Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Wounds and Injuries

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Breast Neoplasms

Inflammation

Fibrosis

Radiation Injuries

Radiation Fibrosis Syndrome

Pneumonia

Radiation Pneumonitis

Syndrome

Lung Diseases

Lung Diseases, Interstitial

Respiratory Tract Diseases

Lung Injury

Camurati-Engelmann Disease

Anti-Arrhythmia Agents

Antihypertensive Agents

All Drugs and Chemicals

Vasoconstrictor Agents

Micronutrients

Antineoplastic Agents

Vitamins

Losartan

Angiotensin Receptor Antagonists

Mitogens

Angiotensin II

Giapreza

Angiotensinogen

Angiotensin-Converting Enzyme Inhibitors

Vitamin A

Retinol palmitate

Angiotensin II Type 1 Receptor Blockers

Retinol

Participants who underwent breast conservation surgery will take losartan in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Participants who underwent breast conservation surgery will take placebo in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Participants who underwent a mastectomy will take losartan in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Participants who underwent a mastectomy will take placebo in a 25 milligram oral capsule once daily starting day one of radiation therapy until one year following the completion of radiation therapy.

Losartan 25 milligram capsule

Placebo

Katie Hess, Bachelors

Paige Bordelon, MPH

Patricia H Hardenbergh, MD

This study will evaluate the efficacy of Losartan (LOS), an FDA-approved transforming growth factor beta-1 (TGF-β1) blocker, to decrease radiation induced fibrosis (RIF) in the breast and the lung of breast cancer patients, testing the hypothesis that Losartan will decrease RIF, TGF- β1 and cellular senescence/inflammation in the breast and the lung of irradiated breast cancer patients relative to placebo treatment and consequently improve clinical outcomes in breast cancer patients.

This single site study will be conducted at the Shaw Cancer Center in Edwards, Colorado. A block, double-blinded, placebo-controlled, randomized phase II design will be utilized .

Study participants will be blocked by surgical intervention (breast conserving surgery vs. mastectomy) and then randomized, 1:1, into the treatment and control arms for a total of four study arms. The research team and study participants will be blinded to the study arm and a placebo will be used to reduce detection bias in the reporting of outcomes. Selection bias will be minimized through the randomization of study arms.

Study participants will be prescribed 25mg capsules of placebo or the investigational drug, Losartan, to be taken by mouth once daily. The treatment start date will be the day that subject begins radiation therapy. Radiation therapy will continue to be prescribed in accordance with local clinic procedures. Treatment with the study intervention will continue for one year upon completion of radiation therapy. All participants will be assessed for fibrosis, cosmetic outcomes, and incidence of reoperation for 18 months following the completion of radiation therapy.

Participants will be blocked by surgical type (breast conservation surgery/mastectomy) and then randomized 1:1 in a parallel design into treatment and control arms. All participants will take an oral 25 milligram tablet once daily of either losartan or placebo.

Assessments of fibrosis will include provider assessments and participant reported outcomes of fibrosis and cosmesis, the participant's decision for reoperation, laboratory assessments of inflammatory biomarkers, a CT scan and bilateral mammograms.

Participants, research staff and clinicians will be blinded from study group assignment.

Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

A Pilot Study of Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients

There is no plan to share individual participant data (IPD) with other researchers.

Fibrosis will be assessed by a radiation oncology provider using the Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) scale. 0=Fibrosis absent, not detectable. 1=Fibrosis is Barely Palpable; 2=Definite increased density; 3=Very marked density, retraction and firmness and fixation

Radiographic lung fibrosis will be assessed with high resolution CT scans of the thorax. Thorax CT scans will be fused to the radiation planning CT scan for confirmation of the overlap of fibrosis with the radiation field.

Cellular senescence, and senescence-associated secretory phenotype (SASP) including TGF-β and inflammation will be quantified in the treatment and control group. A novel and expert approach to measure senescent cells in serum will be utilized.

Bilateral mammographic determination of breast volume will be calculated at routine follow-up intervals. Breast shrinkage associated with radiation-induced fibrosis will be assessed by monitoring the change in the breast volume of the treated breast from baseline to 18 months following completion of radiation therapy. Measurement of breast volume on both breasts will use breast height in centimeters (cm) (H), breast width in cm (W) and compression thickness in cm (C), from a craniocaudal projection. Volume in milliliters (mL) = (π/4) x H x W x C. Mammograms will also provide a distance measurement, in centimeters, on the nipple line from nipple to pectoralis muscle and a length measurement, in centimeters, from the superior to inferior margin that bisects the Posterior to Nipple Line (PNL) at a 90° angle.

Cosmesis will be assessed using a clinician assessment The Harvard Cosmesis Scale: 1=Excellent (Treated breast nearly identical to untreated breast); 2=Good (Treated breast slightly different from untreated breast); 3=Fair (Treated breast clearly different from untreated breast but not distorted); 4=Poor Treated breast seriously distorted.

Self-reported participant quality of life will be assessed by Breast-Q Reconstruction Module. The Breast-Q, Version 2.0 tool was developed to assess participant's perception of clinical outcomes in both psychological and satisfaction domains will be used.

* Psychosocial Well-Being module: measures psychological well being
* Physical Well-Being
* Chest module: measures pain or tightness and difficulty with mobility
* Satisfaction with Breasts (Post-Op) module: satisfaction with breast size, how bras fit, and appearance in mirror clothed or unclothed, as well as how breasts feel when they are touched.
* Adverse Effects of Radiation module: measures physical changes such as soreness of skin.

The participant's decision to have corrective surgery on either breast after radiation will be recorded at each time-point. Post-mastectomy patients will be considered to have been reoperated if corrective surgery occurred after permanent implant placement.

Steadman Philippon Research Institute

Shaw Cancer Center

Medical Director

Pulmonary Fibrosis

Communicable Diseases

Respiratory Tract Infections

Breast Diseases

Skin Diseases

Respiratory System Agents

All participants will be included in the same group, with no subgrouping within this study.

Conformal 3D radiation therapy will be performed 4-12 weeks after surgical treatment of breast cancer on Electa Axesse linear gas pedal with 6 MeV energy in traditional fractionation mode. Different RT schemes will be used depending on the stage of the disease, type of surgical treatment, and morphological variant of the tumor. In organ-preserving surgeries the remaining breast will be irradiated with a single focal dose (FD) of 2 Gy, up to the total focal dose (TFD) of 50 Gy. In the presence of risk factors, irradiation of lymphatic outflow pathways will be performed: axillary, sub/adclavicular and parasternal lymph nodes areas (FD 2 Gy, up to TFD 44-46 Gy). In radical breast resection we'll use irradiation of the anterior chest wall in 2 Gy FD, up to 50 Gy FD, irradiation of lymphatic outflow pathways: axillary, sub/adclavicular and parasternal lymph nodes (2 Gy FD, up to 44-46 Gy FD).

Radiation therapy protocol for Breast cancer

Using the Master Screen Body device you will be asked to take two series of breaths through a special tube for 2-3 minutes. Usually the procedure does not cause any discomfort

Spirography and assessment of pulmonary diffusion capacity

The exercise test is performed on a bicycle ergometer Oxycon Pro. Prior to the test, special sensors for recording the electrocardiogram, a sensor to determine blood saturation, and a cuff to measure blood pressure will be glued on the body. Breathing during the test takes place through a face mask with a built-in gas analyzer sensor. The stress test is conducted up to an individual maximum (according to the age, sex, height and weight of the patient), followed by a recovery period. There is some temporary discomfort associated with performing physical activity. Dyspnea, leg fatigue, and dizziness may occur. Observation continues until full recovery of hemodynamic and gas exchange parameters, in case of appearance of unfavorable symptoms - until their disappearance.

Cardiopulmonary stress test

CT is a method of examination based on X-rays, but unlike conventional X-rays, it gives the most complete picture of the body structure, with less radiation.

Tomography usually does not cause any unpleasant feelings and is performed in a specialized department.

Computed tomography of the chest organs

Standard questionnaire for assessment quality of patient's life https://clinmedjournals.org/articles/jmdt/jmdt-2-023-figure-1.pdf

SF-36 Quality of Life Questionnaire

Age, sex, height. weight, body mass index (BMI)

Demographic and anthropometric measures

Severity of underlying disease (mMRC, BODE, SMRT-CO Respiratory Support Need Scale), and comorbidities (cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease) Medications taken.

Indicators characterizing the severity of the underlying disease

Oksana Kamenskaya, PhD, MD

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.

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.

Inborn females with all inclusion criteria are eligible

Radiotherapy Exposed Lung Injury: Effect on Functioning - Cohort

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

Patient's data of spirometry will be compared between values before the radiotherapy and 3 to 6 months after.

Patient's data of questionnare will be compared between values before the radiotherapy and 3 to 6 months after.

We'll contact with patient and their relatives to assess the mortality rates after radiotherapy on 1? 2 and 3 years after the treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients	NCT05637216	Radiation Induc...	Losartan 25 mil... Placebo	18 Years -	Shaw Cancer Center
Radiotherapy Exposed Lung Injury: Effect on Functioning - Cohort	NCT06069115	Breast Neoplasm... Radiation Pneum... Radiation Pneum... Radiation Induc...	Radiation thera... Spirography and... Cardiopulmonary... Computed tomogr... SF-36 Quality o... Demographic and... Indicators char...	18 Years -	Meshalkin Research Institute of Pathology of Circulation
Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients	NCT05637216	Radiation Induc...	Losartan 25 mil... Placebo	18 Years -	Shaw Cancer Center

Spots Global Cancer Trial Database for radiation induced fibrosis