Biological Optimisation

Question 1

5Rs

Answer 1

Radiosensitivity
* Cells have different radiosensitivities
Repair
* Cells can repair sub-lethal radiation damage
Repopulation
* Cells repopulate during fractionated radiotherapy
Redistribution
* In proliferating cell population through the cell cycle increases the cell kill in fractionated therapy relative to a single session
Reoxygenation
* of hypoxic cells during fractionated treatment makes them more sensitive to subsequent doses of radiation

Question 2

A/b ratio of some late reacting tumours

Answer 2

Kidney - 2-2.4gy
Rectum - 2.5-5Gy
Lung - 2.7-4Gy
Bladder: 3-7Gy
CNS: 1.8-2.2Gy
Prostate: 1-3gy
Melanoma: 0.6Gy

Question 3

Fractionation - rationale

Answer 3

Dividing of dose into multiple fractions spares normal tissues through a repair of sub-lethal damage between dose fractions and repopulation of cells
• The former is greater for late-reacting tissues, and the latter for early-reacting tissues
• Concurrently, fractionation increases tumour damage through • Reoxygenation and redistribution of tumour cells

High a/b cells - not sensitive to change in fraction size
Low a/b cells - sensitive to dose/fraction

Question 4

Indirect action of cell damage by irradiation

Answer 4

1. Primary photon interaction producing high energy electrons
2. High energy electrons in moving through the tissue produce free radicals in water [H+ and OH-]
3. Free radicals may produce changes in DNA from breakage of chemical bonds
4. Changes in chemical bonds result in biological effects

Steps 3 and 4 are biological

Question 5

What factors make cells less radiosensitive

Answer 5

Low oxygen or hypoxic state
– Low dose rates
– Fractionation
– Cells synchronised in the late S phase of the cell cycle

Question 6

Biological planning

Answer 6

Use biological metrics to more directly reflect the clinical goals of radiotherapy

Question 7

Biologically guided RT

Answer 7

Use of relevant information of individual patient biological response of the tumour and normal tissues to design dose distributions
– Tumour and normal tissue radio-sensitivity, oxygenation status, proliferation rate

Question 8

Biologically based treatment planning

Answer 8

Use of feedback from biological response models in the treatment planning process
– Feedback could be automated (inverse planning) or manual (forward planning)

Question 9

Biological models

Answer 9

Variety of dose response models for the tumour and normal tissue are available
– Mechanistic (Model from first principles) • Preferable but more complex and difficult
– Phenomenonological (Models that fit the available empirical data)
• Simpler but may only be relevant in the data space in which they were validated. Extrapolation may be dangerous

Question 10

Dose response models

Answer 10

• Biological cell survival models are required for tumours and normal tissues
• The models should predict observations seen in clinical dose response data
• There is an increasing amount of clinical dose response data that is being accumulated
• A number of models of tumour and normal tissue response have been developed

Question 11

Generalised EUD

Answer 11

Uniform dose that would yield the same radiobiological effect as non uniform dose

Question 12

Linear quadratic model

Answer 12

most often used to describe the cell survival curve assuming there are two components to cell kill

The ratio α/β gives the dose at which the linear and quadratic components of cell kill are equal

• SF(D) is the clonogenic cell survival fraction as a function of dose D

Question 13

What does the value of a represent

Answer 13

Represents the intrinsic radiosensitivity of the cell
– Non-repairable type of cell damage
– Linearly dependent on dose

Question 14

What does the value of B represent

Answer 14

Repairable type of cell damage with time
– Responsible for the dose/fraction variations
– Proportional to the square of the dose

Question 15

What is BED

Answer 15

Biologically effective dose

Question 16

Early responding tissues

Answer 16

Occurs immediately or during radiotherapy
– Cell depletion within rapidly dividing cells
– e.g. skin, mucosal layer of gut
•
– Symptoms – pain, discomfort

Question 17

Late responding

Answer 17

Starts ~6-12 months after radiotherapy
– Cell depletion within slowly dividing cells
– e.g. spinal chord, kidney
– Symptoms - Progressive and irreversible –
Potentially life threatening

Question 18

Oxygen effect

Answer 18

The presence or absence of molecular oxygen within a cell influences the biological effect of ionising radiation
• More pronounced for low LET radiations

Question 19

Early reaction tumours a/b Ratios

Answer 19

Skin -9-12Gy
Colon - 9-11Gy
Testis - 12-13Gy
Mucosa- 9-10Gy
VOCAL CHORD - 9.9
Larynx - 25-35
Oropharynx - 13-19

Question 20

Why do we have a standard fractionation schedule

Answer 20

Most tumours are rapidly proliferating
• Therefore have high α/β (10 Gy and above)
• Therefore use a large number of small dose/fraction
• Limit damage to late reacting normal tissue (lower α/β

Prostates are an exception: low a/b ratio

Question 21

Sensitivity to fraction size - high a/b

Answer 21

Rapidly proliferating cells
Not very sensitive to changes in fraction size or dose rates
True for most types of tumour (not true for prostate)

Question 22

Sensitivity to fraction size - low a/b

Answer 22

Late reacting
Plenty of repair capability
Very sensitive to dose/fraction
Late responding normal tissues are therefore sensitive to large dose/fraction

Question 23

Fractionation for prostate carcinoma

Answer 23

Low proliferation rate
Low a/b (lower than rectum and bladder) - meaning more radioresistant than nearby organs
Likely to benefit from fewer and larger fractions

Question 24

What is biologically equivalent dose

Answer 24

Dose delivered in 2Gy fractions that is equivalent to a total dose

Question 25

Linear quadratic model equation

Answer 25

SF (D) = e^-aD-bD2