Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy

Study Overview
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Brief Summary
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Since medical therapies offer only modest palliation and minimal hopes for improved survival to COPD patients, surgical therapies have been designed that may provide greater benefits in selected patients. Lung transplantation, for example, clearly improves survival and quality of life in patients with end stage COPD. This comes at substantial economic cost, however, as well as the at the cost of complications that may result from the complex surgery and from life-long immunosuppression. In addition, nearly all lung transplants will fail within 5 years as a result of progressive bronchiolotis obliterans, which we currently have no way to prevent or treat. A second operation designed to treat severe COPD patients is lung volume reduction surgery (LVRS). This operation, designed for patients with predominant emphysema rather than chronic bronchitis, is among the most carefully studied operations ever developed. We believe that by reducing the volume of emphysematous lung with the precise target localization made possible by image-guided SABR, that we will be able to duplicate the benefits of surgical lung volume reduction with far less risk. We believe that this may represent a major advance in the therapy of emphysema - a highly prevalent disease. It may provide not only palliation but also increased survival, as does surgical lung volume reduction, in carefully selected patients.

Detailed Description
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Stereotactic Ablative Radiotherapy (SABR), also called stereotactic body radiation therapy (SBRT), is a relatively recent advance in radiotherapy which allows high doses of radiation to be transmitted to focused areas (typically malignancies), allowing higher rates of tumoricidal activity, generally lower complications, and greater convenience for patients since it can be delivered in 1 to just a few sessions. As the radiation is administered from multiple directions according to stereotactic planning, high doses can be delivered to the tissues with rapid fall-off to relatively low doses in even nearby, surrounding normal tissues. This technique was initially applied to brain tumors- an application which over the years has met with great success. More recently, it has been applied with substantial success and is gaining increasing acceptance as a primary mode of therapy for stage I lung malignancies, and malignancies in multiple other body areas. In the lung, the rate of pneumonitis resulting from SABR is far lower than the rates incurred by conventional external beam radiotherapy. In conventional external beam radiotherapy reported pneumonitis rates range from 13-37% (7), depending on dose and field size. Reported rates of symptomatic pneumonitis after lung SABR are significantly lower and generally are  5% (8). SABR does, however, typically leave a scar in the area of lung that has been treated (9). Importantly, there appears to be contraction of surrounding lung parenchyma into this scar resulting in an effect that is essentially a lung volume reduction. One often sees clear loss of lung volume following any form of lung radiotherapy. With SABR, this volume reduction is achieved with a far lower risk of morbidity - in particular, less risk of pneumonitis.

Official Title
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Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy

Conditions
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Emphysema

Intervention / Treatment
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* Radiation: Stereotactic Ablative Radiotherapy (SABR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pulmonary Function: Severe COPD with severe reduction in quality of life due to dyspnea Moderate to Severe emphysematous destruction of lung parenchyma on chest CT FEV1 < 45% predicted and >18% predicted FEV1/FVC < .7 DLCO > 18% predicted Residual Volume > 160% predicted (by plethysmography) Arterial Blood Gas: paO2>40 on room air at rest paCO2<55 General: Successful completion of 16 sessions of pulmonary rehabilitation Exclusion Criteria: Predominate chronic bronchitis (none or mild emphysematous destruction of lung on chest CT). Pulmonary function tests / lung volumes that do not meet above criteria. Active coronary ischemia (stress test required if clinical symptoms). Inability to complete 16 sessions of pulmonary rehabilitation. Pregnancy. Presence of lung cancer.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stereotactic Ablative Radiotherapy<br>Experimental stereotactic ablative radiation treatment | Radiation: Stereotactic Ablative Radiotherapy (SABR)<br>* The prescribed dose will be 45 Gy in three fractions of 15 Gy, on each side that is treated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of patients with grade 3 or higher adverse events. | Adverse events will be based upon National Cancer Institute Common Terminology Criteria | 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline value in Forced Expiratory Volume in 1 second (liters) | Forced Expiratory Volume will be taken both prior and following the procedure | 1.5 years | 
| Change from baseline in Diffusing Capacity for Carbon Dioxide (% predicted) | Diffusing Capacity for Carbon Dioxide will be measured both prior and following the procedure | 1.5 years | 
| Change from baseline in Total Lung Capacity (liters) | Total Lung Capacity will be measured both prior and following the procedure | 1.5 years | 
| Change from baseline in 6 Minute Walk Test (feet) | The walk test will be done both prior and following the procedure | 1.5 years | 
| Change from baseline in SF 36 Quality of Life Survey Physical Component Summary Score | The Physical Component Summary Score of the SF-36 Survey (range 0-100; higher score reflects better health state) | 1.5 year |