Stereotactic Body Radiation Therapy in Treating Patients With Stage I or Stage II Non-Small Cell Lung Cancer That Can Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue near the tumor. PURPOSE: This phase II trial is studying how well stereotactic body radiation therapy works in treating patients with stage I or stage II non-small cell lung cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine whether treatment with radiotherapy involving a high biological dose with limited treatment volume (using stereotactic body radiotherapy [SBRT] techniques) achieves acceptable primary tumor control (i.e., ≥ 90% at 2 years) in patients with resectable early-stage non-small cell lung cancer. Secondary Determine whether treatment with radiotherapy involving a high biological dose with limited treatment volume (using SBRT techniques) achieves acceptable treatment-related toxicity. Estimate the disease-free survival and the overall survival rate at 2 years. Observe patterns of failure in the first 2 years. Assess the level of comorbidity burden on morbidity and efficacy. Determine if blood markers prior to, during the course of treatment (between the second and the last dose of SBRT), and at the first follow-up after SBRT predict 2-year primary tumor control and predict for grade ≥ 2 treatment-related toxicities OUTLINE: This is a multicenter study. Patients receive 3 fractions of stereotactic body radiotherapy over 14 days. Patients with disease progression undergo surgical resection as salvage local therapy. After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years and then annually thereafter.

Official Title
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A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients With Operable Stage I/II Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer, including any of the following primary tumor types: Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Large cell neuroendocrine tumor Non-small cell carcinoma not otherwise specified No pure type bronchoalveolar cell carcinoma Stage I or II disease based on 1 of the following combinations of primary tumor, regional nodes, metastasis (TNM) staging: T1, N0, M0 T2 (≤ 5 cm), N0, M0 T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only) No T2 or T3 primary tumors > 5 cm or T3 primary tumors involving the central chest and structures of the mediastinum No primary tumor of any T-stage within or touching the zone of the proximal bronchial tree, defined as a volume of 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, or right and left lower lobe bronchi) Patients with hilar or mediastinal lymph nodes ≤ 1 cm AND no abnormal hilar or mediastinal uptake on positron emission tomography (PET) scan will be considered N0 Patients with > 1 cm hilar or mediastinal lymph nodes on CT scan OR abnormal PET scan (including suspicious but nondiagnostic uptake) will still be eligible if directed tissue biopsies of all abnormally identified areas are negative for cancer No direct evidence of regional or distant metastases after appropriate staging studies Considered a reasonable candidate for surgical resection of the primary tumor, according to the following criteria: Primary tumor predicted to be technically resectable with a high likelihood of negative surgical margins (as determined by a qualified thoracic surgeon) Baseline forced expiratory volume (FEV)_1 > 35% predicted Postoperative predicted FEV_1 > 30% predicted Diffusion capacity > 35% predicted No hypoxemia (e.g., partial pressure of arterial oxygen (PaO2) of ≤ 60 mm Hg) and/or hypercapnia (e.g., partial pressure of arterial carbon dioxide (PaCO2) > 50 mm Hg) at baseline No severe pulmonary hypertension No severe cerebral, cardiac, or peripheral vascular disease No severe chronic heart disease Pleural effusion, if present, must be deemed too small to tap under CT scan guidance and must not be evident on chest x-ray Pleural effusion that appears on chest x-ray will be allowed only after thoracotomy or other invasive procedure PATIENT CHARACTERISTICS: Zubrod performance status 0-1 Absolute neutrophil count ≥ 1,800/mm³ Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.0 g/dL (transfusion allowed) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No synchronous primary or other invasive malignancy within the past 3 years other than nonmelanoma skin cancer or in situ cancer No active systemic, pulmonary, or pericardial infection No weight loss > 5% for any reason within the past 3 months PRIOR CONCURRENT THERAPY: No prior radiotherapy for lung cancer Prior radiotherapy as part of treatment for head and neck cancer, breast cancer, or other non-lung cancer is allowed provided there will not be significant overlap with the stereotactic body radiotherapy fields No prior chemotherapy or surgical resection for this lung cancer No other concurrent local or regional antineoplastic therapy (including standard fractionated radiotherapy, non-approved systemic therapy, and surgery), except at disease progression

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: SBRT<br>Stereotactic body radiation therapy (SBRT) | Radiation: SBRT<br>* SBRT delivered in 3 fractions of 20 Gy/fraction over 1.5 to 2 weeks for a total of 60 Gy<br>* Other names: SABR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Tumor Control at 2 Years | Primary tumor control is defined as the absence of primary tumor failure by 2 years after the start of SBRT. Primary tumor failure was considered as the development of either failure within the SBRT treatment fields (in-field failure) or failure within 1.0 cm of the treatment field (marginal failure). An acceptable tumor control rate at 2 years was considered to be 90% (monthly hazard of 0.00439), and an unacceptable rate was 70% (monthly hazard of 0.01486). A one-sided type 1 error of 0.05 and statistical power of 90% was used. A one-sided Z-test was used to determine if the difference between the logarithm of the observed hazard rate and the logarithm of the hypothesized hazard rate of 0.01486 was statistically significant. | From start of treatment to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Treatment-related Grade 3 or 4 Toxicity | The development of any treatment-related toxicity from among the following: Gastrointestinal: dysphagia, esophagitis, esophageal stricture/stenosis, esophageal ulceration; Cardiac: pericarditis, pericardial effusion, restrictive cardiomyopathy, ventricular dysfunction (left ventricular diastolic dysfunction, left ventricular systolic dysfunction, right ventricular dysfunction); Neurologic: myelitis, neuropathy (cranial and motor); Hemorrhage: pulmonary or upper respiratory; Pulmonary: decline in pulmonary function as measured by pulmonary function tests (DLCO, FEV1,FVC), pneumonitis, pulmonary fibrosis, hypoxia, pleural effusion, cough, and dyspnea; Any grade 4 or 5 adverse event attributed to the therapy | From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis. | 
| Other Grade 3-5 Adverse Events | The development of any treatment-related toxicity not from among the following: Gastrointestinal: dysphagia, esophagitis, esophageal stricture/stenosis, esophageal ulceration; Cardiac: pericarditis, pericardial effusion, restrictive cardiomyopathy, ventricular dysfunction (left ventricular diastolic dysfunction, left ventricular systolic dysfunction, right ventricular dysfunction); Neurologic: myelitis, neuropathy (cranial and motor); Hemorrhage: pulmonary or upper respiratory; Pulmonary: decline in pulmonary function as measured by pulmonary function tests (DLCO, FEV1,FVC), pneumonitis, pulmonary fibrosis, hypoxia, pleural effusion, cough, and dyspnea; Any grade 4 or 5 adverse event attributed to the therapy | From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis. | 
| Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years | PTF: the development of either failure within the SBRT treatment fields (in-field failure) or failure within 1.0 cm of the treatment field (marginal failure) within the first two years after start of SBRT. RF: the development of measurable tumor within lymph nodes along the natural lymphatic drainage typical for the location of the treated primary disease only with dimension of at least 1.0 cm on imaging studies (preferably CT scans) within the lung, bronchial hilum, or the mediastinum within the first two years after start of SBRT. MD: the appearance after protocol therapy of cancer deposits characteristic of metastatic dissemination from non-small cell lung cancer within the first two years after start of SBRT. DFS: the state of being alive without development of progressive disease, with failure considered the earliest development of either progression or death. OS: the state of being alive, with failure is considered death due to any cause. | From start of treatment to 2 years. | 
| Level of Comorbidity Burden on Morbidity and Efficacy |  | From start of treatment to end of follow-up. | 
| Assessment of Predictive Value of Blood Markers for Primary Tumor Control at 2 Years and Treatment-related Adverse Events ≥ Grade 2 | Assess if blood markers prior to, during the course of treatment (between the second and the last dose of SBRT), and at the first follow-up after SBRT predict 2 year primary tumor control and predict for grade ≥ 2 treatment-related adverse events. Unfortunately, there were not enough specimens submitted to perform this analysis. The specimens that were collected remain in the NRG Oncology Biobank and are available to be combined with other specimens from other studies for an appropriately powered project. | From start of treatment to 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I non-small cell lung cancer, stage II non-small cell lung cancer, adenocarcinoma of the lung, large cell lung cancer, squamous cell lung cancer, adenosquamous cell lung cancer