The main objective of this study is to analyze the impact on the health-related quality of life of patients with refractory symptoms, who have been referred to the HUGCDN Chronic Pain Unit for adjuvant palliative treatment with ozone therapy between June-2022 and December-2025

Chronic Pain Unit in the absence or failure of standard treatment, or when the standard treatment is associated with high morbidity or high risk. Frequently, these patients present alterations in self-perceived health-related quality of life (HRQoL), anxiety, depression, and other symptoms. This study aims to evaluate in these patients the effect of adjuvant symptomatic/palliative ozone therapy on the HRQoL and the potential changes from baseline on several parameters after treatment.

MAIN OBJECTIVES: To evaluate in these patients: 1) the clinical effect on the HRQOL of adding ozone to the standard treatment.

SECONDARY OBJECTIVES: To evaluate in these patients changes from baseline on 2) anxiety and depression, 3) pain (if applicable), 4) grade of toxicity (if applicable), 5) requirements of invasive procedures for symptom management, 6) evolution of main symptoms, 7) evolution of oxidative stress and inflammation (if systemic ozone therapy).

METHODOLOGY: Prospective and observational study of patients referred to our Chronic Pain Unit for symptomatic/palliative treatment with ozone therapy between 2022 and 2025.

MAIN VARIABLE: 1) HRQoL through the EQ-5D-5L questionnaire

SECONDARY VARIABLE: 2) anxiety and depression through the hospital anxiety/depression (HAD) questionnaire, 3) Pain through the visual analog scale (VAS), 4) grade of toxicity in cancer patients through the CTCAE v5.0 scale, 5) the number of invasive procedures required for symptom management, 6) self -reported percentage of symptom improvement, 7) biochemical parameters of oxidative stress and inflammation.

Assessments at weeks: 0 (baseline), 16 (end of O3/O2 treatment, objective), 28 (12 weeks after the end of ozone), and 40 (24 weeks after the end of ozone, control) Length of treatment: as required; initially, planned 16 weeks. Follow-up: 24 weeks after finishing O3/O2 treatment. Planned length of the clinical trial: 49 months.

Inclusion Criteria:

1. Adults > = 18 years old.
2. Patients submitted to the Chronic Pain Unit of the Hospital Universitario de Gran Canaria Dr. Negrín for symptomatic/palliative treatment with ozone therapy because conventional treatment does not exist, it has been unsuccessful, or it is associated with high risk or high morbidity.
3. After evaluation of symptoms and patients, it exists a potential benefit of adding ozone treatment to the current treatment.
4. Patients have no contraindications for ozone treatment.
5. Patients have signed and dated the informed consent for the compassionated ozone treatment and the specific informed consent for this study

Exclusion Criteria:

1. Age < 18 years old.
2. Psychiatric illness or social situations that would limit compliance with study requirements.
3. Those who are incapable to fill in the scales used to measure variables.
4. Hemodynamically or clinically unstable patients or uncontrolled severe illness.
5. Uncontrolled cancer disease requiring chemotherapy treatment.
6. Life expectancy < 6 months
7. Contraindication or disability or to attend scheduled treatments.
8. Known allergy to ozone.
9. Pregnancy at the time of enrollment (for systemic ozone therapy). 10 Hemochromatosis (for systemic ozone therapy).

11. Known significant glucose-6-phosphate dehydrogenase deficiency (favism, acute hemolytic anemia) (for systemic ozone therapy).

12. Patients who do not meet all the inclusion criteria

Patients submitted to the Chronic Pain Unit of the Hospital Universitario de Gran Canaria Dr. Negrín for symptomatic/palliative treatment with ozone therapy because standard treatment does not exist, it has been unsuccessful, or it is associated with high risk or high morbidity.