Non-Small Cell Lung Cancer
Conditions
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
RADIATIONStandard fractionation
60-66y Gy delivered in 1.8-2.0 Gy fractions over 30-36 treatments
RADIATIONStereotactic Body Radiation Therapy (SBRT)
40-60 Gy delivered in 5-20 Gy fractions over 3-8 treatments
PROCEDUREFour 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.
Sponsors
University of Wisconsin, Madison
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Temporal Changes in Reduced Elasticity Determined by the Volume of Lung Where Expansion is Improved (Percent Change) | During therapy to 12 months post-RT | Changes in Reduced Elasticity (defined as \< 0.94\*median) 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 Reduced Elasticity Determined by the Volume of Lung Where Expansion is Improved (Ratio) | During therapy to 12 months post-RT | Changes in Reduced Elasticity (defined as \< 0.94\*median) 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 (Percent Change) | During therapy to 12 months post-RT | Changes in Increased Elasticity (defined as \> 1.06\*median) 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 (Ratio) | During therapy to 12 months post-RT | Changes in Increased Elasticity (defined as \> 1.06\*median) 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 (Percent Change) | During therapy to 12 months post-RT | Changes in Expansion of Lung Determined by the Volume of Lung Where "Meaningful" Expansion (defined as \> 1.1\*median ) Occurs (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 (Ratio) | During therapy to 12 months post-RT | Changes in Expansion of Lung Determined by the Volume of Lung Where "Meaningful" Expansion (defined as \> 1.1\*median ) Occurs (During therapy 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. |
| 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. |
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCarri K Glide-Hurst, PhD, DABR, FAAPM
University of Wisconsin, Madison
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Laboratory Biomarker Analysis: Correlative studies
Standard fractionation: 60-66y Gy delivered in 1.8-2.0 Gy fractions over 30-36 treatments
Stereotactic Body Radiation Therapy (SBRT): 40-60 Gy delivered in 5-20 Gy fractions over 3-8 treatments
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. | 61 |
| 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.
Laboratory Biomarker Analysis: Correlative studies
Standard fractionation: 60-66y Gy delivered in 1.8-2.0 Gy fractions over 30-36 treatments
Stereotactic Body Radiation Therapy (SBRT): 40-60 Gy delivered in 5-20 Gy fractions over 3-8 treatments
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. | 55 |
| Total | 116 |
Baseline characteristics
| Characteristic | Standard of Care | Total | Pulmonary Function Damage Reduction |
|---|---|---|---|
| Age, Customized median age | 69 years | 70 years | 71 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 116 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 58 Participants | 111 Participants | 53 Participants |
| Region of Enrollment United States | 61 participants | 116 participants | 55 participants |
| Sex: Female, Male Female | 24 Participants | 56 Participants | 32 Participants |
| Sex: Female, Male Male | 37 Participants | 60 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 61 | 3 / 55 |
| other Total, other adverse events | 61 / 61 | 55 / 55 |
| serious Total, serious adverse events | 7 / 61 | 10 / 55 |
Outcome results
Primary
Pulmonary Function, Based on Changes in Tissue Elasticity Measured From 4DCT
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).
Time frame: 3 months post RT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Pulmonary Function, Based on Changes in Tissue Elasticity Measured From 4DCT | 1.09 ratio |
| Pulmonary Function Damage Reduction | Pulmonary Function, Based on Changes in Tissue Elasticity Measured From 4DCT | 1.13 ratio |
Secondary
Change in Level of Plasma Cytokines
All statistical tests will be two-sided and assessed for significance at the 5% level.
Time frame: Baseline up to 12 months post-RT
Secondary
Change in Level of Plasma TGF-beta
All statistical tests will be two-sided and assessed for significance at the 5% level.
Time frame: Baseline up to 12 months post-RT
Secondary
Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs)
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.
Time frame: Pre-RT up to 12 months post-RT
Population: This measures a change from baseline, not all participants completed all time points
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 3 months | -12 percent predicted |
| Standard of Care | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 12 months | -5 percent predicted |
| Standard of Care | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 12 months | 12 percent predicted |
| Standard of Care | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 3 months | -6 percent predicted |
| Standard of Care | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 12 months | 2 percent predicted |
| Standard of Care | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 6 months | -4 percent predicted |
| Standard of Care | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 6 months | -11 percent predicted |
| Standard of Care | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 6 months | -4.5 percent predicted |
| Standard of Care | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 3 months | -5 percent predicted |
| Pulmonary Function Damage Reduction | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 6 months | -2 percent predicted |
| Pulmonary Function Damage Reduction | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 3 months | -11 percent predicted |
| Pulmonary Function Damage Reduction | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 12 months | 8 percent predicted |
| Pulmonary Function Damage Reduction | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 6 months | -4 percent predicted |
| Pulmonary Function Damage Reduction | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 3 months | -3 percent predicted |
| Pulmonary Function Damage Reduction | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 12 months | 12 percent predicted |
| Pulmonary Function Damage Reduction | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 12 months | 5 percent predicted |
| Pulmonary Function Damage Reduction | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 6 months | -9.5 percent predicted |
| Pulmonary Function Damage Reduction | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 3 months | 1.5 percent predicted |
| Standard of Care: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 6 months | -0.5 percent predicted |
| Standard of Care: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 3 months | -2 percent predicted |
| Standard of Care: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 6 months | -2 percent predicted |
| Standard of Care: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 12 months | -2 percent predicted |
| Standard of Care: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 3 months | 0 percent predicted |
| Standard of Care: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 12 months | 0 percent predicted |
| Standard of Care: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 3 months | -2.5 percent predicted |
| Standard of Care: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 6 months | -6.5 percent predicted |
| Standard of Care: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 12 months | 2.5 percent predicted |
| Pulmonary Function Damage Reduction: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 3 months | -2 percent predicted |
| Pulmonary Function Damage Reduction: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 3 months | 0 percent predicted |
| Pulmonary Function Damage Reduction: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 12 months | -1 percent predicted |
| Pulmonary Function Damage Reduction: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 12 months | 1 percent predicted |
| Pulmonary Function Damage Reduction: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the DLCO percent predicted from baseline to 6 months | -0.5 percent predicted |
| Pulmonary Function Damage Reduction: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 6 months | -3 percent predicted |
| Pulmonary Function Damage Reduction: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 12 months | 2 percent predicted |
| Pulmonary Function Damage Reduction: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FVC percent predicted from baseline to 6 months | -2 percent predicted |
| Pulmonary Function Damage Reduction: SBRT Cohort | Median Absolute Change in the Percent Predicted for Pulmonary Function Tests (PFTs) | Median Absolute Change in the FEV1 percent predicted from baseline to 3 months | -2 percent predicted |
Secondary
Temporal Changes in Fraction of Expanding Lung Determined by the Volume of Lung Where Meaningful Expansion Occurs
All statistical tests will be two-sided and assessed for significance at the 5% level.
Time frame: During therapy to 12 months post-RT
Secondary
Temporal Changes in Increased Elasticity Determined by the Volume of Lung Where Expansion is Improved
All statistical tests will be two-sided and assessed for significance at the 5% level.
Time frame: During therapy to 12 months post-RT
Secondary
Temporal Changes in Reduced Elasticity Determined by the Volume of Lung Where Expansion is Improved
All statistical tests will be two-sided and assessed for significance at the 5% level.
Time frame: During therapy to 12 months post-RT
Secondary
Validation in Consistency of Tissue Elasticity Changes Measured With Values Predicted Based on Existing Radiation Dose Response Curves
All statistical tests will be two-sided and assessed for significance at the 5% level.
Time frame: Up to 12 months post-RT
Secondary
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
All statistical tests will be two-sided and assessed for significance at the 5% level.
Time frame: Up to 12 months post-RT