Radiobiology

Question 1

How does radiation cause damage? (3 marks)

Answer 1

Directly via ionising radiation, but primarily indirectly by hydroxyl free radicals.

Cell division is stopped by irreparable double strand breaks in DNA at the same location.

Can be caused by a two (alpha) ionisation tracks or a single track (beta).

Question 2

What is the equation for the survival fraction related to RT treatment? And explain the linear quadratic rationale? (4 marks)

Answer 2

SF = exp( alpha D [1 + (d / alpha/beta )]

Linear quadratic rationale:

• double strand breaks caused by two single ionisation tracks (2 hits per cell) = alpha x dose
• ” “ “ “ one ionisation track = beta x dose^2
• total is these combined

Question 3

What is the alpha/beta ratio represent, what is it for normal tissue and tumours, and how can it be determined? (4 marks)

Answer 3

• alpha/beta = fractionation sensitivity, low number means suffers relatively less damage at low doses compared to a higher a/b tissue
• tissue = 3 (late reacting), tumour = 10 (early reacting)
• a/b can be determined graphically by plotting the SF , interpolating the initial linear gradient and determining where this is equal to double the SF, hence the damage from a = damage to b

Question 4

What effect does fractionation have on a SF curve? (4 marks)

Answer 4

Best demonstrated with a sketch:

• takes advantage of initial steeper gradient of early reacting tissues (tumours)
• spares normal tissue excessive damage from higher doses
• results in more damage being done to tumours than normal tissue repeated for each fraction
• lines appear more linear than quadratic as linear component dominates at smaller doses

Question 5

What is the BED? (3 marks)

Answer 5

• Biologically effective dose
• BED = -ln(SF)/alpha = D[1 + ( d / (a/b) ) ]
• allows a comparison between different dose regimes for different tissues

Question 6

What is the TCP, what parameters affect it and how, and what shape is it? (5 marks)

Answer 6

• Tumour control probability = probability of no active cologenic cells (local control) following the end of treatment
• TCP = exp(-k_0 x SF) where k_0 is the initial number of active tumour cells
• affected by
  - > increasing alpha causes shift to the left and steeper (increase in alpha means increase in damage so less dose required to kill cells)
  - > increase in k_0 causes a shift to the right (more tumour => more dose needed)
• S-like shape

Question 7

What is meant by NTCP and what shape is it? (6 marks)

Answer 7

• Normal tissue complication probability = probability of late side effects
• e.g. TD 5 / 5 = 20 Gy is 5% chance of effect after 5 years for 20 Gy, could be for secondary tumour etc
• also an S shape, hopefully shifted more to the right than the TCP curve… wouldn’t be ideal if it was further left

Question 8

What is meant by the proliferation correction? (3 marks)

Answer 8

• added into BED equation = - gamma x (T- T_delay) / alpha
• gamma/alpha ~ 0.5 Gy per day
• T_delay ~ 28 days