Emphysema
Conditions
Brief summary
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 bronchiolitis 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
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.
Interventions
The prescribed dose will be 45 Gy in three fractions of 15 Gy, on each side that is treated.
Sponsors
Study design
Eligibility
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Patients With Grade 3 or Higher Adverse Events. | 18 months | Adverse events will be based upon National Cancer Institute Common Terminology Criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters) | Baseline and months 6, 12, and 18 | Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18) |
| Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted) | Baseline and months 6, 12, and 18 | Diffusing Capacity for Carbon Dioxide will be taken both prior (baseline) and following the procedure (months 6, 12, and 18) |
| Change From Baseline in 6 Minute Walk Test (Meters) | Baseline and month 6 | The walk test will be done both prior (baseline) and following the procedure (month 6) |
| Change From Baseline Value in Forced Expiratory Volume Percent Predicted | Baseline and months 6, 12, and 18 | Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18) |
| Residual Volume (RV) (% of Predicted Value) | Baseline and date of last available time-point in follow-up period (up to 18 months) | Residual volume (RV) is the volume of air remaining in the lungs after maximum forceful expiration. In other words, it is the volume of air that cannot be expelled from the lungs, thus causing the alveoli to remain open at all times. |
| Short Form (SF)-36 Quality of Life Survey Score | Baseline and months 6 | The SF-36 Physical Component Summary (PCS) assesses limitations in physical functioning due to health problems, limitations in usual role because of physical health problems, bodily pain, and general health perceptions; the mental component summary (MCS) assesses vitality, limitations in social functioning because of physical or emotional problems, limitations in usual role due to emotional problems, and general mental health. The PCS and MCS scores each range from 0 (worst) to 100 (best). Increases from baseline indicate improvement. |
| Modified Borg Dyspnea Scale | Baseline and months 6, 12, and 18 | This is a patient-reported scale to rate the difficulty of breathing. The scale ranges from 0 to 10, wherein 0 indicates no difficulty breathing, and 10 indicates a maximal difficulty in breathing. Patients may report in whole numbers, from 0 to 10, in addition to reporting 0.5, which indicates very, very slight (just noticeable) difficulty in breathing. A negative change in score indicates a reduction in patient-reported breathing difficulty. The greater the negative change, the better the patient-reported breathing. |
| Total Lung Capacity (% of Predicted Value) | Baseline and date of last available time-point in follow-up period (up to 18 months) | Total Lung Capacity will be measured both prior (baseline) and following the procedure (up to 18 months) |
Countries
United States
Participant flow
Pre-assignment details
9 participants signed consent; 8 were allocated to the study arm.
Participants by arm
| Arm | Count |
|---|---|
| Stereotactic Ablative Radiotherapy Stereotactic Ablative Radiotherapy (SABR): 45 Gy in three fractions of 15 Gy, on each side that is treated. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death following intervention | 3 |
| Overall Study | Death prior to intervention | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Stereotactic Ablative Radiotherapy |
|---|---|
| Age, Continuous | 73.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 9 |
| other Total, other adverse events | 3 / 9 |
| serious Total, serious adverse events | 4 / 9 |
Outcome results
Count of Patients With Grade 3 or Higher Adverse Events.
Adverse events will be based upon National Cancer Institute Common Terminology Criteria
Time frame: 18 months
Population: Participants who received SABR
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic Ablative Radiotherapy | Count of Patients With Grade 3 or Higher Adverse Events. | 3 Participants |
Change From Baseline in 6 Minute Walk Test (Meters)
The walk test will be done both prior (baseline) and following the procedure (month 6)
Time frame: Baseline and month 6
Population: Participants with available data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Ablative Radiotherapy | Change From Baseline in 6 Minute Walk Test (Meters) | Baseline | 289.0 meters |
| Stereotactic Ablative Radiotherapy | Change From Baseline in 6 Minute Walk Test (Meters) | 6 months | 406.0 meters |
| Stereotactic Ablative Radiotherapy | Change From Baseline in 6 Minute Walk Test (Meters) | Change at 6 months | 27.0 meters |
Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)
Diffusing Capacity for Carbon Dioxide will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)
Time frame: Baseline and months 6, 12, and 18
Population: Participants who received SABR and with data at each respective time point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Ablative Radiotherapy | Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted) | Baseline | 40.0 percentage of predicted value |
| Stereotactic Ablative Radiotherapy | Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted) | Change at 6 months | -8.0 percentage of predicted value |
| Stereotactic Ablative Radiotherapy | Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted) | Change at 12 months | -10.0 percentage of predicted value |
| Stereotactic Ablative Radiotherapy | Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted) | Change at 18 months | -3.5 percentage of predicted value |
Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)
Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)
Time frame: Baseline and months 6, 12, and 18
Population: Participants who received SABR and with data at each respective time point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Ablative Radiotherapy | Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters) | Baseline | 0.79 liters |
| Stereotactic Ablative Radiotherapy | Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters) | Change at 6 months | 0.13 liters |
| Stereotactic Ablative Radiotherapy | Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters) | Change at 12 months | 0.14 liters |
| Stereotactic Ablative Radiotherapy | Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters) | Change at 18 months | 0.02 liters |
Change From Baseline Value in Forced Expiratory Volume Percent Predicted
Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)
Time frame: Baseline and months 6, 12, and 18
Population: Participants who received SABR and with data at each respective time point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Ablative Radiotherapy | Change From Baseline Value in Forced Expiratory Volume Percent Predicted | Baseline | 28.5 percentage of predicted value |
| Stereotactic Ablative Radiotherapy | Change From Baseline Value in Forced Expiratory Volume Percent Predicted | Change at 6 months | 5.0 percentage of predicted value |
| Stereotactic Ablative Radiotherapy | Change From Baseline Value in Forced Expiratory Volume Percent Predicted | Change at 12 months | 3.0 percentage of predicted value |
| Stereotactic Ablative Radiotherapy | Change From Baseline Value in Forced Expiratory Volume Percent Predicted | Change at 18 months | 5.5 percentage of predicted value |
Modified Borg Dyspnea Scale
This is a patient-reported scale to rate the difficulty of breathing. The scale ranges from 0 to 10, wherein 0 indicates no difficulty breathing, and 10 indicates a maximal difficulty in breathing. Patients may report in whole numbers, from 0 to 10, in addition to reporting 0.5, which indicates very, very slight (just noticeable) difficulty in breathing. A negative change in score indicates a reduction in patient-reported breathing difficulty. The greater the negative change, the better the patient-reported breathing.
Time frame: Baseline and months 6, 12, and 18
Population: Data were not collected for this outcome measure
Residual Volume (RV) (% of Predicted Value)
Residual volume (RV) is the volume of air remaining in the lungs after maximum forceful expiration. In other words, it is the volume of air that cannot be expelled from the lungs, thus causing the alveoli to remain open at all times.
Time frame: Baseline and date of last available time-point in follow-up period (up to 18 months)
Population: Participants who received SABR and with data at last available time-point in follow-up period
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Ablative Radiotherapy | Residual Volume (RV) (% of Predicted Value) | Baseline | 191 percentage of predicted value |
| Stereotactic Ablative Radiotherapy | Residual Volume (RV) (% of Predicted Value) | Last available time-point in follow-up period | 188 percentage of predicted value |
Short Form (SF)-36 Quality of Life Survey Score
The SF-36 Physical Component Summary (PCS) assesses limitations in physical functioning due to health problems, limitations in usual role because of physical health problems, bodily pain, and general health perceptions; the mental component summary (MCS) assesses vitality, limitations in social functioning because of physical or emotional problems, limitations in usual role due to emotional problems, and general mental health. The PCS and MCS scores each range from 0 (worst) to 100 (best). Increases from baseline indicate improvement.
Time frame: Baseline and months 6
Population: Participants who received SABR and with data at each respective time point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Ablative Radiotherapy | Short Form (SF)-36 Quality of Life Survey Score | PCS-Baseline | 31.9 score on a scale |
| Stereotactic Ablative Radiotherapy | Short Form (SF)-36 Quality of Life Survey Score | PCS-6 months | 24.9 score on a scale |
| Stereotactic Ablative Radiotherapy | Short Form (SF)-36 Quality of Life Survey Score | MCS-baseline | 48.0 score on a scale |
| Stereotactic Ablative Radiotherapy | Short Form (SF)-36 Quality of Life Survey Score | MCS-6 months | 51.5 score on a scale |
Total Lung Capacity (% of Predicted Value)
Total Lung Capacity will be measured both prior (baseline) and following the procedure (up to 18 months)
Time frame: Baseline and date of last available time-point in follow-up period (up to 18 months)
Population: Participants who received SABR and with data at last available time-point in follow-up period
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stereotactic Ablative Radiotherapy | Total Lung Capacity (% of Predicted Value) | Baseline | 127.5 percentage of predicted value |
| Stereotactic Ablative Radiotherapy | Total Lung Capacity (% of Predicted Value) | Last available time-point in follow-up period | 119.5 percentage of predicted value |