Principles of Radiotherapy & Chemotherapy (MRCP Part 1)

TL;DR:

Radiotherapy and chemotherapy are tested in MRCP Part 1 through principles rather than protocols. Expect questions on mechanisms of action, cell-cycle effects, oxygen sensitivity, toxicity patterns, and how clinicians choose between local and systemic treatment. Mastering these fundamentals lets you answer unfamiliar oncology questions with confidence.

Why this topic matters for MRCP Part 1

Oncology questions in MRCP Part 1 are deliberately principle-driven. You are unlikely to be asked about detailed regimens or doses. Instead, examiners focus on why a treatment works, when it is appropriate, and what complications logically follow. Radiotherapy and chemotherapy frequently appear as comparison questions, single-best-answer stems, or mechanism-based MCQs.

If you are building your core revision around the MRCP Part 1 overview👉 https://crackmedicine.com/mrcp-part-1/this topic sits at the intersection of oncology, cell biology, and pharmacology.

Scope of examinable knowledge

For MRCP Part 1, you should be comfortable with:

• Basic mechanisms of tumour cell kill

• Cell-cycle sensitivity

• Local versus systemic disease control

• Early and late toxicities

• Principles of fractionation and combination therapy

You are not expected to memorise cancer-specific chemotherapy protocols.

Core principles: Radiotherapy vs Chemotherapy

1. Mechanism of action

Radiotherapy and chemotherapy both ultimately damage DNA, but they differ in how and where they act.

Feature	Radiotherapy	Chemotherapy
Target	DNA via ionising radiation	DNA synthesis, mitosis, or metabolic pathways
Selectivity	Spatial (treatment field)	Biological (cell-cycle or pathway)
Effect	Local	Systemic
Normal tissue damage	Dose-limiting	Dose-limiting

Exam pearl: Radiotherapy is locally selective; chemotherapy is systemically selective.

2. Cell-cycle sensitivity (very high yield)

• Radiotherapy

  • Most effective in G2 and M phase

  • Least effective in S phase (enhanced DNA repair)

• Chemotherapy

  • May be cell-cycle specific (e.g. antimetabolites)

  • Or cell-cycle non-specific (e.g. alkylating agents)

Questions frequently ask which phase is most radiosensitive.

3. The oxygen effect (radiotherapy favourite)

• Oxygen enhances radiation-induced DNA damage

• Hypoxic tumour cells are radio-resistant

• Explains poorer response in bulky or necrotic tumours

Key contrast: Oxygen tension has no equivalent role in chemotherapy efficacy.

4. Fractionation and the “4 Rs”

Radiotherapy is delivered in fractions to allow:

1. Repair of normal tissue

2. Reoxygenation of tumour cells

3. Redistribution into sensitive cell-cycle phases

4. Repopulation control

The “4 Rs of radiotherapy” are classic MRCP Part 1 material.

5. Local versus systemic disease control

• Radiotherapy

  • Local tumour control

  • Palliation (e.g. bone pain, spinal cord compression)

• Chemotherapy

  • Treats micrometastatic and disseminated disease

Exam framing: Local compressive symptoms → think radiotherapy.Widespread or chemosensitive malignancy → think chemotherapy.

6. Curative and palliative intent

• Radiotherapy can be curative (e.g. early head and neck cancers)

• Chemotherapy is often palliative, except in highly chemosensitive tumours (e.g. lymphomas, germ-cell tumours)

Understanding intent helps eliminate distractors in SBA questions.

7. Toxicity patterns

Predictable toxicity patterns are commonly tested.

Radiotherapy

• Skin erythema

• Mucositis

• Late fibrosis (important exam point)

Chemotherapy

• Myelosuppression

• Nausea and vomiting

• Alopecia

Late effects strongly favour radiotherapy in MCQs.

8. Combination therapy principles

• Chemotherapy may act as a radiosensitiser

• Combined treatment increases efficacy and toxicity

• Used when local and systemic control are both required

9. Radiosensitivity of tumours

Relatively radiosensitive tumours:

• Lymphoma

• Seminoma

• Leukaemia

Relatively radio-resistant tumours:

• Melanoma

• Renal cell carcinoma

Lists like these often appear as option clusters.

10. Patient factors influencing treatment choice

Examiners frequently test constraints on treatment:

• Performance status

• Bone marrow reserve

• Comorbidities

• Pregnancy

Sometimes the patient factor, not the tumour, determines the correct answer.

Mini-case (exam style)

A 64-year-old man with head and neck cancer receives radiotherapy in daily fractions rather than a single high dose. What is the main biological advantage of this approach?

Answer: Allows repair of normal tissues between doses.

Explanation: Fractionation improves therapeutic ratio by protecting normal tissue while maintaining tumour cell kill.

Common pitfalls (high-frequency)

• Confusing local control with systemic control

• Forgetting that S phase is radio-resistant

• Assuming all cancers are chemotherapy-responsive

• Ignoring late radiotherapy toxicities

• Over-learning drug names instead of mechanisms

Practical study-tip checklist

• Focus on mechanisms, not regimens

• Memorise cell-cycle effects

• Link toxicities to tissue biology

• Practise principle-based questions in the question bank👉 https://crackmedicine.com/qbank/

• Test retention with timed practice👉 https://crackmedicine.com/mock-tests/

For visual reinforcement, short oncology explainers are available here:👉 https://crackmedicine.com/lectures/

FAQs

Is radiotherapy cell-cycle specific?

Yes. Cells are most radiosensitive in G2/M phase and most resistant in S phase.

Why is chemotherapy considered systemic treatment?

Because drugs circulate in the bloodstream and act on primary and metastatic disease.

What is the oxygen effect in radiotherapy?

Oxygen enhances radiation-induced DNA damage, making hypoxic tumour cells relatively radio-resistant.

Does MRCP Part 1 test chemotherapy regimens?

No. The exam focuses on principles, mechanisms, and toxicities rather than protocols.

Ready to start?

Ready to turn these principles into exam marks?👉 Practise high-yield oncology questions with instant explanations in our MRCP Part 1 Question Bank:https://crackmedicine.com/qbank/

Once you’re confident, test yourself under exam conditions using our timed mocks:https://crackmedicine.com/mock-tests/

For structured revision alongside questions, start from the MRCP Part 1 hub:https://crackmedicine.com/mrcp-part-1/

Sources

• MRCP(UK) Examination Syllabus – https://www.mrcpuk.org/mrcpuk-examinations

• Oxford Handbook of Oncology – Oxford University Press

• Hall EJ, Giaccia AJ. Radiobiology for the Radiologist – Wolters Kluwer