Stereotactic Body Radiation Therapy in Treating Patients With Inoperable Stage I or Stage II Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Stereotactic body radiation therapy may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. PURPOSE: This phase II trial is studying how well stereotactic body radiation therapy works in treating patients with inoperable stage I or stage II non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine whether treatment with stereotactic body radiotherapy results in acceptable local control (i.e., ≥ 80%) in patients with medically inoperable stage I or II non-small cell lung cancer. Secondary Determine treatment-related toxicity in patients treated with this therapy. Determine disease-free survival, overall survival, and patterns of failure in patients treated with this therapy. OUTLINE: This is a multicenter study. Patients receive 3 fractions of stereotactic body radiotherapy over 8-14 days in the absence of disease progression or unacceptable toxicity. Patients are followed up at 6 and 12 weeks, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 26 months.

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

Conditions
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Lung Cancer

Intervention / Treatment
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* Radiation: stereotactic body radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) The following primary cancer subtypes are eligible: Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Bronchoalveolar cell carcinoma Non-small cell carcinoma not otherwise specified Stage I or II disease based on 1 of the following tumor node metastasis (TNM) stage criteria: T1, N0, M0 T2 (≤ 5 cm), N0, M0 T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only) No primary tumor of any T-stage within or touching the zone of the proximal bronchial tree* NOTE: *Defined as a volume 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, and right and left lower lobe bronchi) No primary T3 tumors involving the central chest (≤ 2 cm toward carina invasion) or structures of the mediastinum Any hilar or mediastinal lymph nodes > 1 cm on CT scan OR demonstrating suspicious uptake on positron-emission tomography scan must be biopsied and confirmed negative for NSCLC The primary tumor must be deemed technically resectable with a reasonable possibility of obtaining a gross total resection with negative margins (defined as a potentially curative resection (PCR)) Deemed medically inoperable based on pulmonary function for surgical resection of NSCLC secondary to an underlying physiological problem, including any of the following medical conditions*: Baseline forced expiratory volume (FEV)_1< 40% of predicted Postoperative predicted FEV_1 < 30% of predicted Severely reduced diffusion capacity Baseline hypoxemia and/or hypercapnia Exercise oxygen consumption < 50% of predicted Severe pulmonary hypertension Diabetes mellitus with severe end organ damage Severe cerebral, cardiac, or peripheral vascular disease Severe chronic heart disease NOTE: *Patients who refuse a PCR due to preference, ideology, emotional or psychological issues, mental illness, or inability to give informed consent are not eligible No evidence of regional or distant metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular See Disease Characteristics No active pericardial infection Pulmonary See Disease Characteristics No active pulmonary infection Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active systemic infection No other concurrent illness that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent biologic therapy No concurrent vaccine therapy Chemotherapy No concurrent chemotherapy Endocrine therapy Not specified Radiotherapy No prior lung or mediastinal radiotherapy No concurrent standard fractionated radiotherapy No concurrent intensity modulated radiotherapy No concurrent cobalt-60 or charged particle beams (including electrons, protons, or heavier ions) Surgery See Disease Characteristics No concurrent surgery Other No other concurrent antineoplastic therapy

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 body radiation therapy (SBRT)<br>20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy | Radiation: stereotactic body radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Control at 2 Years | Local control is defined as absence of local failure, which is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Local control time is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local failure (censored). Rates are estimated using the Kaplan-Meier method. | From the start of treatment to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Specified Adverse Events | Specified adverse events are defined as any treatment-related adverse events that are grade 4, grade 5, or any of the following treatment-related grade 3 adverse events: Gastrointestinal: dysphagia, esophagitis, esophageal stricture, esophageal ulceration; Cardiac: pericarditis, pericardial effusion, cardiomyopathy, ventricular dysfunction; Neurologic: myelitis, neuropathy (cranial and motor) Hemorrhage: pulmonary or upper respiratory Pulmonary: decline in pulmonary function as measured by pulmonary function tests, pneumonitis, pulmonary fibrosis, hypoxemia, pleural effusion. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. | From randomization to last follow-up. Analysis occurred after all patients had been on study for at least 2 years. Maximum follow-up at time of analysis was 4.2 years. | 
| Rate of Local Recurrence at 2 Years | Local failure is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Time to local recurrence is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local recurrence (censored). | From the start of treatment to 2 years | 
| Rate of Regional Recurrence at 2 Years | Regional recurrence is defined as hilar, mediastinal, and supraclavicular nodal failure.Time to regional recurrence is defined as time from start of treatment to the date of first regional recurrence, last known follow-up (censored), or death without regional recurrence (competing risk). Rates are estimated using the cumulative incidence method. | From the start of treatment to 2 years | 
| Rate of Disseminated Recurrence at 2 Years | Disseminated recurrence is defined as uninvolved lobe failures and failures beyond the lungs and regional lymph nodes. Time to disseminated recurrence is defined as time from start of treatment to the the date of disseminated recurrence, last known follow-up (censored), or death without disseminated recurrence (competing risk). Rates are estimated using the cumulative incidence method. | From the start of treatment to 2 years | 
| Rate of Disease-free Survival at 2 Years | Disease is defined as local or regional progression or development of distant metastases. Disease-free survival time is defined as time from start of treatment to the date of disease, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method. | From the start of treatment to 2 years | 
| Rate of Overall Survival at 2 Years | Overall survival time is defined as time from start of treatment to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. | From the 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, squamous cell lung cancer, large cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer