Hall 23 - Time, Dose, Fractionation

Question 1

What are the four R’s of radiobiology in order?

Answer 1

1. Repair (of SLD)
2. Reassortment (of cells within the cell cycle)
3. Repopulation
4. Reoxygenation
   (5. Resistance)

Question 2

Why does fractionation spare normal tissues?

Answer 2

Repair of SLD and repopulation

Question 3

Why does fractionation increase tumor damage?

Answer 3

Reoxygenation of previously hypoxic cells and reassortment of cells into more sensitive phases of the cell cycle

Question 4

How does prolonged treatment time influence early and late reactions?

Answer 4

Spares early reactions
Little effect on late reactions

Question 5

What is the alpha beta ratio?

Answer 5

Dose at which cell killing by the linear (single-event) and quadratic (multiple-event) components are equal

Question 6

What is the alpha beta for early effects?

Answer 6

Large (~10)

Alpha dominates at low doses and dose response curve doesn’t bend until higher doses

Faster dividing tissues -> reassortment & repopulation are important

Question 7

What factors affect early effects?

Answer 7

Fraction size
Overall treatment time

Faster dividing tissues -> reassortment & repopulation are important

Question 8

What is the alpha beta for late effects?

Answer 8

Small (~2-3)

Beta influence at low doses and dose response curve bends sooner and is more curved

More prominent shoulder = greater repair capacity, greater sparing with fractionation

*More sensitive to fractionation

Question 9

Are isoeffect curves steeper for late or early reactions?

Answer 9

Late

= total dose vs fraction size (high to low) to produce an equal biological effect

Question 10

What factor is most important for late effects?

Answer 10

Fraction size
(not overall treatment time)

Question 11

What is accelerated repopulation?

Answer 11

When treatment with any cytotoxic agent (RT, chemo) triggers surviving cells to divide faster than before (as tumor shrinks)

Question 12

When does repopulation accelerate for head and neck cancers?

Answer 12

~28 days
After this, a dose increment of 0.6 Gy per day is required to compensate

Question 13

How many additional Gy of radiation per week do you need for fast growing tumors treating past 5 weeks?

Answer 13

3 Gy

Ex) 50 Gy in 5 weeks = 56 Gy in 7 weeks

Question 14

What is the downside to hypofractionation?

Answer 14

Less reoxygenation/reassortment to take advantage of

Possible late effects (higher dose per fraction)

Question 15

What is the biologic effect (formula) for a single acute dose D, without cell proliferation?

Answer 15

E = αD + βD^2

Question 16

What is the biologic effect (formula) for n fractions of dose d, without cell proliferation?

Answer 16

E = n (αd + βd^2) = α * nd * [1 + d/(α/β)]

Question 17

What is BED?

Answer 17

Biologically effective dose
The quantity by which different fractionation regimens are intercompared

= E/α = nd * [1 + d/(α/β)]

= total dose x relative effectiveness

Also corresponds to the effect produced as the fraction size approaches 0 and the number of fractions approaches infinity

Question 18

What is the equi-effective dose?

Answer 18

Total dose needed to produce the same biological effect as another treatment but using different fraction size
Ex) EQD2

Set BEDs equal to each other and solve for total dose

Question 19

What is the formula for the number of clonogens N at any given time with cell proliferation?

Answer 19

N = N0 * e^(λt)

λ = (ln2) / Tpot = 0.693 / Tpot

*Same equation used in radioactive decay except effect is exponential growth not decay (opposite exponent sign)

Question 20

What is the BED formula with cell proliferation?

Answer 20

BED = total dose x relative effectiveness - 0.693 x number of cell doublings / α

E = nd * [1 + d/(α/β)] - 0.693/Tpot /α

*Rapid proliferation for cell doubling doesn’t start until 21 days (Tk)

Typical Tpot = 5 days, α = 0.3