Radiotherapy is an essential modality in the curative and palliative management of head and neck malignancies, but it is frequently accompanied by a spectrum of acute and late toxicities, including radiation dermatitis, xerostomia, cranial nerve injury, and dysphagia. Radiation dermatitis, an inflammatory skin reaction to ionizing radiation, develops in the majority of patients undergoing external beam radiotherapy to the head and neck region and ranges from mild erythema and dry desquamation to moist desquamation and ulceration in severe cases. Clinically significant skin injury not only compromises patients' quality of life through pain, pruritus and cosmetic disfigurement, but may also necessitate treatment interruptions or dose reductions, which have been associated with inferior tumor control and survival outcomes in several studies.
The pathophysiology of radiation dermatitis is multifactorial and involves direct radiation-induced DNA damage, endothelial cell injury, cytokine-mediated inflammatory cascades, and generation of reactive oxygen species (ROS). ROS, particularly superoxide anions, play a central role in propagating oxidative stress, lipid peroxidation and subsequent tissue injury. Current management strategies for radiation dermatitis are largely supportive and empirical, including skin hygiene measures, topical corticosteroids, emollients, dressings for moist desquamation, and pain control; however, there is no universally accepted standard of care and robust high-quality evidence for many interventions remains limited.
Antioxidant-based topical and topical-delivery agents have been explored as prophylactic and therapeutic options to mitigate radiation-induced skin injury by neutralizing ROS and modulating inflammatory responses. Superoxide dismutase (SOD) is a key endogenous antioxidant enzyme that catalyzes the dismutation of superoxide radicals into oxygen and hydrogen peroxide, thereby reducing oxidative stress. Preclinical studies and early clinical reports suggest that SOD-containing formulations or SOD-mimetic compounds can decrease markers of oxidative damage, attenuate inflammatory signaling, and reduce histologic evidence of radiation-induced dermal injury.
The investigational SOD spray evaluated in this trial is formulated for topical aerosolized delivery to irradiated skin surfaces, which may offer advantages in ease of application, uniform coverage of complex anatomical regions in the head and neck, and patient compliance compared with creams. Early-phase studies of topical sprays delivering antioxidants or SOD-mimetic agents have demonstrated favorable tolerability and potential reductions in the severity of acute radiation dermatitis, though data remain limited and heterogeneous. The SOD spray in this study has undergone third-party safety assessment and meets human-use standards, supporting its tolerability for topical application.
Given the biological plausibility, encouraging preliminary data for antioxidant approaches, and the unmet clinical need for effective prophylaxis against radiation dermatitis, this randomized clinical trial aims to evaluate the efficacy and safety of SOD spray in preventing radiation dermatitis among patients with head and neck cancer undergoing definitive or adjuvant radiotherapy. Primary endpoints include incidence and maximal grade of acute radiation dermatitis based on standardized scoring systems, while secondary endpoints will assess time to onset, patient-reported skin symptoms and quality of life, treatment interruptions, and safety/tolerability metrics. The trial's findings may inform evidence-based recommendations for topical antioxidant prophylaxis in the radiotherapy setting and potentially improve treatment adherence and patient outcomes.
