Surgery Versus Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The development of stereotactic body radiation therapy (SBRT) for the treatment of stage I non-small cell lung cancer (NSCLC) has inspired a close partnership between thoracic surgery and radiation oncology. In this study, patients with stage I NSCLC will be screened prior to treatment and will be consented after their treatment plan has been determined. Prospectively collected patient-reported outcomes (PROs) will be collected for 3 years, as will outcomes data.

Official Title
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Comparing the Effectiveness of Surgery Versus Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer (SORT)

Conditions
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Non Small Cell Lung Cancer, Non-small Cell Lung Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical stage I NSCLC (T1 or T2a, N0, M0) by CT performed within 90 days of screening. PET/CT is required within 90 days of screening except under circumstances where the clinical picture suggests, or biopsy confirms, a low-grade adenocarcinoma. Biopsy is strongly encouraged. In the event biopsy is not performed, rationale must be provided for performing empiric treatment. Patients with hilar or mediastinal lymph nodes ≤ 1 cm and no abnormal hilar or mediastinal uptake on PET will be considered N0. Pre-treatment mediastinal lymph node sampling by any technique is allowed but not required. Patients with > 1 cm hilar or mediastinal lymph nodes on CT or abnormal PET (including suspicious but nondiagnostic uptake) are be eligible only if directed tissue biopsies of all abnormally identified areas are negative for cancer. First primary NSCLC on the ipsilateral side. At least 18 years of age. Clinically eligible for either treatment (surgical resection or SBRT). Because this is a pragmatic study and treatment decisions are at the discretion of the treating physicians and their patients, patients must be eligible for either treatment. To be considered eligible for either treatment, patients must have: ECOG performance status ≤ 2 No home oxygen use FEV1 and DLCO ≥ 40% predicted No symptomatic congestive heart failure as documented by NYHA I-II functional classification Been deemed operable by a thoracic surgeon, per clinical visit or review of the medical record and as documented by e-mail, tumor board, study meetings, or other acceptable source documentation. In addition to operability, the surgeon must define what anticipated surgical approach and procedure would be undertaken. Been deemed treatable by a radiation oncologist with 10 or fewer fractions of SBRT, per clinical visit or review of the medical record and as documented by e-mail, tumor board, study meetings, or other acceptable source documentation. In addition to suitability for SBRT, the radiation oncologist must define which dose and fractionation would be undertaken. Ability to understand and willingness to sign an IRB-approved written informed consent document. Agrees to receive treatment for clinical stage I NSCLC (either surgical resection or SBRT). Exclusion Criteria: Prior or concurrent malignancies, unless the natural history of the prior or concurrent malignancy does not have the potential to interfere with the interpretation of the results of the study. Clinically diagnosed or biopsy proven low-grade neuroendocrine carcinoma (carcinoid). Prior thoracic radiation therapy that would overlap with the lung cancer being treated on study. Previous chemotherapy, radiotherapy, or surgical resection specifically for the lung cancer being treated on study. Prior lung resection on the ipsilateral side positive for malignancy. Patients with central tumors requiring a sleeve lobectomy or pneumonectomy. Ultra-central lesions (defined as a lesion that directly contacts or overlaps the trachea, main bronchus, esophagus, or pulmonary vessels). Concurrent enrollment in a therapeutic trial for the index cancer. Synchronous primary lung cancer. Uncontrolled or symptomatic psychiatric condition.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Surgery<br>Participants will have standard of care lobectomy/segmentectomy/wedge resection. Decision for treatment will be made at the discretion of the treating physician. PROMIS instruments include 8 domains and will be completed prior to treatment, 1 month post-treatment, 6 months post-treatment, 12 months post-treatment, 24 months post-treatment, and 36 months post-treatment Bank 2.0 - Physical Function Bank v1.1 - Pain Interference Bank v1.0 - Fatigue Bank v1.0 - Depression Bank v1.0 - Anxiety Bank v1.0 - Dyspnea Severity Bank v2.0 - Ability to Participate in Social Roles and Activities Bank v2.0 - Cognitive Function | |
| Stereotactic body radiotherapy (SBRT)<br>Participants will have standard of care 1-10 fractions of radiation therapy. Decision for treatment will be made at the discretion of the treating physician. PROMIS instruments include 8 domains and will be completed prior to treatment, 1 month post-treatment, 6 months post-treatment, 12 months post-treatment, 24 months post-treatment, and 36 months post-treatment Bank v2.0 - Physical Function Bank v1.1 - Pain Interference Bank v1.0 - Fatigue Bank v1.0 - Depression Bank v1.0 - Anxiety Bank v1.0 - Dyspnea Severity Bank v2.0 - Ability to Participate in Social Roles and Activities Bank v2.0 - Cognitive Function | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) | DFS is defined as time from the date of treatment to date of disease recurrence or death, whichever occurs earlier. | Through 36 months post-treatment (estimated to be 36 months and 1 week) | 
| Change in patient-reported outcomes as measured by the PROMIS Bank survey | Surveys will occur at baseline, 1 month post-treatment, 6 months post-treatment, 12 months post-treatment, 24 months post-treatment, and 36 months post-treatment The PROMIS scores will be compared across the 8 pre-specified domains: Cancer Bank v1.1 - Physical Function Cancer Bank v1.1 - Pain Interference Cancer Bank v1.0 - Fatigue Cancer Bank v1.0 - Depression Cancer Bank v1.0 - Anxiety Bank v1.0 - Dyspnea Severity Bank v2.0 - Ability to Participate in Social Roles and Activities Bank v2.0 - Cognitive Function PROMIS is scored 1-100 and normalizes to the population mean of 50 with each 10 being a standard deviation. A higher score indicates a worse patient-reported outcome. | From baseline through 36 months post-treatment (estimated to be 36 months and 1 week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer-specific survival (CSS) | Cancer-specific survival (CSS) is defined as time from the date of treatment to date of cancer-related death. The alive patients without any signs or symptoms of that cancer are censored at the last follow-up. | Through 36 months post-treatment (estimated to be 36 months and 1 week) | 
| Overall survival (OS) | Overall survival (OS) is defined as time from the date of treatment to date of death. The alive patients are censored at the last follow-up. | Through 36 months post-treatment (estimated to be 36 months and 1 week) | 
| Treated-related mortality |  | At 30 days (estimated to be 1 month and 1 week) | 
| Number of post-treatment events (grade 3 and above) | Post-treatment grade 3-5 events measured via CTCAE version 5.0 | Through 36 months post-treatment (estimated to be 36 months and 1 week) |