Radiotherapy & Drug–Radiotherapy Combinations

What is the most common type of radiotherapy used?

External beam radiotherapy (X‑ray/photon).

What are the two main ways ionising radiation damages DNA?

 Direct DNA damage and indirect damage via free radicals.

What are the most lethal DNA lesions caused by radiotherapy?

 Double‑strand breaks (DSBs).

What physical property gives proton therapy its clinical advantage?

 The Bragg peak, allowing high dose at depth with no exit dose.

 Why is proton therapy preferred in paediatric cancers?

Reduced normal tissue dose → fewer late toxicities and second cancers.

 What is brachytherapy/ internal radiotherapy

where radioactive sources are placed inside or next to the tumour.

What is Radium‑223 (Xofigo®) used for?

Treating bone metastases; acts as a calcium analogue.

What drug is first‑line for managing brain radiotherapy‑induced oedema?

Steroids.

What alternative is used if steroids are not tolerated for brain RT oedema?

Bevacizumab (anti‑angiogenic).

Name three chemotherapy agents commonly used with radiotherapy.

Cisplatin, 5‑FU, gemcitabine (also carboplatin, mitomycin C).

What is the mechanism of radiosensitisation by cisplatin?

Forms DNA crosslinks; combined with RT breaks → complex, hard‑to‑repair lesions.

How does 5‑FU enhance radiotherapy?

• inhibits thymidylate synthase,

• depletes nucleotide triphosphate pools

• incorporates into DNA increasing cytotoxicity

• increasing RT‑induced sensitivity

 What is gemcitabine’s radiosensitising mechanism?

• Pyrimidine analogue

• Depletes deoxynucleotide triphosphate (dNTP) pools

• Incorporates into DNA corelating to cytotoxicity

• increases radioactive sensitivity

When is cetuximab used instead of cisplatin in head & neck cancer?

When patients cannot tolerate cisplatin.

Why do patients with MGMT promoter methylation benefit more from temozolomide?

MGMT repairs TMZ‑induced O6‑methylguanine lesions

Methylation → reduced MGMT expression → less repair of TMZ‑induced lesions.

Unmethylated → poorer response

What DNA repair pathway is PARP‑1 involved in?

Base excision repair (BER).

What is the rationale for combining PARP inhibitors with radiotherapy?

 Blocking repair of RT‑induced DNA damage → increased tumour cell death.

 How does radiotherapy influence PD‑L1 expression?

 RT can upregulate PD‑L1, promoting immune evasion.