This is a pilot study to improve local tumor control while maintaining the same rate of
      treatment toxicity by adapting therapy to the uninvolved lung and esophagus while continuing
      to adapt therapy to the tumor for patients with Stage II/III NSCLC.

      Lung cancer is the leading cause of cancer death in the United States and worldwide. In 2012,
      there were 226,160 new cases and 160,340 deaths related to lung cancer in the United States.
      Approximately, 80-85% of lung cancers are NSCLC (Non-small Cell Lung Cancer), and 40% of
      these are locally advanced (stage II/III) at diagnosis. The current standard of care for
      these patients is "one size fits all" RT (Radiation Therapy) with concurrent chemotherapy in
      uniform regimens. Even after concurrent chemoradiation, however, the five year overall
      survival was still about 15%; almost one half of the patients failed locally. At the same
      time, intensification of both radiotherapy and concurrent chemotherapy may result in
      excessive toxicity or incomplete treatment. Therefore, it is critical to tailor the treatment
      to each individual's sensitivity in combination with functional imaging guided
      response-driven treatment and biomarker guided individualized dose prescription, thus taking
      into consideration both the tumor and toxicity profile.

      Evidence suggests that high-dose radiation has the potential to improve local-regional
      control and overall survival in patients treated with fractionated therapy with concurrent
      chemotherapy.

      However, it is challenging to deliver high dose RT in the majority of patients with locally
      advanced NSCLC without exceeding doses to organs at risk and causing significant side
      effects.

      Investigators hypothesized that they could develop safer and more effective therapy by
      adapting treatment to the individual patient's response. With respect to the tumor,
      investigators hypothesized, that they could improve outcome by redistributing dose to the
      more aggressive regions of the tumor, assessed using mid-treatment FDG-PET (Positron Emission
      Tomography) scanning. With respect to uninvolved organs, investigators need methods of
      estimating tolerable radiation doses for the individual patient rather than the population
      average. Such a strategy requires assessing both global and regional normal lung function and
      the technology to deliver dose in a manner that minimizes damage to functional lung and
      esophagus.

      During-RT FDG-PET/CT potentially can provide important benefits to individual patients by
      intensifying dose to more resistent tumor, allowing early changes to alternative, more
      efficacious treatment or by avoiding the unnecessary toxicity related to ineffective therapy.

      Patients will also undergo a during treatment V/Q SPECT (Single-photon Emission Computed
      Tomography) scan, as an adaptive plan based on during-treatment SPECT may further optimize
      PART (Personalized Adaptive Radiotherapy) to avoid high dose radiation to the
      well-functioning regions, and would thus decrease RILT (Radiation Induced Lung Toxicity).

      The combination of pre- and during V/Q SPECT can classify the lung into different functional
      regions, and a strategy to give differential priority to the regions has been developed to
      minimize lung damage.

      Investigators plan to continue to collect data on serum biomarkers to further refine their
      biophysical model with the ultimate goal of individualizing radiation dose prescription.

      By identifying high risk patients and adjusting OAR (Organs at Risk) dose limits to the
      threshold of tolerance, investigators anticipate a significant reduction in the incidence of
      toxicity from UMCC 2007.123 (NCT01190527) without compromised tumor control by applying the
      model to optimize radiation planning.