Angiotensin-Converting Enzyme Inhibitor Reduces Radiation-Induced Periprosthetic Capsular Fibrosis.

BACKGROUND: The capsular contracture is one of the main complications after radiotherapy in patients with implant-based reconstruction. The aim of this study is to evaluate the efficacy of ramipril for the prevention of radiation-induced fibrosis around the silicone implant. MATERIALS AND METHODS: Thirty Wistar rats in 5 groups were used. Group 1: implant; group 2: implant + radiation; group 3: ramipril + implant; group 4: ramipril + implant + radiation; group 5: sham. Ramipril treatment was started 5 d before surgery and continued for 12 wk after surgery. A mini silicone implant was placed in the back of the rats. A single fraction of 21.5 Gy radiation was applied. Tissues were examined histologically and immunohistochemically (TGF-ß1, MMP-2, and TIMP-2 expression). The alteration of plasma TGF-ß1 levels was examined before and after the experiment. RESULTS: After applying implant or implant + radiation, capsular thickness, percentage of fibrotic area, tissue and plasma TGF-ß1 levels significantly increased, and MMP-2/TIMP-2 ratio significantly decreased compared with the sham group. In ramipril-treated groups, the decrease in capsular thickness, fibrosis, TGF-ß1 positivity, and an increase in MMP-2/TIMP-2 ratio were found significant. In the ramipril + implant + radiation group, the alteration values of TGF-ß1 dramatically decreased. CONCLUSIONS: Our results show that ramipril reduces radiation-induced fibrosis and contracture. The results of our study may be important for the design of the clinical trials required to investigate the effective and safe doses of ramipril, which is an inexpensive and easily tolerated drug, on humans.

The evaluation of the feasibility of carotid sparing intensity modulated radiation therapy technique for comprehensive breast irradiation.

PURPOSE: To investigate the feasibility of carotid sparing intensity modulated radiation therapy (CS-IMRT) to minimize the radiation dose to carotid arteries for comprehensive irradiation of breast cancer patients who have risk factors for atherosclerosis. The dose distribution of CS-IMRT technique and the conventional irradiation technique were also compared. PATIENTS AND METHODS: Ten patients who were previously treated with comprehensive three-dimensional conformal radiation therapy (3DCRT) were selected. DICOM data were used to contour the carotid artery and to create the virtual CS-IMRT plans for each patient. 3DCRT and CS-IMRT plans were compared in terms of conformity index, homogeneity index, and the doses to organ at risk and carotid arteries. RESULTS: The homogeneity and conformity indices were better with CS-IMRT plans compared to 3DCRT plan. The homogeneity index was 1.13 vs 1.11 (p=0.007) for 3DCRT and CS-IMRT and the conformity index was 0.96 vs 0.97 (p=0.006) for 3DCRT and CS-IMRT. The radiation dose to the carotid arteries were reduced by applying CS-IMRT without compromising the target volume coverage. When the carotid artery was considered as organ at risk for CS-IMRT planning, the median of V50 was decreased to 0% from 12.5% compared to 3DCRT plans (p=0.017). The median of the maximum dose to the carotid artery was decreased under 50Gy with CS-IMRT. CONCLUSIONS: CS-IMRT can significantly reduce the unnecessary radiation dose to the carotid arteries compared with conventional 3DCRT technique while maintaining target volume coverage. CS-IMRT technique can be considered for breast cancer patient with high risk of atherosclerosis.