SRS Study in Patients With Non-Small Cell Lung Cancer

Stereotactic body radiotherapy is designed to provide an image guided, more focused, dose
escalated radiotherapy over a shorter time frame (1 week rather than 7 weeks) than
conventional radiation therapy. The goal of SBRT is to improve tumor control while reducing
the side effects.

If you are found to be eligible to take part in this study, you will receive daily SBRT for
4 days in a row over a 45 minute time period. During the treatment, you will lie still on a
table for about 45 minutes per day in the same position. The machine will deliver the dose
according to the plan developed by the doctor and the dose will be controlled by a computer.

During the treatment, you will be seen by a doctor and research nurse once a week to
evaluate possible side effects. A physical exam and a medical history will be done at these
visits.

You will be taken off study early if the disease gets worse or intolerable side effects
occur.

You will have a follow-up visit 6 weeks after completion of radiotherapy to check for side
effects. You will continue to have follow-up visits that will decrease in frequency over
time. You will have imaging tests (chest CT or positron emission computed tomography (PET)
scan) and routine blood tests (about 2 teaspoons) at these follow-up visits.

This is an investigational study. SBRT is FDA approved for the treatment of lung cancer.
About 138 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Cohort 1: Histologically or cytologically documented NSCLC.

2. Cohort 1: Inoperable stage IA (T1N0MO), IB (T2N0MO) and selective stage II (T3 due to
chest wall involvement, N0M0). Patient refuses surgery is eligible. Secondary lung
cancer is eligible if primary cancers have been cured or stable with life expectance
longer than 2 years. If primary cancer is lung cancer, patient needs to be lung
cancer free for more than 5 year for same histology or more than 2 years for
different histology.

3. Cohort 1: 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 on-diagnostic
uptake) may still be eligible if directed tissue biopsy of all abnormally identified
areas are negative for cancer. Patient who received induction chemotherapy or other
systemic therapy are eligible.

4. Cohort 1: Performance score Karnofsky performance status (KPS) 60-100.

5. Cohort 2: Histologically or cytologically documented NSCLC.

6. Cohort 2: Inoperable isolated lung parenchyma recurrent NSCLC without evidence of
lymph node or mediastinal involvement (clinical stage T1-2, chest wall involvement
T3, N0M0) after surgical resection or definitive radiotherapy with/without
chemotherapy. Recurrent disease is defined as NSCLC with same histology, same lobe
that recurs within 5 years after initial definitive therapy. Patient refuses surgery
is also eligible. Patient received systemic therapy is eligible.

7. Cohort 2: Performance score KPS 60-100.

8. Cohort 3: Histologically or cytologically documented NSCLC.

9. Cohort 3: Previous history of NSCLC that has been cured or stable. New development of
inoperable isolated lung parenchyma lesion that has been documented histologically or
cytologically as NSCLC without evidence of lymph node or mediastinal involvement
(clinical stage T1-2, chest wall involvement T3, N0M0) and not eligible for cohort 1
and recurrent disease as defined in Cohort 2. This includes NSCLC happens within 5
years after initial definitive treatment of prior NSCLC, and/or is located in the
different lobes.

10. (cont.) Cohort 3: Possible stage IV disease is eligible as long as it meets the
criteria above since there is no definitive way to confirm it. Patient refuses
surgery is eligible. Patient received systemic therapy is eligible.

11. Cohort 3: Performance score KPS 60-100.

Exclusion Criteria:

1. Any tumor involving main bronchus, major vessels, heart, esophagus, trachea, carina,
spinal cord.

2. Any tumor that causes collapsed lobe of lung.

3. Any tumor with malignant pleural effusion.

4. Direct evidence of hilar, mediastinal lymph node or distant metastasis based on
staging work up.

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