Proton therapy overview

Proton therapy is an advanced form of radiation treatment that offers significant benefits for patients with head and neck cancers.¹ This technique uses protons instead of traditional X-rays to target and destroy tumour cells. Radiation therapy targets the size, form, and depth of your tumour, enabling clinicians to treat the cancer while protecting neighbouring healthy tissues, such as the brain, eyes, and spine.² This also reduces the likelihood of a subsequent tumour and minimises the risk of both short- and long-term adverse effects.²

Prevalence of head and neck cancers

Head and neck cancers account for approximately 4.5% of cancer diagnoses and deaths globally, with an estimated 890,000 new cases and 450,000 deaths annually.³ These cancers include malignancies of the oral cavity, pharynx, larynx, nasal cavity, and salivary glands.³ They are more common in men than women, with a male-to-female ratio of approximately 2:1, and typically affect individuals over 50.³ Risk factors include tobacco use, alcohol consumption, and human papillomavirus (HPV) infection, with HPV-related cases on the rise in recent years. It is estimated that HPV will overtake tobacco as the leading contributor to the global head and neck squamous cell carcinoma (HNSCC) burden.³

Overview of head and neck cancers                                    

Types of head and neck cancers 

Head and neck cancers refer to a group of cancers that originate in the tissues and organs of the head and neck region, including the mouth, throat, larynx, nasal cavity, and sinuses. These cancers are often grouped by the area in which they begin.⁴ 

1. Hypopharyngeal Cancer (Cancer of the hypopharynx): This type of cancer develops in the tissues of the lower throat, located behind the voice box
2. Oropharyngeal Cancer (Cancer of the oropharynx): This cancer affects the tissues in the middle of the throat, specifically at the back
3. Nasopharyngeal Cancer (Cancer of the nasopharynx): Cancerous cells occur in the tissues of the upper throat, situated behind the nasal cavity
4. Paranasal Sinus and Nasal Cavity Cancer: This type involves the tissues in the small, air-filled spaces surrounding the nose, called the paranasal sinus, as well as the nasal cavity located just behind the nose
5. Oral Cavity Cancer: This cancer appears in various regions of the mouth, including the lips, teeth, gums, the front portion of the tongue, the inner linings of the cheeks and lips, the floor of the mouth, the roof of the mouth, and the area behind the wisdom teeth
6. Salivary Gland Cancer: Cancer arises in the salivary glands, located under the tongue, along the sides of the face, near the ears, and under the jaw. These glands are also present in other parts of the upper digestive system
7. Laryngeal Cancer: Cancer develops in the larynx, commonly starting on the mucosal surfaces as squamous cell carcinoma (SCC). Less frequent types may include cancers of the salivary glands or cancers originating in muscles, cartilage, or other structural tissues (sarcomas)
8. Skin Cancer of the Head and Neck: Cancer forms in the tissues on the skin's surface
9. Melanoma of the Head and Neck: This cancer begins in melanocytes, the cells responsible for skin pigmentation
10. Basal Cell Carcinoma: A nonmelanoma skin cancer, basal cell carcinoma arises from abnormal basal cells and affects the head and neck
11. Sarcoma of the Head and Neck: Sarcomas affect the soft tissues, including muscles, connective tissue (tendons), blood or lymph vessels, joints, and fat in the head and neck
12. Squamous Cell Carcinoma: Another type of nonmelanoma skin cancer, squamous cell carcinoma is the second most common form and tends to be more aggressive, sometimes requiring extensive surgery depending on the location and involvement of nerves
13. Head and Neck Cancer of Unknown Primary Origin: This type presents as a lump in the neck, often indicating that cancer has spread to the lymph nodes. However, the original site of the cancer is not identifiable

Common symptoms of head and neck cancers include

• A newly formed lump or swelling in the neck, face, or areas involved in breathing and swallowing
• A sore that persists and fails to heal
• A chronic sore throat that doesn’t improve
• Trouble with swallowing
• Noticeable changes in the voice
• The onset of hoarseness
• Red or white patches appearing on the gums, tongue, or inside the mouth
• Swelling in the jaw that affects the fit and comfort of dentures
• Unexplained bleeding or discomfort in the mouth, throat, or nasal passages
• Frequent sinus infections that do not improve with antibiotic treatments
• Numbness or loss of movement in the muscles of the face
• Pain in the ear

Treatment challenges

Proximity to vital organs and risk of side effects

Radiation therapy for head and neck cancers presents significant challenges due to the intricate anatomy of the region.⁵ Tumours often develop near critical structures such as the brainstem, optic nerves and chiasm, parotid glands, spinal cord, and cochlea.⁵ Due to the anatomical complexity of the head and neck region, treatment requires a high level of precision to accurately target the tumour while minimising harm to the surrounding healthy tissues. The primary objective is to achieve effective tumour control while preserving essential functions, such as speech and swallowing, and reducing the likelihood of severe side effects that could negatively impact the patient's quality of life.⁵

High Risk of Long-Term Side Effects: Traditional radiation treatments in this region can cause lasting side effects, including:⁵

• Dry mouth (xerostomia) due to damage to salivary glands
• Difficulty swallowing (dysphagia) from harm to throat muscles
• Hearing loss, nerve damage, or changes in taste and speech. These complications significantly impact the quality of life, making the precision of treatment techniques like proton therapy crucial for minimising harm

Mechanism of proton therapy

Protons differ from X-rays and gamma rays due to their unique physical properties, particularly their mass, allowing them to deliver energy more precisely than X-rays or gamma rays. In contrast, X-rays consist of photons, particles with no mass. As protons pass through the body, they slow down and gradually deposit energy, with most of this energy being released at the Bragg Peak - the point just before the proton stops. This concentrated energy release causes maximum damage to cancer cells. Unlike X-rays, which disperse energy evenly throughout the body, protons deposit very little energy before reaching the tumour and almost none after passing it. This minimises damage to surrounding healthy tissues and allows for more accurate targeting of cancer cells. The proton’s behaviour is easier to control, making it more effective for cancer treatment than X-rays or gamma rays, which release energy before and after hitting the tumour.⁶

Benefits of proton therapy

1. Improved targeting precision: Proton therapy targets tumours more precisely while reducing radiation to nearby healthy tissues. This is especially important in the head and neck area because of the complex anatomy and closeness of vital organs¹
2. Reduced side effects: By limiting radiation to nearby organs, proton therapy can potentially decrease the risk of complications such as:¹
   • Vision and hearing loss
   • Damage to salivary glands
   • Difficulty swallowing
   • Dry mouth
   • Brain and spinal cord exposure

3. Better dose distribution: Proton therapy offers superior dose distribution and conformity to tumour targets compared to conventional radiation techniques. This allows for high doses to the tumour while sparing healthy tissues^1,7
4. Potential for dose escalation: The precise targeting of proton therapy may allow for higher radiation doses to be delivered to the tumour without increasing toxicity to surrounding tissues⁷
5. Improved quality of life: By reducing damage to healthy tissues, proton therapy can lead to fewer short- and long-term side effects, potentially resulting in a faster recovery and better overall quality of life for patients¹
6. Option for re-irradiation: Proton therapy may be a viable option for patients who have previously undergone radiation therapy and require additional treatment¹

Limitations and challenges 

Sensitivity to anatomical changes: Proton therapy is highly sensitive to changes in tissue density and anatomy. For head and neck cancers, tumour shrinkage or changes in filling air cavities/sinuses during treatment can result in deviations from the planned dose distribution, potentially leading to underdosage of the tumour or overdosage of healthy tissues.⁸

Uncertainties in dose delivery: Significant uncertainty in dose delivery can arise from the fast dose fall-off that occurs beyond the Bragg Peak, even though it is advantageous for organ preservation. If not handled appropriately, this could result in an under dosage in the tumour volume.⁹

Robustness issues: Proton beams are less robust against anatomical changes occurring throughout treatment than photon-based therapies. This requires careful treatment planning and potentially more frequent imaging and plan adaptations.¹⁰

Potential for unexpected toxicities: There are concerns about potential toxicity in critical organs at risk if the effective dose delivered is higher than expected, particularly at the distal edge of the proton beam.¹¹

Cost and availability: Proton therapy is more expensive than traditional radiation therapy and not as widely available, which can limit access for many patients.¹²

Summary

Proton therapy is an advanced form of radiation treatment that targets head and neck cancers with high precision while minimising damage to surrounding healthy tissues. This approach is precious due to the complex anatomy and proximity of vital organs like the brain and spinal cord. Head and neck cancers account for around 4.5% of global cancer cases, with risk factors including tobacco use, alcohol, and HPV.³

Proton therapy’s effectiveness stems from the Bragg Peak, where protons release most of their energy at the tumour site, reducing radiation exposure to nearby healthy tissues compared to traditional X-ray therapy. This precision lowers the risk of side effects such as dry mouth, difficulty swallowing, and nerve damage, common with other treatments.⁶

While proton therapy offers improved targeting, fewer side effects, and better dose distribution, it also faces challenges like sensitivity to anatomical changes, cost, and limited availability. Despite these challenges, proton therapy presents a promising option for treating head and neck cancers while preserving patients' quality of life.⁹