Imaging and radiation therapy Flashcards
What color is stuff on MRI for T2 weighted imaging?
- fluid and tissues with increased fluid (edema, inflammation, neoplasia) are hyperintense
fat intensity is variable (other sources say fat appears dark) - Normal bone marrow is hyperintense to muscle and equal to or slightly hypointense to SQ fat. Infiltrated bone marrow should appear hyperintense to normal bone marrow.
What color is stuff on MRI for T1 weighted imaging?
- fat is hyperintense, fluid and bone are hypointense, and soft tissues are medium intensity
- Normal marrow contains water and fat; it should be hypointense to fat but hyperintense to normal muscle.
- Infiltrated bone marrow should appear hypointense relative to muscle and normal marrow.
What is the % ability to predict primary brain tumor type based on MRI findings?
70%
Match the radioactive molecules for PET and what they are markers for:
radioactive molecules:
- 18F-fluorodeoxyglucose (FDG)
- 3’-deoxy-3’-fluorothyidine (FLT)
- 60Cu-ATSM
- 18F-sodium fluoride (NaF)
a. hypoxia
b. metabolism
c. cell proliferation
d. skeletal
18F-fluorodeoxyglucose (FDG) - metabolism
3’-deoxy-3’-fluorothyidine (FLT) - cell proliferation
60Cu-ATSM - hypoxia
18F-sodium fluoride (NaF)- skeletal
What are the extrinsic markers for hypoxia in a tumor:
- Noninvasive imaging:
- IHC staining:
Extrinsic markers:
1. Non-invasive imaging: [18F]-labeled nitromidazoles (18F-misonidazole or 18F-FAZA)- injected into patients and form protein adducts within hypoxic regions in the tumor and imaged with PET
- IHC staining: staining with antibodies with pimonidazole adducts is used on tissue sections
What are intrinsic marker for hypoxia in a tumor with IHC staining?
Intrinsic markers:
HIF-1a, GLUT-1, CA-9 and osteopontin [OPN], VEGF
What does meningioma look like on MRI?
Hyperintense on T2
What is a pure beta emitter?
Strontium-90 (yttrium-90, what Sr decays to) are beta emitters (but technically emits a small amount of gamma particles)
Based on a graph of dose curves for RT for an incompletely excised MST which depth would you choose:
1, 2, 3, and 4 mm?
and which modality would you choose?
electrons, photons, protons?
electron RT: 1 mm
What are the 4 Rs?
- Repair
- Repopulation
- Redistribution
- Reoxygenation
During what phases of the cell cycle are cells most susceptible and least susceptible to DNA damage with RT?
most susceptible during G2/M, least during S
T/F: normoxic cells are 2-3X more sensitive to RT than hypoxic cells?
True
What effects do the four Rs on radiation total dose?
Repair and repopulation increase the total dose required
Redistribution and reoxygenation decrease the total dose required
In an isobologram, what does each section mean?
- above the curve?
- In the middle of the two curves?
- below the curves?
- sub-additive/protective/antagonistic
- envelope of additivtiy
- supra-additive/synergistic
- What is LET?
2. High LET refers to which of the following? protons neutrons electrons charged particles carbon ions
- Low LET refers to which of the above?
- Identify whether high vs low LET kill via direct or indirect DNA damage?
- the average density of energy loss along the track of the particle
- High LET = charged particles and neutrons – Bragg peak
- Low LET = photons and electrons
- High= kills mostly by direct DNA damage
Low= 2/3 of kill is from indirect (free radical) damage
- What LET do protons have compared to other particles?
2. What happens to the LET at the Bragg peak?
- Protons generally have lower LET than alpha particles, carbon ions, or neutrons
On AVERAGE, the proton’s LET is only a little higher than photons (and relatively lower than true high LET particles) - end of a proton’s Bragg peak, LET becomes super high
What would the survival curve look like for High LET?
Increased LET = steeper survival curve, smaller shoulder of the curve
What is the curve or shoulder of the survival curve indicative of?
cell’s ability to repair DNA damage
What is hypofractionation in RT?
higher dose per fraction, lower number of fractions and lower total dose
What is hyperfractionation in RT?
reduced dose per fraction, increased total dose
What is an accelerated dosing scheme in RT?
the duration of treatment is reduced, but the dose per fraction and total dose are unchanged
- What does beta mean as part of the linear equation, or in other words, what does it mean to have a broad shoulder?
- What does alpha mean?
- B= causes the curve to bend (repair of SLD)
component is large when SLD is easily repaired
decreases with fractionation - a = initial slope (initial irreparable damage)
Choose High a/B or Low a/B for the definitions described below:
- little sparing with fractionation, early tissues and tumors undergoing apoptosis (radiosensitive cells), straighter line
- Low a/B = curved line/large shoulder, benefits from hypofractionation, late tissues (radioresistant cells), less repair capacity
- High a/B
- Low a/B
• High a/B = more linear appearance
o Most early responding tissues and tumors
• Low a/B = parabolic shape
o Tissues are more radiation resistant, greater capacity for repair of sublethal damage
o Most late-responding tissues and some tumors
Which tumors have a Low a/B?
melanoma, OSA, prostatic, TCC, STS
What is the Compton effect?
the photon interacts with an electron and donates part of its energy. The photon then continues on its way but is deflected from its original path.
o
X
Compton effect dominates at what energy range?
Compton = megavoltage RT (cobalt 60 and linac)
linac range energy- greater than 10 eV are considered ionizing radiation
When using 10MeV radiation, the Compton effect is most common
Choose which one (Compton vs Photoelectic) goes with which statement?
- The mass absorption coefficient is independent of the atomic number of the absorbing material.
- The mass absorption coefficient is dependent on atomic number (Z) and proportional to Z^3
- Compton
2. Photoelectric
How does radiosensitization occur with gemcitabine?
Due to inhibition of ribonucleotide reductase and DNA polymerase
RNR inhibition–> depletion of deoxyadenosine triphosphate (dATP)
- What is gross tumor volume (GTV)?
- What is clinical target volume (CTV)?
- What is planning target volume (PTV)?
- Gross tumor volume (GTV): only the gross tumor
- Clinical target volume (CTV): GTV plus an expansion to account for microscopic disease
- Planning target volume (PTV): includes expansion for an internal margin (IM) accounting for variations in size and shape relative to anatomic landmarks (e.g., urinary bladder, respiration) and set-up margin
What happens to GTV and CTV if cytoreductive sx occurs?
There is no GTV if cytoreductive surgery has been performed and the CTV is based on the scar, regions of surgical disruption, and an expansion for microscopic disease beyond the surgical site
Identify a direct vs. indirect damage by RT?
- Direct damage = a secondary electron resulting from absorption of an x-ray photon interacts with DNA to produce an effect
o Direct damage is greater with higher LET (neutrons, protons) - Indirect damage = a secondary electron usually interacts with H2O to produce a free radical that damages DNA
o About 2/3 of x-ray damage to DNA is due to hydroxyl radical formation
What determines risk of late RT effects?
Fraction size and the interval between treatment fractions are more important in late responding tissues
o Higher dose per fraction
- Ocular lesions occur in all dogs receiving _____ Gy?
- Ideally, dose to organs at risk (OAR) = no more than ___ % of brain, and eyes receiving nor more than ____ Gy
- Ideally, ___ % of the PTV should get 95% of the dose.
Look for all these things and then interpret irradiation to normal tissues on a DVH.
- ocular lesions occur in all dogs receiving 36+ Gy near the nasal cavity
- 50%, 10 Gy
- 100%
What is photodynamic therapy?
relies on light of an appropriate activating wavelength, oxygen, and a photosensitizer that accumulates within a tumor. The excited PS interacts with molecular O2, creating ROS that are responsible for causing vascular stasis and necrosis, membrane damage, and apoptosis and for initiating signaling cascade resulting in an influx of inflammatory cells
MTHPC photodynamic tx in cats – effectiveness? Side effects?
84% ORR: 61% CR and 22% PR
Median PFS not reached; mean PFS 35 months
MST 50 months
Tumor invasiveness was the only factor associated with outcome; invasive tumors all progressed within 6 months
No systemic AE. Mild local AE in 42% (erythema, edema) that resolved within 2-7 days.
ALA photodynamic therapy in cats with nasal SCC – ORR? Relapse? Chance of new lesions?
ORR was 96%, but 51% recurred and response duration was short. In patients with recurrence, it was documented at a median of 157 days. (Bexfield et al, JVIM, 2008)
Which tumor dies interphase death (apoptosis) after clinically relevant RT doses rather than metaphase death?
a. Lymphoma
b. Meningioma
c. SCC
d. Melanoma
a. Lymphoma
• Salivary gland epithelium, oocytes, spermatocytes, thymocytes as well
• Potentially due to sphingomyelin-dependent signaling pathway
oCeramide induces apoptosis in endothelial cells, lymphocytes, and hematopoietic cells
Risk factors for RT related late AE in the pelvic/peri-anal region
Based on the appearance of a port film for AGASACA which fraction size would decrease GI toxicity ?
Some people treat 2.5 Gy instead of 3.0 to decrease the risk of late AEs like rectal stricture or perforation
51 dogs undergoing dRT to pelvic region = 39% developed 1+ late AE; those with perineal tumors or larger RT fields were at highest risk; recommend keeping fraction size < 3 Gy
16 dogs undergoing dRT to pelvic region = colitis was most common late AE (56%); doses >3 Gy had more AE, majority received radiation potentiators
In another study using IMRT, only 19% developed grade 3+ late AE
Hemoclips for post-op RT would be useful for what tumor type?
- Tumor on side of body
- Study showed that there was a significant difference in RT field size using hemoclips vs. scar alone for truncal tumors. 79% of tumors had hemoclips outside of what would have been the RT treatment field. It mattered much less for extremities.
90Sr emits a dose of what Gy?
> 100 Gy
90Sr susceptible tumors?
feline superficial nasal SCC, feline cutaneous MCT, canine limbal melanoma and HSA, canine lingual plasmacytoma, equine corneolimbal SCC
Boron capture therapy:
- understand the basic concepts
- pros/cons?
- When would you use clinically?
- Make a neutron therapy agent that enables boron to concentrate in tumor. Then treat with thermal neutrons, which will interact only with tumor and spare normal tissues.
- Problems: (1) How to get tumor to absorb boron? (2) Thermal neutrons have poor penetration to deeper tissues (3) Need source of thermal neutrons, which live in nuclear reactors
