Improving Pulmonary Function Following Radiation Therapy

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Radiation: Standard fractionation; Radiation: Stereotactic Body Radiation Therapy (SBRT); Procedure: Four Dimensional Computed Tomographic Imaging (4DCT)

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Johnson Creek, Wisconsin, United States, 53038
      • UW Johnson Creek
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: Cancer Radiotherapy; Radiation; Radiation: Stereotactic Body Radiation Therapy (SBRT); 40-60 Gy delivered in 5-20 Gy fractions over 3-8 treatments; Other Names: SBRT; Cancer Radiotherapy; Radiation; 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: 4DCT
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: Cancer Radiotherapy; Radiation; Radiation: Stereotactic Body Radiation Therapy (SBRT); 40-60 Gy delivered in 5-20 Gy fractions over 3-8 treatments; Other Names: SBRT; Cancer Radiotherapy; Radiation; 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: 4DCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	3 months post RT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	During therapy to 12 months post-RT
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.	During therapy to 12 months post-RT
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.	During therapy to 12 months post-RT
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.	Up to 12 months post-RT
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.	Pre-RT up to 12 months post-RT
Change in Level of Plasma TGF-beta	All statistical tests will be two-sided and assessed for significance at the 5% level.	Baseline up to 12 months post-RT
Change in Level of Plasma Cytokines	All statistical tests will be two-sided and assessed for significance at the 5% level.	Baseline up to 12 months post-RT
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.	Up to 12 months post-RT

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Carri K Glide-Hurst, PhD, DABR, FAAPM, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Baschnagel AM, Flakus MJ, Wallat EM, Wuschner AE, Chappell RJ, Bayliss RA, Kimple RJ, Christensen GE, Reinhardt JM, Bassetti MF, Bayouth JE. A Phase 2 Randomized Clinical Trial Evaluating 4-Dimensional Computed Tomography Ventilation-Based Functional Lung Avoidance Radiation Therapy for Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2024 Aug 1;119(5):1393-1402. doi: 10.1016/j.ijrobp.2024.02.019. Epub 2024 Feb 20.

Helpful Links

• UW Carbone Cancer Center Home Page

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2016
• Primary Completion (Actual): October 28, 2022
• Study Completion (Actual): August 16, 2023

Study Registration Dates

• First Submitted: July 15, 2016
• First Submitted That Met QC Criteria: July 20, 2016
• First Posted (Estimated): July 26, 2016

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: UW16037; NCI-2016-01085 (Registry Identifier: NCI Trial ID); 2016-0610 (Other Identifier: Institutional Review Board); A539933 (Other Identifier: UW Madison); SMPH\VOLUNTEER STAFF\HUM ONCOL (Other Identifier: UW Madison); Protocol Version 6/9/2022 (Other Identifier: UW Madison); R01CA166703 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes