Breast Cancer Lung Late Effects

NCT02725840 | Completed

• 3 other identifiers: IRB201600387OCR149626BC09
• Study Type: observational
• Target: 41
• Locations: 1 country
• Sites: 2

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.

Conditions

Radiation Injury; Breast Cancer

Keywords

pulmonary vasculature; radiation late effects; proton therapy

Outcome Measures

Primary Outcomes (5)

• 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.

  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 years

• 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.

  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.

  2 years

• 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.

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

  2 years

• 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.

  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.

  2 years

• 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.

  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.

  1 year

Secondary Outcomes (2)

• 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.

  8 years

• 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.

  8 years

Other Outcomes (1)

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

  2 years

Study Arms (2)

Proton beam radiation therapy

The participants in this group will be receiving proton therapy of the affected breast and chest wall as part of their standard of care. In addition, a Computed Tomography (CT) Scan of the chest wall will be performed, and pulmonary function test (PFT).

Radiation: Proton beam radiation therapy.; Procedure: Computed Tomography (CT) Scan; Procedure: Pulmonary Function Test (PFT)

X-ray based radiation therapy

The participants in this group will be receiving X-ray radiation therapy of the affected breast and chest wall as part of their standard of care. In addition, a Computed Tomography (CT) Scan of the chest wall will be performed, and pulmonary function test (PFT).

Radiation: X-ray based radiation therapy; Procedure: Computed Tomography (CT) Scan; Procedure: Pulmonary Function Test (PFT)

Interventions

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.

Also known as: PTI

Proton beam radiation therapy

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.

Also known as: conformal RT

X-ray based radiation therapy

Computed Tomography (CT) Scan PROCEDURE

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

Proton beam radiation therapy; X-ray based radiation therapy

Pulmonary Function Test (PFT) PROCEDURE

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

Proton beam radiation therapy; X-ray based radiation therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• Florida Department of Health: collaborator

Study Sites (2)

Department of Radiation Oncology Davis Cancer Pavilion

Gainesville, Florida, 32611, United States

Location

University of Florida Health Proton Therapy Institute

Jacksonville, Florida, 32206, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood plasma collection

MeSH Terms

Conditions

Radiation Injuries; Breast Neoplasms

Interventions

Proton Therapy; Respiratory Physiological Phenomena

Condition Hierarchy (Ancestors)

Wounds and Injuries; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Walter O'Dell, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Julie Bradley, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2016
• First Posted: April 1, 2016
• Study Start: May 1, 2016
• Primary Completion: January 14, 2022
• Study Completion: January 14, 2022
• Last Updated: August 22, 2024

Record last verified: 2024-08

Locations

US (2)