Randomized Study to Compare CyberKnife to Surgical Resection In Stage I Non-small Cell Lung Cancer

International Randomized Study to Compare CyberKnife® Stereotactic Radiotherapy With Surgical Resection in Stage I Non-small Cell Lung Cancer

Lung cancer remains the most frequent cause of cancer death in both men and women in the world. Surgical resection using lobectomy with mediastinal lymph node dissection or sampling has been a standard of care for operable early stage NSCLC. Several studies have reported high local control and survival using SBRT in stage I NSCLC patients. SBRT is now an accepted treatment for medically inoperable patients with stage I NSCLC and patients with operable stage I lung cancer are entered on clinical protocols. The purpose of this study is to conduct a phase III randomized study to compare CyberKnife SBRT with surgery, the current standard of care for stage I operable NSCLC.

Objectives:

Primary Goal: To compare overall survival at 3 years.

Secondary goals:

1. To compare disease specific survival at 3 years.
2. To compare 3 year progression free survival at the treated primary tumor site
3. To compare grade 3 and above acute and/or chronic toxicities.
4. To evaluate predictive value of pre and post treatment PET scan in clinical outcome.

Inclusion Criteria:

1. Histological confirmation of non-small cell cancer will be required by either biopsy or cytology. The following primary cancer types are eligible: squamous cell carcinoma, adenocarcinoma with or without BAC features, large cell carcinoma with or without neuroendocrine features, neuroendocrine carcinoma, bronchioloalveolar cell carcinoma, or non-small cell carcinoma not otherwise specified.

2. Eligible patients must have appropriate staging studies identifying them as specific subsets of the revised IASCL state IA or IB based on only one of the following combinations of TNM staging:

   T1, N0, M0 or T2 (<=4 cm), N0, M0

3. A PET/CT scan is required. Patients with hilar or mediastinal lymph nodes with short axis diameter < 1 cm and no abnormal hilar or mediastinal uptake on PET will be considered N0. Patients with > 1 cm short axis diameter of 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. Solitary pulmonary lesions <4 mm will not be considered significant.

4. The patients must be considered a reasonable candidate for surgical resection of the primary tumor. Standard justification for deeming a patient medically operable based on pulmonary function for surgical resection of NSCLC may include any of the following: Baseline FEV1 > 40% predicted, post-operative predicted FEV1 > 30% predicted, diffusion capacity > 40% predicted, absent baseline hypoxemia and/or hypercapnia, exercise oxygen consumption > 50% predicted, absent severe pulmonary hypertension, absent severe cerebral, cardiac, or peripheral vascular disease, and absent severe chronic heart disease.

5. Patients must be ≥ 18 years of age.

6. The patient's Zubrod performance status must be Zubrod 0-2.

7. Mandatory staging studies: Must be done within 8 weeks prior to study entry

8. Patients must sign a study-specific consent form.

9. Patients (men and women) of child bearing potential should use an effective (for them) method of birth control throughout their participation in this study.

Exclusion Criteria:

1. Patients with primary tumors > 4 cm;
2. Patients with well-differentiated neuroendocrine carcinoma (carcinoid tumor)
3. Direct evidence of regional or distant metastases after appropriate staging studies, or synchronous primary or prior malignancy in the past 5 years other than nonmelanomatous skin cancer or in situ cancer;
4. Previous lung or mediastinal radiotherapy;
5. Plans for the patient to receive other concomitant local therapy (including standard fractionated radiotherapy and surgery) while on this protocol except at disease progression;
6. Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus;
7. Cannot achieve acceptable SRT planning to meet minimal requirement of target coverage and dose-volume constraints of critical structures (see RT techniques).