Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer

• Phase I: Maximally tolerated dose (MTD) of stereotactic boost radiotherapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Determination of the MTD and dose-limiting toxicities of a stereotactic boost to chemoradiotherapy for stage II/III non-small cell lung cancer
• Phase II: Two-year local control rate following stereotactic boost radiotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  Local failure is defined as biopsy-proven recurrent disease, or if a biopsy is not attainable, by increasing fludeoxyglucose (FDG)-avidity on positron emission tomography-computed tomography (PET-CT) on 2 consecutive scans at least 1 month apart

• Risk of grade 2-3 radiation pneumonitis [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  To evaluate the risk of radiation pneumonitis following stereotactic boost radiotherapy
• Overall survival rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To determine the 2-year overall survival following stereotactic boost radiotherapy
• Disease-free survival rate [ Time Frame: 2 year ] [ Designated as safety issue: No ]
  To determine the 2-year disease-free survival
• Regional control rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To determine the 2-year regional control rate.
• Change in pulmonary function [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To characterize the change in pulmonary function tests over the first 2 years after chemoradiotherapy

In this research study the investigators are looking for the highest dose of a stereotactic radiation boost that can be given safely. Because stereotactic radiation is so precise, the investigators are testing whether it can be used to increase the dose to the primary tumor without significantly increasing the side effects the participant experiences; the goal is to improve the likelihood of killing the tumor.

• Participants will undergo a radiation treatment simulation, or "mapping session" 7-14 days prior to starting radiation treatment. This is part of standard radiation treatment.
• Participants will start radiation to the primary tumor site and to the lymph nodes and chemotherapy in the same week. The treatment will be identical to standard chemotherapy and radiation treatment until the 5th week. During the fifth week, participants will undergo another radiation mapping session to prepare for the stereotactic boost. After that, the radiation treatments to the lymph nodes will continue but the radiation treatment to the primary cancer site will stop until the last week (week 7). During week 7, participants will receive 2 doses of stereotactic radiotherapy to the site of the primary tumor instead of the lower doses of radiotherapy that they were treated with up to that point.
• Participants will be seen by the radiation oncologist at least once every week during treatment.
• After the final dose of radiation treatment, all follow-up visits and tests are performed in accordance with standard cancer care. Participants will see the radiation oncologist, with or without the medical oncologist at the following time intervals: 1 week after treatment ends, 1 month after treatment ends, 2 months after treatment ends, and then every 3 months for two years.

• Non-small Cell Lung Cancer
• Lung Cancer
• NSCLC

Inclusion Criteria:

• Histologically or cytologically confirmed stage II or stage III non-small cell lung cancer, or stage IV non-small cell lung cancer that will be treated with curative intent
• Evaluated by a surgeon and deemed inoperable
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 10mm or greater with chest CT scan.
• No active malignancy within the past 5 years, except for non-melanoma skin cancers or carcinoma in situ of the cervix
• 18 years or older
• Life expectancy of greater then 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Normal organ and marrow function as outlined in the protocol
• Forced expiratory volume (FEV1) of 1 L or greater OR 50% or greater of predicted

Exclusion Criteria:

• Primary tumor size greater then 6cm
• Prior history of thoracic radiotherapy
• May not be receiving any other study agents
• History of pulmonary fibrosis
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin or etoposide
• Primary tumor < 1.5 cm beyond hilar lymphadenopathy (if any) and 1.5 cm from proximal bronchial tree, defined as the trachea, right and left mainstem bronchus, and lobar bronchi until the 1st lobar segment
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breast feeding women
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
• Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy
• Patients who are planned to receive the following medication: granulocyte colony-stimulating factor (G-CSF), bevacizumab, cetuximab, cyclosporine, anti-tumor necrosis factor agents, amifostine.