What is the principle of radiotherapy in the treatment of cancer?

Principles of Radiotherapy in Cancer Treatment

The fundamental principle of radiotherapy is to deliver precise, high-dose ionizing radiation to cancer cells to damage their DNA and halt cell division, while simultaneously minimizing radiation exposure to surrounding normal tissues to optimize the therapeutic ratio between tumor control and treatment-related toxicity. 1

Core Mechanism of Action

Radiotherapy works by depositing high-energy radiation that targets the DNA within tumor cells, either through:

• Direct DNA damage: Ionizing radiation directly breaks DNA strands, restricting cancer cell proliferation 2, 3
• Indirect damage: Generation of free radicals that cause secondary DNA injury and cellular destruction 3, 4

The biological effectiveness depends on linear energy transfer (LET), total dose delivered, number of fractions, and the inherent radiosensitivity of the targeted cells 5.

The Therapeutic Ratio Paradigm

The overarching goal is maximizing tumor control while minimizing normal tissue injury—this balance defines the therapeutic ratio. 1

This is achieved through:

• Evidence-based dosing: Delivering appropriate radiation doses to cancer targets based on tumor type and stage 1
• Normal tissue avoidance: Limiting doses to sensitive adjacent structures to their tolerance thresholds 1
• Technological optimization: Leveraging advanced planning and delivery techniques to achieve conformal dose distribution 1

Technical Implementation Strategies

Simulation and Planning Procedures

• CT simulation-guided planning with integration of fusion imaging (MRI, PET) to precisely define target volumes 1
• Patient immobilization and bladder/rectum filling instructions to ensure reproducible positioning 1
• Fiducial marker placement for accurate target localization during treatment 1
• Rectal spacers (for prostate cancer) to physically separate organs at risk from the target 6

Advanced Delivery Techniques

Clinicians should utilize highly conformal radiation therapy techniques as the minimum standard to optimize outcomes. 1, 6

• Intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) to reduce dose to major organs (salivary glands, temporal lobes, mandible, bladder, rectum) 7, 6
• Image-guided radiation therapy (IGRT) using cone-beam CT or fiducial markers for daily positioning verification 1, 6
• Stereotactic techniques (SBRT, radiosurgery) for highly focused, ablative doses to small targets 1
• Particle-beam therapy with protons or carbon ions for specialized cases requiring maximum normal tissue sparing 1

Dose Escalation Principles

Higher radiation doses improve tumor control—dose escalation should be utilized when treating with curative intent, provided normal tissue tolerances are respected. 1

• For prostate cancer: Escalated doses (78-79 Gy) consistently demonstrate improved biochemical progression-free survival compared to conventional doses 1
• For residual microscopic disease: 60-66 Gy in 2.0 Gy fractions is standard 7
• For gross residual tumors: ≥60 Gy should be delivered if adjacent structure tolerances permit 1

Fractionation Strategy

Radiation is typically delivered in multiple small fractions rather than a single large dose to exploit differential repair capacity between normal and cancer cells. 3, 5

• Conventional fractionation: 1.8-2.0 Gy per fraction, 5 days per week 7
• Altered fractionation: Delivering ≥1000 cGy/week for specific indications (T3 N0-1 oropharyngeal cancer without concurrent chemotherapy) 7, 8
• Hypofractionation: Larger doses per fraction, fewer total fractions (used in SBRT) 1

Timing Considerations

The interval from surgery to completion of radiotherapy must be minimized—ideally less than 6 weeks for high-risk features. 7, 8

• For early oral cancer: Surgery should not be delayed beyond 8 weeks from diagnosis 8
• For early laryngeal cancer: If surgical delay of 4-8 weeks is anticipated, proceed immediately with radiotherapy instead 8
• For advanced disease: Surgery should not be delayed beyond 4 weeks; if unavoidable, initiate radiotherapy or chemoradiotherapy immediately 8

Multimodality Integration

Radiotherapy is rarely used as monotherapy for curative intent:

• Adjuvant radiotherapy: After surgery to sterilize microscopic residual disease and reduce local recurrence 1
• Neoadjuvant radiotherapy: Before surgery to downstage tumors (19.8-50.4 Gy preoperatively) 1
• Concurrent chemoradiotherapy: Cisplatin 100 mg/m² every 3 weeks with radiation for high-risk features (extracapsular extension, positive margins) 7, 8
• Palliative radiotherapy: For symptom relief (pain, bleeding, obstruction) or treatment of metastases 1

Critical Caveats

• Radiotherapy alone is not recommended for certain cancers (e.g., malignant pleural mesothelioma) where it must be part of multimodality treatment 1
• High-dose hemithoracic radiotherapy in the setting of intact lung has not shown survival benefit and carries significant toxicity 1
• Radiation resistance develops in some cancers (pancreas, ovary, liver, kidney, colon), limiting effectiveness 2
• Pre-radiation dental assessment is mandatory for head and neck radiotherapy; teeth with poor prognosis within the radiation field must be extracted before treatment 8
• Contraindications: Patients with inflammatory bowel disease or prior pelvic radiotherapy should not receive pelvic external beam radiotherapy due to dramatically increased risk of severe complications 6