RT Flashcards
What is the unit of absorbed dose for RT and what does it 1 equal?
Gray; 1 Gy= one joule absorbed per kg of tissue
Megavoltage/orthovoltage photons are the predominant form of RT used in vet med?
megavoltage
Megavoltage photons interact with tissue primarily by ____ that produces _____ that work via direct or indirect actions.
Compton effect; high energy electrons
How can megavoltage photons cause either direct or indirect effects
Direct: electrons cause ionization events to critical molecules Indirect: electrons cause ionizing events to water located near critical molecules
What is the most common form of cell death caused by RT?
Mitotic catastrophe
What phase are cells most resistant to RT in?k
Late S-phase; cells with a long G1 period also; also G0 because not cycling
What phase are cells most sensitive to RT
G2 or M; also late G1 to early S phase
Are normoxic or hypoxic cells more sensitive to RT?
Normoxic - need O2 to generate reactive oxygen spp that cause much of the damage from RT
How do low energy photons interact with tissues?
mostly photoelectric effect
orthovoltage x-rays distrubte the max doses in what tissue?
Skin –> bad acute tox in skin and SQ usually dose limiting
Describe the indirect effects of ionizing RT
Photon interacts with water, generates free radicals that damage the target
What are the energy ranges for orthovoltage vs. megavoltage RT?
Ortho: lower energy, 150-300 kVp Megavoltage: higher energy, >1MeV
What is the relative biologic effectiveness (RBE)
Measure of the amount of energy transferred per unit path length - uses LET + other factors including biologic endpoint, fractionation, RT dose rate and dose
What tissue/cells are particularly prone to apoptosis from RT?
lymphoid tissues
High doses of RT cause apoptosis of endothelial cells which is called _____.
vascular collapse
In vet med, what is considered the range and total dose for standard fractionation? How does this compare to human RT?
2.7-4.0Gy to a total of 42-57Gy Most vet med protocols considered hypofx compared to human
What is hyperfractionation?
dose per fraction reduced and the total dose is increased
What is accelerated RT?
overall time of treatment reduced
What are the 5Rs of RT?
Repair, Redistribution, Reoxygenation, Repopulation and Radiosensitivity
Which of the 5 R’s becomes an issue for tumor control, usually after 4-6 weeks of therapy?
Repopulation - after this cells may repop more quickly; this is why treatment breaks can result in poor tumor control
Repopulation may have a greater adverse effect on slowly/rapidly dividing tumors
rapidly
What is the only tissue that early-delayed RT effects have been found? When does this usually happen?
Nervous tissue - usually 2wks - 4mo
What are possible causes of early-delayed RT effects?
Demyelination Cerebral edema-associated cytokine release w/ tumor cell death
What cytokine is thought to play a critical role in radiation fibrosis?
TGF-beta
What strategies are used in human RT to mitigate late RT side effects?
use of antioxidants and free radical scavengers (superoxide dismutase, vit E, thiol radioprotectors), vascular directed therapies (clopidogrel, pentoxifylline), ACE inhibitors, antiinflammatory agents (steroids) and stem cell therapies
What four criteria have to be true for a tumor to be considered RT induced?
- Must arise w/in RT field 2. Sufficient latency b/w RT and development (usually ≥1yr 3. different histology than original tumor 4. tissue where new tumor forms must have been normal prior to RT exposure
What three things does SRT require?
- Macroscopic disease 2. treatment planning and admin that allows rapid dose drop off 3. method of stereotactically verifying patient positioning
In veterinary med, pubs show comparable STs between SRT and conventionally fractionated protocols in what tumors? What cancer may have longer STs for SRT vs. conventional fractionation?
Comparable: nasal and brain Improved w/ SRT: feline acromegaly
What is the surviving fraction (S)?
The proportion of remaining cells after a dose of RT that have not been killed
What is the equation that can be used to describe the relationship between dose and surviving fraction?
Linear quadratic equation: S(D) = e-(αD + βD2) (D = dose, D after β should be squared, not D2 but this program won’t let me double superscript things…)
α and β are constants:
α = cell death that increases linearly, β = cell death that increases in proportion to the square of the dose
At low dose fractions, tissues or cells with low α/β ratio are relatively (radiosensitive/radioresistant) compared to those with a high α/β ratio
radioresistant
What are tissues/cells with a low α/β ratio more radioresistant? Also what types of side effects (acute, late, etc) are these tissues more likely to have?
low α/β have greater capacity for repair of sublethal RT damage (i.e. bigger shoulder on a cell survival curve)
more likely to have late tox
What are tumors that generally have lower α/β ratios?
Melanoma, prostatic tumors, STS, TCC and OSA
What is the equation for biologic effective dose (BED)?
BED = nd[1 + d/(α/β)]
d = dose per fraction
Most early-responding tissues have a (high/low) α/β ratio while late-responding tissues have a (high/low) α/β ratio
early: high
Late: low
Orhtovoltage RT is preferentially absorbed by what tissue (other than having high skin distribution) which leads to a high rate of what side effect?
bone –> high probability of late effects to bone (bone necrosis) high
What scenarios might be okay for orthovoltage?
Small, superficial tumors (nasal planum) or to superficial tumor beds after surgical excision
In tx planning, what is the CTV?
Clinical target volume - includes GTV + expansion to account for regional microscopic disease
expansion based on tumor type - ex. sarcomas usually have wider expansion than carcinoma
In SRT, what are the differences in GTV, CTV and PTV compared to traditional fractionation?
GTV same as traditional
CTV not applied (i.e. GTV = CTV)
PTV usually decreased to spare important adjacent normal tissues
What does the shoulder of a cell kill curve represent?
Portion of cells that sustain sublethal doses of RT - able to repair to some degree but above a certain dose, cells begin to die
What are the advantages and disadvantages of CRT?
Ad: fast plans and treatments
disad: not as good for irregular targets (i.e. harder to spare normal tissue); larger PTV (i.e. more normal tissue included in tx field
What are the advantages and disadvantages of IMRT?
Ad:
- better for irregularly shaped targets (esp if near critical structures),
- Build up dose in areas of tumor with minimizing dose in surrounding tissue
- more efficient treatment planning w/ correct software
disad:
- longer treatment times
- more complicated plans - need physics involvement
What are the advantages of pre-op RT?
lower total dose
smaller tx field
no delay to start of RT
possible downstaging - extent of sx needed may decrease pending reponse to RT
easier to plan - have a target
What are the disadvantages of pre-op RT?
- Lack of initial surgical staging
- Post-surgical wound healing complications possible
- Hypoxic regions in bulky tumors may decrease response to RT
What are the advantages of post-op RT
- Surgical staging - tailoring of RT target volumes and doses
- RT most effective in microscopic disease
- No negative impact on post-sx wound healing
- No delay in surgery
- Have histo of entire mass - could change dx
What are the disadvantages of post-op RT?
- Volume of normal tissue irradiated is large
- Increased risk of tumor cell dissemination at surgery
- alteration in blood supply to tumor cells
- Delay to start of RT if sx complications with wound healing occur
- Higher overall dose
What does 60Cobalt produce and what is its relative energy?
Produces gamma-rays as it decays to nickel
Averagy energy relatively low (1.25 MeV), only 0.5cm of skin sparing so difficult to treat deep-seated tumors
What depth of skin sparing dose a 6MeV photon bean have? Does this depth increase or decrease with increasing photon energy?
6MeV has 1.4cm skin sparing
skin sparing increases as photon energy increases
Chemotherapy drugs that are used with concurrent RT ideally kill cells in what phase?
S phase - kill in most resistant phase and redistribute more cells into G2-M phase (most sensitive)
What was the rate of late complications in dogs treated with >45gy total for pelvic region irradiation? (Arthur VRU 2008)
39% had late complications, recommended reducing dose per fraction to < 3Gy
What was the outcome of combining RT + gemcitabine as a radiosensitizer for dogs and cats with head/neck carcinomas? (LeBlanc VRU 2004)
High dose of tox - 12/15 dogs and 5/10 cats needed dose reduction or treatment delatys due to heme tox or normal tissue tox
conclusion: not a good plan to use this combo
What were the AEs associated with concurrent carbo and RT in dogs? What dose of carbo was used? (Hume JVIM 2009)
200mg/m2 median dose
21% grade 3-4 neutropenia
20% grade 3-4 thrombocytopenia
10% grade 3-5 GI tox
What was the residual setup error for dogs with intracranial tumors for megavoltage, kilovoltage or CBCT image guidance set up? (Morimoto VCO 2019)
MV: 1.7mm
kV: 1.5mm
CBCT: 2.2 mm
conclusion - likely only need mm margins for PTV for intracranial region tumors
What margin shoud be used w/in the PTV when MV or kV planar imaging is used for RT set up by matching bony landmarks of the skull compared to CBCT? (Magestro VCO 2019)
at least 1mm for Mv or kV planar imaging used
What was the rate of complications for VAPS in dogs treated with RT? (Mayer JAVMA 2008)
17% malposition of catheter tip
30% seroma formation
13% breakage of port-anchoring sutures
1 dog (4%) fatal septicemia
7% of anesthetic episodes had temporary withdrawal occlusion
What are the recommendations regarding VAPs and RT based on the Mayer JAVMA 2008 study?
Fluoroscopy for positioning the catheter tip
Removal of VAP at completion of RT unless needed
What was the rate of complications when surgical flaps were irradiated? (Seguin Vet Surg 2005)
77% had complications - necrosis, infection, dehiscence, ulceration
6/26 needed second flap procedure
4 /26 had unresolved complications
What was the response rate of sialoceles in dogs to RT? (Poirier JVIM 2018)
54% CR, 45% PR
conclusion: RT useful for treating recurrent sialocele refractory to surgery
What total dose of RT is effective in treatment for sialoceles in dogs? (Poirier JVIM 2018)
16-20 Gy
all originally had at least 12Gy but 2 dogs needed additional RT to 20Gy total
What was significantly associated with developing pneumonia in dogs receiving repeated anesthesia for RT? (Baetge VRU 2018)
Presence of a neuro tumor
Presence of respiratory disease
Presence of megaesophagus
# of fractions of RT completed
What changes in anesthetic protocol resulted in decreased risk of pneumonia in dogs treated with RT and repeated anesthesia (Baetge VRU 2018)
- decrease in anticholinergic (glycopy.) and pure-mu opioid use (hydro, changed to torb if needed)
- change in positioning during intubation and recovery (sternal w/ head raised)
- prophylactic treatment of nausea (metoclopramide)
- timing of cuff inflation and deflation
- aseptic handling of intubation equipment
What was the result of treatment with prophylactic cephalexin in dogs starting halfway through definitive RT protocols? (Keyerleber Vet Derm, 2018)
- No sig difference in prevalence of bacterial infection, but MDR infections significantly increased for dogs with cephalexin compared to controls
- Clinician and client-perceived severity of tox greater and median duration of moist desquamation was sig longer in dogs getting cephalexin
- conclusion: no prophylactic cephalexin
