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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)

Phase 3
18 Years
Open (Enrolling)
Lung Cancer

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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)



- 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).


- 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.


- 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

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

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.

Inclusion Criteria


- Lung nodule suspicious for non-small cell lung cancer (NSCLC)

- Biopsy confirmation is strongly recommended but not required; if biopsy is
attempted and non-diagnostic, if the patient refuses biopsy, or if the risk of
biopsy is considered too high, patients may be enrolled if the mass is
suspicious for NSCLC based on two or more of the following criteria:

- Positive smoking history

- Absence of benign calcifications within suspicious nodule

- Activity on PET greater than normal tissue

- Evidence of growth compared to previous imaging

- Presence of spiculation

- Tumor ≤ 4 cm maximum diameter, clinical stage IA or selected IB (i.e., with visceral
pleural involvement) by PET/CT scan of the chest and upper abdomen performed within
60 days prior to registration

- All clinically suspicious mediastinal N1, N2, or N3 lymph nodes (> 1 cm short-axis
dimension on CT scan and/or positive on PET scan) confirmed negative for involvement
with NSCLC by one of the following methods: mediastinoscopy, anterior mediastinotomy,
endoscopic and/or endobronchial ultrasonography (EUS/EBUS)-guided needle aspiration,
CT-guided, or video-assisted thoracoscopic or open lymph node biopsy

- Tumor verified by a thoracic surgeon to be in a location that will permit sublobar

- Tumor located peripherally within the lung, defined as not touching any surface
within 2 cm of the proximal bronchial tree in all directions

- Patients with non-peripheral (central) tumors are NOT eligible

- No evidence of distant metastases


- ECOG performance status (PS) 0, 1, or 2

- Patient at high-risk for surgery by meeting a minimum of one major criteria or two
minor criteria as described below:

- Major criteria

- FEV1 ≤ 50% predicted

- DLCO ≤ 50% predicted

- Minor criteria

- Age ≥ 75 years

- FEV1 51-60% predicted

- DLCO 51-60% predicted

- Pulmonary hypertension (defined as a pulmonary artery systolic pressure
greater than 40 mm Hg) as estimated by echocardiography or right heart

- Poor left ventricular function (defined as an ejection fraction of 40% or

- Resting or exercise arterial pO2 ≤ 55 mm Hg or SpO2 ≤ 88%

- pCO2 > 45 mm Hg

- Modified Medical Research Council (MMRC) Dyspnea Scale ≥ 3

- Not pregnant or nursing

- Negative urine or serum pregnancy test

- Fertile patients must use effective contraception

- No prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration
(except non-melanoma skin cancer, in-situ cancers).


- No prior intra-thoracic radiotherapy

- Prior radiotherapy as part of treatment for head and neck, breast, or other
non-thoracic cancer is permitted

- Prior chemotherapy or surgical resection for the lung cancer being treated on this
protocol is NOT permitted

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

5-year OS rate

Safety Issue:


Principal Investigator

Hiran C. Fernando, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Boston Medical Center



Study ID:




Start Date:

May 2011

Completion Date:

Related Keywords:

  • Lung Cancer
  • stage IA non-small cell lung cancer
  • stage IB non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



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