Stereotactic Body Radiation Therapy for Un-biopsied Early- Stage Non Small Cell Lung Cancer

This purpose of this study is to learn about the good and bad effects of treating early stage
lung cancer without having a biopsy of the tumor. Participants in this research will receive
a type of radiation treatment called Stereotactic Body Radiation Therapy (SBRT). This type of
radiation is targeted directly at the tumor so that damage to surrounding normal tissue can
be avoided. SBRT is often used in treating patients with biopsy proven early stage lung
cancer who cannot have surgery for medical reasons. In this study, SBRT is considered
experimental because the tumor has not been biopsied. SBRT for early-stage NSCLC has
consistently proven to provide excellent local control and improved overall survival in the
medically inoperable patient. The constancy of this finding over a variety of dose schedules
confirms the robustness of SBRT. This study will utilize 54 Gy in 3 fractions delivered twice
weekly for peripheral lesions. In order to respect the increased risk of adverse events our
dose for centrally located lesions will be reduced to 50 Gy in 5 fractions delivered twice
weekly and for chest wall or rib adjacent lesions will be 60 Gy in 5 fractions. These doses
are consistent with Radiation Therapy Oncology Group (RTOG) 0236 for peripheral lesions and
RTOG 0813 for central lesions and are both ≥100 Gy Biological Effective Dose (BED) as
previously discussed . The investigators of this study routinely prescribe 60 Gy in 5
fractions for rib adjacent lesions.

The primary objective is to assess acute and chronic toxicities associated with SBRT of
unbiopsied early-stage NSCLC.

Secondary objectives include:

To evaluate the disease specific outcomes of local control, lobar failure-free survival,
regional/nodal failure-free survival, distant metastasis-free survival, disease-free
survival, cause-specific survival, and overall survival associated with SBRT of unbiopsied
early-stage NSCLC patients.

To evaluate Pulmonary Function Test (PFT) changes over time following SBRT of unbiopsied
early-stage NSCLC patients.

To evaluate the patient's overall quality of life before and after treatment with SBRT of
unbiopsied early-stage NSCLC patients.

Inclusion Criteria

- • Presence of parenchymal lung nodule, without pathological diagnosis, highly
suspicious for NSCLC as defined by at least one of the criteria below. Validated
clinical prediction model estimates probability of malignancy is ≥ 85% or

- Multidisciplinary tumor board determines patient's history, clinical findings,
and radiographic findings are consistent with high probability of malignancy.

Medically-inoperable patient due to one of the criteria below

- Poor pulmonary function for resection including baseline Forced Expiratory Volume in 1
second (FEV1), FEV1 <50%, post-operative predicted FEV1<30% predicted, diffusion
capacity <50%, baseline hypoxemia and/or hypercapnia. Patients with severe obstructive
or restrictive lung disease will be eligible for inclusion.

- Pulmonary hypertension

- Cerebral, cardiac, or peripheral vascular disease

- Chronic heart disease

- Diabetes mellitus with end organ damage

- Age ≥75

- Patient declines surgery

Absence of pathological diagnosis due to one of the criteria below

- High risk of complications from transbronchial or transthoracic biopsy

- Biopsy was performed or attempted but with complications requiring abortion of
procedure

- Biopsy was performed and non-diagnostic for malignancy but without other diagnosis to
explain the clinical and radiographic findings

- Patient declines biopsy Stage T1-3, N0, M0 (AJCC Staging, 7th Ed.) based upon the
following diagnostic workup

- History/Physical examination by an experienced thoracic cancer clinician (thoracic
surgeon, interventional pulmonologist, medical oncologist, or radiation oncologist)
within 4 weeks prior to registration

- Diagnostic imaging (CT and/or PET/CT) Serial computed tomography and/or positron
emission tomography imaging clinically consistent with lung malignancy.

- CT scan with contrast (unless medically contraindicated) within 6 weeks of
registration. The tumor dimensions will be measured on CT with greatest dimension
≤5cm.

- Whole body Positron Emission Tomography / Computerized Tomography (PET/CT) within 12
weeks of registration. Standard uptake value (SUV) must be available but no minimum
SUV is required for inclusion.

No clinical or radiographic evidence of nodal disease or distant metastases No previous
local therapy such as external beam radiotherapy, lobectomy, or sublobar resection.

Women of child-bearing potential must undergo pregnancy testing prior to enrollment on
study. Should a woman become pregnant or suspect she is pregnant while participating in
this study, she should inform her treating physician immediately.

- A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 12 consecutive months.

Patients with prior history of malignancy are permitted registration but must not be
undergoing active cytotoxic or biologically-targeted therapy, must be disease-free from any
malignancy for the previous three years, and must not have any history of brain metastases
with the following exceptions:

- Patients with history of basal cell carcinoma and/or squamous cell carcinoma may be
permitted access within 3 years of being disease-free and is up to the discretion of
the treating physicians

- Patients with any prior history of lung cancer may not participate in this study.

Age ≥ 18 years. Ability to understand and willingness to sign a written informed consent
document.

Exclusion Criteria:

- • Prior history of lung cancer.

- Prior local therapy (surgery or radiotherapy) for the current,
clinically-diagnosed NSCLC.

- Patients receiving any other investigational agents.

- Patients with a known history of malignancy with a disease-free interval <3 years
prior to enrollment or a history of brain metastases

- Uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection, severely symptomatic congestive heart failure, cardiac
arrhythmia, or psychiatric illness/social situations that could limit compliance
with study requirements.

- Patients who are currently pregnant or nursing due to the potential for
congenital abnormalities and potential harm to nursing infants.

- Patients enrolled on a competing investigational study.