Radiation Therapy Flashcards
What is the definition of a Gray (Gy)?
1.0 Joule/kg of tissue (it is a measure of absorbed dose in tissue)
What is the law of Bergonie and Tribondeau?
Radiosensitivity is directly related to mitotic activity and inversely related to cell differentiation.
(Think about bone marrow - high turnover, not well differentiated.)
How are lymphocytes different from other cells in their radiation response?
They experience immediate interphase death. Other cells will not die until they proceed to mitosis.
Identify the acute tissue responders to radiation therapy.
i. Skin
ii. Oral mucosa
iii. Bone
iv. Kidney
v. GI mucosa
vi. Spinal cord
a. i, ii, iii, iv
b. iii, iv, vi
c. i, ii, v
d. iv, v, vi
e. i, ii, iv, vi
Answer: C
What are the five R’s in regards to the most important biological factors influencing the responses of tumors and normal tissues to fractionated radiotherapy?
i. Redistribution
ii. Repopulation
iii. Redirection
iv. Radiosensitvity
v. Repair
vi. Reoxygenation
vii. Regulation of cell cycle
a. i, ii, iii, iv, v
b. ii, iv, v, vi, vii
c. i, iii, iv, vi, vii
d. i, iii, iv, v, vi
e. i, ii, iv, v, vi
Answer: e
Which of the following is true in regards to tumor hypoxia and radiation response?
a. OER is the degree of sensitization afforded by oxygen and is defined as the ratio of doses required to give the same biological effect in the absence or the presence of oxygen
b. Cells irradiated under conditions of severe acute hypoxia are 3 times more sensitive than cells irradiated in the presence of air
c. The oxygen level (pO2) in tumor tissue that is considered hypoxic ranges from 20-80 mmHg
d. Hypoxic cells represent a radiation-sensitive subpopulation in tumors, therefore the therapeutic ratio might be improved by techniques to increase the influence of hypoxic cells on tumor response
Answer: a
Explanation: p. 367-372; In summary, cells that hypoxic are more resistant than cells that are exposed to oxygen and hypoxia is seen in areas of the tumor where the pO2 is less than 5 mmHg
The oxygen enhancement ratio is dependent on which of the following:
i. quantity of Gy administered ii. type of radiation therapy administered (i.e. photons versus particles) iii. linear energy transfer iv. tumor type v. phase of the cell cycle
a. i, ii, iii
b. ii, iii, iv
c. iii, iv, v
d. i, ii, iii, iv
e ii, iii, iv, v
Answer: D
Which of the following are intrinsic markers of hypoxia?
i. hypoxia inducible factor 1 ii. glucose transporter 1 iii. carbonic anhydrase-9 iv. osteopontin v. p16
a. i, ii, iii
b. i, ii, iv
c. i, iii, v
d. ii, iii, iv, v
e. i, ii, iii, iv
Answer: E
P16 can be used to look at induction of E67 and papilloma virus.
Which of the following tissues is most likely to be intolerant to a second course of definitive radiation therapy?
a. Skin
b. Gastrointestinal tract
c. Spinal cord
d. Lung
e. Kidney
Answer: e
The ability to perform a second course of radiation is dependent on the recovery of late-responding tissues. The skin, mucosa, spinal cord, and lung all substantially recover over a period of 3-6 months. The kidney and urinary bladder, however, show little evidence of recovery.
Which of the following compounds could counteract early side effects (e.g., erythema) associated with radiation therapy?
a. ACE inhibitor
b. Serotonin antagonist
c. Vitamin D
d. Glucocorticoids
e. Nitromidazoles
Answer: b
Early erythema, nausea and vomiting occur as a result of the release of 5-hydroxytryptamine (aka serotonin) by mast cells.
Which of the following is true regarding the hypoxic cell population of tumors?
a. Chronically hypoxic cells are more resistant to radiation than acutely hypoxic cells.
b. Hypoxic tumor cells are orderly distributed near a central core of necrosis.
c. Shortened treatment schedules are more likely to target hypoxic cells.
d. Tirapazamine is a cell sensitizer that is metabolized only in hypoxic conditions.
e. The oxygen enhancement ratio (OER) is increased with high-LET radiation.
Answer: d
In hypoxic conditions, tripazamine is metabolized to an active compound that produces DNA damage. In the presence of oxygen, the active compound is oxidized and reverts to its parent compound. Distractors: a) Acute hypoxia is more RT-resistant. b) Hypoxic regions are randomly distributed throughout the tumor. c) Larger fraction sizes are more prone to the protective effects of hypoxia. e) The OER is decreased with high-LET radiation, making hypoxic cells less protected from RT.
Which of the following could decrease the risk of pulmonary fibrosis in a patient undergoing RT to the thorax?
i. Enalapril
ii. Hyperbaric oxygen
iii. Amifostine
iv. Prednisone
a. i, iii
b. ii, iii
c. iii, iv
d. i, iv
Answer: a.
Explanation: Enalapril has been shown to decrease pulmonary fibrosis in RT patients, and amifostine helps protect lung and other tissues while leaving tumor response unchanged. Prednisone can delay pulmonary fibrosis but does not appear to prevent it, and hyperbaric oxygen should make both normal and tumor tissues more sensitive.
Which of the following statements relating to whole body radiation is true?
a. Neurovascular syndrome occurs last, and takes the least amount of radiation to induce.
b. Gastrointestinal syndrome occurs first, and takes the most radiation to induce.
c. Gastrointestinal and neurovascular syndromes can both be survived with appropriate supportive care.
d. Hematopoietic syndrome occurs last, after doses of approximately 3-9 Gy.
Answer: d.
Explanation: Neurovascular occurs 1st (hours to days), >20 Gy. Gastrointestinal occurs 2nd (~1 week), 5-15 Gy. Hematopoietic occurs last (12-30 days), 2-8 Gy in humans or 3-10 Gy in rodents. Gastro and hemato can in part be ameliorated with supportive care.
You are performing a retrospective study using banked formalin fixed tissue samples (now in paraffin blocks), and you wish to investigate tissue hypoxia. Which of the following would be best used to identify hypoxic cells?
a. Antibodies to pimonidazole conjugates
b. Antibodies to osteopontin
c. Antibodies to [18F]-misonidazole
d. Antibodies to both pimonidazole conjugates and osteopontin could be used
Answer: b.
Explanation: [18F] is injected and then assessed via PET scan; good for assessment in live patient. Pimonidazole conjugates can be assessed via IHC, but must be injected before the sample is taken. Osteopontin is the only intrinsic marker on the list that can be used in this retrospective fashion. Page 369.
Which of the following have a low α/β ratio?
i. Epidermis
ii. Melanoma
iii. Liver
iv. Squamous cell carcinoma
v. Spinal cord
a. i, iii, iv
b. i, ii, iv
c. i, iii, v
d. ii, iii, v
Answer: d.
Explanation: late responding tissues and some tumor types (melanoma, STS, TCC, prostatic carcinoma, osteosarcoma) have lower a/b ratios. Early responding tissues and most tumors have high a/b ratio. Tissues with low a/b ratios tend to have a larger repair capacity. Looking a survival fraction/dose graphs the curve for a tissue/tumor with high a/b ratios is linear and the curve for tissues/tumors with low a/b ratios is more parabolic (see Withrow 183).
What is the OER (oxygen enhancement ratio) for most tissues when treated with X- or γ-radiation at doses greater than 3 Gy?
a. 2.5
b. 3.5
c. 4.0
d. 5.2
Answer: a.
2.5-3.3 is the range.
Cells irradiated in the presence of air are about ¬¬¬___ times more sensitive than cells irradiated under conditions of severe acute hypoxia.
a. 2
b. 3
c. 5
d. 10
Answer: B
Which of the following can cause an apoptotic response in lymphocytes undergoing irradiation in absence of DNA damage?
a. Endothelin
b. Ceramide
c. Vimentin
d. Synaptophysin
e. Calcium
Answer: B
Explanation: “In endothelial, lymphoid, and hematopoietic cells, ceramide mediates apoptosis, whereas in other cells, ceramide may play no role in the death response.”
Linear energy transfer is based on which of the following factors:
i. velocity of the particle ii. charge of the particle iii. neutron density of the tissue iv. electron density of the tissue v. quantity of water molecules per cm3
a. I, ii, iii
b. ii, iii, iv
c. ii, iii, v
d. I, ii, iv
e. I, iii, v
Answer: D
Which of the following mutations would make cells the most sensitive to ionizing radiation therapy?
a. xeroderma pigmentosum
b. BRCA2
c. ataxia telangiectasia-mutated
d. BRCA1
e. FANC-D2
Answer: c
In what phase of the cell cycle are tumor cells most resistant to radiation therapy?
a. G0
b. G1
c. S
d. G2
e. M
Answer: c
Generally, cells in late S phase are more likely to survive following radiation. A variety of tumor cell lines have shown resistance during S phase in vitro. Cells in mitosis are the most sensitive to radiation. There is, however, some variability between cell types.
Which of the following is true regarding the cell death/survival response to ionizing radiation?
a. Cells that are killed by irradiation will no longer divide.
b. In the majority of cells, radiation-induced death occurs via apoptosis.
c. Following radiation, senescent cells are metabolically inactive, do not proliferate, and eventually undergo apoptosis.
d. Necrosis results in cell membrane blebbing, nuclear inclusion bodies, and DNA fragmentation.
e. The relative biologic effectiveness (RBE) of high-LET radiation is greater than that of low LET-radiation.
Answer: e
False answers: a) Cells that are killed following radiation may still divide a few times, but they form only small “abortive” colonies. b) Radiation-induced cell death can occur via apoptosis, necrosis, mitotic catastrophe or senescence. In the majority of cells, this death occurs secondary to mitotic catastrophe. c) Senscent cells are metabolically active, do not proliferate, and undergo necrosis. d) This describes apoptosis, not necrosis.
Cells in different phases of the cell cycle have different radio-sensitivity and active repair mechanisms. During which phase of the cell cycle does homologous recombination (HR) occur?
a. During all the phases of the cycle
b. During mitosis
c. During Go and G1
d. During S and G2 phases
Answer: d
non-homologous end joining recombination occurs in all phases of the cell cycle
Cell cycle checkpoints in cells are activated following irradiation and the molecular events relating to G1 and G2 phase cell cycle arrest appear to involve which of the following complexes that are associated with cell-cycle regulation.
i. Myc
ii. ATM
iii. P53
iv. C-ABL
v. Cyclin-CDK
a. i, ii, iii, iv, v
b. ii, iii, v
c. i, iv
d. ii, iii, iv,
Answer: b
