The Effect of the iNOS Inhibitor S-Methylisothiourea and Hyperbaric Oxygen Treatment on Radiation Colitis in Rats.

INTRODUCTION: External radiotherapy is one of the main treatment modalities for a variety of malignancies. However, the lower gastrointestinal tract is sensitive to the ionizing radiation. Hyperbaric oxygen treatment (HOT) has been suggested as a viable treatment for refractory radiation colitis, but the effect of S-Methylisothiourea (SMT) in the radiation colitis have not reported. To investigate the effect of SMT, HOT and the combination of both in an acute radiation-induced enterocolitis model. METHODS: Sixty Sprague-Dawley rats were divided randomly into five equal groups. A single dose of gamma irradiation (25 Gy) was administered through the colorectal region to anesthetized rats. In the control group, we applied 2 ml of saline solution intraperitoneally for five days. In the HOT group, 100-per-cent oxygen at 2.5 atm pressure was applied for five days. In the SMT group, 10 mg/kg/day of SMT was applied intraperitoneally for five days. In the HOT+SMT group, HOT and SMT were both applied in the same dosages as in the preceding two groups. At the end of five days, the rats were sacrificed and colon samples were collected for histological grading. Blood samples were collected to test for : tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-1ß, transforming growth factor-ß (TGF-ß) and intercellular adhesion molecule-1 (ICAM-1) mRNA. RESULTS: The TNF-α, IL-1ß, IL-10 and TGF-ß levels were reduced by SMT, HOT and HOT+SMT applications (p < 0.05). However ICAM-1 mRNA levels were not significantly lower (p:0.19). The microscopic scores differed significantly between the SMT, HOT and HOT+SMT groups and the control group. There was significant improvement histologically, especially in the HOT+SMT group. When we compared the weight of the rats before and after the study, weight loss was significantly lower in the SMT, HOT and HOT+SMT groups compared with the control group (p < 0.05). CONCLUSION: HOT and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately.

Evaluation of active breathing control-moderate deep inspiration breath-hold in definitive non-small cell lung cancer radiotherapy.

The purpose of this study is to evaluate the effect of Active Breathing Control-moderate deep inspiration breath-hold (ABC-mDIBH) on tumor motion and critical organ doses in non-small cell lung cancer (NSCLC) radiotherapy. 23 patients with locally advanced NSCLC were included in the study. All patients were scanned at free breathing and ABC-mDIBH for radiation treatment planning. 3 separate treatment plans were generated for each patient including one plan with ABC-mDIBH and uniform margins, one plan with free breathing and uniform margins, and one plan with free breathing and 3-dimensional non-uniform margins determined by Cone Beam Computed Tomography (CBCT) and XVI Motion View (X-ray Volume Imaging, Elekta, UK). Critical organ dose-volumes and physical lung parameters were comparatively evaluated on 3 separate dose-volume histograms of each patient acquired from planning software. Individual tumor motion of each patient with and without ABC-mDIBH was documented and compared. Use of ABC-mDIBH resulted in statistically significant improvement in physical lung parameters of V20 (lung volume receiving ≥ 20 Gy) and mean lung dose (MLD) which are predictors of radiation pneumonitis (p<0.001). Reduction in spinal cord dose and tumor motion with ABC-mDIBH was also statistically significant (p<0.001). ABC-mDIBH increases normal lung tissue sparing in definitive NSCLC radiotherapy by improving physical lung parameters along with spinal cord dose reduction through exact tumor immobilization. The incorporation of ABC-mDIBH into NSCLC radiotherapy may have implications for potential margin reduction and dose escalation to improve treatment outcomes.