Lung Cancer
Conditions
Keywords
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
Brief summary
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
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.
Interventions
RADIATIONstereotactic body radiation therapy
Sponsors
National Cancer Institute (NCI)
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 (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Control at 2 Years | From the start of treatment to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Local Recurrence at 2 Years | From the start of treatment to 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). |
| Rate of Regional Recurrence at 2 Years | From the start of treatment to 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. |
| Proportion of Subjects With Specified Adverse Events | 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. | 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. |
| Rate of Disease-free Survival at 2 Years | From the start of treatment to 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. |
| Rate of Overall Survival at 2 Years | From the start of treatment to 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. |
| Rate of Disseminated Recurrence at 2 Years | From the start of treatment to 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stereotactic Body Radiation Therapy (SBRT) 20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy
stereotactic body radiation therapy | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible / No protocol treatment | 4 |
Baseline characteristics
| Characteristic | Stereotactic Body Radiation Therapy (SBRT) |
|---|---|
| Age, Continuous | 72 years |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 49 / 55 |
| serious Total, serious adverse events | 11 / 55 |
Outcome results
Primary
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.
Time frame: From the start of treatment to 2 years
Population: Eligible patients who started protocol treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic Body Radiation Therapy (SBRT) | Local Control at 2 Years | 97.6 percentage of subjects |
Comparison: Null hypothesis = 60% two-year local control (0.02128/mo. hazard rate); alternative = 80% (0.0093/mo.) assuming at least approximately exponential distribution of time to local progression. Using the asymptotic properties of the ratio of the logarithms of hazard rates, less than 18 cases of local progression were required for a Type I error rate of 0.05 with 80% power to detect a difference in local control rates at least this large. Hazard rate estimated using life table two-year estimates.p-value: 0.013z-test, one-sided
Secondary
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.
Time frame: 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.
Population: All eligible patients who started study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic Body Radiation Therapy (SBRT) | Proportion of Subjects With Specified Adverse Events | 9 Participants |
Secondary
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.
Time frame: From the start of treatment to 2 years
Population: Eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic Body Radiation Therapy (SBRT) | Rate of Disease-free Survival at 2 Years | 67.3 percentage of participants |
Secondary
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.
Time frame: From the start of treatment to 2 years
Population: Eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic Body Radiation Therapy (SBRT) | Rate of Disseminated Recurrence at 2 Years | 11.1 percentage of participants |
Secondary
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).
Time frame: From the start of treatment to 2 years
Population: Eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic Body Radiation Therapy (SBRT) | Rate of Local Recurrence at 2 Years | 2.4 percentage of participants |
Secondary
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.
Time frame: From the start of treatment to 2 years
Population: Eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic Body Radiation Therapy (SBRT) | Rate of Overall Survival at 2 Years | 72.7 percentage of participants |
Secondary
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.
Time frame: From the start of treatment to 2 years
Population: Eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stereotactic Body Radiation Therapy (SBRT) | Rate of Regional Recurrence at 2 Years | 0 percentage of participants |