Improving Pulmonary Function Following Radiation Therapy

Not Applicable

Completed

Conditions: Non-Small Cell Lung Cancer

Interventions: Other: Laboratory Biomarker Analysis
Radiation: Standard fractionation
Radiation: Stereotactic Body Radiation Therapy (SBRT)
Procedure: Four Dimensional Computed Tomographic Imaging (4DCT)

Registration Number: NCT02843568

Lead Sponsor: University of Wisconsin, Madison

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 122

Inclusion Criteria

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.
Treatment includes localized radiation therapy with or without chemotherapy
Karnofsky ≥ 60%
Not pregnant per radiation oncology standard procedures
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Prior (within last 6 months) or future planned therapeutic surgery for the treatment of the existing lung cancer
Prior thoracic radiotherapy
Severe COPD defined as disease requiring an inpatient stay for respiratory deterioration within the past 3 months
Oxygen dependence of > 2 L/min continuously throughout the day at baseline
Known underlying collagen vascular disease or intrinsic lung disease that could complicate expected sequelae of radiation (idiopathic pulmonary fibrosis, Wegener's granulomatosis)
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Laboratory Biomarker Analysis	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.
Standard of Care	Stereotactic Body Radiation Therapy (SBRT)	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.
Standard of Care	Standard fractionation	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.
Pulmonary Function Damage Reduction	Stereotactic Body Radiation Therapy (SBRT)	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.
Pulmonary Function Damage Reduction	Standard fractionation	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.
Standard of Care	Four Dimensional Computed Tomographic Imaging (4DCT)	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.
Pulmonary Function Damage Reduction	Four Dimensional Computed Tomographic Imaging (4DCT)	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.
Pulmonary Function Damage Reduction	Laboratory Biomarker Analysis	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Temporal Changes in Reduced 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 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.
Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs)	Pre-RT up to 12 months post-RT	Median absolute change in the percent predicted following pulmonary function tests reported: Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC), and diffusing capacity of carbon monoxide (DLCO). All statistical tests will be two-sided and assessed for significance at the 5% level.
Change in Level of Plasma TGF-beta	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	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.

Trial Locations

Locations (2): University of Wisconsin Carbone Cancer Center
🇺🇸
Madison, Wisconsin, United States
UW Johnson Creek
🇺🇸
Johnson Creek, Wisconsin, United States