Clinical trial NCT06069115: Radiotherapy Exposed Lung Injury: Effect on Functioning - Cohort
Official title: Investigation of Oxygen Metabolism and Reserve Capabilities of Cardiovascular and Respiratory Systems in Patients with Malignant Neoplasms of the Breast in the Course of Complex Treatment
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Neoplasms
Radiation Pneumonia
Radiation Pneumonitis
Radiation Induced Fibrosis
Keywords: breast cancer
radiation therapy
radiation induced lung fibrosis
Lead sponsor: Meshalkin Research Institute of Pathology of Circulation
Sponsor class: NETWORK
First posted: 2023-10-05
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 200 patients aged 18 years and older with established diagnosis of breast malignant neoplasm, admitted to the Federal State Budgetary Institution "Meshalkin National Medical Center" of the Ministry of Health of Russia to undergo a course of radiation therapy

Brief summary: Prospective cohort research to study the state of oxygen metabolism, reserve capabilities of cardiovascular and respiratory systems in patients with breast cancer to create a program of prevention and rehabilitation of lung damage in the process of complex treatment of the disease.

The aim of the study is to study the dynamics of oxygen metabolism and reserve capabilities of cardiovascular and respiratory systems in the process of complex treatment of breast neoplasias.

Objectives of the study:

1. Explore the dynamics of pulmonary ventilation and gas exchange disorders in patients with breast cancer in the course of radiation therapy
2. Establish an algorithm for risk stratification of post-radiation disorders of pulmonary ventilation and gas exchange in patients with breast cancer.
3. Analyze the prognostic significance of cardiopulmonary exercise testing in assessing the cardiotoxic effect of chemo- and radiation therapy in patients with breast cancer.
4. Analyze the influence of post-radiation disorders of pulmonary ventilation and gas exchange on the quality of life and psycho-emotional status of patients with breast cancer.
5. Develop a fundamental basis for the program of prevention and rehabilitation of post-radiation lung damage in patients with breast neoplasias based on the study of individual parameters of oxygen metabolism and reserve capabilities of cardiovascular and respiratory systems.

All participants go through 5-week radiation therapy in standard protocol, will have investigation of their lung functioning by spirography and assessment of pulmonary diffusion capacity, cardiopulmonary stress tests and CT-scan on the lungs before radiotherapy course. Researchers will analyze such parameters as stage of the disease, surgery type, all patient's medications, complications, nutritional status, psychological status.

Detailed description: After a discussion about the possibility of participating in the study, the patient is presented with an informed consent form and all questions of interest are explained. If consent to participate in the study is obtained, the patient and the researcher fill in all the required fields of two copies of the informed consent form and sign it. If necessary, the researcher re-explains any information regarding the study. One copy of the informed consent remains with the patient and the second copy is kept, as required by Good Clinical Practice, by the researcher.

Once informed consent has been obtained, an Individual Registration Card (IRC) is completed for the patient included in the study. Completion of the IRC also continues until all phases of the study are completed.

Pulmonary function tests, cardiopulmonary stress testing (CPST), indirect calorimetry are performed in patients with breast cancer who have undergone surgical treatment of the disease and referred for radiation therapy in the FGBU "NMC named after E.N. Meshalkin" of the Ministry of Health of Russia using MasterScreen Pneumo (Jaeger, Germany), Oxycon Pro ergospirometry (Jaeger, Germany), and indirect calorimetry systems for evaluation of external respiratory function in accordance with international standards. External respiration indices were adjusted to BTPS conditions (body temperature (37°C), ambient pressure and gas saturated with water vapor), and gas exchange - STPD (standard temperature (0°C or 273 K) and pressure (760 mm Hg) and no water vapor). The protocol of stress testing is selected individually, based on the proper values in accordance with the age, sex and anthropometric data of the patient. The study is conducted up to the individual maximum followed by a recovery period. The anaerobic threshold is determined using the V-slope method. After reaching the peak load, it is gradually reduced. Observation continues until full recovery of hemodynamic parameters, gas exchange, in case of adverse symptoms - until their disappearance. Repeated testing is performed in the first week after the end of the course of radiation therapy.

MSCT of the chest is performed on the 1-2 day of patient inclusion in the study to assess the initial state of the bronchopulmonary system of patients.

The SF-36 quality of life questionnaire, ECOG scale for assessing the general condition of the oncologic patient, mMRC respiratory disturbance scale, anxiety and depression scales, postcovicular functional limitations scale, and cognitive impairment scale are completed at inclusion in the study and after the course of radiation therapy.

Statistical analysis:

If the data are normally distributed, they will be compared using t-test, multivariate analysis of variance and χ2 test. If the data are not normally distributed, non-parametric tests will be used. A 95% confidence interval will be applied when calculating the mean and standard deviation/median and percentiles. Dependencies between continuous quantitative variables will be studied using linear regression, in case of discrete variables Spearman correlation will be used. Binary logistic regression will be applied to study qualitative traits having 2 categories. Manual stepwise variable inclusion technique will be used to formulate multivariate regression models with a cut-off point of significance level of 0.20. In all other cases, statistical significance will be established at a probability of type one error of less than 5%. All statistical analyses will be blinded.

Eligibility criteria: Inclusion Criteria:

* established diagnosis of malignant breast neoplasm;
* signed informed voluntary consent of the patient to participate in the study.

Exclusion Criteria:

* contraindications to the use of inhaled corticosteroids (presence of active or inactive pulmonary tuberculosis, fungal, viral or bacterial infection of the respiratory organs);
* lung diseases requiring baseline therapy with glucocorticosteroids (chronic obstructive pulmonary disease, bronchial asthma);
* mental and/or musculoskeletal impairments that make it impossible to adequately perform the exercise test, cooperate with the patient and interpret the results;
* conditions and diseases requiring emergency surgical intervention and/or observation and treatment in an ICU setting;
* patient's refusal to participate in this clinical trial at any stage of the study.

Primary outcomes:
measure: Peak oxygen consumption (VO2peak)
timeFrame: 3-6 months
Secondary outcomes:
measure: Quality of life as measured by the SF-36 questionnaire.
timeFrame: 3-6 months
measure: 1-year mortality from any cause
timeFrame: 1, 2, 3 years
measure: Dynamics of lung diffusion capacity (∆DLCO)
timeFrame: 3-6 months
Other outcomes:
Locations:
city: Novosibirsk
country: Russian Federation
facility: Meshalkin Scientific Research Center of the Ministry of Health of Russia
state: Novosibirsk oblast
Study officials:
affiliation: Meshalkin Scientific Research Center of the Ministry of Health of Russia
name: Oksana Kamenskaya, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: