Lung Cancer
Conditions
Keywords
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
Brief summary
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
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.
Interventions
RADIATIONSBRT
SBRT delivered in 3 fractions of 20 Gy/fraction over 1.5 to 2 weeks for a total of 60 Gy
Sponsors
National Cancer Institute (NCI)
NRG Oncology
Radiation Therapy Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Tumor Control at 2 Years | From start of treatment to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Treatment-related Grade 3 or 4 Toxicity | From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis. | 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 |
| Other Grade 3-5 Adverse Events | From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis. | 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 |
| Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years | From start of treatment to 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. |
| 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 | From start of treatment to 2 years. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SBRT Stereotactic body radiation therapy (SBRT) delivered in 3 fractions of 20 Gy/fraction over 1.5 to 2 weeks for a total of 60 Gy | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not treated per protocol and re | 1 |
| Overall Study | Protocol Violation | 5 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | SBRT |
|---|---|
| Age, Continuous | 73 years |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 26 |
| serious Total, serious adverse events | 1 / 26 |
Outcome results
Primary
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.
Time frame: From start of treatment to 2 years.
Population: All eligible patients who started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT | Primary Tumor Control at 2 Years | 96.2 percentage of patients |
Secondary
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.
Time frame: From start of treatment to 2 years.
Population: The data required for this analysis was not obtained and will not be obtained.
Secondary
Level of Comorbidity Burden on Morbidity and Efficacy
Time frame: From start of treatment to end of follow-up.
Population: The data required for this analysis was not obtained and will not be obtained.
Secondary
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
Time frame: From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis.
Population: All eligible patients who started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT | Other Grade 3-5 Adverse Events | 3.9 percentage of participants |
Secondary
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.
Time frame: From start of treatment to 2 years.
Population: All eligible patients who started study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SBRT | Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years | Primary Tumor Failure at 2 Years | 3.8 percentage of participants |
| SBRT | Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years | Regional Failure at 2 Years | 7.7 percentage of participants |
| SBRT | Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years | Metastatic Dissemination at 2 Years | 11.5 percentage of participants |
| SBRT | Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years | Disease-Free Survival at 2 Years | 73.1 percentage of participants |
| SBRT | Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years | Overall Survival at 2 Years | 84.6 percentage of participants |
Secondary
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
Time frame: From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis.
Population: All eligible patients who started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT | Rate of Treatment-related Grade 3 or 4 Toxicity | 7.7 percentage of participants |