· Assess and compare the incidence and time to development of CTCAE v3.0 grade > 3 treatment related pneumonitis (TRP) or local failure, whichever comes first, among patients with locally advanced (stage II-IIIb and selected stage IV) non-small cell lung cancer (NSCLC) treated with image-guided adaptive photon therapy (IGAXT, Group 1) or proton therapy (IGAPT, Group 2) using Bayesian randomization.
· Assess and compare the incidence and time to development of CTCAE v3.0 grade > 3 radiation esophagitis in treatment Groups 1 and 2.
- Investigate the association of inflammatory cytokines with the incidence and time to development of TRP and outcomes in treatment Groups 1 and 2.
- Investigate the association of relevant pharmacogenetic markers, biomarkers, and gene polymorphisms with the time to development of TRP and treatment outcomes in treatment Groups 1 and 2. Serum of the blood samples will be transferred to collaborating laboratories at The Methodist Research Institute for analysis of specific biomarkers. All material transfer will follow institutional policy and all transferred material will be de-identified.
- For the proposed research, we will use a rapid and high-throughput nanopore-based array to enrich low molecular weight (LMW) proteins to identify circulating LMW peptide markers in blood samples from patients with or without NSCLC. By optimizing the nanotexture of silica films through the engineering of the physicochemical properties (e.g., pore size, pore structure, surface affinity) on the nanoporous silica chip, we can selectively enrich low-abundance, LMW peptides from serum samples. We will process the samples on nanoporous silica chips for LMW protein fractionation, and analyze the isolated fractions by MALDI-TOF mass spectrometry and principal component analysis. LMW peptide signatures associated with lung cancer will be identified by LC-MS/MS.
- Evaluate IGAXT using weekly computed tomography (CT) on-rail or cone beam CT in the assessment of tumor response and impact on treatment planning and delivery.
- Compare overall survival, progression-free survival, and median survival time in treatment Groups 1 and 2.
- Evaluate the role of functional imaging with FDG-PET in assessing and predicting the time to the development of TRP and tumor response.
- Document and compare symptom burden weekly during treatment, monthly up to 6 month after the treatment, and at each follow-up visit by using the M. D. Anderson Symptom Inventory for Lung (MDASI-Lung) in treatment Groups 1 and 2.
- For Group 3 and Group 4 patients who are treated with protons or photons depending on higher dose achievable, compare the local control, overall survival, progression-free survival, median survival and toxicities of protons vs. photons (see Section 7.5).