Improving Pulmonary Function Following Radiation Therapy
Study Details
Study Description
Brief Summary
The purpose of this study is to develop radiation plans that will help preserve lung function in healthy tissue surrounding the tumor. We believe that 4DCT scans can be useful in designing radiation treatment plans that help us avoid healthy normal functioning lung tissue close to lung tumors. Currently 4DCT scans are used to help us determine exactly where the tumor is and how it moves when you breathe. In this study we will also use the 4DCT scans to try to identify high functioning normal lung tissue.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Standard of Care Subjects undergo four-dimensional computed tomographic imaging (4DCT) scans: 1 at simulation, and 2 scans at each of the 3 post-radiation therapy time points (3, 6, and 12 months). 4DCT determines lung tissue elasticity and for standard of care radiation treatment planning. Subjects undergo laboratory biomarker analysis, including spirometry, diffusion capacity (DLCO), and lung volumes (FEV, FEV1). Subjects complete a self-assessment, RTOG defined acute evaluation toxicity evaluation, RTOG late toxicity evaluation, and constitutional assessment. Radiation doses between 60-66 Gy using standard fractionation (1.8-2.0 Gy/fx) and 40-60 Gy stereotactic body radiation therapy (SBRT) hypofractionation schemes are utilized. Treatment volumes are at the discretion of the treating radiation oncologist and should follow standard of care. |
Other: Laboratory Biomarker Analysis
Correlative studies
Radiation: Standard fractionation
60-66y Gy delivered in 1.8-2.0 Gy fractions over 30-36 treatments
Other Names:
Radiation: Stereotactic Body Radiation Therapy (SBRT)
40-60 Gy delivered in 5-20 Gy fractions over 3-8 treatments
Other Names:
Procedure: Four Dimensional Computed Tomographic Imaging (4DCT)
Subjects undergo a total of 7 research-ordered four dimensional computed tomographic imaging (4DCT) scans: 1 at simulation, and 2 scans at each of the 3 post-radiation therapy time points (3, 6, and 12 months). 4DCT determines lung tissue elasticity and for standard of care radiation treatment planning.
Other Names:
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| Experimental: Pulmonary Function Damage Reduction All criteria and specifications in the standard of care arm are applicable for this arm, including the same 4DCT scans, and laboratory biomarker analysis. Subjects randomized to this arm of the trial will have the same prescribed radiation dose to the tumor volume and held to the same radiation dose criteria as the subjects in the standard of care arm (60-66 Gy using standard fractionation (1.8-2.0 Gy/fx) and 40-60 Gy stereotactic body radiation therapy (SBRT) hypofractionation). The fundamental difference will be radiation doses for these subjects will be redistributed away from regions predicted to cause the greatest reduction in pulmonary function if damaged. |
Other: Laboratory Biomarker Analysis
Correlative studies
Radiation: Standard fractionation
60-66y Gy delivered in 1.8-2.0 Gy fractions over 30-36 treatments
Other Names:
Radiation: Stereotactic Body Radiation Therapy (SBRT)
40-60 Gy delivered in 5-20 Gy fractions over 3-8 treatments
Other Names:
Procedure: Four Dimensional Computed Tomographic Imaging (4DCT)
Subjects undergo a total of 7 research-ordered four dimensional computed tomographic imaging (4DCT) scans: 1 at simulation, and 2 scans at each of the 3 post-radiation therapy time points (3, 6, and 12 months). 4DCT determines lung tissue elasticity and for standard of care radiation treatment planning.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Pulmonary function, based on changes in tissue elasticity measured from 4DCT [3 months post RT]
The primary endpoint of this study will be the ratio of the tissue elasticity map following RT to the elasticity map before RT (i.e., the Jacobian ratio of (post RT /pre RT)) calculated from 4DCT at 3 months post-RT. Based on the randomness of our measurement technique, diminished expansion (i.e. substantial change) is defined as a Jacobian ratio <0.94 (i.e., less than 94% of the pre-RT value).
Secondary Outcome Measures
- Temporal changes in reduced elasticity, Jacobian ratio [During therapy to 12 months post-RT]
All statistical tests will be two-sided and assessed for significance at the 5% level.
- Temporal changes in increased elasticity determined by the volume of lung where expansion is improved [During therapy to 12 months post-RT]
All statistical tests will be two-sided and assessed for significance at the 5% level.
- Temporal changes in fraction of expanding lung determined by the volume of lung where "meaningful" expansion occurs [During therapy to 12 months post-RT]
All statistical tests will be two-sided and assessed for significance at the 5% level.
- Validation in consistency of tissue elasticity changes measured with values predicted based on existing radiation dose response curves [Up to 12 months post-RT]
All statistical tests will be two-sided and assessed for significance at the 5% level.
- Changes in PFTs [Pre-RT up to 12 months post-RT]
All statistical tests will be two-sided and assessed for significance at the 5% level.
- Change in level of plasma TGF-beta1 measured by molecular specific enzyme linked immune sandwich assay [Baseline up to 12 months post-RT]
All statistical tests will be two-sided and assessed for significance at the 5% level.
- Change in level of plasma cytokines measured by LINCOplex (microsphere-based sandwich immunoassay) [Baseline up to 12 months post-RT]
All statistical tests will be two-sided and assessed for significance at the 5% level.
- Variation of the tissue elasticity calculated between scan 1 and scan 2 at each time point will be quantified and compared to longitudinal changes in tissue elasticity [Up to 12 months post-RT]
All statistical tests will be two-sided and assessed for significance at the 5% level.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologic diagnosis of non-small cell lung cancer or lung metastasis from a solid tumor. One biopsy site is adequate for multiple sites of thoracic disease.
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Treatment includes localized radiation therapy with or without chemotherapy
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Karnofsky ≥ 60%
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Not pregnant per radiation oncology standard procedures
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Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
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Prior (within last 6 months) or future planned therapeutic surgery for the treatment of the existing lung cancer
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Prior thoracic radiotherapy
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Severe COPD defined as disease requiring an inpatient stay for respiratory deterioration within the past 3 months
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Oxygen dependence of > 2 L/min continuously throughout the day at baseline
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Known underlying collagen vascular disease or intrinsic lung disease that could complicate expected sequelae of radiation (idiopathic pulmonary fibrosis, Wegener's granulomatosis)
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Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UW Johnson Creek | Johnson Creek | Wisconsin | United States | 53038 |
| 2 | University of Wisconsin Carbone Cancer Center | Madison | Wisconsin | United States | 53792 |
Sponsors and Collaborators
- University of Wisconsin, Madison
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Carri K Glide-Hurst, PhD, DABR, FAAPM, University of Wisconsin, Madison
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- UW16037
- NCI-2016-01085
- 2016-0610
- A539933
- SMPH\VOLUNTEER STAFF\HUM ONCOL
- Protocol Version 6/9/2022
- R01CA166703