Chemotherapy Toxicity, Dysbiosis, Gynecological Tumors, Pelvic Toxicity, Quality of Life, Radiation Cystitis, Radiation Proctitis, Radiation Toxicity, Vaginal Mucositis, Vulvar Mucositis
Conditions
Keywords
Gut microbiota, Ozone, Ozone therapy, Gynecological tumors, Radiotherapy, Chemotherapy, Side effects, Actinic proctitis, Actinic cystitis, Quality of life, Dysbiosis
Brief summary
Patients treated for gynecological tumors with radiotherapy (RT) and/or chemotherapy (CT) frequently develop pelvic toxicity (TPIRQT), a condition that can become persistent, progressive, and refractory to standard treatments. This toxicity, affecting the rectum (proctitis), bladder (cystitis), and vagina (mucositis), severely deteriorates quality of life. Standard options for refractory cases are limited; at our center, rectal ozone therapy is used with high rates of symptomatic improvement (66-75%). Emerging evidence suggests a link between gut microbiota and the development of TPIRQT. However, it is unknown how rectal ozone therapy may influence the gut microbiome or if this modulation is part of its therapeutic mechanism. This prospective observational study will investigate the potential relationship between gut microbiome profiles (composition and diversity), the presence and severity of TPIRQT, and the response to rectal ozone therapy.
Detailed description
Patients treated for gynecological tumors with radiotherapy (RT) and/or chemotherapy (CT) frequently develop pelvic toxicity (TPIRQT), a condition that can become persistent, progressive, and refractory to standard treatments. This toxicity, affecting the rectum (proctitis), bladder (cystitis), and vagina (mucositis), severely deteriorates quality of life. Standard options for refractory cases are limited; at our center, rectal ozone therapy is used with high rates of symptomatic improvement (66-75%). Emerging evidence suggests a link between gut microbiota and the development of TPIRQT. However, it is unknown how rectal ozone therapy may influence the gut microbiome or if this modulation is part of its therapeutic mechanism. This prospective observational study will investigate the potential relationship between gut microbiome profiles (composition and diversity), the presence and severity of TPIRQT, and the response to rectal ozone therapy.
Interventions
None listed
Sponsors
Dr. Negrin University Hospital
Complejo Hospitalario Universitario Insular Materno Infantil (CHUIMI)
Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna
CIBER (Infectious diseases)
Bernardino Clavo, MD, PhD
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for all patients (Cases and Controls): 1. Adult women (\>=18 years). 2. Diagnosed with gynecological tumors (any location and stage). 3. Previously treated with radiotherapy and/or chemotherapy. 4. Must accept and sign the specific informed consent for this study. Additional Inclusion Criteria for inclusion in the TPIRQT Group (Cases): 5. Must present chronic TPIRQT with \>= 3 months of duration after habitual symptomatic treatment. 6. Must have a toxicity Grade of 2 (moderate symptoms, limiting instrumental ADL) or higher, according to the CTCAE v.5.0 scale.
Exclusion criteria
for all patients (Cases and Controls): 1. Not meeting all inclusion criteria. 2. Presence of active inflammatory bowel disease (e.g., Crohn's Disease, Ulcerative Colitis) or a history of major gastrointestinal resection (excluding appendectomy) that could significantly alter gut anatomy and microbiota. 3. Any uncontrolled intercurrent illness or psychiatric condition that, in the investigator's opinion, would limit compliance with study requirements or interfere with the interpretation of results. 4. Unwillingness or inability to provide written informed consent for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of gut microbiome profile (composition and diversity) between TPIRQT and Control groups | Baseline (single time point for controls, pre-ozone for cases) | Gut microbiome composition and diversity (from a single sample) in control patients will be compared to the baseline profile of patients with TPIRQT. |
| Change in gut microbiome profile (composition and diversity) in patients with TPIRQT after rectal ozone therapy. | Baseline (pre-ozone therapy) , 4 Months (post-ozone therapy) | Gut microbiome composition and diversity will be analyzed from stool samples using 16S ribosomal RNA gene sequencing. |
| Correlation of gut microbiome profile with grade of pelvic toxicity. | Baseline (for Control group); Baseline, 4 Months (for TPIRQT group). | Toxicity will be assessed using: i) the CTCAE v.5.0 scale from the NCI , and ii) the EORTC QLQ-CX24 questionnaire. This will be evaluated for its relationship to microbiome data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of gut microbiome profile with health-related quality of life (HRQoL). | Baseline (for Control group); Baseline, 4 Months (for TPIRQT group). | HRQoL will be assessed using: i) the EQ-5D-5L questionnaire, and ii) the EORTC QLQ-C30 questionnaire. This will be evaluated for its relationship to microbiome data. |
| Correlation of gut microbiome profile with anxiety and depression levels. | Baseline (for Control group); Baseline, 4 Months (for TPIRQT group). | Anxiety and depression will be assessed using the Hospital Anxiety and Depression Scale (HADS). This will be evaluated for its relationship to microbiome data. |
| Correlation of gut microbiome profile with biochemical markers of oxidative stress and inflammation. | Baseline (for Control group); Baseline, 4 Months (for TPIRQT group). | Serum samples will be collected to analyze biochemical parameters of oxidative stress and inflammation and their potential relationship with gut microbiome composition. |
Countries
Spain
Contacts
Primary ContactBernardino Clavo, MD, PhD
Backup ContactFrancisco Rodríguez-Esparragón, BSc, PhD
Outcome results
None listed