This research study is examining the benefit of a novel radiation planning approach on the likelihood of developing severe esophagitis (irritation and inflammation of the esophagus) during the course of radiation therapy with concurrent chemotherapy which is associated with very painful and difficult swallowing.

This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.

The U.S. Food and Drug Administration (FDA) has approved radiation with chemotherapy as a treatment option for your disease.

Currently, there are no established rules to avoid esophagitis in the treatment of lung cancer with radiation therapy. We have developed an IMRT-based technique, termed CEST, to reduce the radiation dose to the part of the esophagus that is located opposite to the tumor. The reason behind this approach is that a lower radiation dose causes less esophagus inflammation and irritation and, therefore, may preserve the swallowing function of the esophagus better. In our clinical experience, reducing the radiation dose to part of the esophagus in this fashion has shown the potential to dramatically decrease the likelihood of severe esophagitis in many though not all people with lung cancer. We therefore wish to analyze this technique further.

There is no firm data to indicate that different chemotherapy regimens given at the same time of radiation therapy result in different rates of esophagitis. The Investigators will, therefore, allow any type of standard-of-care chemotherapy regimen at the discretion of the patient's medical oncologist.

Inclusion Criteria:

Participants must meet the following criteria on screening examination to be eligible to participate in the study.

• Histologically or cytologically proven diagnosis of NSCLC or SCLC

• NSCLC, patients with clinical stage IIB-IV patients (AJCC, 7th ed.) are eligible, and for SCLC, limited-stage patients are eligible, if documented to be a candidate for definitive radiation and concurrent chemotherapy in the radiation oncologist or medical oncologist clinic note.

  • Stage IV NSCLC patients are eligible only if they have a solitary brain metastasis

  • Patients with non-malignant pleural effusion are eligible. --- If a pleural effusion is present, the following criteria must be met to exclude malignant involvement:

    • When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.
    • Exudative pleural effusions are excluded, regardless of cytology;
    • Effusions that are minimal (ie, not visible on chest x-ray) that are too small to safely tap are eligible.

• Gross tumor (primary tumor or involved lymph node) must be within 1 cm of esophagus on the most recent chest CT scan.

• ECOG performance status 0-1 within 30 days prior to registration;

• Age ≥18

• Women of childbearing potential must indicate that there is not a possibility of being pregnant at the time of enrollment or have a negative serum pregnancy test prior to the initiation of radiation therapy.

• Women of childbearing potential and male participants must practice adequate contraception.

• Patient must provide study-specific informed consent prior to study entry.

Exclusion Criteria:

Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.

• Greater than minimal, exudative, or cytologically positive pleural effusions
• Tumor suspected or known to invade the esophagus
• Prior chemotherapy if this precludes administration of concurrent chemotherapy for protocol treatment. Note that induction chemotherapy is allowed as long as concurrent chemotherapy is possible.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
• Any history of allergic reaction to chemotherapies used