CyberKnife Radiosurgical Treatment of Inoperable Early Stage Non-Small Cell Lung Cancer

The objectives of this clinical evaluation are to assess the outcomes of patients who
undergo stereotactic radiosurgery (SRS) to treat primary early stage non-small cell lung
cancer (NSCLC) in patients (comprising of two cohorts, peripheral and central) who are not
candidates for surgical resection because of high operative risks. In particular, the effect
of CyberKnife SRS on clinical response rate, local control, progression-free survival,
overall survival, dyspnea and QOL (for U.S. sites), and radiological findings over two years
after treatment will be evaluated.

Inclusion Criteria:

1. Patient must be over the age of 18 years

2. Pulmonary nodule with maximum diameter ≤ 5 cm

3. Histological confirmation of primary NSCLC

4. The following stage of NSCLC patients are eligible:

- Stage I: T1 N0 M0 or T2 N0 M0 (Tumor size ≤ 5 cm)

- Stage II: T3 N0 M0 (Chest wall invasion only, Tumor size ≤ 5 cm)

5. ECOG/Zubrod status of 0, 1 or 2

6. Thoracic surgery consultation should be obtained from a Board Certified Thoracic
surgeon who in collaboration with a radiation oncologist should determine that the
patient is not a surgical candidate.

7. In order to be considered medically inoperable, the patient must meet at least one
major criteria or a minimum of 2 minor criteria as described below:

MAJOR CRITERIA:

1. FEV1 < 50% or predicted postoperative FEV1 < 40%

2. DLCO < 50% or predicted postoperative DLCO < 40%

3. Exercise induced maximal exercise oxygen consumption M VO2 < 15 mL/kg/min

4. High-risk cardiac disease: Any one of the following:

- Poor left ventricular function (defined as an ejection fraction of <=20%)

- Unstable coronary syndromes (unstable angina or severe angina Canadian
class III or IV).

- Severe valvular disease (critical valvular stenosis),

- Recent myocardial infarction (< 1 month),

- Significant arrhythmia defined by one of the following: High-grade AV
block, Symptomatic ventricular arrhythmias in the presence of underlying
heart disease, Supraventricular arrhythmias with uncontrolled ventricular
rate

MINOR CRITERIA:

1. Age > 75

2. Pulmonary hypertension (defined as a pulmonary artery systolic pressure greater
than 40 mm Hg)

3. Oxygen requirement (using the Medicare criteria for home oxygen requirements
[i.e., room air oxygen saturation of 88% or less])

4. Resting or exercise arterial pO2 ≤ 55 mm Hg OR SpO2 ≤ 88%.

5. pCO2 > 45 mm Hg

6. Congestive heart failure (any three of the following must be documented:
dyspnea, peripheral edema, chest x-ray with interstitial edema or cardiomegaly,
rales, or congestion)

7. Moderately depressed left ventricular function (defined as an ejection fraction
of 21-40% or less)

8. Severe cerebral (with CVA or recent TIA) or severe peripheral vascular disease

9. Diabetes Mellitus with severe organ damage such as ESRD, Blindness, Vascular
disease.

10. Severe end organ damage from other causes resulting in ESRD, cirrhosis of the
liver or vascular disease

11. FEV1 51%-60% or predicted postoperative FEV1 41-50%

12. DLCO 51-60% or predicted postoperative DLCO 41-50%

13. Modified Medical Research Council Dyspnea Scale ≥ grade 3

8. Females of child-bearing age must be using a reliable form of birth control.

9. The patient must have a PET-CT scan within 8 weeks of registration.

10. The patient must provide a signed and dated written informed consent PRIOR to
registration and prior to undergoing any study-related procedures.

11. The patient must provide written authorization to allow the use and disclosure of
their protected health information.

Exclusion Criteria:

1. Excluding the primary cancer targeted for this treatment, the patient has a prior
history of cancer (within the last 5 years) or concurrent cancer other than basal
cell or squamous skin cancer.

2. Visible endobronchial lesion seen in the trachea, carina, major bronchus, lobar or
segmental bronchus on bronchoscopy or microscopic disease detected in the trachea,
carina, major bronchus, lobar or segmental bronchus.

3. The patient's weight exceeds the tolerances of the institution's imaging and
CyberKnife platform/couch.

4. The patient has received thoracic radiation therapy in the same field as the planned
treatment area in the past.

5. The patient has completed chemotherapy within less than 30 days of treatment.

6. T2: Tumor size > 5 cm, T3 tumors (except T3 by virtue of chest wall invasion and ≤ 5
cm), T4 tumors. Presence of N1, N2 or N3 disease per previously described criteria
would be excluded.

7. Pancoast tumors would be excluded.

8. Current distant metastatic disease (M1) (preferably biopsy proven).

9. The patient is a female with child-bearing potential who refuses to take a pregnancy
test prior to treatment.

10. The patient is pregnant or a female who is nursing an infant.

11. The patient is planning on undergoing systemic therapy within 2 weeks after the last
fraction of radiation

12. The patient has an active systemic or pulmonary infection.