovi PetXMark™
• Marginally resected grade II sarcoma with a linear scar
• <15 cm
• Liquid fiducial used to define a surgical scar
• Other tumors of the skin/subQ can be treated off protocol
• PetCure will retreat in the event of early local failure or geographic miss
• This clinical trial is closed for ongoing enrollment
• Nanovi Trial: Results, All Tumors
• 173 patients injected to date
• 161 treated
• 12 rejected for comorbidities
• 144 alive
• 11 Dead not tumor
• 5 dead to tumor
• 1 lost to follow up
• 1 possible/presumed reaction to the injection
• 2 confirmed local recurrence
• 2 significant local toxicity cases
• 1 owner non-compliance with prevention of self-trauma
• 1 developed fungal infection after swimming in a lake
• Standard of Care = CFRT
• 18–20 daily treatments
• Moderate–severe acute toxicity that lasts 4–6 weeks
• 85% chance for long-term local tumor control
• Tumors commonly treated with radiation therapy
• Lung
• Alternative to surgery for primary lung tumors
• SRS experience—local control >12 months
• Human experience: SRS achieves similar or better outcome compared to surgery as primary treatment for non-small cell lung cancer
• Currently enrolling canine patients for prospective clinical trial of SRS for primary lung tumors
• Canine Lung Tumor Clinical Trial
• Solitary lung tumor
• No life-threatening comorbidities
• SOC1 = 3x20 Gy
• SOC2 = 1x24 Gy
• Trial Closed July 2020
• Tumors commonly treated with radiation therapy—Thyroid tumors*
• Descriptive data
• 23 total cases, 16 censored
• 18–808 days
• Median survival estimate 627 days = 21 months
• Most of these cases have massive tumor volume and were deemed inoperable
• Tumors commonly treated with radiation therapy—Adrenal tumors*
• Descriptive data
• 5 total cases, 5 censored
• 4–632 days
• No survival estimates possible at this time—no uncensored cases
• Side Effects with SRS
• Acute toxicity is significantly reduced with SRS, but patients may still experience side effects in the location of the treatment. If we never saw side effects, it would mean we weren’t treating the cancer aggressively enough.
• Side Effects of Radiation Therapy
• Acute (early) effects
• Days–Weeks after treatment
• Correlates with short life span of mature cell population
• Rapidly dividing tissues
• Skin, mucosa (oral, GI), bone marrow
• Moderate–severe with CFRT
• Mild–Moderate with SRS
• None–Mild with palliative radiation
• Should resolve without intervention, though supportive care may be required
• Treat symptomatically!
• Will resolve with time, prevention of self-trauma and appropriate supportive care
• Skin desquamation:
• ∼10–14 days post-SRS; resolves in ∼10–14 days
• Pain medication
• Prevention of self-trauma
• Keep clean/dry
• But don’t encourage owners to clean/groom/etc.
• Do not bandage
• Antibiotics for secondary infections
• Skin
• Hair loss
• Permanent hair coat color change
• Hyperpigmentation
• Mild–moderate inflammation/desquamation
• Treat symptomatically!
• Will resolve with time, prevention of self-trauma and appropriate supportive care
• Mucositis
• ∼10–14 days post-SRS; resolves in ∼7–10 days
• Anti-inflammatory dose of steroids
• Magic mouthwash—compounding pharmacies
• ± pain medication as needed
• Consider softening food or providing canned food
• Avoid hard chew toys
• Colitis
• ∼5–7 days post-SRS; resolves in ∼3–5 days
• Metronidazole—owners are sent home with this if anticipated
• Ocular changes—refer to ophthalmologist
• Dry eye
• Conjunctivitis
• Early-delayed/transient demyelination
• 3–6 months post-SRS
• Reported in 20–40% of patients
• Recurrence of initial clinical signs
• Steroid-responsive
• Treatment = aggressive supportive care and steroid therapy
• SLOW steroid taper following recovery
• 25% every 4 weeks if no relapse
• Late effects
• Months–years after treatment
• Slowly proliferating tissues
• Brain, spinal cord, heart, liver, lung, bone
• May improve, but never completely repaired
• Goal = minimize risk
• 5% risk acceptable
• Where do YOU come in?
• The role of veterinary technicians in radiation oncology
• Role of Veterinary Technician in Radiation Oncology
• Patient evaluation
• Record review
• Medical history
• Triage
• Diagnostics
• Bloodwork
• X-rays
• Explanation of process
• Reviewing estimates
• "Show and tell"
• Treatment plan review
• Discussion of anticipated side effects and follow up recommendations
• CT Simulation
• Anesthesia
• Induction
• Monitoring
• Recovery
• Determine ideal positioning
• Create immobilization devices
• Acquire images
• Treatment
• Anesthesia
• Induction
• Monitoring
• Recovery
• Reproduce position
• Image verification
• Beam on!
• Role of the Veterinary Technician in Radiation Oncology—Invaluable Skill
• General oncology knowledge
• Strong anesthesia skills
• Strong background in anatomy
• Experience reviewing CTs
• Attention to detail