Radiation Therapy

Question 1

What is the definition of a Gray (Gy)?

Answer 1

1.0 Joule/kg of tissue (it is a measure of absorbed dose in tissue)

Question 2

What is the law of Bergonie and Tribondeau?

Answer 2

Radiosensitivity is directly related to mitotic activity and inversely related to cell differentiation.
(Think about bone marrow - high turnover, not well differentiated.)

Question 3

How are lymphocytes different from other cells in their radiation response?

Answer 3

They experience immediate interphase death. Other cells will not die until they proceed to mitosis.

Question 4

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 4

Answer: C

Question 5

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 5

Answer: e

Question 6

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 6

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

Question 7

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 7

Answer: D

Question 8

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 8

Answer: E

P16 can be used to look at induction of E67 and papilloma virus.

Question 9

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 9

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.

Question 10

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 10

Answer: b

Early erythema, nausea and vomiting occur as a result of the release of 5-hydroxytryptamine (aka serotonin) by mast cells.

Question 11

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 11

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.

Question 12

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 12

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.

Question 13

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 13

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.

Question 14

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 14

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.

Question 15

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 15

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).

Question 16

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 16

Answer: a.

2.5-3.3 is the range.

Question 17

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 17

Answer: B

Question 18

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 18

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.”

Question 19

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 19

Answer: D

Question 20

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 20

Answer: c

Question 21

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 21

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.

Question 22

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 22

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.

Question 23

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 23

Answer: d

non-homologous end joining recombination occurs in all phases of the cell cycle

Question 24

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 24

Answer: b

Question 25

Which of the following cell types dies primarily via apoptosis following exposure to radiation?

i. spermatocytes
ii. lymphocytes
iii. enterocytes
iv. fibroblasts
v. thymocytes

a. i, ii, iii
b. iii, iv
c. i, ii, v
d. ii, iii, v

Answer 25

Answer: c.
Explanation: Most normal and tumor cells die secondary to mitotic catastrophe, but there are some cells that primary die via apoptosis – lymphocytes, thymocytes, spermatocytes, and salivary epithelium.

Question 26

Which of the following best defines the Compton effect?

a. Photon collides with a free electron, both are scattered in different directions and proceed to interact with other electrons and molecules.
b. Low energy photon collides with a tightly bound electron and transfer almost all energy to the electron. The electron then goes on to ionize surrounding molecules.
c. Photon interacts with a nucleus. The photon gives up its energy to the nucleus and creates a pair of positively and negatively charged electrons. The positive electron (positron) ionizes until it combines with a free electron.
d. Generation of a free radical from ionization of water. Theses radicals then damage molecules within the cell.

Answer 26

Answer: a.
Explanation: The Compton effect is the most important mechanism leading to deposition of energy into tissue as a result of clinical radiation therapy. The probability of a Compton interaction is inversely proportional to the energy of the incoming photon and is independent of anatomic number. The Compton effect is the reason why Port films have less detail; energy is higher and photoelectric effect does not predominate. “b” is the definition for photoelectric effect and “c” is the definition of pair production, the other possible interaction for a photon in tissue. “d” is what happens subsequent to the photon-electron interaction when energy is deposited into tissue and describes the indirect effect.

Question 27

Choose the correct statement:

a. Low energy x-ray beams are typically in the 800-1500 keV range and deposit their energy deeper in tissue while sparing the skin.
b. High energy x-ray beams are typically in the 100-500 MeV range and deposit their energy near the surface of the skin.
c. Low energy x-ray beams are typically in the 50-250 keV range and deposit their energy near the surface of the skin.
d. Low (50-250 keV) and high (18-25 MeV) energy x-ray beams deposit their energy at the same tissue depth, but the high energy beams are more likely to result in the Compton effect than photo electric effect.

Answer 27

Answer: c.
Explanation: (a) has a keV range that is too high for low-energy beams, and the tissue depth is wrong. (b) is wrong for the same reason – should be 18-25 MeV and deep tissue penetration. (d) both and high energy beams in these ranges should result primarily in the Compton effect but the tissue depths will be different.

Question 28

What is the definition of one Gray (Gy)?

a. 1 joule/kg body weight
b. 100 joule/kg body weight
c. 1 joule/mg tissue weight
d. 100 joule/mg tissue weight

Answer 28

Answer: a.

Question 29

Which of the following would be expected to have a very steep radiation dose/survival curve (ie, one with little to no shoulder)?

i. fibroblasts containing the AT (ataxia telangiectasia) mutation
ii. Chinese hamster ovary (CHO) cells
iii. Cells in late S phase
iv. Cells with a mutation preventing repair of double-strand breaks

a. ii, iv
b. i, iv
c. ii, iii
d. i, iii

Answer 29

Answer: b.
Explanation: Cells with no shoulder on the survival curve are those that laci the capacity for repair and that do not immediately undergo RT-induced apoptosis (lymphocytes, spermatocytes, etc.). ATM cells and those that could not repair DS breaks fit this category. CHO cells should have normal repair and RT responsiveness, and cells in late S phase are relatively resistant (see fig 15-10).