Sublobar Resection or Stereotactic Ablative Radiotherapy in Treating Patients with Stage I Non-small Cell Lung Cancer

This phase III trial compares sublobar resection (surgery to remove a portion of a lobe) and stereotactic ablative radiotherapy to see how well they work in treating patients with stage I non-small cell lung cancer. Sublobar resection is a less invasive type of surgery for non-small cell lung cancer and may have fewer side effects and improve recovery. Stereotactic radiosurgery, also known as stereotactic ablation radiation therapy, is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. It is not yet known whether sublobar resection is more effective than stereotactic ablative radiotherapy in treating patients with non-small cell lung cancer.

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status (PS) 0, 1, or 2
• Radiographic findings consistent with non-small cell lung cancer, including lesions with ground glass opacities with a solid component of 50% or greater; those with ground glass opacities and < 50% solid component will be excluded
• The primary tumor in the lung must be biopsy confirmed non-small cell lung cancer within 180 days of randomization
• Tumor =< 4 cm maximum diameter, including clinical stage IA and selected IB by positron emission therapy (PET)/computed tomography (CT) scan of the chest and upper abdomen performed within 90 days prior to randomization
• 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 ultrasound (EUS)/endobronchial ultrasound (EBUS) guided needle aspiration, CT-guided, video-assisted thoracoscopic or open lymph node biopsy within 180 days of randomization
• Tumor verified by a thoracic surgeon to be in a location that will permit sublobar resection
• Tumor located peripherally within the lung; NOTE: peripheral is 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
• Availability of pulmonary function tests (PFTs – spirometry, diffusing capacity of the lungs for carbon monoxide [DLCO], +/- arterial blood gases) within 90 days prior to registration; patients with tracheotomy, etc, who are physically unable to perform PFTs are potentially still eligible if a study credentialed thoracic surgeon documents that the patient’s health characteristics would otherwise have been acceptable for eligibility as a high risk but nonetheless operable patient (in particular be eligible for sublobar resection)
• Patient at high-risk for surgery by meeting a minimum of one major criteria or two minor criteria as described below: * Major criteria ** Forced expiratory volume in 1 second (FEV1) =< 50% predicted ** DLCO =< 50% predicted * Minor criteria ** 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 catheterization ** Poor left ventricular function (defined as an ejection fraction of 40% or less) ** Resting or exercise arterial partial pressure of oxygen (pO2) =< 55 mm Hg or peripheral capillary oxygen saturation (SpO2) =< 88% ** Partial pressure of carbon dioxide (pCO2) > 45 mm Hg ** Modified medical research council (MMRC) dyspnea scale >= 3 ** Study credentialed thoracic surgeon believes the patient is potentially operable but that a lobectomy or pneumonectomy would be poorly tolerated by the patient for tangible or intangible reasons
• No prior intra-thoracic radiation therapy; NOTE: previous radiotherapy as part of treatment for head and neck, breast, or other non-thoracic cancer is permitted so long as possible radiation fields would not overlap; previous chemotherapy or surgical resection specifically for the lung cancer being treated on this protocol is NOT permitted; no prior lung resection on the ipsilateral side
• Non-pregnant and non-lactating; women of child-bearing potential must have a negative urine or serum pregnancy test prior to registration; peri-menopausal women must be amenorrheic >= 12 months prior to registration to be considered not of childbearing potential
• No prior invasive malignancy, unless disease-free for >= 3 years prior to registration (exceptions: non-melanoma skin cancer, in-situ cancers)
• Ability to understand and the willingness to sign a written informed consent

PRIMARY OBJECTIVES:

I. To test the hypothesis that overall survival rate in high risk operable patients with stage I non-small cell lung cancer (NSCLC) is greater in patients who undergo stereotactic ablative radiotherapy (SAbR) as compared to standard sublobar resection (SR).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo sublobar resection.

ARM II: Patients undergo stereotactic ablative radiotherapy over approximately 60 minutes for 3 fractions within 16 days.

After completion of study treatment, patients are followed up at 4 weeks, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 months.

Lead Organization
UT Southwestern / Simmons Cancer Center-Dallas

Principal Investigator
Robert D. Timmerman