Title A Randomized Phase III Study of Sublobar Resection (+/- Brachytherapy) versus Stereotactic Body Radiation Therapy in High Risk Patients with Stage I Non-Small Cell Lung Cancer (NSCLC)
IRB RTOG 1021/ ACOSOG Z4099
Hospital Main Campus
Phase Phase 3
- To ascertain whether patients treated by SBRT have a 3-year overall survival (OS) rate that is no more than 10% less than patients treated with SR.
- To compare loco-regional recurrence-free survival between study arms. See Evaluation of Outcomes (Section 7) for recurrence definitions.
- To compare disease-free survival between study arms.
- To compare grade 3 or higher specific adverse event profiles between study arms; specific comparisons will include AEs at 1, 3, 6 and 12 months post therapy.
- To compare pulmonary function between patients treated with SBRT and patients treated with SR.
- To compare the adverse events and PFTs in each arm for patients with low or high Charlson comorbidity index scores, including a test interaction between Charlson comorbidity index scores (low vs. high) and treatment arm.
- Age ≥ 18 years
- ECOG performance status (PS) 0, 1, or 2.
- Lung nodule suspicious for non-small cell lung cancer (NSCLC). NOTE: Biopsy confirmation is strongly recommended but not required. If biopsy is attempted and non-diagnostic, if the patient refuses biopsy, or if the risk of biopsy is considered too high, patients may be enrolled if the mass is suspicious for NSCLC based on two or more of the following criteria:
- Positive smoking history
- Absence of benign calcifications within suspicious nodule
- Activity of PET greater than normal tissue
- Evidence of growth compared to previous imaging
- Presence of spiculation
- Tumor ≤ 4 cm maximum diameter, clinical stage Ia or selected Ib by PET/CT scan of the chest and upper abdomen performed within 60 days prior to registration.
- All clinically suspicious mediastinal N1, N2, or N3 lymph nodes (> 1 cm short-axis dimension on CT scan and/or positive on PET scan) confirmed negative for involvement with NSCLC by one of the following methods: mediastinoscopy, anterior mediastinotomy, EUS/EBUS guided needle aspiration, CT-guided, video-assisted thoracoscopic or open lymph node biopsy.
- Tumor verified by a thoracic surgeon to be in a location that will permit sublobar resection.
- Tumor located peripherally within the lung. NOTE: Peripheral is defined as not touching any surface within 2 cm of the proximal bronchial tree in all directions. See the diagram in Section 2.2. Patients with non-peripheral (central) tumors are NOT eligible.
- No evidence of distant metastases.
- PFTs with DLCO within 90 days prior to registration.
- Patient at high-risk for surgery by meeting a minimum of one major criteria or two minor criteria as described below:
- Major Criteria: FEV1 ≤ 50% predicted
- DLCO ≤ 50% predicted
- Minor Criteria: Age ≥ 75
- FEV1 51-60% predicted
- DLCO 51-60% predicted
- Pulmonary hypertension (defined as a pulmonary artery systolic pressure greater than 40mm Hg) as estimated by echocardiography or right heart catheterization
- Poor left ventricular function (defined as an ejection fraction of 40% or less)
- Resting or Exercise Arterial pO2 ≤ 55 mm Hg or SpO2 ≤ 88%
- pCO2 > 45 mm Hg
- Modified Medical Research Council (MMRC) Dyspnea Scale ≥ 3.
- No prior intra-thoracic radiation therapy. NOTE: Previous radiotherapy as part of treatment for head and neck, breast, or other non-thoracic cancer is permitted. Previous chemotherapy or surgical resection for the lung cancer being treated on this protocol is NOT permitted.
- Non-pregnant and non-lactating. Women of child-bearing potential must have a negative urine or serum pregnancy test within 60 days prior to registration. Peri-menopausal women must be amenorrheic ≥ 12 months prior to registration to be considered not of childbearing potential.
- No prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration (exceptions: non-melanoma skin cancer, in-situ cancers).