Ozone Therapy for Cancer Therapy-Related Oral Mucositis (OMUC-O3)

Retrospective Evaluation of Combined Chairside and Domiciliary Ozone Therapy for the Management of Cancer Therapy-Related Oral Mucositis

This retrospective observational study will evaluate clinical data already available from adult cancer patients who developed cancer therapy-related oral mucositis during radiotherapy and/or chemotherapy and who were managed in routine clinical practice with combined chairside and domiciliary ozone therapy.

The study will not assign participants to any treatment and will not involve any new intervention, visit, examination, or change in patient care. Data will be extracted from existing medical records and clinical documentation.

The main purpose of the study is to describe the clinical course of oral mucositis and to evaluate the time needed to reach oral mucositis grade 1 or lower according to the World Health Organization Oral Toxicity Scale. The study will also assess changes in oral pain intensity, measured using a 0 to 10 Visual Analogue Scale, from baseline to follow-up visits up to 15 days.

Exploratory analyses will compare clinical trends between patients with head and neck cancers and patients with cancers in other anatomical sites. The results will be interpreted as descriptive and exploratory because the study is retrospective, single-arm, and has no control group.

Study Overview

• Status: Completed
• Conditions: Oral Mucositis
• Intervention / Treatment: Other: Combined Ozone-Based Oral Care Protocol

Detailed Description

Oral mucositis is a clinically relevant complication of anticancer treatments, especially radiotherapy and chemotherapy. It can cause erythema, ulcerations, oral pain, dysphagia, impaired oral intake, and reduced quality of life. In routine clinical practice, selected patients with cancer therapy-related oral mucositis were managed with a combined ozone-based protocol including professional chairside ozone application and domiciliary ozonized oral care products.

This study is designed as a retrospective observational analysis of data already available from medical records and clinical documentation. No prospective enrollment, treatment allocation, randomization, study-specific intervention, biological sampling, imaging, or additional clinical visit will be performed.

The study will include adult oncological patients with documented cancer therapy-related oral mucositis grade 1 or higher according to the World Health Organization Oral Toxicity Scale. Available data will include demographic and clinical information, oncological disease site, oral mucositis severity, and oral pain intensity measured using a 0 to 10 Visual Analogue Scale.

The retrospective observation period includes clinical data collected during routine care between November 2023 and September 2025. Outcome data will be analyzed from baseline to available follow-up visits up to 15 days. Additional exploratory analyses will describe clinical trends according to cancer site, comparing patients with head and neck cancers with patients with malignancies in other anatomical sites.

The findings will be interpreted as descriptive and exploratory, because the study is retrospective, single-arm, and does not include a control group.

• Study Type: Observational
• Enrollment (Actual): 58

Contacts and Locations

Study Locations

• Italy
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • Section of Dentistry - Department of Clinical, Surgical, Diagnostic and Paediatrics - University of Pavia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult oncological patients with cancer therapy-related oral mucositis whose clinical data are already available in medical records and/or clinical documentation. Patients were previously managed in routine clinical practice for oral mucositis occurring during radiotherapy and/or chemotherapy. The study population includes patients with documented oral mucositis grade 1 or higher according to the World Health Organization Oral Toxicity Scale and available baseline and follow-up assessments of oral mucositis severity and oral pain intensity. No prospective enrollment, treatment assignment, or study-specific intervention will be performed.

Description

Inclusion Criteria:

• Age 18 years or older
• Oncological patients undergoing radiotherapy and/or chemotherapy
• Clinical diagnosis of cancer therapy-related oral mucositis grade 1 or higher according to the World Health Organization Oral Toxicity Scale
• Availability of clinical documentation including World Health Organization Oral Toxicity Scale assessments and Visual Analogue Scale pain scores at baseline and at one or more follow-up timepoints
• Availability of relevant demographic and clinical information required for the retrospective analysis

Exclusion Criteria:

• Age younger than 18 years
• Absence of a documented diagnosis of cancer therapy-related oral mucositis
• Incomplete or unavailable clinical documentation for the primary and/or main secondary outcome
• Missing baseline World Health Organization Oral Toxicity Scale assessment
• Missing baseline Visual Analogue Scale pain assessment
• Any condition making the available data unsuitable for retrospective analysis

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cancer Therapy-Related Oral Mucositis Cohort; Adult oncological patients with documented cancer therapy-related oral mucositis grade 1 or higher according to the World Health Organization Oral Toxicity Scale. Patients were previously managed in routine clinical practice with a combined ozone-based protocol including professional chairside ozone application and domiciliary ozonized oral care products. This is a retrospective observational cohort; no treatment assignment, randomization, or study-specific intervention will be performed.

Other: Combined Ozone-Based Oral Care Protocol; Adult oncological patients with cancer therapy-related oral mucositis were previously managed in routine clinical practice with a combined ozone-based oral care protocol. The protocol included professional chairside ozone application to oral mucosal lesions using an ozone device with a mucosa-specific probe, followed by domiciliary use of ozonized oral care products, including ozonized hydrogel, toothpaste, and mouthwash, according to routine clinical instructions. In this retrospective observational study, no intervention will be assigned or performed for research purposes, and no change to patient management is planned.; Other Names: Chairside and Domiciliary Ozone Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Achieve Oral Mucositis Grade 1 or Lower	Time, expressed in days, required to achieve oral mucositis grade 1 or lower according to the World Health Organization Oral Toxicity Scale. The outcome will be assessed retrospectively using clinical data already available from medical records and clinical documentation. Patients who did not reach WHO grade 1 or lower by the last available follow-up will be censored at their last valid assessment.	At baseline before ozone therapy (T0), immediately after the first professional ozone application (T1), 48 hours after T1 (T2), 5 days after T1 (T3), 8 days after T1 (T4), 12 days after T1 (T5), and 15 days after T1 (T6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Oral Pain Intensity	Absolute change in oral pain intensity from baseline to the end of follow-up, assessed using a Visual Analogue Scale from 0 to 10, where higher scores indicate greater pain intensity. The outcome will be assessed retrospectively using clinical data already available from medical records and clinical documentation.	At baseline before ozone therapy (T0), immediately after the first professional ozone application (T1), 48 hours after T1 (T2), 5 days after T1 (T3), 8 days after T1 (T4), 12 days after T1 (T5), and 15 days after T1 (T6)
Change in Oral Mucositis Severity Over Time	Change in oral mucositis severity across the available follow-up timepoints, assessed using the World Health Organization Oral Toxicity Scale. Scores will be extracted retrospectively from existing clinical documentation at baseline and follow-up visits. Lower scores indicate lower oral mucositis severity.	At baseline before ozone therapy (T0), immediately after the first professional ozone application (T1), 48 hours after T1 (T2), 5 days after T1 (T3), 8 days after T1 (T4), 12 days after T1 (T5), and 15 days after T1 (T6)
Change in Oral Pain Intensity Over Time	Change in oral pain intensity across the available follow-up timepoints, assessed using a Visual Analogue Scale from 0 to 10. Scores will be extracted retrospectively from existing clinical documentation at baseline and follow-up visits. Higher scores indicate greater pain intensity.	At baseline before ozone therapy (T0), immediately after the first professional ozone application (T1), 48 hours after T1 (T2), 5 days after T1 (T3), 8 days after T1 (T4), 12 days after T1 (T5), and 15 days after T1 (T6)
Oral Mucositis Severity Trends by Cancer Site	Exploratory comparison of oral mucositis severity trends between patients with head and neck cancers and patients with malignancies in other anatomical sites, assessed using the World Health Organization Oral Toxicity Scale across the available retrospective follow-up timepoints.	At baseline before ozone therapy (T0), immediately after the first professional ozone application (T1), 48 hours after T1 (T2), 5 days after T1 (T3), 8 days after T1 (T4), 12 days after T1 (T5), and 15 days after T1 (T6)
Oral Pain Intensity Trends by Cancer Site	Exploratory comparison of oral pain intensity trends between patients with head and neck cancers and patients with malignancies in other anatomical sites, assessed using a Visual Analogue Scale from 0 to 10 across the available retrospective follow-up timepoints. Higher scores indicate greater pain intensity.	At baseline before ozone therapy (T0), immediately after the first professional ozone application (T1), 48 hours after T1 (T2), 5 days after T1 (T3), 8 days after T1 (T4), 12 days after T1 (T5), and 15 days after T1 (T6)

Collaborators and Investigators

• Sponsor: University of Pavia

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): October 31, 2025

Study Registration Dates

• First Submitted: June 4, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Radiotherapy; Chemotherapy; Visual Analogue Scale; Oral Mucositis; Oral Pain; Ozone Therapy; Supportive Cancer Care; Cancer Therapy-Related Oral Mucositis; Ozonized Oral Care Products; World Health Organization Oral Toxicity Scale
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Stomatitis
• Other Study ID Numbers: 2026-OMUC-O3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be available upon motivated request to the corresponding authors.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No