FLARE RT for Patients With Stage IIB-IIIB Non-small Cell Lung Cancer: Personalizing Radiation Therapy Using PET/CT and SPECT/CT Imaging

PRIMARY OBJECTIVE:

I. To test the superiority of 2 year (yr) overall survival (OS) in the functional lung
avoidance and response-adaptive dose escalation (FLARE) radiation therapy (RT) patient cohort
over the 60 gray (Gy) cohort of Radiation Therapy Oncology Group (RTOG) 0617 (57% 2yr OS) for
historical control.

SECONDARY OBJECTIVE:

I. Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4 grade 2 or higher
pneumonitis incidence from FLARE RT compared to historical controls (non-inferiority test).

II. 1 yr local control, progression-free survival, and pulmonary function test decline.

III. Identification of baseline fludeoxyglucose (FDG) PET/CT and mid-treatment FDG PET/CT
imaging biomarkers for predicting patient survival.

IV. Identification of baseline perfusion SPECT/CT imaging biomarkers for predicting grade
(G)2+ pneumonitis and pulmonary function tests (PFT) decline.

V. Collection of plasma and urine samples for future correlative studies between imaging
biomarkers and cytokine biomarkers of radiation response in both tumor and normal tissue.

OUTLINE: This is a dose-escalation study of radiation therapy.

Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo
fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and
undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid
SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT
must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and
be within one month of treatment start, therefore some patients may need to repeat a baseline
PET/CT if their PET/CT is from an outside institution or > 1 month old. Patients not
responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.

After completion of study treatment, patients are followed up for 2 years.

Inclusion Criteria:

- Pathologically proven (either histologic or cytologic) diagnosis of stage IIB-IIIB
non-small cell lung cancer (NSCLC); according to American Joint Committee on Cancer
(AJCC) staging, 7th edition

- Staging workup must include: brain imaging (CT head or magnetic resonance imaging
[MRI] brain) and PET/CT

- Pleural effusions must have cytology to rule out malignant involvement unless too
small to undergo thoracentesis per radiology

- Patients must be considered unresectable or inoperable

- Patient must not have received prior radiation for this lung cancer

- Patients must be having concurrent chemotherapy

- Nodal recurrences can be treated on this protocol but prior curative surgery for lung
cancer must have been at least 6 months prior to the nodal recurrence

- Patients must have measurable or evaluable disease that is FDG avid with standardized
uptake value (SUV) > 3 on PET/CT

- Zubrod performance status 0-1

- PFTs including forced expiratory volume in 1 second (FEV1) within 26 weeks prior to
registration; for FEV1, the best value obtained pre- or post-bronchodilator must be >=
0.8 liters/second or >= 50% predicted

- Blood cell count (CBC)/differential obtained within 8 weeks prior to registration on
study

- Absolute neutrophil count (ANC) >= 1,800 cells/mm^3

- Platelets >= 100,000 cells/mm^3

- Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve
hemoglobin (Hgb) >= 10.0 g/dl is acceptable)

- Serum creatinine within normal institutional limits or creatinine clearance >= 40
ml/min

- Bilirubin must be within or below normal institutional limits

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x the
institutional upper limit of normal (IULN)

- Patient must sign study specific informed consent prior to study entry

Exclusion Criteria:

- > 10% unintentional weight loss within the past month

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the
breast, oral cavity, or cervix are all permissible

- Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields

- Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception