Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy

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.

Study Overview

• Status: Completed
• Conditions: Emphysema
• Intervention / Treatment: Radiation: Stereotactic Ablative Radiotherapy (SABR)

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline and months 6, 12, and 18
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)	Baseline and months 6, 12, and 18
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)	Baseline and months 6, 12, and 18
Change From Baseline in 6 Minute Walk Test (Meters)	The walk test will be done both prior (baseline) and following the procedure (month 6)	Baseline and month 6
Total Lung Capacity (% of Predicted Value)	Total Lung Capacity will be measured both prior (baseline) and following the procedure (up to 18 months)	Baseline and date of last available time-point in follow-up period (up to 18 months)
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.	Baseline and date of last available time-point in follow-up period (up to 18 months)
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.	Baseline and months 6
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.	Baseline and months 6, 12, and 18

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Varian, a Siemens Healthineers Company
• Investigators: Study Director: Joseph B Shrager, M.D, Stanford University

Publications and helpful links

General Publications

• Kamtam DN, Binkley MS, Kapula N, Sadeghi C, Nesbit S, Guo HH, Chang J, Maxim PG, Diehn M, Loo BW Jr, Shrager JB. First in Human Phase 1 Clinical Trial of Stereotactic Irradiation to Achieve Lung Volume Reduction (SILVR) in Severe Emphysema. Int J Radiat Oncol Biol Phys. 2024 Apr 12:S0360-3016(24)00479-6. doi: 10.1016/j.ijrobp.2024.03.049. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2013
• Primary Completion (Actual): August 2, 2021
• Study Completion (Actual): August 2, 2021

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: September 13, 2018
• First Posted (Actual): September 17, 2018

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Chronic Disease; Pulmonary Emphysema; Emphysema
• Other Study ID Numbers: e-protocol 23203