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, stage IIIA non-small cell lung cancer, adenocarcinoma of the lung
Brief summary
RATIONALE: Prognostic testing for early signs of metastases may help doctors detect metastases early and plan more effective treatment. PURPOSE: Phase III trial to study the relationship between early signs of metastases and survival in patients who have stage I, stage II, or stage III non-small cell lung cancer that can be removed by surgery.
Detailed description
OBJECTIVES: * Determine the relationship between three indicators of occult metastases (cytological examination of pleural lavage, immunohistochemistry (IHC) assay of lymph nodes, and IHC assay of rib bone marrow) and survival of patients with resectable non-small cell lung cancer. * Determine the relationship between these indicators and conventional histology. * Model survival considering the indicators and other patient attributes that are of prime prognostic significance. * Determine the relationships between the indicators and the site of first recurrence in these patients. * Determine the prevalence of the indicators in these patients. * Determine the relationships between the indicators and disease free survival in these patients.
Interventions
OTHERimmunohistochemistry staining method
PROCEDUREbiopsy
PROCEDUREsurgery
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient must be ≥ 18 years old. 2. Patient must have ECOG/Zubrod status \< 3. 3. Patient must have clinically resectable, NSCLC (squamous cell, adenocarcinoma, or large cell) and be clinical Stage I, IIa, IIb or IIIa, according to the 1998 staging system of the American Joint Commission on Cancer for lung cancer. 4. Patient must have N1 or N2 disease. NOTE: Patient must undergo mediastinoscopy if preoperative studies suggest N3 disease. 5. Patient must have a pathologic diagnosis (pre-operative or intra-operative) of NSCLC prior to registration. 6. Patient must be anticipated to have a thoracotomy with the intention of a curative resection for primary NSCLC. NOTE: The preoperative assessment of resectability should, at a minimum, include a CT scan of the chest and upper abdomen, including the adrenal glands, within 60 days prior to registration. 7. Patient must be medically fit for surgery. 8. Patient must be a candidate for complete resection of the carcinoma via pneumonectomy, bilobectomy, lobectomy, or anatomic segmentectomy with or without sleeve resection. 9. Patient or the patient's legally acceptable representative must provide a signed and dated written informed consent prior to registration and any study-related procedures. 10. Patient must be available for follow-up. 11. If the patient is a survivor of a prior cancer, all of the following criteria must apply: 1. Patient has undergone potentially curative therapy for all prior malignancies, 2. No evidence of any prior malignancies for at least 5 years with no evidence of recurrence (except for effectively treated basal cell or squamous carcinoma of the skin, carcinoma in-situ of the cervix that has been effectively treated by surgery alone, or lobular carcinoma in-situ of the ipsilateral or contralateral breast treated by surgery alone), 3. Patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies.
Exclusion criteria
1. Patient has evidence of pleural effusion by physical assessment, lateral chest x-ray, or by chest CT scan. 2. Patient has had ipsilateral thoracotomy or thoracoscopy within the past 5 years. 3. Patient has received prior chemotherapy or radiotherapy for this cancer. 4. Patient is considered a poor surgical risk due to non-malignant systemic disease (cardiovascular, renal, etc.) that would preclude the treatment options. 5. Patient for whom the surgeon plans to perform only a wedge resection for treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in Lymph Nodes Examined Patients | Up to 5 years | Overall survival was defined as the time period between patient registration and death. All histologically negative lymph nodes (N0) participants were examined for occult metastases (OM), diagnosed by cytokeratin immunohistochemistry (IHC). |
| Overall Survival in Bone Marrow Examined Patients | Up to 5 years | Overall survival was defined as the time period between patient registration and death. Rib bone marrow on participants were examined for occult metastases (OM), diagnosed by cytokeratin immunohistochemistry (IHC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival in Lymph Nodes Examined Patients | Up to 5 years | Disease-free survival was defined as the time period from registration to the date of first evidence recurrent disease in patients following curative pulmonary resection or death. All histologically negative lymph nodes (N0) participants were examined for occult metastases (OM), diagnosed by cytokeratin immunohistochemistry (IHC). |
| Disease-Free Survival in Bone Marrow Examined Patients | Up to 5 years | Disease-free survival was defined as the time period from registration to the date of first evidence recurrent disease in patients following curative pulmonary resection or death. Rib bone marrow on participants were examined for occult metastases (OM), diagnosed by cytokeratin immunohistochemistry (IHC). |
Countries
Canada, United States
Participant flow
Recruitment details
One thousand-three hundred and ten participants were enrolled between July 1999 and March 2004. Data was analyzed in June 2009 when all eligible participants could have been observed for at least 5 years.
Pre-assignment details
Two-hundred and sixty-three participants were ultimately removed from the study for various reasons (e.g. initially ineligible, final histology other than non-small-cell lung cancer), leaving 1047 participants evaluable for study endpoints.
Participants by arm
| Arm | Count |
|---|---|
| Surgery All patients undergo complete lymph node sampling or dissection. Patients are followed at 1, 4, 8, and 12 months, every 6 months for 2 years, and then annually for 2 years. | 1,047 |
| Total | 1,047 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Chest X-Ray not done prior registration | 1 |
| Overall Study | CT Scan not within protocol requirement | 2 |
| Overall Study | Ineligible | 6 |
| Overall Study | Medical problems | 6 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Surgery |
|---|---|
| Additional components of resection Bronchial sleeve resection | 33 Participants |
| Additional components of resection Chest wall resection +/- reconstruction | 33 Participants |
| Additional components of resection Intrapericardial resection | 20 Participants |
| Additional components of resection Vascular sleeve resection/arterioplasty | 13 Participants |
| Age, Continuous | 67.2 years |
| Extent of resection R0 | 996 Participants |
| Extent of resection R1 | 31 Participants |
| Extent of resection R2 | 20 Participants |
| Gender Female | 509 Participants |
| Gender Male | 538 Participants |
| Operation performed (pulmonary resection) Bilobectomy | 51 Participants |
| Operation performed (pulmonary resection) Exploration, no resection | 16 Participants |
| Operation performed (pulmonary resection) Lobectomy | 832 Participants |
| Operation performed (pulmonary resection) Pneumonectomy | 71 Participants |
| Operation performed (pulmonary resection) Segmentectomy | 79 Participants |
| Operation performed (pulmonary resection) Wedge resection | 24 Participants |
| Overall Pathologic Stage IA | 324 Participants |
| Overall Pathologic Stage IB | 367 Participants |
| Overall Pathologic Stage IIA | 32 Participants |
| Overall Pathologic Stage IIB | 158 Participants |
| Overall Pathologic Stage IIIA | 137 Participants |
| Overall Pathologic Stage IIIB | 29 Participants |
| Pathologic N Stage N0 | 739 Participants |
| Pathologic N Stage N1 | 171 Participants |
| Pathologic N Stage N2 | 129 Participants |
| Pathologic N Stage NX | 8 Participants |
| Pathologic T Stage Not available | 2 Participants |
| Pathologic T Stage T1=Tumor<=3cm, surrounded by lung/visceral pleura | 384 Participants |
| Pathologic T Stage T2=Tumor > 3 cm, main bronchus, >=2cm distal to ca | 575 Participants |
| Pathologic T Stage T3=Tumor of any size directly invades certain area | 55 Participants |
| Pathologic T Stage T4=Tumor of any size that invades certain area | 29 Participants |
| Pathologic T Stage TX=Primary tumor cannot be assessed | 2 Participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants |
| Race/Ethnicity, Customized Black/African American | 60 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 11 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 959 Participants |
| Region of Enrollment Canada | 177 participants |
| Region of Enrollment United States | 870 participants |
| Tumor histology Adenocarcinoma | 524 Participants |
| Tumor histology Adenosquamous | 14 Participants |
| Tumor histology Large cell | 54 Participants |
| Tumor histology Non-small-cell lung cancer, other subtype or other | 137 Participants |
| Tumor histology Squamous cell carcinoma | 318 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Overall Survival in Bone Marrow Examined Patients
Overall survival was defined as the time period between patient registration and death. Rib bone marrow on participants were examined for occult metastases (OM), diagnosed by cytokeratin immunohistochemistry (IHC).
Time frame: Up to 5 years
Population: Eligible participants who had underwent pulmonary resection with rib bone marrow were examined for OM
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OM Negative in Lymph Nodes | Overall Survival in Bone Marrow Examined Patients | NA years |
| OM Positive in Lymph Nodes | Overall Survival in Bone Marrow Examined Patients | NA years |
p-value: 0.88695% CI: [0.69, 1.54]Regression, Cox
Primary
Overall Survival in Lymph Nodes Examined Patients
Overall survival was defined as the time period between patient registration and death. All histologically negative lymph nodes (N0) participants were examined for occult metastases (OM), diagnosed by cytokeratin immunohistochemistry (IHC).
Time frame: Up to 5 years
Population: Eligible participants with N0 non-small-cell lung cancer who had underwent pulmonary resection and were examined for OM
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OM Negative in Lymph Nodes | Overall Survival in Lymph Nodes Examined Patients | NA years |
| OM Positive in Lymph Nodes | Overall Survival in Lymph Nodes Examined Patients | NA years |
p-value: 0.00795% CI: [1.13, 2.23]Regression, Cox
Secondary
Disease-Free Survival in Bone Marrow Examined Patients
Disease-free survival was defined as the time period from registration to the date of first evidence recurrent disease in patients following curative pulmonary resection or death. Rib bone marrow on participants were examined for occult metastases (OM), diagnosed by cytokeratin immunohistochemistry (IHC).
Time frame: Up to 5 years
Population: Eligible participants who had underwent pulmonary resection with rib bone marrow were examined for OM
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OM Negative in Lymph Nodes | Disease-Free Survival in Bone Marrow Examined Patients | NA years |
| OM Positive in Lymph Nodes | Disease-Free Survival in Bone Marrow Examined Patients | NA years |
p-value: 0.33295% CI: [0.48, 1.28]Regression, Cox
Secondary
Disease-Free Survival in Lymph Nodes Examined Patients
Disease-free survival was defined as the time period from registration to the date of first evidence recurrent disease in patients following curative pulmonary resection or death. All histologically negative lymph nodes (N0) participants were examined for occult metastases (OM), diagnosed by cytokeratin immunohistochemistry (IHC).
Time frame: Up to 5 years
Population: Eligible participants with N0 non-small-cell lung cancer who had underwent pulmonary resection and were examined for OM
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OM Negative in Lymph Nodes | Disease-Free Survival in Lymph Nodes Examined Patients | NA years |
| OM Positive in Lymph Nodes | Disease-Free Survival in Lymph Nodes Examined Patients | NA years |
p-value: 0.00995% CI: [1.13, 2.36]Regression, Cox