Trial Information

A Randomized Phase III Study of Sublobar Resection (+/- Brachytherapy) Versus Stereotactic Body Radiation Therapy in High Risk Patients With Stage I Non-Small Cell Lung Cancer (NSCLC)

OBJECTIVES:

Primary

- To ascertain whether patients treated by stereotactic body radiation therapy (SBRT)
have a 3-year overall survival (OS) rate that is no more than 10% less than patients
treated with sublobar resection (SR).

Secondary

- To compare loco-regional recurrence-free survival between study arms.

- To compare disease-free survival between study arms.

- To compare grade 3 or higher specific adverse event profiles between study arms at 1,
3, 6, and 12 months post-therapy.

- To compare pulmonary function between patients treated with SBRT and patients treated
with SR.

- To compare the adverse events and pulmonary function tests (PFTs) in each arm for
patients with low or high Charlson comorbidity index scores, including a test
interaction between Charlson comorbidity index scores (low vs high) and treatment arm.

Tertiary

- To compare the quality-adjusted survival between the SBRT and SR treatments in terms of
time to death (primary) and time until recurrence (secondary).

- To examine whether pre-operative and post-operative clinically significant deficits in
previously identified prognostic PRO domains (overall quality of life [QOL], fatigue,
anxiety, and dyspnea) are associated with shorter patient survival in this patient
population and to compare the relative effectiveness of each treatment (SBRT and SR).

- To contribute to an ACOSOG bank of normative data in order to improve short/long-term
outcomes of cancer patients by identifying patients experiencing clinically significant
deficits in patient-reported outcomes and the relationship to genetic variables.

- To explore whether blood-based biomarkers, including osteopontins, will be able to
predict which patients will be at high risk for recurrence by treatment with either
SBRT or SR. (exploratory)

- To explore whether blood-based biomarkers, including TGF-β1, will be able to predict
which patients will be at high risk for pulmonary complications by treatment with
either SBRT or SR. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to planned
brachytherapy (yes vs no) and ECOG performance status (0 vs 1 vs 2). Patients are randomized
to 1 of 2 treatment arms.

- Arm I: Patients undergo sublobar resection comprising either a wedge resection or
anatomical segmentectomy with or without intraoperative brachytherapy* comprising an
iodine I 125 implant at the resection margin.

- Arm II: Patients undergo 3 fractions of stereotactic body radiation therapy at 2-8 days
apart.

NOTE: *Patients may receive brachytherapy at the discretion of treating physician.

Patients may undergo blood sample collection at baseline and periodically during study for
correlative studies. Tumor tissue samples may also be collected from patients who undergo
resection.

Patients complete the Lung Cancer Symptom Scale (LCSS), the Linear Analogue Self-Assessment
(LASA), and the UCDS Shortness of Breath quality-of-life questionnaires at baseline and
periodically during study and follow-up.

After completion of study treatment, patients are followed up for 30 days, every 3 months
for 2 years, every 6 months for 1 year, and then yearly for 2 years.