Clinical trial NCT02725840: Breast Cancer Lung Late Effects
Official title: Early Markers of Subclinical Pulmonary Vascular Radiation Toxicity in Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Radiation Injury
Breast Cancer
Keywords: pulmonary vasculature
radiation late effects
proton therapy
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Florida Department of Health
First posted: 2016-04-01
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Breast cancer patients who are 18 years of age or older and have Stage II or higher disease and who are scheduled to receive conventional X-ray RT (n=30) or proton therapy (n=25) to the breast and chest wall for the treatment of breast cancer will be enrolled in this study.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: 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.
timeFrame: 1 year
Secondary outcomes:
measure: 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.
timeFrame: 8 years
measure: 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.
timeFrame: 8 years
Other outcomes:
measure: Document patterns of metastatic presentation as observed from chest CT scans at 1,3,6, 12 and 24 months (= 2 years).
timeFrame: 2 years
Locations:
city: Gainesville
country: United States
facility: Department of Radiation Oncology Davis Cancer Pavilion
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Proton Therapy Institute
state: Florida
Study officials:
affiliation: University of Florida
name: Walter O'Dell, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Julie Bradley, PhD
role: PRINCIPAL_INVESTIGATOR
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