A currently unpredictable outcome of radiotherapy on lung cancer patients is radiation pneumonitis (lung inflammation). This study was the first performed on humans to determine how antioxidant response may be used to predict this “potentially lethal treatment-related complication”. The oxidative stress link had been established through studies on irradiated mice.
Type of study: Observational study on humans; physicians grading for pneumonitis were blinded to antioxidant data
Method used to conduct study: Fifteen total lung cancer patients were found eligible for the study after signing informed consents, having stage III disease, receiving concurrent definitive radiotherapy and paclitaxel-based chemotherapy, and having good performance status. Excluded were patients who had received radiotherapy or chemotherapy previously and those with unfavorable Eastern Cooperative Oncology Group performance status or chronic obstructive pulmonary disease.
Blood samples were collected at baseline and weekly during the 6-week treatment. Radiation pneumonitis was diagnosed three months after the treatment according to different grades ranging from mild, moderate, and severe. Cross-validation was used to analyze test sensitivity to variables. Detection of proteins was performed through gel electrophoresis, secondary antibody and enhanced chemiluminescence in the blot analysis.
Summary: Researchers found that the patients who developed pneumonitis had higher levels of superoxide dismutase (SOD) and lower levels of glutathione peroxidase (GPX) overall. The data suggest that higher SOD activity increased the conversion of superoxide anion to hydrogen peroxide. In conjunction with low GPX, an increase of hydrogen peroxide and hydroxyl radicals would occur creating oxidative stress that would predispose patients to radiation pneumonitis.
Critique of research design quality and relevance: Blinding methods and appropriate exclusions make this a well-designed study with few confounding variables. Although strong data from animals confirm its findings, the study’s great weakness is that of being a small one. Its relevance, however, may be large since using GPX/SOD as predictive markers may save lives in the future.
Nutritional implications and implications of future study: High SOD/low GPX activity may serve as a marker for prediction of radiation pneumonits and that increasing the ratio of GPX/SOD would reduce risk of radiation pneumonitis. Clinical trials on use of antioxidant supplements is warranted; however, the researchers warn, antioxidant therapies must take into account other treatments (e.g. chemotherapy) and how it would affect the patient as "a whole".
Park EM, Ramnath N, Yang GY et al. High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis. Free Radic Biol Med 2007;42:280-7. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1892164