Image-Guided, Intensity-Modulated Photon or Proton Beam Radiation Therapy in Treating Patients With Stage II-IIIB Non-small Cell Lung Cancer

PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) of image-guided intensity-modulated photon (IMRT) and proton therapy (IMPT) both with simultaneous integrated boost (SIB) dose escalation to the SIBVi (internal SIB volume; defined as the gross tumor volume with consideration of respiratory motion plus setup uncertainty margin) for patients with stage II/IIIB non-small cell lung cancer (NSCLC) receiving concurrent standard chemotherapy and proton irradiation. (Phase I) II. Assess and compare survival free of grade III treatment related toxicity and local progression-free survival from day 1 of concurrent chemoradiation for stage II-IIIB NSCLC patients treated with image-guided robustly-optimized IMPT versus (vs.) IMRT, both delivered with simultaneous integrated boost (SIB). (Phase II) SECONDARY OBJECTIVES: I. Determine treatment-related acute and late toxicity. II. Correlate changes in standardized uptake values (SUV) on positron emission tomography (PET) and study endpoints (toxicity, tumor response, local control). III. Correlate changes in peripheral blood biomarkers (genes, micro-ribonucleic acid \[RNA\], proteins) and the study endpoints. IV. Estimate progression-free and overall survival. V. Document and compare symptom burden before starting chemoradiation, weekly during treatment, bi-weekly from end of treatment until first follow up, and at each follow-up visit thereafter by using the MD Anderson Symptom Inventory - Plus (MDASI-Plus) and European Quality of Life Instrument-5 dimensions (EQ-5D). VI. Perform cost effectiveness between IMPT and IMRT both with SIB treatment. VII. Correlate imaged response, clinical response, blood biomarkers and symptom burdens to dose distribution patterns. OUTLINE: This is a phase I, dose-escalation study followed by a randomized phase II study. PHASE I: Patients undergo image-guided IMRT with SIB or IMPT with SIB once daily (QD) 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo image-guided IMRT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo image-guided IMPT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4-8 weeks, every 3-4 months for 3 years, every 6 months for 2 years, and then annually thereafter.