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Principles of radiobiology for FRCR CO1 > 1.7 Normal tissue radiobiology > Flashcards

1.7 Normal tissue radiobiology Flashcards

1
Q

What physical factors determine radiotherapy toxicity? (7)

A
  1. Total dose
  2. Dose fractionation
  3. Overall treatment time
  4. Radiation modality
  5. Immobilisation strategy
  6. Image guidance
  7. Quality assurance
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2
Q

What biological factors determine radiotherapy toxicity? (5)

A
  1. Tissue tolerence
    - Radiosensitivity of tissue
    - Kinetics (cell turn ver) and tissue structure
  2. Patient factors
    - Performance status
    - Comorbidities e.g. NF or IBD
    - Polypharmacy
  3. Irradiated volume
  4. Synergistict sact
  5. Retreatment
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3
Q

What does normal tissue response to radiotherapy depend on?

A
  1. Cellular radiosensitivity - directly related to mitotic activity and inversley proportional to the degree of differentiation
  2. Kinetics of the population - high proliferatvie cells show earlier response
  3. Organisation of cells in tissue - hierarchical, flexible, or functional subunits
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4
Q

In what time period do early normal tissue effects occur?

A

<90 days

Seen days - weeks after exposure

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5
Q

What tissues are affected by early normal tissue effects?

A
  • Hierarchical
  • Highly proliferating

e.g. bone marrow, intestinal mucosa, epidermis

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6
Q

How does the cell survival curve look in early normal tissue effects?

A

Straighter

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7
Q

What is the a/B ratio in early normal tissue effects?

A

High ~10Gy

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8
Q

What impact does fractionation have on early normal tissue effects?

A

Minimal impact - they are less sensitive to fraction size

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9
Q

What does the severity of early normal tissue effects depend on?

A
  • Total dose
  • Overall treatment time
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10
Q

What are the biological effects in early normal tissue effects?

A

Usually transient
1. Direct to SSB and DSB
2. Indirect to Reactive Oxygen Species
3. Inflammation
4. Vascular permeability

Hypoplasia due to parenchymal and vascular effets

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11
Q

What tissues do early normal tissue effects occur in most?

A

Impairs cell proliferation so most signficant in highly proliferative

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12
Q

What are the early normal tissue effects?

A
  • Mucositis - moist desquamation
  • Dermatitis - erythema
  • Diarrhoea
  • Hair loss
  • Cystitis
  • Proctitis
  • Pneumonitis
  • Bone marrow suppression
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13
Q

What does latency depend on in early normal tissue damage?

A

Lifespan of functional cells
Not dose dependent or extent of damage

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14
Q

How does regeneration occur in early normal tissue damage?

A

Proliferation or migration of stem cells (dose dependent)

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15
Q

In what time period do late normal tissue effects occur?

A

> 90 days (limit of wound healing)

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16
Q

What tissues are affected by late normal tissue effects?

A
  • Flexible
  • Slowly proliferating

e.g. kidney, bladder, lung, CNS

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17
Q

How does the cell survival curve look in late normal tissue effects?

A

Curvier

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18
Q

What is the a/B ratio in late normal tissue effects?

A

Lower (~3Gy)

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19
Q

What impact does fraction size have on late normal tissue effects?

A

Major impact
Much more sensitive to fraction size - quadratic cell survival curve

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20
Q

What does the severity of late normal tissue effects depend on?

A

Extent of damage
Can result from severe early toxicity

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21
Q

What is the latency for late normal tissue effects?

A

Dose dependent
Side effects occur erlier and progress quicker

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22
Q

What are the biological effects in late normal tissue effects?

A

Progressive and irreversible changes:

  1. Fibrosis (increased TGF-B signalling)
  2. Tissue remodelling
  3. Vascular changes
  4. Depletion of functional cells and impairment of tissue function
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23
Q

What are the late normal tissue effects? (10)

A
  1. Hardening of breast tissue
  2. Lung fibrosis
  3. Small bowel malabsorption
  4. Structures
  5. Ischaemia (bowel)
  6. Haematuria
  7. Telangectasia
  8. Hormone deficiency
  9. Indertility
  10. secondary cancers
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24
Q

What is normal tissue tolorence?

A

Maximum dose of radiation an organ can receive before it fails - in 2Gy per fraction

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25
Q

What is the structural tolorence of normal tissue?

A

Tolerence dependent on radiosensitivity and independent of volume

(also depends on ability of clonogenic cells to maintain mature cell populations above a critical level)

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26
Q

What is functional tolerence of normal tissue?

A

Whether the organ as a whole can function - depends on tissue organisation and reserve capacity

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27
Q

What are functional subunits?

A

Largest tissue volume or unit of cells that can be regenerated from a single surviving clonogenic cell

Can be parallel or in series

(No clear anatomical defeinition - e.g. could be a single nephron or the whole skin. Tumours can also be considered FSU)

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28
Q

What factors does normal tissue tolerence depend on?

A
  1. Intrinsic radiosensitivity and repair (stem and progenitor cell presence)
  2. Kinetics of cell turnover - highly proliferative = early responses
  3. Structural organisation of tissue (hierarchical, flexible, functional subunit)
  4. Wound healing ability
  5. Comorbidity/polypharmacy
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29
Q

How are tolorence doses measured?

A

TD 5/5
TD 50/5

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30
Q

What is TD 5/5?

A

Maximum dose for 5% complication risk at 5 years

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31
Q

What is TD 50/5?

A

Maximum dose for 50% complication risk at 5 years?

32
Q

Early Skin toxicity

A
  • Stem cells in basal layer of epidermis
  • Damage after 2-3 weeks
  • Erythema and radiodermatitis followed by dry or moist desquamation
  • Low sensitivity to fractionation
33
Q

Oral mucosa toxicity

A
  • Erythema, ulceration, and pain
  • Usually disappears 2-3 weeks after completion
  • Xerostomia - loss of serous glands
  • Secondary infection risk
34
Q

Intestinal mucosa toxicity

A
  • hierarchical 3-5 day turnover
35
Q

Late skin toxicitiy

A
  • Pigmentation
  • Telangectasia - damage to fibroblasts and vascualture
  • Alopecia
  • Fibrosis
  • Atrophy
  • Ulceration
36
Q

Lung toxicity - 2 stages

A
  1. Pneumonitis 2-6 months after treatment (subacute or early-late response). Due to damage to type II pneumocytes and caillary endothelial cell loss
  2. Fibrosis 6-24 months after teratment. Progressive and reversible
37
Q

What does the severity of lung toxicity depend on?

A
  • Volume irradiated (parallel tissue)
  • Dose
  • Fractionation
  • Combination with SACT
38
Q

Kidney toxicities - 2 stages

A

Relatively radiosensiitive

  1. Acute radiation nephritis 6-12 months after treatment - fatigue, oedema, SOB
    2 Chronic radiation nephritis: HTN, proteinuria, anaemia, CKD, atrophy
39
Q

What are Consequential Late Effects (CLES)?

A

Late effects that are influenced by the extent (severity, duration) of the early effect

40
Q

Which organs have high radiosensitivity?

A

Lymphoid organs
e.g.
- bone marrow
- testes & ovaries
- small intestines

41
Q

Which organs have fairly high radiosensitiviy?

A

Epithelial organs
e.g. skin, cornea, mouth, oesophagus, Gi tract, bladder, vagina, uterine cervix, uterus, rectum

42
Q

Which organs have medium radiosensitivity?

A
  • Vessles
  • Growing cartilage
  • Growing bones
43
Q

Which organs have fairly low radiosensitivity?

A
  • Glands; pancreas, adrenal, pituitary, thyroid, salivary
  • Mature cartilage and bone
  • Lungs
  • Kidneys
  • Liver
44
Q

What organs have low radiosensitivity?

A

Muscle
Brain
Spinal cord

45
Q

What are the repair process is normal tissue after irradiation?

A
  • Recovery (minutes - hours) - incomplete recovery of sublethal damage - early or late damage
  • Repopulation (days-weeks) repopulation of cells and tissue regeneration - not seen in late effects
  • Restoration (months-years) - restoration of function or progression of damage
46
Q

How do normal tissues repopulate after radiation?

A

Only seen in early damage tissue

  • Loss of asymmetric cell division - stem cells undergo symmetric division to produce more stem cell daughter cells (asymmetric produces one stem one differentiated)
  • Accelerated stem cell proliferation - increased rate of stem cell proliferation after irradiation
  • Abortive divisions - injured cells have division limited
47
Q

What is Equivalent Uniform dose?

A

Method of summarizing and reporting inhomogenous dose distributions

The absorbed dose that if homogenously delivered, causes the same biological effect as the actual clinically absorbed dose distribution (which is heterogenous)

48
Q

What is the benefit of Equivalent Uniform Dose?

A

Accounts for cold and hot spots

49
Q

Which tissues have large volume effects?

A

Parallel tissues - depend on dose distribution to the whole organ

50
Q

Which tissues have low volume effetcs?

A

Serial tissues - strongly influenced by hotspots

51
Q

What are the indications for re-treatment with radiotherapy?

A
  1. New primary tumour
  2. Locoregional recurrence (within/close to original GTV)
  3. Progression - nodes or metastases
52
Q

What factors should be taken into account when thinking about re-treatment?

A
  1. Do not treat if radiation tolerence of an organ has already been exceeded
  2. Curative vs palliative intent
  3. Dose of previous treatment (EQD2)
  4. Volume treated
  5. How close to the new fields
  6. How long since last treatment
  7. Other additional treatments that were given
  8. Which organs/tissues were involved
  9. Rapidly repopulating (hierarchical) may tolerate re-treatment better, slowly repopulating (flexible) may not
53
Q

What is the spinal cord tolerence?

A

50Gy in 2Gy per #
if a/B is 2gy for radiation myelopathy

Can be irradiated to 140% if >6-12 months since previous

54
Q

What organ should not be re-irradiated?

A

Kidneys - as time passes the kidney injury continues to progress so waiting longer between irradiation actually would make situation worse

55
Q

What is Deterministic radiation damage?

A

Lethal cell damage
As dose increases severity increases
Only occurs above a certain threshold

56
Q

is the threshold dose for eye lens? (cataracts)

A

0.5Gy

57
Q

What is the threshold for bone marrow suppression?

A

0.5Gy

58
Q

What is the threshold for permanenet sterility?

A

3-6Gy

59
Q

What is the threshold for skin burns?

A

5-10Gy

60
Q

What is stochastic radiation damage?

A

Non-lethal cell mutations that lead to cancer of birth defects

  • No threshold
  • Liklihood but not severity increases with doses
61
Q

What is tumour cell potential doubling time? Tpot

A

Tpot = the time it would take a tumour to double its cell number in the absence of cell loss

62
Q

What is Acute Radiation Syndrome?

A

Multiple clinical syndromes that occur in stages over hours-weeks after exposure

63
Q

What occurs to tissues in ARS?

A

Depletion of immature parenchymal stem cells in tissue

64
Q

At what dose does ARS occur?

A

0.7Gy

65
Q

What does the extent and severity of ARS depend on?

A
  • Total dose received
  • Rate of dose
  • Distribution of dose
66
Q

What are the syndromes that make up ARS?

A
  1. Haemopoetic syndrome
  2. Gastrointestinal syndrome
  3. Neurovascular syndrome
67
Q

What is Haemopoetic Syndrome?

A
  1. Neutropenia (first) - B cells > T cells
    note: macrophages are radioresistant
  2. Thrombocytopenia (second)
  3. Hb (third)

(death due to infection or haemorrhage) - bone marrow is very radiosensitivie

68
Q

What is the time to death of haemopoetic syndrome?

A

1-2 months

69
Q

What is the whole body dose that causes haemopoetic syndrome?

A

3-10 Gy

70
Q

What is gastrointestinal syndrome?

A

Irreversible destructive changes in GI tract (loss of intestinal crypt cells) resulting in dehydration and electrolyte imbalance

Small bowel most affected

71
Q

What is the time to death of haemopoetic syndrome?

A

1-2 weeks

72
Q

What is the whole body dose that causes gastrointestinal syndrome?

A

10-30Gy

73
Q

What is neurovascular syndrome?

A

Collapse of circulatory system and increased pressure in cranial vault from oedema, vasculitis, and meningitis

prodromal phase: burning sensation
later: CNS signs, confusion

74
Q

What is the time to death of neurovascular syndrome?

A

1-2 days

75
Q

What is the whole body dose that causes neurovascular syndrome?

A

> 30Gy

76
Q

What are the stages of Acute Radiation Syndrome?

A
  1. Prodromal - nausea, vomiting, diarrhoea (days)
  2. Latent - patient feels well (weeks) - damage processing
  3. Manifest illness - several months
    - infection, sepsis, haemorrhage
  4. Recovery or death

Principles of radiobiology for FRCR CO1 (3 decks)

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