Traditional Chinese Medicine Oral Liquids and Mouthwashes for Radiation-induced Oral Mucositis in Head and Neck Cancer Patients

The Radiation Therapy Oncology Group (RTOG) toxicity criteria were utilized to assess RIOM. Grade 0 shows no change from baseline; Grade 1 of RIOM is associated with mucosal erythema or hyperemiam,and may cause mild pain not requiring analgesics. Grade 2 presents with patchy mucositis that may produce an inflammatory serosanguinous discharge and may be associated with moderate pain; Grade 3 consists of confluent, fibrinous mucositis and may include severe pain requiring narcotics; Grade 4 is characterized by ulceration, hemorrhage, or necrosis. Grades 1 and 2 are considered mild to moderate, while grades 3 and 4 are classified as severe.

Time from the first documentation of RTOG grade 1-2 oral mucositis during radiotherapy to the first return to RTOG grade 0 (no mucositis) sustained for ≥48 hours.

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

The proportion of participants whose oral mucositis has decreased to RTOG grade 0 at 4 and 8 weeks after completion of radiotherapy, respectively.

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.

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

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.

The Radiation-Induced Oral Mucositis Symptom Score Scale is a 17-item patient-reported outcome measure assessing the severity of radiotherapy-related oral mucositis symptoms. The scale covers both oral local manifestations and systemic discomforts. Each item is rated on a 4-point Likert scale (0-3) corresponding to no, mild, moderate, and severe symptoms, respectively. The total score is calculated by summing the scores of all items. Higher total scores indicate greater symptom severity and a heavier symptom burden, whereas lower scores reflect milder symptoms or better symptom relief.

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.

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