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Oncology lecture B > Radiobiology FRCR part 1 > Flashcards

Radiobiology FRCR part 1 Flashcards

1
Q

How is a dose of radiation measured?

A

1J/Kg = gray (Gy)

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2
Q

Ho is equivalent dose defined?

A

ED = different effectiveness of tissue x dose

Measured in Sieverts

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3
Q

What are the phases of radiobiological effects?

A

physical - energy deposition, ionisation

Chemical - free radical, chemical modification

Biological - cell effects and toxicity

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4
Q

Where is RT most effective in the cell?

A

Nucleus, where DNA is attached to the nuclear membrane

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5
Q

How are free radical formed.

A

1st -excitement of H2O produces ionised H2O

2nd - Ionised water produce hydroxide ion and H free radical

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6
Q

How does radiation indirectly interact with DNA?

A

Photon excites e- leading to free radical formation with H2O, leading to DNA damage

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7
Q

How does radiation directly interact with DNA?

A

Photon excitements e- which damages DNA without H2O intermediate

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8
Q

What is the fenton reaction?

A

Peroixide catalyses with Fe2+ to hydroxy ions when oxidised to FE3+

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9
Q

What types of enzyme induced double-strand breaks (dsb) are there?

A

Blunt-ended

Cohesive end - exposed ss

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10
Q

What type of DNA breaks is associated with cell kill?

A

dsb

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11
Q

How does dsb lead to cell death?

A

chromosomal abberations

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12
Q

How does O2 increase DNA damage due to RT?

A

O2 is fixed to Irradaited DNA leading to the damage

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13
Q

What is the oxygen enhancement ratio (OER)?

A

ratio of radiation dose in hypoxia to the dose in air to produce the same biological effects

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14
Q

How is linear energy transfer (LET) defined?

A

Energy deposited per unit length of track (of radiation)

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15
Q

How are the tracks different in low LET?

A

Many branching tracks, sparsely ionising. From gamma or X-rays

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16
Q

How are the tracks different in high LET?

A

Fewer branching tracks, densely ionising. From alpha or carbon ions

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17
Q

How does LET effect cell kill?

A

higher LET has higher cell kill due to increased dsb.

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18
Q

What is optimum LET?

A

the value of LET which has the highest RBE

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19
Q

What is relative biological effectiveness (RBE)?

A

Ratio of dose of reference compared to rest radiation to compare equal effect.

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20
Q

What is the significant of cluster damage?

A

multiple breaks within a small length of DNA. more complex and difficult to fix, specially with dsb. DNA repair is LET dependent.

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21
Q

What types of DNA repair are there?

A 
Direct substitution of damaged base. 
BER -base excision repair 
NER - nucleotide excision repair 
MMR- mismatch repair 
HR - homologous recombination 
NHEJ - non homologous end joining
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22
Q

What repair mechanisms are there for dsb?

A

Homolous recombination and non-homologous end-rejoining

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23
Q

Does direct substitution work?

A

Direct reversal - methyl taken from guanine to the cytosine on O6MGT to preserve the guanine….

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24
Q

Does direct substitution occur in RT?

A

No

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25
Q

How does base excision repair work?

A
  1. base recognised and removed
  2. cleavage of phosphodiester backbone.
  3. re-polymerised using undamaged strand as template
  4. resealing gap
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26
Q

What pathways of Ssd are there?

A

short patch (PARP) and long patch

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27
Q

What detects ssb?

A

PARP, which then recruits SSB repair scaffold protein.

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28
Q

What is nucleotide excision repair?

A

remove helix distortions in the helix due to a patch of bases

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29
Q

Does nucleotide excision repair occur in RT?

A

Radiation-induced crosslinks under hypoxic conditions

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30
Q

When in the cell cycle is homologous repair used?

A

S and G2 phase

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31
Q

When is homologous repair used?

A

In responce to dsb

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32
Q

How does homologous repair work?

A
  • dsb detected
  • endonuclease produces single strands from dsb
  • homologous strand inversion
  • new DNA based on homologous DNA strand template
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33
Q

When does NHEJ work?

A

End of G1 though throughout cell cycle

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34
Q

How does HR work with key involved protiens

A

o ATM - sensitisation and phosphorylated in DBS
o Recruitment of BRCA-1
o Stripped and then stabilised by RPA
o Damaged and duplicate strands approximate due to cohesin
o RAD51 – stabilises the homologuos (Holliday) structure
o DNA polymerase then repaures the homologous strands

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35
Q

How does NHEJ work?

A
  1. Ku binds to dsb
  2. DNA polymerase
  3. ligase 4 recruited, sticking helix back together
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36
Q

Which is more error prone HR or NHEJ?

A

NHEJ is error prone

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37
Q

What its the role of PARP, Ku and ATM?

A

dsb damage sensors

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38
Q

How is the majority of dsb repaired in RT?

A

NHEJ

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39
Q

What is the concept of synthetic lethality?

A

Normal cell have to methods of DNA repair, HR using BRCA and BER using PARP. therefore give PARPi to BRACA mt.

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40
Q

How are oxidised bases and ssb repaired?

A

Base excision repair

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41
Q

What is the survival fraction?

A

Colonies counted/ (cells seeded * plating efficiency%)

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42
Q

In the linear-quadratic model what is the alpha term?

A

Initial slope, the single-hit probability of inactivation target directly

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43
Q

In the linear-quadratic model what is the beta term?

A

probability of two independent formed single hits combining to form a lethal hit

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44
Q

What value of alpha/beta ration in dicates a radiosensitive tumour?

A

high a/b ratio

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45
Q

What does a large shoulder of the linear-quadratic curve represent?

A

A radio resistant tumour, low a.b ratio

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46
Q

what checkpoint is induced by RT in the cell cycle?

A

cell cycle checkpoint at G2

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47
Q

What is the most radio-resistant phase of the cell cycle?

A

Late S phase

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48
Q

What is the most radio-sensitive phase of the cell cycle?

A

G2 or M phase

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49
Q

What is potentially lethal damage repair?

A

cellular damage that is repaired between the treatment and analysis via assay.

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50
Q

What is sublethal damage repair?

A

increase in survival if a dose is split between two fractions in time.

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51
Q

How does fractionation affect cell kill?

A
  • Increased sublethal damage repair.

- RBE increases RBE

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52
Q

How does dose rate effect cell kill?

A

Similar to fractionation.

lower rate = SLDR

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53
Q

What happens between two exposure of radiation

A
  • initial increase in survival (SLD)
  • decrease due redistribution/resortment
  • Increase due to repopulation from 6 hours
54
Q

What happens in resortment in radioteherapy?

A

Initial radiotherapy dose pushes cell into G2 cell cycle check, a radiosensitive phase of the cell cycle. => incereased cell kill

55
Q

What happens in resortment in radioteherapy?

A

Initial radiotherapy dose pushes cell into G2 cell cycle check, a radiosensitive phase of the cell cycle. => increased cell kill

56
Q

What is the bystander effect in RT?

A

Increased cell kill as a response to neighbour cells being irradiated

57
Q

What is hyper-radiosensitivity?

A

cell are radio-sensitive due to low dose RT but become radio resistant at higher Gy RT.

58
Q

What two models are there for measuring radiotherapy and cell survival?

A

Linear-quadratic and muilti-target model

59
Q

What part of the cell cycle is stained by proliferation markers?

A

S phase

60
Q

How can cell kinetics be measured?

A

Percentage-labelled mitosis (PLM) = proportion of labelled cell as a function of time.

61
Q

What is the growth fraction?

A

Same as labelling index?

proliferative cell/ total cells.

62
Q

What is Tpot?

A

potential doubling time of a tumour and is proportional to the duration of S phase/ labelling index.

63
Q

How is cell loss measured?

A

Cell lose factor - cells loss as proportion to cell created by mitosis (1 - (Tpot/Td) (1 - potential vs actual tumour doubling time)

64
Q

How is Cell loss fracture calculated?

A

1- (the ratio in potential and actual doubling time)

65
Q

What is the repopulation paradox?

A

When tumours are treated, there is a decrease in tumour doubling time. This leads to a smaller tumour which has an aggressive growth rate.

66
Q

Impact of hypoxia on tumour biology?

A
  • angiogenesis
  • apoptosis
  • motility
  • genomic stability
  • invasion
67
Q

Impact of hypoxia entreatment response?

A

lots

68
Q

Why are hypoxic cell less radio-sensitive?

A

Less fixing of oxygen for DNA damage

69
Q

What factors have a decreased OER between hypoxic and normal tumours?

A

Lower RT doses

Higher LET

70
Q

What is the principle of reoxygenation in RT?

A

RT kills aerobic cells rather than hypoxic. Some hypoxic tumour cell transition to aerobic Subsequent RT dose would be effective for a new group of aerobic cells.

71
Q

Makers of tumour cell hypoxia?

A

Pimidazole and EF5.

72
Q

Problem with pimanidazole?

A

Injected prior to biopsy.

73
Q

What is a a prognostic factor for radio-responce with hypoxia modification medication?

A

F-FMISO from CT-PET

74
Q

Methods for increasing O2?

A
  • treat aneamia
  • ## hyperbaric oxygen
75
Q

what hypoxic medication has proven benefit in bladder cancer?

A

nicotinamide

76
Q

What markers are there of hypoxia (association)?

A

HIF1a
CA9
Glut1

77
Q

What cancers are RT +platinum ChT used for?

A

H+N
Cervix
NSCLC

78
Q

What cancers are temozolamide and RT used for?

A

Glioblastoma

79
Q

What Cht agents target DNA repair when used along side RT?

A
  • Cisplatin
  • Bleomycin
  • Doxorubicin
  • Nucleoside analogues (gemcitabine)
  • PARPi
80
Q

How can VEGF inhibitors assist RT?

A
  • blocks VEGF as a survival factor

- promotes normal vasculisation

81
Q

What are gefitinib and erlotinib?

A

intra-cellular kinase inhibitors for EGFR

82
Q

What therapeutic strategies may be feasible in treating hypoxic tumours?

A

PI3K inhibits
Malarone (atorvaquine)
EGFR-i

83
Q

What featured of normal tissue are predisposed to early toxicity?

A

Highly proliferative tissues. Hypoplasia induced.

84
Q

What featured of normal tissue are predisposed to early toxicity?

A

slowly proliferative cells. depletion of functional cells

85
Q

What a-b ratio predisposes to early toxicity?

A

Higher a/b.

86
Q

How can tissue be organised in the ‘model system’.

A

Hierachical - stem cells>precursors>functional cells.

Flexible - proliferative and functional ability of cells

87
Q

In the ‘model system’ of normal tissue, what type of tissue are predisposed to acute toxicity?

A

hierarchic tissue - bone marrow, intestines, mucosa, gonads

88
Q

In the ‘model system’ of normal tissue, what type of tissue are predisposed to Late toxicity?

A

Flexible - kidney, spinal cord, adrenal, pancrease, endocrine organs.

89
Q

Does dose effect time of onset of toxicity?

A

Not in early toxicity but in late toxicity effects.

90
Q

What are consequential late effects?

A

Late effects which are influenced by the extent (duration and severity) of early effects

91
Q

What are the 5 Rs for normal tissue tolerance?

A 
Radiosensitivity
Recovery 
Repopulation 
?Irradiated volume 
Retreatment
92
Q

What classification of late effects (toxicity) on normal tissue are there?

A

LENT/SOMA

Late effects in normal tissue/ subjective objective management analytic

93
Q

radiation responce in normal cell depends on?

A
  • Cellular radio-sensitivity (CSC).
  • Kinetics (proliferation)
  • organisation (hierarchical, flexible or functional subunit)
94
Q

What does ataxia talengesia have to do with RT?

A

abnormal DNA repair caused by ATM gene. ATM detects DSBs. These patient have more toxicity

95
Q

What factors effect toxicity in RT?

A

Age, DM, IBD, connective tissue disease, etc.

96
Q

What effect the latency (time of onset) for early toxicity?

A

Life span of functional cells.

GI sooner the bone marrow

97
Q

What is meant by the structural tissue (per unit area) tolerance?

A

Reflected cellular radio-sensitivity and ability for clonogenic stem cell to maintain mature cell population

98
Q

What is meant by the functional tissue tolerance?

A

Depends on wether an irradiated area contribute to whole organ function. Depends tissue organisation and its radio-sensitivity against its reserve capacity.

99
Q

How can functional sub-units be organised in a tissue?

A

Parallel or in series

100
Q

What is the definition of a functional sub unit?

A

the largest tissue volume by which a single surviving colonogenic cell can regenerate.

101
Q

What examples are there of tissue which are arranged n a parallel FSU?

A

lung
liver
kidney

102
Q

What examples are there of tissue which are arranged n a series FSU?

A

spinal cord, oesophagus, intestine

103
Q

How does tissue with parrallel FSU deal with RT?

A
  • complication due to total dose, not hot spots.
  • Tolerates small volumes of RT well.
  • Good functional reserve capacity
104
Q

How does tissue with series FSU deal with RT?

A
  • Complication due to hot spots not total organ.

- low functional reserve

105
Q

What is the equivalent uniform dose (EUD)?

A

Absorbed dose that if homogenously delivered causes the same response as the actual clinical absorber dose distribution.

106
Q

When does RT dose affect onset and when does it affect severity of toxicity?

A

Maximum severity is dose dependent in early toxicity effect

Latency time is dose dependent in late toxicity effect

107
Q

What is meant by deterministic effect in relation to radiation exposure?

A

Deterministic is the functional impairment of an organ or tissue due to radiation exposure.

Has threshold. Due to cell kill.

108
Q

What is meant by Stochastic effect in relation to radiation exposure?

A

Probability of radiation exposure effect. Has no threshold. Due to non-lethal cell modification.

109
Q

What is Excess relative risk (EER)?

A

Proportion increase in risk compared to background risk. (e.g; RR of 2.2 is an ERR of 1.2)

110
Q

What is relative risk (RR)?

A

Ratio of overall to background risk

111
Q

What is the excess absolute risk (EAR)?

A

difference in additional absolute risk compared to background. (Not a ratio) (increased - background risk)

112
Q

Solid cancer have what type of relationship between incidence and radiation exposure?

A

Men - linear-quadratic
Women - linear dose
= both dose-

113
Q

What type of cancer are susceptible to background radiation?

A

Solids, not CLL, Hopkins, malignant melanoma.

114
Q

Factors affecting cancer development risk due to radiation?

A 
Dose
Dose rate
Sex
Age of exposure 
Time since 
Attained age
115
Q

Hereditary cancer due to radiation exposure is an example of a deterministic or stochastic effect?

A

Stochastic

116
Q

What methods can be used to direct/ focus proton beam therapy onto a patient’s tumour?

A

Scattering (filters, barriers)

Scanning (range shifter)

117
Q

How does an x ray photon deliver radiation dose?

A 
Photo-electric effect  (e- only)
Compton scattering (y and e-)
Pair production (e- and e+)
118
Q

How do protons deliver radiation dose?

A

Coloumb (Rutherford) scattering

Proton inelastic reactions (release of neutron and y with lesser p’)

119
Q

How can a briggs peak be spread out?

A

Different depths producing a spread out braggs pack (SOBP)

120
Q

How do dsb effect the rate of repair?

A

Depend on the slow repair component. This is prolonged with dsb. Therefore repair takes longer

121
Q

What are the 3As of tissue repopulation?

A

loss of Asymetric cell division
Abortive decision
Accelerated stem cell differentiation

122
Q

What is asymmetric cell division and its implications on RT?

A

stem cells produce either differentiated or stem cells from mixed (asymtet-). This means that increased RT is needed for increased treatment time.

123
Q

What is the implications of accelerated stem cell proliferation on RT?

A

dictates the rate of dose compensation

124
Q

What is the implication of ‘abortive decision’ for tumour repopulation?

A

Corresponds to cell loss

125
Q

What is the RF2 in radiotherapy?

A

Survival fraction at 2 Gy. Predicts radio sensitivity

126
Q

What is the Dar in radiotherapy?

A

Mean inactivation dose. Calculated from the area under the survival curve (AUC).

127
Q

What features for hypoxia RT sensitisers have?

A

Not metabolised, electron- affinic (mimic O2)

128
Q

What is a Hyopoxic RT sensitiser?

A

Nimorazole

129
Q

Name examples of radio protectors

A

Amifostine
Pentoxifylline
Pravastatin
Stem cell therapy

130
Q

What is the therapeutic index?

A

The therapeutic is the rumour response for a fixed level of normal tissue damage.

131
Q

What is the therapeutic ratio?

A

The therapeutic ratio is the relationship between the probability of tumour control and the likelihood of normal tissue damage.

132
Q

What factors influence chance of cure in RT?

A
  • Clonogenic number one tumour
  • Hypoxia
  • Repopulation ability
  • Radiosensitivity of tumour
  • Radiosensitivity of patient

Oncology lecture B (4 decks)

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