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Radiotherapy in ENT - A Comprehensive Simplified Guide

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1. What is Radiotherapy?

• Alone (definitive RT) - as the primary treatment
• After surgery (adjuvant/postoperative RT) - to kill any remaining microscopic disease
• With chemotherapy (chemoradiation) - for enhanced cell kill
• For palliation - to relieve symptoms in incurable disease

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2. How Does Radiation Kill Cells? (Radiobiology)

DNA Damage - The Main Mechanism

• Direct effect: Radiation hits the DNA directly (less common)
• Indirect effect: Radiation ionizes water molecules → produces free radicals (like H₂O₂) → these free radicals then damage DNA (more common)

• Single-strand breaks - usually repaired easily; not fatal to the cell
• Double-strand breaks - the most lethal; causes cell death

Other Mechanisms of Cell Death

• Apoptosis - programmed cell death triggered by radiation
• Mitotic death - cells die when they try to divide
• Cell cycle arrest - at G1 and G2 checkpoints (mediated by p53)

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3. Radiosensitivity

More rapidly dividing = more radiosensitive

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4. Fractionation - Splitting the Dose

Types of Fractionation Used in ENT

• Microscopic disease control: ~50 Gy
• Positive surgical margins: ~60 Gy
• Gross tumor (T3/T4): ~70 Gy

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5. Treatment Planning - How RT is Delivered

Step 1 - Simulation

Step 2 - Volume Delineation (the Target Volumes)

1. GTV (Gross Tumor Volume) - the visible tumor on imaging
2. CTV (Clinical Target Volume) - GTV + areas at risk for microscopic spread (lymph nodes, adjacent tissue)
3. PTV (Planning Target Volume) - CTV + margin for patient movement/setup error

Step 3 - Beam Planning

• Multiple beams are chosen to converge on the tumor from different angles
• Normal tissues (spinal cord, parotid glands, eyes, etc.) are identified as organs at risk (OARs)
• A dose-volume histogram (DVH) is used to check that normal tissue doses are within safe limits

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6. Types of RT Delivery Techniques

6a. Conventional 2D Radiotherapy

• Simple opposing parallel beams
• Less precise; now largely replaced
• Still used in some palliative settings

6b. 3D Conformal Radiotherapy (3D-CRT)

• CT-based planning
• Beams shaped to tumor volume
• Better sparing of normal tissue than 2D

6c. Intensity-Modulated Radiotherapy (IMRT)

• The current gold standard for head and neck cancer
• Multiple beams with varying intensities
• Can treat irregularly shaped tumors while sparing critical structures
• Each green beam in the plan targets a specific region; the red zone is the tumor target

• Spares parotid glands → reduces xerostomia (mean dose to parotid kept under 26 Gy preserves salivary flow)
• Spares pharyngeal constrictors → reduces chronic dysphagia
• Better dose distribution around the spinal cord and brainstem

6d. Volumetric Modulated Arc Therapy (VMAT)

• A form of IMRT where the gantry rotates continuously
• Even better dose distribution
• Shorter treatment time

6e. Image-Guided Radiotherapy (IGRT)

• Imaging done before each fraction (using CT or electronic portal imaging)
• Ensures the beam tracks the tumor accurately each day
• Important in head and neck where patients lose weight and anatomy changes over treatment course

6f. Stereotactic Body Radiotherapy (SBRT) / Stereotactic Radiosurgery (SRS)

• Very high doses in very few fractions (1-5)
• Used for small, well-defined tumors (e.g. skull base tumors, acoustic neuromas)
• Requires very high precision

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7. Particle Therapy (Advanced Techniques)

Proton Therapy

• Protons deposit most energy at the Bragg peak (end of beam path)
• Very little dose before or after the target
• Reduces radiation to surrounding normal tissue significantly
• Useful in pediatric cases to reduce risk of secondary malignancies
• Also beneficial for nasopharynx and paranasal sinus tumors near optic nerves/brain
• Mean doses to parotid glands reduced by up to 50% compared with IMRT

Neutron Therapy

• Has a niche role in salivary gland tumors (particularly malignant ones)
• A randomized trial showed a survival benefit for neutron over photon RT in salivary gland tumors

Carbon Ion Therapy

• Has both the conformality of protons AND higher biological effectiveness
• More effective in hypoxic cells
• Promising results in adenoid cystic carcinoma and locally advanced head and neck SCC

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8. Brachytherapy (Internal Radiotherapy)

• Radioactive sources are placed inside or adjacent to the tumor
• Used for:
  • Oral cavity cancers (tongue, floor of mouth)
  • Nasopharyngeal carcinoma (boost dose)
  • Some lip/oropharyngeal tumors
• Delivers a very high local dose with rapid falloff - sparing surrounding structures

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9. Applications of RT in Specific ENT Cancers

9a. Laryngeal Cancer

• RT gives equivalent oncologic outcomes to surgery
• Major advantage: voice preservation
• Hypofractionation (2.25 Gy/day) shown to give better local control (92% vs 77% at 5 years) than conventional 2 Gy/day

• Landmark VA Larynx Study: neoadjuvant chemotherapy + definitive RT preserved larynx in 66% of survivors
• Concomitant chemoradiation (CRT) became standard of care after the RTOG trial showed better laryngeal preservation (84%) vs RT alone (66%)

9b. Hypopharyngeal Cancer

• RT alone useful for T1 and selected T2 tumors (exophytic lesions of medial piriform sinus wall)
• Concurrent CRT used for advanced disease
• Complications: mucositis, stricture, laryngeal edema, chondronecrosis, dysphagia
• IMRT significantly reduces these side effects

9c. Nasopharyngeal Carcinoma (NPC)

• RT is the primary treatment (surgery has a very limited role due to anatomy)
• IMRT has become standard; prospective studies show better outcomes vs conventional 2D RT
• Combined chemoradiation (cisplatin-based) improves survival in locoregionally advanced NPC
• Dose: 66-70 Gy to primary + elective nodal irradiation

9d. Oropharyngeal Cancer

• IMRT with or without chemotherapy is the mainstay
• For HPV-positive tumors: there is interest in treatment de-escalation (lower doses) due to the very favorable prognosis
• TORS (transoral robotic surgery) followed by risk-stratified adjuvant radiation is another option

9e. Salivary Gland Tumors

• Adjuvant RT after surgery for high-grade or incompletely excised tumors
• Neutron therapy shows particular benefit for malignant salivary gland tumors

9f. Paranasal Sinus and Nasal Cavity Tumors

• Surgery + postoperative RT is standard
• IMRT particularly useful given proximity to optic nerves, brain, orbits
• Proton therapy offers additional dose reduction to these nearby critical structures

9g. Graves Ophthalmopathy (Thyroid Eye Disease)

• RT to the orbit used for more than 85 years; ~60% historical response rate
• Mechanism: anti-inflammatory effect on lymphocytes; inhibits fibroblast proliferation and mucopolysaccharide secretion
• Dose: 20 Gy to both orbits in 10 fractions over 2 weeks (most common regimen)
• Benefits especially diplopia/ocular motility problems
• Contraindicated in diabetics (increased risk of retinopathy)
• Reserved for those who fail or refuse surgical orbital decompression

9h. Skin Cancers of the Head and Neck

• RT for basal cell and squamous cell carcinomas where surgery is not feasible
• Also used postoperatively for high-risk features (perineural invasion, close margins)

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10. Postoperative (Adjuvant) Radiotherapy

Indications for Postoperative RT (PORT):

• Involved or close surgical margins
• Perineural invasion
• Bone or cartilage invasion
• Advanced primary (T3/T4) or nodal (N2/N3) disease
• Extracapsular nodal extension

Adding Chemotherapy to PORT:

• Two landmark trials (EORTC and RTOG) showed that adding concurrent cisplatin to PORT significantly improves survival:
  • EORTC: 5-year overall survival 53% (CRT) vs 40% (RT alone)
  • Better progression-free survival and locoregional control
  • At the cost of more acute mucosal toxicity

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11. Side Effects of Radiotherapy in ENT

Acute Side Effects (during/immediately after treatment)

Late Side Effects (months to years after treatment)

Amifostine for Xerostomia Prevention

• Cytoprotective drug
• In a randomized trial of 315 patients: reduced significant acute xerostomia from 78% to 51%, and chronic xerostomia from 57% to 34%
• Did NOT affect tumor control
• Not widely used due to cost, side effects, and conflicting data with chemoradiation

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12. Chemoradiotherapy (CRT) in ENT

• Cisplatin is the most common agent (also used: carboplatin, 5-FU, taxanes, hydroxyurea)
• Chemotherapy radiosensitizes tumor cells (increases their radiation sensitivity)
• Meta-analysis (Pignon et al.): significant benefit of concomitant CRT over RT alone

Important Toxicities of CRT:

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13. Summary Table - RT in Key ENT Sites

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