Common Adverse Reactions and Management of Heavy Ion Radiotherapy for Head and Neck Tumors

Common Adverse Reactions and Management of Heavy Ion Radiotherapy for Head and Neck Tumors

Wang Xinlan1, Hu Tingchao1, Zhang Yaoling1, Zhang Tian'e1
1Affiliation: Department of Radiotherapy, Gansu Wuwei Cancer Hospital, Gansu Wuwei 733000
Corresponding author: Wang Xinlan Email: 956915435@qq.com

Abstract: Radiotherapy is a commonly used treatment method for head and neck tumors. However, the anatomy of head and neck tumors is closely adjacent to important organs, and the main limitation of conventional radiotherapy is its dose-related damage. In recent years, heavy ions have shown unique advantages in the treatment of head and neck tumors due to their high biological effects and the physical characteristics of the Bragg peak, making them the ideal radiation for replacing photon radiotherapy. However, although heavy ion radiotherapy has shown excellent results in improving treatment efficacy, its associated adverse reactions cannot be ignored. This article reviews the adverse reactions and management methods of heavy ion radiotherapy in head and neck tumors to provide a reference for clinical applications.

Keywords: Head and neck tumors; Heavy ion radiotherapy; Adverse reactions; Management methods

I. Introduction

Head and neck tumors are one of the common malignant tumors, ranking sixth among male cancers in China, accounting for approximately 10% of all malignant tumors. These include nasopharyngeal carcinoma, oropharyngeal carcinoma, hard palate carcinoma, laryngeal carcinoma, paranasal sinus carcinoma, and various oral cancers [1]. Radiotherapy is an important treatment modality for head and neck tumors. Some tumors, such as nasopharyngeal carcinoma, can be cured by radiotherapy. Radiotherapy is often used in combination with chemotherapy as a radical method to preserve organ function or as adjuvant therapy after surgery [2]. However, while radiation therapy targets tumor cells, it also affects surrounding normal tissues, leading to various adverse reactions. Common adverse reactions include dry mouth, radiation-induced oral mucositis, radiation dermatitis, taste changes, parotid gland swelling, and trismus. These adverse reactions are closely related to the irradiated site, radiation dose, irradiation range, and whether chemotherapy is administered concurrently [3].

Heavy ion radiotherapy uses high-energy particle beams to precisely irradiate tumor cells, killing cancer cells by directly damaging DNA and indirectly inducing apoptosis. Heavy ion radiotherapy can better protect important organ functions and reduce the risk of complications. These characteristics make heavy ion radiotherapy an effective treatment modality for head and neck tumors. In the head and neck region, heavy ion radiotherapy is mainly used to treat locally advanced radioresistant tumors, such as adenoid cystic carcinoma, adenocarcinoma, and mucosal malignant melanoma [4].

The National Institute of Radiological Sciences (NIRS) in Japan treated 236 head and neck tumor patients with carbon ions from 1997 to 2006. The radiation dose ranged from 57.6 to 64.0 GyE (16 sessions, 4 weeks). The incidence of grade 3 and 4 acute adverse reactions was less than 10%, and no grade 3 or higher late adverse reactions occurred [5]. Domestic researchers have also observed the adverse reactions and short-term efficacy of proton and carbon ion radiotherapy for head and neck adenoid cystic carcinoma, finding it safe and effective [6]. Comparisons between carbon ion and X-ray intensity-modulated radiotherapy for recurrent locally advanced nasopharyngeal carcinoma have shown that the incidence of acute adverse reactions in the carbon ion group is lower than that in the X-ray group, with similar short-term efficacy [7].

The following sections review the adverse reactions of carbon ion radiotherapy for head and neck tumors and their management methods.

Currently, the international standards for evaluating acute and late adverse reactions in patients are the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and the Common Terminology Criteria for Adverse Events (CTCAE) [8][9].

II. Common Radioactive Adverse Reactions and Management Methods

1. Oral Mucositis

Radiation-induced oral mucositis (RIOM) is the most common complication of radiotherapy for head and neck tumors, occurring in over 80% of patients. It typically begins when the radiation dose reaches 15 Gy (RBE) and approaches 100% when the total dose exceeds 30 Gy (RBE) [10]. RIOM often peaks at the end of radiotherapy and persists for 2–4 weeks post-treatment, with recovery depending on the severity of the condition and whether chemotherapy or targeted therapy is used [11].

RIOM manifests as congestion, erosion, and ulceration of the oral mucosa, leading to pain, difficulty swallowing, and speech impairment. Severe cases may require enteral feeding. Management strategies include:

• ​Grade 0–1: Maintain oral hygiene, stay hydrated, use epidermal growth factor sprays, take vitamin B2, and consider amifostine intravenous infusion during radiotherapy to reduce treatment reactions.
• ​Grade 2: Use lidocaine gel or spray, growth factors, or granulocyte-macrophage colony-stimulating factor (GM-CSF) to promote healing. Combine with painkillers such as lidocaine mouthwash, gabapentin, or opioids, and ensure adequate nutrition.
• ​Grade 3–4: Continue GM-CSF and lidocaine mouthwash. For severe pain, use diclofenac spray or oxycodone sustained-release tablets. If infection occurs, use antibiotics based on throat swab results, combined with corticosteroids for short-term local use to reduce swelling and inflammation. Monitor for fungal infections, which may require oral antifungal drugs like nystatin or fluconazole.

2. Radiation Dermatitis

Radiation dermatitis (RD) is a common skin reaction caused by radiation therapy, affecting 95% of patients [12]. Severe cases (grade III–IV) [13] occur in approximately 49% of head and neck radiotherapy patients, with 20–25% experiencing severe wet desquamation and ulceration.^[14]

RD is divided into acute and chronic forms. Acute RD occurs within days or months of irradiation, while chronic RD develops months to years after treatment. Management focuses on prevention:

• ​Non-pharmacological prevention: Educate patients on skin care, avoid friction and sun exposure, and recommend low-neck clothing to keep the irradiated area clean and dry. Low-level laser therapy may aid wound healing but is not yet a standard preventive measure.
• ​Pharmacological prevention: Topical corticosteroids, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), silver ion dressings/creams, and triethanolamine emollients have shown efficacy in reducing severe dermatitis.

For acute RD:

• ​Grade 1: Use mild emollients and topical corticosteroids (1–2 times/day), continuing for 2 weeks post-radiotherapy.
• ​Grades 2–3: Use wet dressings and painkillers as needed.
• ​Grade 4: Manage with multidisciplinary care, including antibiotics for infection and hyperbaric oxygen therapy if necessary.

For chronic RD, options include topical pentoxifylline with vitamin E, physical therapy, and laser treatment for capillary dilation and pigmentation.

3. Salivary Gland Damage

Radiation to the submandibular and parotid glands reduces saliva production, leading to xerostomia. This affects taste, chewing, swallowing, and speech, increasing the risk of dental caries and malnutrition. Management includes:

• Pre-radiotherapy identification of high-risk patients and education.
• Avoid sugary, acidic, or carbonated beverages; stay hydrated; and use humidifiers.
• Medications like pilocarpine or cevimeline can stimulate saliva production.

4. Taste Disorders

Taste changes occur in over 75% of head and neck cancer patients undergoing radiotherapy, often before xerostomia. Taste recovery varies, with some patients improving within 2–6 months and others experiencing long-term changes. Prevention strategies include protecting taste-related organs during radiotherapy planning and using zinc supplements, though results are inconsistent.

5. Radiation Caries

Radiation caries occurs due to reduced saliva production, with a risk of tooth decay increasing significantly post-radiotherapy. Regular dental follow-ups every 6 months are recommended.

6. Osteoradionecrosis

Osteoradionecrosis is a late complication, typically occurring within 3 years post-radiotherapy, most commonly in the mandible. Prevention includes pre-radiotherapy dental care, maintaining oral hygiene, and optimizing radiation dose. Treatment options range from conservative measures to surgical intervention.

7. Dysphagia

Dysphagia, caused by high radiation doses to the pharyngeal muscles, can lead to malnutrition. Management involves a multidisciplinary approach, including nutritional support, swallowing exercises, and, in severe cases, surgical intervention.

8. Trismus

Trismus, or limited jaw opening, is a late complication of radiotherapy. Management focuses on functional training and, in severe cases, surgical release of fibrosis.

9. Endocrine Dysfunction

Radiation to the hypothalamus, pituitary, or thyroid can cause hormonal imbalances, requiring regular monitoring and hormone replacement therapy.

10. Laryngeal Edema

Laryngeal edema is common in patients with hypopharyngeal or laryngeal cancer. Management includes anti-inflammatory medications, antibiotics, and corticosteroids. Persistent edema may require surgical intervention.

11. Brachial Plexus Injury

Radiation-induced brachial plexus injury can cause numbness, pain, and muscle weakness in the arm. Management includes painkillers, anticonvulsants, and, in severe cases, surgical exploration.

12. Temporal Lobe Necrosis

Temporal lobe necrosis is a severe late complication, often presenting with headaches, memory loss, and seizures. Management depends on the severity and may include corticosteroids, hyperbaric oxygen therapy, or surgery.

13. Other Adverse Effects

Radiotherapy can also affect the eyes, causing cataracts, keratitis, and dry eye syndrome. Management includes lubricants, antibiotics, and, in some cases, surgery.

III. Conclusion

Although heavy ion radiotherapy shows great potential in controlling head and neck malignancies, its associated side effects must be carefully managed. Personalized treatment plans and supportive care can significantly reduce patient discomfort and improve outcomes. Further research is needed to explore optimized treatment modalities and techniques for better results.

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