Comparison of Different Types of Surgery in Treating Patients With Stage IA Non-Small Cell Lung Cancer

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to tumor
size (< 1 cm vs 1-1.5 cm vs > 1.5-2.0 cm) (based on the maximum dimension determined from the
preoperative CT scan), histology (squamous cell carcinoma vs adenocarcinoma vs other), and
smoking status (never smoked [smoked < 100 cigarettes over lifetime] vs former smoker [smoked
> 100 cigarettes AND quit ≥ 1 year ago] vs current smoker [quit < 1 year ago or currently
smokes]). Patients are randomized to 1 of 2 treatment arms. For more information, please see
the Arms section.

Primary Objective:

To determine whether DFS after sublobar resection (segmentectomy or wedge) is non-inferior to
that after lobectomy in patients with small peripheral (≤ 2 cm) NSCLC.

Secondary Objectives:

1. To determine whether overall survival (OS) (after sublobar resection) is non-inferior to
that after lobectomy.

2. To determine the rates of loco-regional and systemic recurrence (exclusive of second
primaries) after lobar and sublobar resection.

3. To determine the difference between the two arms of the study in pulmonary function as
determined by expiratory flow rates measured at 6 months post-operatively.

4. Imaging Substudy: To explore the relationship between characteristics of the primary
lung cancer, as revealed by pre-operative CT and PET imaging, and outcomes; a
determination of the false-negative rate of the pre-operative PET scan for
identification of involved hilarand mediastinal lymph nodes; and an assessment of the
utility of annual follow-up CT imaging after surgical resection of small stage IA NSCLC.

After completion of study treatment, patients are followed up every 6 months for 2 years and
then annually for 5 years.

Pre-registration Eligibility Criteria:

1. Peripheral lung nodule ≤ 2 cm on preoperative CT scan and presumed to be lung cancer.
The center of the tumor, as seen on CT, must be located in the outer third of the lung
in either the transverse, coronal or sagittal plane. Patients with pure ground glass
opacities or pathologically confirmed N1 or N2 disease are not eligible.

2. The tumor location must be suitable for either lobar or sublobar resection (wedge or
segment).

3. ECOG performance status of 0-2.

4. No prior malignancy within 3 years other than non-melanoma skin cancer, superficial
bladder cancer, or CIS of the cervix.

5. No prior chemotherapy or radiation therapy for this malignancy.

6. No evidence of locally advanced or metastatic disease.

7. Age ≥ 18 years

Intra-operative Randomization Eligibility Criteria:

1. Histologic confirmation of NSCLC (if not already obtained)

2. Confirmation of N0 status by frozen section examination. Right sided tumors require
that node levels 4, 7, and 10 be sampled and diagnosed as negative on frozen section.
Left sided tumors require that node levels 5 or 6, 7 and 10 be sampled and diagnosed
as negative on frozen section. Levels 4 and 7 nodes may be sampled by mediastinoscopy,
endobronchial ultrasound (EBUS) and/or endoscopic ultrasound (EUS), or at the time of
thoracotomy or VATS exploration. Nodes previously sampled by mediastinoscopy (or EBUS
and/or EUS) either immediately prior to or within 6 weeks of the definitive surgical
procedure (thoracotomy or VATS) do not need to be resampled.