Veterans Affairs Lung Cancer Or Stereotactic Radiotherapy

The standard of care for stage I non-small cell lung cancer has historically been surgical
resection in patients who are medically fit to tolerate an operation. Recent data now
suggests that stereotactic radiotherapy may be a suitable alternative. This includes the
results from a pooled analysis of two incomplete phase III studies that reported a 15%
overall survival advantage with stereotactic radiotherapy at 3 years. While these data are
promising, the median follow-up period was short, the results underpowered, and the findings
were in contradiction to multiple retrospective studies that demonstrate the outcomes with
surgery are likely equal or superior. Therefore, the herein trial aims to evaluate these two
treatments in a prospective randomized fashion with a goal to compare the overall survival
beyond 5 years. It has been designed to enroll patients who have a long life-expectancy, and
are fit enough to tolerate an anatomic pulmonary resection with intraoperative lymph node
sampling.

This study is designed to open at Veterans Affairs medical centers with expertise in both
treatments. The recruitment process includes shared decision making and multi-disciplinary
evaluations with lung cancer specialists. Mandatory evaluations before randomization include
tissue confirmation of NSCLC, staging with FDG-PET/CT, and biopsies of all hilar and/or
mediastinal lymph nodes >10mm that have a SUV >2.5. Pre-randomization elective lymph node
sampling is strongly encouraged, but not required. Following treatment, patients will be
followed for a minimum of 5 years.

Inclusion Criteria:

Inclusion Criteria for Screening

- Age 18 or older

- Any patient with a preliminary diagnosis of stage I Non-Small Cell Lung Cancer
(NSCLC), whether pathologically proven by biopsy, or highly suspicious by radiographic
imaging. [Participants will ultimately need biopsy confirmation before enrolling]

- Primary tumor size less than or equal to 5 cm by CT (may include CT images from
PET/CT)

- Karnofsky performance status greater than or equal to 70

- Participant has willingness and ability to provided informed consent for participation

Inclusion Criteria for Randomization

- Biopsy proven non-small cell lung cancer

- Participant's case reviewed at multidisciplinary conference

- Tumor size less than or equal to 5cm (measured on the most recent CT images available,
and may include PET/CT images)

- Tumor is equal to or greater than 1.0cm from the trachea, esophagus, brachial plexus,
1st bifurcation of the proximal bronchial tree, or spinal cord (measured on the most
recent CT images available, and may include PET/CT images).

- Mandatory FDG-PET/CT within 60 days of the randomization date (note: FDG-PET/CT may
need to be repeated prior to treatment if outside of this requirement)

- Mandatory pathological assessment of any lymph nodes >10mm with a SUV >2.5 seen on
FDG- PET/CT

- Mandatory biopsy of any additional concerning lesions seen on FDG-PET/CT, to make
better determination that the patient is not harboring metastatic disease or a
secondary primary malignancy.

- Pre-operative FEV1 greater than or equal to 40% of predicted value and pre-operative
DLCO greater than or equal to 40% of predicted value.

- Formally evaluated and documented by a local thoracic surgeon to be medically fit to
undergo a complete anatomic pulmonary resection (wedge resection not allowed)

- Formally evaluated and documented by a local radiation oncologist to be eligible to
receive protocol-defined stereotactic radiotherapy

- Participant willingness to be randomized

Exclusion Criteria:

Exclusion Criteria for Screening

- Previously evaluated by a local thoracic surgeon and determined to be medically
inoperable

- Pathological confirmation of nodal or distant metastasis

- Prior history of lung cancer, not including current lesion

- Prior history of thoracic surgery or lung or esophageal cancer. [prior cardiac surgery
acceptable]

- Prior history of radiotherapy to the thorax

- Prior history of an invasive malignancy within the past 5 years, whether newly
diagnosed or recurrent, excluding low-risk prostate cancer, non-melanoma skin cancers,
and in-situ cancers

- Ever diagnosed with stage IV metastatic cancer of any type

- History of scleroderma

- Positive Pregnancy test (for women <61 years of age or without prior hysterectomy)

Exclusion Criteria for Randomization

- Pathological confirmation of nodal or metastatic disease