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This study will help researchers test the safety of hypofractionated dose of radiotherapy (HySBst) at different dose levels before or after chemo-radiation for Non Small Cell Lung Cancer.

Patients are assigned to Sub-group 1 or 2 based on the primary lesion size and location. This protocol will utilize a standard 3 + 3 phase I design with three patients enrolled per cohort.

Patients will be offered the opportunity to participate in the blood specimen component of the study.

Patients will be followed up to 2 years post radiation therapy.

Sub-group 1 will receive HySBst for 1 week. Weeks 2-7 will be standard chemo-radiation therapy. Patients have the option of consolidative chemotherapy at week 12.

Sub-group 2 will receive standard chemo-radiation therapy for weeks 1-6 then receive HySBst during week 7. Patients have the option of consolidative chemotherapy at week 12.

HySBst dose escalation for each sub-group is listed below:

Optional: 4 Gy x 4 daily fractions Level 1: 5 Gy x 4 daily fractions Level 2: 5.5 Gy x 4 daily fractions Level 3: 6 Gy x 4 daily fractions

DLTs will be based on events occurring during the course of HySBst.

Chemo-Radiation Therapy is defined as:

Standard Carboplatin & Paclitaxel Doublelet Regimen with weekly Carboplatin AUC 2/week and Paclitaxel 45 mg/ m2/ week during conventionally fractionated IMRT

Image-guided IMRT to 60 Gy, 5 x per week for 6 weeks

Consolidative chemotherapy is defined as Carboplatin AUC 6 and Paclitaxel 200 mg/m2 every 21 days x 2 cycles will be given after ALL radiotherapy is delivered.

Inclusion Criteria:

• Stage II - III Non Small Cell Lung Cancer

Exclusion Criteria:

• Primary tumor directly invading into any mediastinal structures, such as the heart, major blood vessels, esophagus, trachea, and the proximal bronchial tree.
• Prior chemotherapy for NSCLC
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Severe, active co-morbidity
• Pregnancy or women of childbearing potential
• Any history of allergic reaction to paclitaxel or other taxanes, or to carboplatin
• Uncontrolled neuropathy ≥ grade 2.