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NCT Number: NCT02725840

Breast Cancer Lung Late Effects

Through improved early detection and treatment, the number of long term breast cancer survivors continues to increase. There are now 2.8 million breast cancer survivors in the U.S. Florida alone adds over 9,000 women to the survivorship pool each year. Most receive radiation treatment (RT) of the affected breast and chest wall to reduce risk of recurrence. Even with advanced radiation techniques for dose conformality to minimize exposure of the highly sensitive lung, 14% of breast cancer patients treated with radiation develop clinical pulmonary toxicity, with 4% overall experiencing high grade clinical toxicity. Early diagnosis and intervention to mitigate lung radiation toxicity is increasingly important for the long term care of these survivors.

The investigators' goal is to better identify breast cancer patients at high risk for experiencing severe pulmonary toxicity requiring medical intervention, provide a means to identify toxicity early on, and tailor treatment and/or early intervention on a per-patient basis.

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Key information

Conditions

Radiation Injury Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Radiation Injuries Skin Diseases Skin and Connective Tissue Diseases Wounds and Injuries

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

Department of Radiation Oncology Davis Cancer Pavilion, Gainesville, Florida, United States

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About this study

This project involves repeat chest computed tomography (CT) imaging and blood draws in subjects with breast cancer with radiation treatment to the affected breast and chest wall. The investigators are studying women receiving one of 2 types of radiation, either conventional X-rays (IMRT) or protons at the University of Florida Health Proton Therapy Institute (UFHPTI). These subjects typically would not receive follow-up chest CTs as per standard of care. All subjects will have received a pre-treatment chest CT scan as part of the treatment planning process. The investigators will enroll 30 subjects in the X-ray treatment group and 25 subjects in the proton group.

The investigative team has recently solved the technical challenges of extracting and characterizing lung vascular anatomy from clinical CT images of the chest and used these tools to characterize acute and chronic changes to pulmonary vascular structure in breast cancer patients receiving radiation to the chest wall for treatment of their cancer.

In Aim 1 of this study the investigators will compare lung vascular damage in women treated with conventional radiation with those treated at the UFHPTI. In Aim 2 they will use blood samples of the subjects of Aim 1 to investigate the differential role of inflammatory cytokines in the initiation and progression of pulmonary vascular radiation response in conventional versus proton radiation exposures. Aim 3 compares vascular damage with clinical pulmonary function assessment using spirometry and diffusion capacity of carbon monoxide (DLCO). Aim 4 ties together Aims 1-3 by employing and extending existing mathematical models of radiobiological response to improve and solidify the scientific understanding of the biological mechanisms of radiation response.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Women who are at least 18 years of age.
  • Women with Stage II or higher primary breast cancer and who are scheduled to receive conventional X-ray RT (n=30) or proton therapy (n=25) to the breast and chest wall.

Exclusion criteria

  • Patients not willing or able to submit to repeat chest CT scans and blood draws.
  • Pregnant women.
  • Patients who have previously had radiation treatment where any portion of the lung received greater than 5 Gy of radiation exposure.
  • Women with bilateral breast cancer or metastatic disease to sites near the chest where additional radiation exposure to any portion of the lung of greater than 5 Gy is anticipated.
  • Women with allergic reaction to all common CT contrast agents.

Treatment and study plan

Proton beam radiation therapy.

Radiation

Proton bean radiation therapy interact differently with tissue with the result that protons are absorbed completely within the tissue instead of primarily passing through the entire body. The maximal depth of penetration is dependent upon the incoming velocity (energy) of the protons. Proton therapy utilizes this property to deliver radiation with very little dose beyond the targeted lesion. The dose-rate will be managed as part of the standard of care.

Other names: PTI

X-ray based radiation therapy

Radiation

The three-dimensional (3D) mapping of radiation dose distributions permits detailed assessment of local vascular damage as a function of treatment factors of dose, dose-rate. The dose-rate will be managed as part of the standard of care.

Other names: conformal RT

Computed Tomography (CT) Scan

Procedure

Computed Tomography (CT) Scan of the chest will be performed at 1, 3, 6, 12, 18 and 24 months

Pulmonary Function Test (PFT)

Procedure

Pulmonary function test (PFT) will be performed at pre-treatment, and at 6 and 12 months.

Primary outcomes

  1. The lower dose limit for measurable change in number of small blood vessels as characterized from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy.

    Time frame: 2 years

    The investigators seek to identify differences between the treatment modalities (proton versus X-ray) in regards to the lower dose limits for change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique.

  2. Vessel number change dose-response relationship as measured from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy.

    Time frame: 2 years

    Identify change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique, as a function of radiation dose exposure across the lung.

  3. Recovery of number of small blood vessels as measured from chest CT scans acquired at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy.

    Time frame: 2 years

    Identify differences in temporal patterns of vessel regeneration following radiation exposure as a function of dose and of modality (proton versus X-ray).

  4. Temporal patterns of blood cytokines following radiation exposure as measured from blood draws a pre-treatment and at 1,3,6, 12 and 24 months (= 2 years), and compared between proton versus X-ray radiation therapy.

    Time frame: 2 years

    Quantify differences in temporal patterns of levels of cytokines in the blood in breast cancer patients receiving conventional X-ray versus proton RT using serial blood draws that are time-matched with the CT chest scans.

  5. Correlate change in number of small blood vessels as measured from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) with clinical pulmonary function test outcomes at 6 and 12 months.

    Time frame: 1 year

    Correlate change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique, with clinical pulmonary function test (spirometry and diffusion capacity for carbon monoxide) outcomes to identify potential predictive value of early vascular changes to conventional clinical measures of late effects.

Secondary outcomes

  1. Compare incidence of long-term clinical grade 2 and higher radiation toxicity to the lung as documented in patient medical records and compared between proton versus X-ray radiation therapy.

    Time frame: 8 years

    The goal is to monitor long-term (>8 year) incidence of clinical pulmonary toxicity in these subjects to identify any difference between X-ray and proton treatment methodologies.

  2. Compare duration of overall survival and whether death was attributed to lung radiation toxicity as documented in patient medical records and compared between proton versus X-ray radiation therapy.

    Time frame: 8 years

    The goal is to monitor long-term (>8 year) survival in these subjects to identify any difference between X-ray and proton treatment methodologies.

Other outcomes

  1. Document patterns of metastatic presentation as observed from chest CT scans at 1,3,6, 12 and 24 months (= 2 years).

    Time frame: 2 years

    To identify patterns of asymptomatic metastatic progression in those subjects who develop recurrence to the thorax during the follow-up imaging period,

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Collaborators

  • Florida Department of Health

Registry information

Official study title

Early Markers of Subclinical Pulmonary Vascular Radiation Toxicity in Breast Cancer

Acronym: BELLE

Important dates

Study start
2016
Primary completion
2022
Study completion
2022
First posted
Apr 1, 2016
Registry last updated
Aug 22, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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