Spirulina-Derived Product Alleviates Oral Mucositis in Patients Undergoing Radiotherapy for Malignant Head and Neck Tumors

Oral mucositis is assessed by trained radiotherapists according to World Health Organization (WHO) oral toxicity Scale.The WHO Oral Toxicity Scale categorizes oral mucositis into grades 0-4, with the higher the grade the more severe the patient's oral mucositis. Grade 0 means that the oral mucosa is normal and the patient has no symptoms or signs; grade 1 means that the mucosa is erythematous with or without pain and does not interfere with eating; grade 2 means that the mucosa is erythematous and ulcerated, but still able to eat solid food; grade 3 means that the mucosa is severely ulcerated with extensive erythema and unable to eat solid food; and grade 4 means that the ulcers of the mucosa are fused together into a sheet, and their severity is so severe that it is not possible to eat.

Time from the first day of radiotherapy to the first determination of SOM.

The first determination of SOM to the first instance of non-severe OM (WHO grade <3), without a subsequent instance of SOM.

Oral mucositis is assessed by trained physicians according to World Health Organization (WHO) oral toxicity Scale.

Time from the first day of radiotherapy to the first determination of OM.

The first determination of OM to the first instance of non-OM, without a subsequent instance of OM.

Common Terminology Criteria for Adverse Events (CTCAE) 5.0 version

Unstimulated whole saliva samples will be collected via spitting method at three time points: baseline, mid-term radiotherapy (the week corresponding to 50% completion of the planned radiation fractions), and the end of radiotherapy (the final week of RT). 16S rRNA gene sequencing will be performed to assess alterations in the oral microbiota.

Taste strips test.

Patients report mouth and throat soreness (MTS) scores (Likert scale 1 to 5) via the oral mucositis weekly questionnaire （OMWQ）. Higher score indicates more severe symptoms

Patients report the degree to the impact of MTS on oral activities (including swallowing, drinking, eating, talking, sleeping) (Likert scale 1 to 5) via the oral mucositis weekly questionnaire （OMWQ）. Higher score indicates more severe symptoms.

Quantification of absolute counts and percentages of T cells, B cells, and NK cells in peripheral blood from patients.

Xerostomia was graded per CTCAE v5.0 (Grade 1-4), with higher grades indicating worse symptoms.

The number of patients who missed five or more consecutive radiations and the reasons for this are recorded during radiotherapy.

Measurement of circulating levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in patient peripheral blood.

Measurement of circulating levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in patient oral saliva.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) This instrument is a 30-item patient-reported outcome (PRO) measure designed to evaluate core aspects of health-related quality of life in cancer patients, including 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, pain, nausea and vomiting), one global health status/quality of life scale, and 6 single-item symptom measures. Scores are linearly transformed to a range of 0-100. For the functional scales and the global health status scale, higher scores indicate better functional levels or quality of life; for the symptom scales/items, higher scores indicate greater symptom burden.

The EORTC QLQ-H&N35 is a patient-reported outcome (PRO) instrument specifically designed to assess disease-related symptoms and treatment-related side effects in patients with head and neck cancer. It comprises 35 items, organized into seven multi-item subscales (pain, swallowing, senses, speech, social eating, social contact, and sexuality) and eleven single-item measures (such as dental problems, problems opening mouth, sticky saliva, coughing, etc.). All subscale and single-item scores are linearly transformed to a 0-100 scale using a standardized scoring algorithm. Interpretation of Scores: For all subscales and single items, higher scores represent more severe symptoms or greater symptom burden.