Pilot study of cytokine profiles in prostate cancer patients undergoing proton or conventional radiotherapy

The mechanisms responsible for normal tissue late effects following radiotherapy are largely unknown and currently no method for predicting such risks is available. Abnormal levels of cytokine production induced by radiation has been suggested as a contributing factor by multiple investigators. The purpose of the present study was to evaluate plasma levels of transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) in patients with prostate cancer scheduled for radiotherapy (protons, photons, or combination of both). It has been recently shown that ionizing radiation can increase expression of these cytokines and there are indications that they may be associated with morbidity. Blood samples were obtained from 20 subjects (age 51-80) before, during the first week, and immediately after the end of therapy; 3 healthy volunteers served as controls. Significant positive correlations (p<0.05) were obtained between bFGF, IL-1 beta, and TNF-alpha and the integral dose of radiation during the first week of treatment. Correlations approaching significance (p<0.1) were obtained with bFGF and acute treatment-related morbidity. A higher integral dose (due to larger irradiated volumes) was delivered with conventional photon compared to proton irradiation. No significance was obtained with any of the cytokines and pretreatment prostate specific antigen (PSA) levels, patient age, grade or stage of disease, or the integral dose by the end of radiation treatment. These results show that large changes occur in the plasma levels of certain cytokines early after initiation of radiotherapy and that treatment of larger volumes is more likely to induce these changes. Our data support further investigation of the role of cytokines during radiotherapy.