Investigating Radiation-Induced Injury to Airways and Pulmonary Vasculature in Lung Stereotactic Ablative Body Radiotherapy (SAbR)

We will conduct a prospective clinical study involving up to 40 non-Small Cell Lung Cancer (nSCLC) patients to determine dose thresholds for central and peripheral BSS elements. All imaging will be performed under motion control (e.g., with or without abdominal compression) defined as breathing with a resultant motion ≤5mm by fluoroscopy.

In this study, a high-resolution breath-hold CT scan (BHCT) will be acquired from each patient immediately before or after the 4DCT scan.

A follow-up high resolution BHCT (also under motion control) will be acquired from each patient 8-12 months post-SabR, and BSS elements will be segmented in LungPointRT. A radiation oncologist will compare the pre- and post-SabR contours to determine segmental collapse.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Thoracic Cancer

Detailed Description

We will conduct a prospective clinical study involving up to 40 non-Small Cell Lung Cancer (nSCLC) patients to determine dose thresholds for central and peripheral BSS elements. The workflow is illustrated in Fig. 4. all imaging will be performed under motion control (e.g., with or without abdominal compression) defined as breathing with a resultant motion [LessThanorequalTo]5mm by fluoroscopy. Before 4DCT simulation, fluoroscopy using a stand-alone system is used to assess motion under free-breathing conditions. For those with inherent motion [LessThanorequalTo]5mm, no motion manipulation is required (ie, motion is controlled). For those with [Greater Than]5mm motion, it is customary to use progressively tighter abdominal compression applied via commercially available device or a pneumatic belt, until respiration-induced tumor motion, as seen under fluoroscopy, is [LessThanorequalTo] 5mm. Subsequently, a 4DCT scan is acquired with motion control.

in this study, a high-resolution breath-hold CT scan (BHCT) will be acquired from each patient immediately before or after the 4DCT scan. using LungPoint, a virtual bronchoscopy software, individual BSS will be auto-segmented from the BHCT, labeled based on a nomenclature described by netter and exported as Digital imaging and Communications in Medicine radiation Therapy (DiCoMRT) objects to the planning system. The BHCT will be deformably registered to each phase of the 4DCT to create ten high-resolution CT volumes corresponding to ten respiratory phases. acquiring both, the BHCT and the 4DCT, under motion control will ensure that the anatomy is consistently deformed so as to minimize image registration errors. The automatically deformed contours, especially for smaller BSS elements, will be manually verified by a radiation oncologist, and corrected if necessary. a high-resolution maximum intensity projection (MiP) image will be created from the deformed BHCT volumes so as to encompass the extent of respiration-induced motion for each structure in the lung. The high spatial resolution of the MiP will ensure that respiratory motion of smaller, more peripheral BSS segments is captured accurately. The dose to BSS elements from the clinical SabR plan (created without considering BSS) will be computed from the hi-res MiP using the acuros dose calculation algorithm. This algorithm accurately accounts for dose to small structures and tissue inhomogeneities, and has been extensively validated for lung radiotherapy.

a follow-up high resolution BHCT (also under motion control) will be acquired from each patient 8-12 months post-SabR, and BSS elements will be segmented in LungPointRT. a radiation oncologist will compare the pre- and post-SabR contours to determine segmental collapse. univariate and multivariate stepwise generalized estimating equation (Gee) analyses will be conducted to identify significant factors contributing to BSS collapse, accounting for intra-patient correlation within each nSCLC patient. The insights obtained from these analyses will be used to formulate dose-thresholds for BSS segments. For each segment, we will compute the probability of segmental collapse as a function of dose, Cs(D) and also assign a weight [and] #955;s. This weight will be based on the findings of aim 2 and will be proportional to the functional lung volume [Quote]served[Quote] by that segment. This weighting scheme will ensure that the dose-thresholds (DT) are set more conservatively, i.e., with relatively lower Cs(DT) for the more critical BSS segments and vice versa.

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Cancer Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with Lung/Thoracic malignancies who consent to recieving Radiation treatment at the University of Texas Medical Center, will be offered this protocol design.

Description

Inclusion Criteria:

1. Patients with primary or metastatic lesions in the lung, to be treated with definitive proton or photon radiotherapy. There is no limitation on the number of radiotherapy fractions, or the location/number of lesions for this study
2. Age ≥ 18 years. No gender or ethnic restrictions.
3. ECOG performance status ≤ 3
4. Ability to hold breath for ~20 seconds
5. Ability to understand and the willingness to sign a written informed consent.
6. Any types and amounts of prior therapy will be allowed for this study.

7. All men, as well as women of child-bearing potential must agree to use adequate contraception (surgical sterilization [hysterectomy or vasectomy], approved hormonal contraceptives [birth control pills, patch or ring, Depo-Provera, Implanon] or barrier method such as condom or diaphragm with spermicide or an intrauterine device) from consent until the end of study scans. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

   • A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

     • Has not undergone a hysterectomy or bilateral oophorectomy; or
     • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

Exclusion Criteria:

1. Children (age <18 years).
2. Women who are pregnant, nursing, or trying to get pregnant
3. ECOG performance status > 3

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between radiation-induced collapse of Branching Serial Structures (BSS) elements and localized change in pulmonary function.	Evaluating the association between radiation-induced collapse of Branching Serial Structures (BSS) elements, characterized by segmental collapse, and localized change in pulmonary function. a map of collapsed and open BSS elements will be generated from the contoured BSS trees in the pre- and post-SAbR BHCT scans to determine the impact of radiation-induced collapse of BSS elements and localized changes to pulmonary function.	24 months
The radiosensitivity of peripheral Branching Serial Structures (BSS) segments.	Evaluating the radiosensitivity of peripheral BSS segments in terms of dose dependent probability of collapse through Generalized Estimating Equation (GEE).	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Create intensity modulated radiotherapy treatment plans	To create intensity modulated radiotherapy treatment plans that incorporate radiation dose thresholds for BSS elements while achieving other clinical objectives (prescription dose to planning target volume, dose limits to other organs at risk).	24 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2017
• Primary Completion (Actual): September 25, 2023
• Study Completion (Actual): September 25, 2023

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 14, 2022

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: STU-062016-073

Drug and device information, study documents

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