This clinical trial studies image-guided hypofractionated radiation therapy (RT) when given together with hypofractionated RT boost and combination chemotherapy in treating patients with stage II-III non-small cell lung cancer (NSCLC) that cannot be removed by surgery. RT uses high energy x-rays to kill tumor cells. Hypofractionated RT may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving RT together with combination chemotherapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) using hypofractionated RT in patients with stage II-III NSCLC.

SECONDARY OBJECTIVES:

I. To determine the dose-limiting toxicity, if the MTD is reached.

II. To determine the tumor local control (LC).

III. To determine the lung cancer disease specific survival (DSS).

IV. To determine the overall survival (OS).

V. To assess the transforming growth factor-beta (TGF-B), interleukin (IL)-1, and IL-6 levels as predictive biomarkers for treatment induced tissue injury.

OUTLINE: This is a dose-escalation study of image-guided hypofractionated RT.

Patients undergo image-guided hypofractionated RT over 35 minutes 5 days a week for 2 weeks followed by 5 fractions of hypofractionated RT boost. Patients also receive standard carboplatin and paclitaxel for 3 weeks.

After completion of study treatment, patients are followed up at 4-6 weeks, every 3 months for the first 2 years, and then periodically thereafter.

Inclusion Criteria:

• Histologically confirmed primary non-metastatic NSCLC; eligible histological subtypes include: squamous cell carcinoma, adenocarcinoma, squamous-adeno carcinoma, large-cell carcinoma, and non-small cell carcinoma not otherwise specified
• Clinical stage II and III NSCLC as defined by American Joint Committee on Cancer (AJCC) Cancer Staging Manual, seventh edition; acceptable imaging modalities to document nodal positivity include computed tomography (CT) chest, positron emission tomography (PET)-CT, or thoracic magnetic resonance imaging (MRI)
• For clinically stage II patients, the patient must have been evaluated by a thoracic surgeon, and deemed medically or technically inoperable, or the patient must refuse surgery
• Karnofsky performance status >= 70
• If a woman is of childbearing potential, a negative serum pregnancy test must be documented; women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) for duration of study treatment and for up to 4 weeks following the study treatment

Exclusion Criteria:

• Patients who have previously received therapeutic radiation therapy to the chest
• Active systemic, pulmonary, or pericardial infection
• Use of concurrent gemcitabine-based chemotherapy during radiotherapy
• Pregnant women, or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception for the entire study period and for up to 4 weeks after the study treatment
• Refusal to sign the informed consent
• Patients who are participating in a concurrent treatment protocol