Biological Optimisation

Question 1

What are the steps of indirect cell damage by irradiation?

Answer 1

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

Question 2

1. What is biologically guided radiotherapy?

2. What is biologically based treatment planning?

Answer 2

1. Use of individual patient tumour and normal tissue biological response to design dose distributions.
   Takes into consideration; tumour and normal tissue radiosensitivity, oxygenation status and proliferation rate.
2. Use of feedback from biological response models in the treatment planning process. Feedback could be automated (inverse planning) or manual (forward
   planning) .

Question 3

Provide an example of 2 biological models used in treatment planning?

Answer 3

1. Mechanistic (Model from first principles)
   Preferable but more complex and difficult
2. 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 4

What is the generalised equivalent uniform dose (gEUD)?

Answer 4

The uniform dose that would yield the same radiobiological effect as the non-uniform dose (delivered with the same number of fractions).

a less than 0 - gEUD approaches minimum dose - used for tumour
a more than 0 - gEUD approaches the maximum dose (serial organs).
a = 1 gEUD is the arithmetic mean dose.
a = 0, gEUD is the geometric mean dose.

Question 5

What is the linear quadratic model used for?

Answer 5

Used to describe the cell survival curve. Assumes there are 2 components to cell kill..

Question 6

What is the alpha/beta ratio?

Answer 6

(measured in Gy)
The ratio a/b gives the dose at which the linear and quadratic components of cell kill are equal.
a is a constant describing the initial slope of the survival curve.
- represents the radiosensitivity of the cell
- non-repairable type of cell damage
- linearly dependent on dose
b is a smaller constant describing the curvature of the cell survival curve.
- repairable type of cell damage with time
- responsible for the dose/ fraction variations
- proportional to the square of the dose

Question 7

What is the difference between early responding tissue and late responding tissue ?

Answer 7

Early responding
- occurs immediately after or during radiotherapy.
- cell depletion occurs within rapidly dividing cells (e.g.skin, mucosal layer of gut)
- symptoms - pain & discomfort.
- Affects most tumours (large a/b raio [10Gy] and alpha dominates at low doses).
Late responding
- Starts 6-12 months after radiotherapy
- Cell depletion occurs within slowly dividing cells (e.g. spinal cord, kidney)
- Symptoms - progressive and irreversible - potentially life threatening
- affects normal tissue (small a/b ratio [2Gy] and beta has influence at low doses.

Question 8

What is the radiobiological rationale for fractionation?

Answer 8

Dividing dose into multiple fractions spares normal tissues through REPAIR of sublethal damage (greater for late-reacting tissues i.e. kidneys) between dose fractions and REPOPULATION of cells (greater for early reacting tissues i.e. skin, most tumours).
Fractionation increases tumour damage through reoxygenation and redistribution of tumour cells.

Question 9

Describe different sensitivities to fraction size.

Answer 9

Rapidly proliferating cells, with high a/b
- Not very sensitive to changes in fraction size (or dose rate).
- True for most types of tumour
- Evidence now that this is not true for prostate tumours
Slowly proliferating cells with low a/b
- plenty of repair capability
- very sensitive to dose/fraction
- late responding normal tissues are therefore sensitive to large doses per fraction.

Question 10

List 4 early responding tissues and their respective a/b ratio

Answer 10

Skin: 9-12
Colon: 9-11
Testis: 12-13
Mucosa: 9-10

Question 11

List 6 late responding tissues and their respective a/b ratio

Answer 11

Kidney: 2-2.4 
Rectum: 2.5-5
Lung: 2.7-4
Bladder: 3-7 
Brain: 1.8
Spinal Cord: 2.2

Question 12

What are the a/b ratio for human tumour

Answer 12

Vocal Cord 9.9 
Oropharynx: 13-19
Larynx 25-35 or 50 - infinity
Malignant melanoma: 0.6 Gy 
Prostate Carcinoma: 1.2 - 1.5.

Question 13

What is the exception

Answer 13

Most tumours are rapidly proliferating and therefore have a high a/b ratio (10Gy and above). Likely to benefit from larger dose in smaller fractions (hyperfractionation).
EXCEPTION: prostate tumours have a low proliferation rate and thus have a low a/b (1.5). This is lower than rectum and bladder.
Prostate treatments are likely to benefit from smaller dose and larger fractions (Hypofractionation).