Radiation biology of proton interactions with lung tissue, application to gender differences in lung radiation toxicity.
Background and Significance
Radiation toxicity to the lung is common in patients treated with high-dose radiation therapy for tumors in the lung. Several studies have implicated patient specific factors such as age, smoking history, and history of chemotherapy as compounding radiation toxicity in humans. Recent data in mice show that lung toxicity due to environmental exposure to chemical agents is higher in female mice relative to matched male mice.
We seek to evaluate whether gender is an independent risk factor for radiation toxicity to the lung in humans.
The proton therapy institute (PTI) and the UF Health Shands Medical Center has an existing database of pre-, during- and post-treatment chest CT scans in patients treated with proton therapy for lung cancer. Dr. O'Dell's lab at UF Gainesville has developed software tools to quantify changes in the CT appearance of the lung, and changes in the lung vasculature, as a function of dose on a pixel-by-pixel basis. These tools allow for the quantification of an individual patient's lung radiation sensitivity that can then be modeled mathematically to facilitate comparison across patients and over time in the same patient. We will use this image data and software tools to investigate the contribution of gender to radiation toxicity, accounting for known co-factors of age, smoking history and types and duration of chemotherapy. Our image markers will also be correlated with incidence of clinical grade 2+ lung toxicity, and overall survival, with the intent to identify imaging markers at early time points that are predictive of long-term clinical grade toxicity.