W9 Radiotherapy Oct 30

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 ease of killing cells)

2. Repair (sublethal DNA damage recovery; normal > tumour)

3. Redistribution (cell-cycle phases alter sensitivity; G₂/M > S)

4. Reoxygenation (improves kill in formerly hypoxic areas)

5. Repopulation (regrowth during RT; limit overall time)

6. Reactivation of the immune response (RT primes immune attack; enables abscopal effects)

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) by releasing tumour antigens that activate T-cells

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

What are the three main treatment modalities in oncology and how do they differ?

1. Systemic therapy: Treats the whole body, good for microscopic disease but causes systemic side effects

2. Surgery: Local, invasive removal of tumor, giving detailed pathology

3. Radiotherapy: Local, non-invasive irradiation, often given over weeks; balances tumor control against local toxicities

What is ionizing radiation and why is it useful in cancer treatment?

Ionizing radiation is high-energy EM waves (X-rays, gamma) or particles that can eject electrons from atoms.

• This causes DNA damage, either directly or via free radicals, which tumor cells cannot repair as well as normal cells, leading to cell death

How does a linear accelerator (linac) produce treatment beams?

An electron gun emits electrons, they are accelerated to several MeV, then hit a metal target to produce high-energy X-ray photons. The gantry rotates around the patient, and MLC leaves in the head move to shape the beam, enabling conformal dose distributions around the tumor

Define GTV, CTV, and PTV

• GTV: Visible tumor (on CT/MRI, etc.).

• CTV: GTV + margin for microscopic spread; may include elective nodes.

• PTV: CTV + margin for movement and setup uncertainties, ensuring reliable coverage at every fraction.

Why do we take a dedicated planning CT and use immobilization devices?

We need the exact treatment position reproducible every day. Planning CT in that position plus masks/supports allow us to accurately delineate targets and ensure that beams hit the same place each session. Daily CBCT checks that the patient anatomy still matches the plan.

Why is fractionation used instead of one big radiation dose?

Because the tumor is surrounded by normal tissue. Giving many small daily doses lets normal tissues repair between fractions, whereas tumor cells repair poorly. This increases tumor kill relative to normal-tissue damage. Biologically, 1×8 Gy is more damaging than 2×4 Gy, even though both sum to 8 Gy.

What distinguishes curative, oligometastatic, and palliative radiotherapy?

• Curative: Aim to eradicate all tumor + microscopic disease. High doses over many fractions, often with chemo; large volumes including elective lymph nodes.

• Oligometastatic: Limited number of mets; high-dose SBRT to small targets in few fractions.

• Palliative: Symptom relief only; low total dose (e.g., 1×8 Gy), target only the symptomatic lesion.

Typical curative rectal cancer scheme (as in Ms Jones)?

Intent: curative.
Field: rectal tumor plus mesorectum and pelvic lymph nodes.
Dose: 25×2 Gy (50 Gy) with concurrent capecitabine. Large PTV margins due to bowel and bladder movement.

Why do lung SBRT plans for oligometastatic disease use high dose per fraction and how are margins decided?

Because targets are small and we want strong local control with few visits

• High dose per fraction (e.g., 3×18 Gy) is radiobiologically potent

• Margins are expanded to cover respiratory motion, often assessed with 4D-CT

• Proximity to heart and large airways may require more fractions with slightly lower per-fraction dose.

What are early vs late side effects of radiotherapy?

• Early (acute): Days–weeks during or shortly after treatment; reversible; involve rapidly dividing tissues (skin, mucosa, bowel).

• Late: Months–years later; often irreversible and sometimes progressive (fibrosis, strictures, organ dysfunction).

Why is fatigue such a common symptom during radiotherapy?

It’s multifactorial: cancer itself, previous treatments (surgery/chemo), daily travel, emotional stress, plus systemic impact of repeated local tissue injury and repair.

How does palliative radiotherapy relieve bone pain and what key counseling point is needed?

It reduces tumor load in the painful bone or near the nerve, decreasing inflammatory and mechanical stimuli

• A major counselling point is the possibility of a pain flare in the first few days after treatment, so patients should continue or increase analgesics, sometimes with steroids.

Why do we need MRI in addition to CT in radiotherapy planning?

Because many tumors lie in soft tissue where CT has poor contrast. MRI provides high soft-tissue contrast, clearly showing tumour vs normal tissue, and it can do this without extra ionizing radiation. This allows more precise target volumes and better sparing of organs at risk, which directly affects patient outcomes and side effects.

What is the physical quantity “B₀” in MRI and what does it do?

B₀ = main static magnetic field generated by the superconducting magnet

• Aligns hydrogen nuclei and sets their precession (Larmor) frequency

• The stronger B₀ is, the higher the precession frequency and the stronger the net magnetization we can manipulate and measure

What is magnetization (M) and why is it initially “silent”?

Magnetization M = Vector sum of all tiny hydrogen magnetic dipoles in a voxel

• At equilibrium in B₀, M points along the z-axis and is stationary, so it doesn’t change in time and doesn’t induce any signal in the receiver coil

• We need to disturb it with an RF pulse to get a measurable MR signal

What is resonance in MRI?

Resonance occurs when we apply an RF pulse at the Larmor frequency of the nuclei

• The RF energy is efficiently absorbed, tipping M away from the z-axis into the transverse plane

• This is what creates a rotating transverse magnetization that generates the MR signal

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Where does the MR signal actually come from?

After the RF pulse, the transverse magnetization Mxy rotates and gradually decays

• This rotating magnetic dipole induces a tiny voltage in the receiver coil (Faraday’s law). That time-varying voltage is the MR signal

• Unlike CT, the radiation is emitted by the hydrogen nuclei inside the patient, not from an external source

Define T1 and explain its physical meaning

T1 = Longitudinal relaxation time: the time constant describing how fast Mz recovers toward its equilibrium value after excitation

• At time t = T1, Mz has recovered to 63% of its final value

• Short T1 tissues recover quickly (bright on T1-weighted images)

• Long T1 tissues recover slowly (darker)

Define T2 and explain its physical meaning

T2 = Transverse relaxation time: the time constant describing how quickly Mxy decays because spins go out of phase

• At t = T2, Mxy has decayed to 37% of its initial value

• Short T2 tissues lose coherence quickly and appear dark on T2-weighted images

• Long T2 tissues keep coherence longer and appear bright

What are TR and TE and how do they influence image contrast?

• TR (repetition time) = time between successive RF pulses

  • Short TR emphasizes differences in T1 → T1-weighted images

• TE (echo time) = time between RF pulse and signal readout

  • Long TE allows more T2 decay → T2-weighted images

In a T1-weighted image, what kind of tissue appears bright and why?

Tissues with short T1 (e.g., fat, some white matter) appear bright because they recover their longitudinal magnetization quickly between pulses and thus produce a strong signal when the next RF pulse and readout occur

In a T2-weighted image, what does a bright region typically indicate?

A bright region on T2-weighted imaging usually indicates long T2—often due to edema or inflammation (more water), or fluid like CSF

• The spins dephase more slowly, so at the time of readout they still produce strong transverse magnetization and hence strong signal

Why is an acute myocardial infarction bright on T2-weighted images?

Acute infarction causes tissue edema and inflammation, increasing water content and prolonging T2

• On T2-weighted images (long TE), that region retains more Mxy at readout and shows up bright relative to normal myocardium, helping distinguish diseased from healthy tissue

How does MRI help in brain tumour radiotherapy planning?

MRI reveals:

• Tumour core (often bright on T2/FLAIR)

• Peritumoral edema and infiltration

• Surrounding eloquent brain tissue

→ This allows precise delineation of what should be irradiated and what must be spared, minimizing neurologic side effects while still treating the tumour

List the key tissue determinants of MRI contrast

Proton density, T1, T2, and the presence of contrast agents in tissue

List the key machine determinants of MRI contrast

Repetition time (TR) and echo time (TE):

• short TR → T1-weighting

• Long TE → T2-weighting

What are the main advantages of MRI for image-guided radiotherapy over CT?

1. Superior soft-tissue contrast → better tumour and organ-at-risk delineation

2. Real-time imaging (cine MRI every ~100 ms) → track motion like breathing

3. No ionizing radiation → safer repeated imaging, especially in young or pregnant patients

Why is real-time MRI important for lung and upper-abdominal tumors?

These structures move with respiration and sometimes with cardiac motion

• Real-time MRI allows us to see where the tumour is during each breathing phase, enabling motion management (gating, tracking, breath-hold strategies) and thus more accurate dose delivery.

What is the role of positive end-expiratory pressure (PEEP) in MRI-based motion studies?

Applying PEEP can shift the diaphragm downward and reduce the amplitude of respiratory motion

• Real-time MRI cine sequences can visualize and quantify this effect, helping assess whether such interventions can make radiotherapy more precise