Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Heart Diseases

Cardiotoxicity

Unilateral Breast Neoplasms

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Breast Diseases

Skin Diseases

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Other Dietary Supplements

Vitamins

Vitamin A

Retinol palmitate

Pyruvate

Retinol

\[1-13C\]pyruvate: 0.1 mmol/kg dose will be injected at 5 mL/s followed by a 25 mL saline flush at 5 mL/s at the time of imaging performed at baseline (prior to radiation therapy), and 1 month after completion of radiation therapy.

[1-13C]pyruvate along with MRI imaging

Prasanna Alluri, MD, PhD

Patients enrolled in the study will receive standard of care adjuvant or definitive breast, chest wall or thoracic radiation therapy.Cardiac mitochondrial dysfunction is a hallmark of radiation-induced cardiac injury. Reactive oxygen species (ROS) produced by ionizing radiation cause oxidation of mitochondrial proteins and alter oxidative phosphorylation and pyruvate metabolism(5). The goal of this study is to detect early changes in the mitochondrial metabolism in situ as a marker for subclinical radiation-induced cardiotoxicity.

The global burden of cancer continues to rise with an incidence of 17.5 million cancer cases worldwide. Approximately 50% of all cancer patients receive radiation therapy as a component of their cancer care. While radiation therapy has demonstrable benefit in improving survival in patients with many types of malignancies, cardiotoxicity is a major concern in patients receiving chest radiotherapy. The rates of major coronary events increased by 7.4% per gray of mean heart dose; the increased risk was noted within the first 5 years of radiotherapy and persisted into the third decade after treatment. With improvements in multi-disciplinary care of cancer patients, the long-term survival in patients with thoracic malignancies continues to improve and radiation-induced heart disease (RIHD) is now a major source of morbidity and mortality in such patients.In this study, the investigators will enroll five female patients (18 years of age to 100 years of age) with left-sided breast cancer who underwent lumpectomy or mastectomy without tissue expander placement and will receive adjuvant standard-of-care breast or chest wall radiation therapy. They will undergo baseline magnetic resonance spectroscopic imaging with \[1-13C\]pyruvate injection and a proton MRI/spectroscopy scan prior to receipt of adjuvant radiation therapy. Post-treatment imaging will be performed within 3 months of completion of radiation treatments. This study will investigate whether non-invasive MRI scanning approaches will detect damage to the heart from left-sided radiation treatments before structural changes and mechanical functional deficits become apparent. A first-in-human clinical study to evaluate the effect of cardiotoxic chemotherapy on \[1-13C\]Pyruvate metabolism is currently ongoing at UT Southwestern (ClinicalTrials.gov Identifier: NCT03685175; PI: Dr. Vlad Zaha). The proposed study employs the same technology and approach to study radiation-induced cardiac toxicity. The study will also test the prognostic value of decreased myocardial mitochondrial pyruvate flux in predicting clinically significant radiation induced cardiotoxicity. Towards this goal, study will measure myocardial mechanical functional parameters, including left ventricular global longitudinal strain and left ventricular myocardial deformation using cardiac MRI and correlate these changes with \[1-13C\]lactate/ \[13C\]bicarbonate ratio. Previous studies have demonstrated that strain rate imaging by MRI is a sensitive technique for dose-dependent decrease in myocardial function after breast radiotherapy. Although this pilot study is restricted to breast cancer patients, successful demonstration of feasibility will allow extension of the study to all patients receiving thoracic radiation (such as patients receiving radiation therapy for lung cancer, esophageal cancer and thoracic lymphomas). The lack of reliable technologies for early detection of sub-clinical radiation-induced cardiotoxicity limits early intervention in such patients. Thus, identification of early cardiac changes induced by radiation therapy at a stage that offers potential for reversibility remains a major unmet need in cancer care.

Concerns for sexually active men and women: Women should not become pregnant and men should not father a baby while taking part in this study because we do not know how the study drugs/procedures could affect a man's sperm (for some drugs/procedures, the concern may be that the sperm might be affected and in some cases, drugs could being carried by the semen into the vagina and cause harm) or a fetus, if a woman becomes pregnant during the study. It is important that you talk to your study doctor about avoiding pregnancy during this study. If you think you might have become pregnant or if you believe your female partner has become pregnant while you are in this study, you must tell one of the study doctors right away so that management of the pregnancy and the possibility of stopping the study can be discussed.

Hyperpolarized Carbon 13-Based Metabolic Imaging to Detect Radiation-Induced Cardiotoxicity

Single Institution Feasibility Study to Detect Radiation-Induced Cardiotoxicity in Receiving Thoracic Radiation Patients Using Hyperpolarized Carbon 13-Based Magnetic Resonance Spectroscopic Imaging

To determine if radiation-induced cardiac injury causes myocardial mitochondrial dysfunction as measured by increase in \[1-13C\]lactate/ \[13C\]bicarbonate ratio and a decrease in \[5-13C\]glutamate formation in patients receiving radiotherapy to the thorax

As a secondary outcome, we will measure if decreased myocardial mitochondrial pyruvate flux results in changes in myocardial mechanical functional parameters. Towards this goal, we will measure myocardial mechanical functional parameters, including left ventricular global longitudinal strain and left ventricular myocardial deformation using cardiac MRI and correlate them with \[1-13C\] lactate/ \[13C\] bicarbonate ratio. Prior studies that cardiac MRI can detect changes in myocardial strain in patients who received whole breast radiotherapy for treatment of breast cancer.

University of Texas Southwestern Medical Center

Assistant Professor

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Aspiration

Participants will come in for their regularly scheduled radiation planning and treatment. Participants will undergo three scans (with and without DIBH (i.e., free-breathing), with CPAP). Participants will also use the CPAP device before the CT scan, for which they will be educated and trained.

Use of CPAP device at the start of treatment planning.

Continuous Positive Airway Pressure

Treatment during breath holds leads to longer treatment times for patients and radiation oncology departments

Deep inspiratory breath hold

Free Breath

Chirag Shah, MD

Chirag Shah, M.D.

Data collection and assessment on patients with left-sided breast cancer or undergoing lung stereotactic body radiation therapy (SBRT) utilizing continuous positive airway pressure (CPAP) devices.

Lung stereotactic body radiation therapy (SBRT) has emerged as a definitive treatment for patients with early-stage lung cancers as well as for patients with limited metastases to the lung. One challenge with the treatment of the lung is the risk of pulmonary toxicity, particularly for early-stage lungs cancers that are inoperable (those receiving primary lung SBRT) or those with metastatic cancers receiving systemic therapy that may impact pulmonary function (those receiving lung SBRT for metastatic cancers).

Continuous positive airway pressure (CPAP) devices are commonly utilized for patients with obstructive sleep apnea. However, through the use of continuous pressure, lung volumes are increased. Preliminary data in patients undergoing breast radiation as well as lung radiation has demonstrated the safety and feasibility of such an approach, demonstrating increased lung volumes with decreases in heart dose6-8. Additional potential advantages of CPAP include increased ease of use for patients and the potential for cost savings as compared to traditional respiratory management techniques.

This prospective study is to allow for the collection and assessment of data on patients with left-sided breast cancer or undergoing lung SBRT utilizing CPAP. This will allow for the assessment of lung doses with and without CPAP as well as cardiac doses. No additional changes to our standard of care breast or lung radiation will occur. With respect to the safety profile, CPAP is commonly used with limited toxicity concerns. The potential benefit of CPAP has reduced lung and heart doses and, consequently, radiation-related toxicities.

All participants will undergo standard of care radiation treatment. One additional CT scan will be performed with the use of a CPAP device to determine effect on dosimetry.

A Prospective Study to Evaluate Continuous Positive Airway Pressure Devices to Reduce Pulmonary Dose

The primary objective will be to assess changes in lung dosimetry V5 on the affected side when using CPAP compared to free breathing will be measured in percentages.

The primary objective will be to assess changes in lung dosimetry V20 on the affected side when using CPAP compared to free-breathing will be measured in percentages.

The primary objective will be to assess changes in lung dosimetry mean lung on the affected side when using CPAP compared to free-breathing will be measured in Grays.

Total Lung dosimetry will be measured in Grays.

Cardiac dosimetry with CPAP as compared to free-breathing will be measured in Grays.

Simulation scans will be performed with CPAP and free breathing. The breast/chest wall, and tumors (lung SBRT), as well as lung and heart, will be contoured on each scan. Using the CPAP scan as a reference, we will assess breast/chest wall motion, lung tumor motion, and organ at risk (ex. heart, abdominal organs) motion with free-breathing scans for each patient and analyze by treatment site (breast vs. lung SBRT).

Treatment time will be measured for each fraction

At the time of simulation, investigators will create a surface rendering with the patient using CPAP. Investigators will assess maintenance of inflation when using CPAP where all three dimensions will be measured during treatment by comparing the surface rendering obtained during simulation with CPAP to the surface during treatment with CPAP, assessing for the greatest changes over the course of each fraction.

Varian Medical Systems

Case Comprehensive Cancer Center

Coronary Artery Disease

Myocardial Ischemia

Ischemia

Vascular Diseases

Constriction, Pathologic

Coronary Stenosis

Coronary Disease

Pathological Conditions, Anatomical

Arteriosclerosis

Arterial Occlusive Diseases

Assesment of an usual cardiac dosimetry based on 3D CT scan. Only this dosimetry will be used to treat the patients. Because of the crossover model, patients are included in both arms.

Assesment of an experimental cardiac dosimetry based on 4D CT scan. Not used to treat the patients. Because of the crossover model, patients are included in both arms.

10 minutes breathing motion monitoring during an additional CT scan to establish a more accurate cardiac and LAD dosimetry compared to reality

Respiratory gating

Karim Boulanouar

Farid BELKHIR, MD

Farid BELKHIR, MD, PhD

Vincent Kowalski, MD

To establish if the cardiac radiation dose assesment is well aproximated with routine 3D CT scan compared to 4D CT experimental scan with respiratory gating (breath motion monitoring). The study population relates to left side breast cancers female patients that require a radiation therapy treatment.

As a standard of care, the postoperative breast cancers radiation therapy is generally based on a 3 dimensions CT scan that does not incorporate the breathing motion by definition.

Meanwhile, the patients must commonly receive the treatment in free motion breathing condition.

More of that, the Cardiac dose, especially the LAD (left anterior descending artery) dose has been established as the main cause of radiation induced ischemic heart disease (RIHD) and should be consider in the first place.

In more concrete terms, the higher the LAD dose is, the greater the RIHD relates: arise the LAD dose by 1 Gy means a 7.4% higher risk to cause a RIHD during the next 5 years.

That being said, to determine if the cardiac dosimetry and the dose-volume histograms (specifically for the left side breast cancer treatments including or not the internal mammary artery) obtained from a 3D CT scan reflect well or not the reality (which is widely subject to the breathing motion).

Finally, because it has been established that a 4D CT scan can monitor the breathing motion, it seems definitely interesting to compare it with the average 3D CT scan to address this concern.

4D CT Scan Versus 3D CT Scan Concerning Cardiac Dosimetry Assesment for Left Sided Breast Cancers Radiotherapy

4D CT Scan With Respiratory Gating Versus 3D CT Scan Concerning Cardiac Dosimetry Assesment for Left Sided Breast Cancers Radiotherapy

To determine if the mean LAD (left anterior descending artery) dose significantly changes statistically between an usual 3D CT scan versus a 4D CT with breathing motion monitoring (10 breathing phases are monitored).

Based on stastical test with 95% confidence intervals, to evaluate if there is a significant difference between 4D CT LAD mean dose and 3D CT LAD mean dose.

Central Hospital Saint Quentin

Neoplasm Metastasis

Central Nervous System Depressants

Benzocaine

Tannic Acid

After the patient is in the semi-prone position, the body shape and breast position images are obtained by the stereo scanning technology, and then using 3d printing technology to print PERSBRA.

PERSBRA maintain a favorable new breast position in the supine position during routine radiotherapy, the cardiopulmonary dose during radiotherapy can be reduced by wearing PERSBRA.

PERSBRA

Long-Sheng Lu, MD, Ph.D.

Jeng-Feng Chiou, MD, Ph.D.

Breast cancer is the most common malignancy among women worldwide. For early stage breast cancer, adjuvant radiotherapy is essential to minimize loco-regional disease recurrence. However, significant portions of the heart and the lungs are exposed to low dose radiation during radiotherapy, which result in stochastic side effects among breast cancer survivors. Inspired by 3D printing technology, we approached this issue with an in-house made PERSonalized BReAst holder system (PERSBRA). PERSBRA is composed of a 3D-printed plastic holder covering the whole breast and an air-filled interface. Its main function is to reproducibly adjust the breast position to decrease heart and lung radiation exposure in tangential fields. Here we propose to measure the performance of PERSBR in terms of radiation dosimetry in 50 patients receiving scheduled whole breast irradiation. For customized PERSBRA, body shape of the patient with or without a bustier corset will be captured with a handheld 3D scanner and input into a 3D printer for PERSBRA design and manufacturing. A participant will receive two more CT scans in addition to the simulation scan with PERSBRA in place before the first and the sixth fractions of irradiation. These images will be analyzed for dosimetric parameters in the presence/absence of PERSBRA as well as position reproducibility. The data will provide proof-of-principle evidence for the clinical utility of PERSBRA and will facilitate its further refinement.

1. Patients with early breast cancer or ductal carcinoma in situ treated with breast conservation surgery.
2. Adjuvant radiotherapy to the breast is part of the patient's initial treatment plan.
3. Non-contrast CT scan is a routine procedure for the patient's radiotherapy treatment planning.

Evaluation of the Feasibility of Developing Personalized Breast Cancer Radiotherapy Assistive Device With 3D Printing

Evaluation of the Feasibility of Developing Personalized Breast Cancer Radiotherapy Assistive Device With Three-dimensional Printing Secondary IDs:

Radiation dose distribution of the cardiopulmonary on the affected side.

Radiation dose distribution of the left anterior descending artery on the affected side.

Radiation dose distribution of the lung on the affected side.

Radiation dose distribution of clinical target volume.

Irradiated dose of axillary lymphatic area.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hyperpolarized Carbon 13-Based Metabolic Imaging to Detect Radiation-Induced Cardiotoxicity	NCT04044872	Thoracic Cancer Left Sided Brea...	[1-13C]pyruvate...	18 Years -	University of Texas Southwestern Medical Center
A Prospective Study to Evaluate Continuous Positive Airway Pressure Devices to Reduce Pulmonary Dose	NCT05142358	Lung Cancer Left Sided Brea...	Continuous Posi... Deep inspirator... Free Breath	18 Years -	Case Comprehensive Cancer Center
Hyperpolarized Carbon 13-Based Metabolic Imaging to Detect Radiation-Induced Cardiotoxicity	NCT04044872	Thoracic Cancer Left Sided Brea...	[1-13C]pyruvate...	18 Years -	University of Texas Southwestern Medical Center
4D CT Scan Versus 3D CT Scan Concerning Cardiac Dosimetry Assesment for Left Sided Breast Cancers Radiotherapy	NCT05726604	Breast Cancer Radiation-Induc... Left Anterior D... Radiotherapy Si... Cardiac Ischemi... Left Sided Brea... LAD (Left Anter...	Respiratory gat...	18 Years -	Central Hospital Saint Quentin
Evaluation of the Feasibility of Developing Personalized Breast Cancer Radiotherapy Assistive Device With 3D Printing	NCT04929197	Breast Neoplasm... Breast Cancer Left Sided Brea...	PERSBRA	-	Taipei Medical University Hospital
A Prospective Study to Evaluate Continuous Positive Airway Pressure Devices to Reduce Pulmonary Dose	NCT05142358	Lung Cancer Left Sided Brea...	Continuous Posi... Deep inspirator... Free Breath	18 Years -	Case Comprehensive Cancer Center
Evaluation of the Feasibility of Developing Personalized Breast Cancer Radiotherapy Assistive Device With 3D Printing	NCT04929197	Breast Neoplasm... Breast Cancer Left Sided Brea...	PERSBRA	-	Taipei Medical University Hospital
4D CT Scan Versus 3D CT Scan Concerning Cardiac Dosimetry Assesment for Left Sided Breast Cancers Radiotherapy	NCT05726604	Breast Cancer Radiation-Induc... Left Anterior D... Radiotherapy Si... Cardiac Ischemi... Left Sided Brea... LAD (Left Anter...	Respiratory gat...	18 Years -	Central Hospital Saint Quentin
4D CT Scan Versus 3D CT Scan Concerning Cardiac Dosimetry Assesment for Left Sided Breast Cancers Radiotherapy	NCT05726604	Breast Cancer Radiation-Induc... Left Anterior D... Radiotherapy Si... Cardiac Ischemi... Left Sided Brea... LAD (Left Anter...	Respiratory gat...	18 Years -	Central Hospital Saint Quentin

Spots Global Cancer Trial Database for left sided breast cancer