Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Single-fraction stereotactic body radiation therapy (SBRT); Multiple-fraction stereotactic body radiation therapy (SBRT)
Intervention description: 34 Gy in 1 fraction to the prescription line at the edge of the planning target volume (PTV). The maximum dose must exist within the PTV, and the prescription isodose surface must be ≥ 60% and < 90% of the maximum dose. 99% of the PTV must receive a minimum of 90% of the prescription dose. The maximum dose to any point ≥ 2 cm away from the PTV in any direction must be at least < 50% of the prescription dose. The percent of the lungs (excluding PTV) receiving 20 Gy or more must be < 10%.; 48 Gy in four 12 Gy fractions to the prescription line at the edge of the planning target volume (PTV). Treatments are given on 4 consecutive calendar days, but at least 18 hours apart. The maximum dose must exist within the PTV, and the prescription isodose surface must be ≥ 60% and < 90% of the maximum dose. 99% of the PTV must receive a minimum of 90% of the prescription dose. The maximum dose to any point ≥ 2 cm away from the PTV in any direction must be at least < 50% of the prescription dose. The percent of the lungs (excluding PTV) receiving 20 Gy or more must be < 10%.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 94.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage I non-small cell lung cancer; squamous cell lung cancer; adenocarcinoma of the lung; large cell lung cancer

Summary:

      RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized
      radiation therapy that delivers a high dose of radiation directly to the tumor may kill more
      tumor cells and cause less damage to normal tissue. It is not yet known which regimen of
      stereotactic body radiation therapy is more effective in treating patients with non-small
      cell lung cancer.

      PURPOSE: This randomized phase II trial is studying the side effects of two radiation therapy
      regimens and to see how well they work in treating patients with stage I non-small cell lung
      cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histological confirmation (by biopsy or cytology) of non-small cell lung cancer
             (NSCLC) prior to treatment; the following primary cancer types are eligible: squamous
             cell carcinoma, adenocarcinoma, large cell carcinoma, large cell neuroendocrine, or
             non-small cell carcinoma not otherwise specified; Note: although bronchioloalveolar
             cell carcinoma is a subtype of NSCLC, patients with the pure type of this malignancy
             are excluded from this study because the spread of this cancer between adjacent
             airways is difficult to target on computed tomography (CT).

          2. Stage T1, N0, M0 or T2 (≤ 5 cm), N0, M0, (AJCC Staging, 6th Ed.), based upon #3.

          3. Minimum diagnostic workup:

               -  History/physical examination, including weight and assessment of Zubrod
                  performance status, within 4 weeks prior to registration;

               -  Evaluation by an experienced thoracic cancer clinician (a thoracic surgeon,
                  medical oncologist, radiation oncologist, or pulmonologist) within 8 weeks prior
                  to registration;

               -  CT scan with intravenous contrast (unless medically contraindicated) within 8
                  weeks prior to registration of the entirety of both lungs and the mediastinum,
                  liver, and adrenal glands; the primary tumor dimension will be measured on the
                  CT. Positron emission tomography (PET) evaluation of the liver and adrenal glands
                  also is permitted. In addition, if the enrolling institution has a combined
                  PET/CT scanner and both aspects are of diagnostic quality and read by a trained
                  radiologist, the PET/CT will meet the staging requirements for both CT and PET.

               -  Whole body or wide field FDG-PET within 8 weeks prior to registration with
                  adequate visualization of the primary tumor and draining lymph node basins in the
                  hilar and mediastinal regions and adrenal glands; in the event of lung
                  consolidation, atelectasis, inflammation or other confounding features, PET-based
                  imaging correlated with CT imaging will establish the maximal tumor dimensions.
                  Standardized uptake value (SUV) must be measured on PET. To be included in this
                  analysis, the patient's PET studies must be performed with a dedicated bismuth
                  germanium oxide (BGO), lutetium oxyorthosilicate (LSO), or gadolinium
                  oxyorthosilicate (GSO) PET or PET/CT scanner. PET scanners with sodium iodide
                  (Nal) detectors are not acceptable. If the baseline PET study is performed at the
                  treating institution (or its affiliated PET facility), it is recommended that the
                  reassessment PET scans be performed at the same site.

               -  Pulmonary function tests (PFTs): Routine spirometry, lung volumes, and diffusion
                  capacity, within 8 weeks prior to registration; arterial blood gases are
                  optional. Note: All patients enrolled in this study must have these pulmonary
                  assessments whether or not the reason for their medical inoperability is
                  pulmonary based, since the objective assessment of pulmonary factors is a
                  component of the outcomes assessment for this study.

          4. Patients with hilar or mediastinal lymph nodes ≤ 1cm and no abnormal hilar or
             mediastinal uptake on PET will be considered N0. Patients with > 1 cm hilar or
             mediastinal lymph nodes on CT or abnormal PET (including suspicious but non-diagnostic
             uptake) may still be eligible if directed tissue biopsy of all abnormally identified
             areas are negative for cancer.

          5. The patient's resectable NSCLC must be considered medically inoperable by an
             experienced thoracic cancer clinician (a thoracic surgeon, medical oncologist,
             radiation oncologist, or pulmonologist) or a standard lobectomy and mediastinal lymph
             node dissection/sampling procedure. The patient may have underlying physiological
             medical problems that would prohibit a surgery due to a low probability of tolerating
             general anesthesia, the operation, the postoperative recovery period, or the removal
             of adjacent functioning lung. These types of patients with severe underlying health
             problems are deemed "medically inoperable." Standard justification for deeming a
             patient medically inoperable based on pulmonary function for surgical resection of
             NSCLC may include any of the following:

               -  Baseline forced expiratory volume in one second (FEV1) < 40% predicted;

               -  Postoperative FEV1 < 30% predicted;

               -  Severely reduced diffusion capacity;

               -  Baseline hypoxemia and/or hypercapnia;

               -  Exercise oxygen consumption < 50% predicted;

               -  Severe pulmonary hypertension;

               -  Diabetes mellitus with severe end organ damage;

               -  Severe cerebral, cardiac, or peripheral vascular disease;

               -  Severe chronic heart disease. If the patient has resectable disease but declines
                  surgery after consulting with a thoracic surgeon, he/she will be considered
                  eligible.

          6. The patient must have measurable disease.

          7. Zubrod Performance Status 0-2;

          8. Age ≥ 18;

          9. Negative serum or urine pregnancy test within 72 hours prior to registration for women
             of childbearing potential;

         10. Women of childbearing potential and male participants must agree to use a medically
             effective means of birth control, such as condom/diaphragm and spermicidal foam,
             intrauterine device (IUD), or prescription birth control pills, throughout their
             participation in the treatment phase of the study

         11. The patient must provide study specific informed consent prior to study entry.

        Exclusion Criteria:

          1. Patients with T2 primary tumors > 5 cm or involving the central plural and/or
             structures of the mediastinum;

          2. The primary tumor of any T-stage within or touching the zone of the proximal bronchial
             tree, defined as a volume 2 cm in all directions around the proximal bronchial tree
             (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius
             bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe
             bronchi);

          3. Direct evidence of regional or distant metastases after appropriate staging studies,
             or synchronous primary malignancy or prior malignancy in the past 2 years except for
             invasive malignancy that has been treated definitively and the patient remains disease
             free for > 3 years with life expectancy of > 3 years or carcinoma in situ or early
             stage skin cancers that have been treated definitively;

          4. Previous radiotherapy to the lung or mediastinum;

          5. Previous chemotherapy for this lung or mediastinum tumor; chemotherapy for another
             invasive malignancy is permitted if it has been treated definitively and the patient
             has remained disease free for > 3 years.

          6. Previous surgery for this lung or mediastinum tumor;

          7. Plans for the patient to receive other concomitant antineoplastic therapy (including
             standard fractionated radiotherapy, chemotherapy, biological therapy, vaccine therapy,
             and surgery) while on this protocol except at disease progression;

          8. Patients with active systemic, pulmonary, or pericardial infection;

          9. Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo
             or fetus.