W9 Radiotherapy 1/4

What is radiotherapy ultimately trying to optimize?

The therapeutic window—achieving high TCP while keeping low NTCP

Clinically this means precise imaging/targeting to concentrate dose in tumour, respecting organ dose–volume limits, and using biology-informed schedules that kill cancer cells more than healthy ones.

• TCP = Tumour Control Probability (how likely we cure the tumour)

• NTCP = Normal Tissue Complication Probability (how likely we harm healthy tissue)

Why do we split dose into daily fractions instead of one large dose?

Fractionation lets normal tissues repair sublethal damage better than tumour, and between fractions tumour cells redistribute into more sensitive phases (G2/M) and reoxygenate as perfusion improves

• Together widening the therapeutic window

• The survival “shoulder” reflects this repair; repeated fractions exploit it safely

If treatment gets delayed by a week in a fast-growing head & neck tumour, what’s the concern?

Accelerated repopulation → you effectively lose control; roughly ~0.7 Gy/day biological “value” can be lost, so delays matter

Why are hypoxic tumours harder to cure with radiation?

Less oxygen → less fixation of DNA damage (higher OER), so they need more dose

Name the cell-cycle phase most radiosensitive and the one most resistant

• Most sensitive: G₂/M.

• Most resistant: late-S

What rare but famous immune phenomenon can happen after local RT?

The abscopal effect (distant tumour shrinkage via systemic immunity)

Define OER 

Oxygen Enhancement Ratio: dose in hypoxia / dose in air (~3).

How much more dose hypoxic cells need vs oxygenated (~3)

What’s the single most important microscopic event caused by radiation, and why does oxygen matter?

DNA double-strand breaks (DSBs) are the lethal lesions

• ~70% of damage arises indirectly via ROS generated from water

• Oxygen “fixes” these injuries (oxygen enhancement):

  • without oxygen, many lesions are reversible, making hypoxic cells far harder to kill.

What are the 6 R’s of radiobiology and how do they guide planning?

1. Radiosensitivity (inherent killability)

2. Repair (normal > tumour),

3. Redistribution (cell-cycle timing)

4. Reoxygenation (overcoming hypoxia)

5. Repopulation (tumour regrowth during therapy)

6. Reactivation of the immune response (RT primes immunity)

Planners tune dose per fraction, total dose, and overall time to amplify the first four while suppressing repopulation and leveraging immune effects.

How do hypoxia and reoxygenation change dose needs?

Hypoxia can require roughly ~3× the dose for the same kill (high OER) because ROS fixation is limited.

• With fractionation, killing the oxygenated rim can restore oxygen deeper in the tumour, reoxygenating previously resistant cells so later fractions are more effective.

Why does overall treatment time (OTT) and the immune system matter?

Prolonged OTT enables accelerated repopulation, eroding control (e.g., head & neck losing roughly ~0.7 Gy/day of effect).

Meanwhile, RT can activate systemic immunity (occasionally causing abscopal responses)

Moderate fractionated regimens tend to synergize better with immunotherapy than single very high doses that may suppress immune effectors.