Surface guided radiotherapy (SGRT) improves breast cancer patient setup accuracy.

PURPOSE: The purpose of the study was to investigate if surface guided radiotherapy (SGRT) can decrease setup deviations for tangential and locoregional breast cancer patients compared to conventional laser-based setup (LBS). MATERIALS AND METHODS: Both tangential (63 patients) and locoregional (76 patients) breast cancer patients were enrolled in this study. For LBS, the patients were positioned by aligning skin markers to the room lasers. For the surface based setup (SBS), an optical surface scanning system was used for daily setup using both single and three camera systems. To compare the two setup methods, the patient position was evaluated using verification imaging (field images or orthogonal images). RESULTS: For both tangential and locoregional treatments, SBS decreased the setup deviation significantly compared to LBS (P < 0.01). For patients receiving tangential treatment, 95% of the treatment sessions were within the clinical tolerance of ≤ 4 mm in any direction (lateral, longitudinal or vertical) using SBS, compared to 84% for LBS. Corresponding values for patients receiving locoregional treatment were 70% and 54% for SBS and LBS, respectively. No significant difference was observed comparing the setup result using a single camera system or a three camera system. CONCLUSIONS: Conventional laser-based setup can with advantage be replaced by surface based setup. Daily SGRT improves patient setup without additional imaging dose to breast cancer patients regardless if a single or three camera system was used.

Technical evaluation of a laser-based optical surface scanning system for prospective and retrospective breathing adapted computed tomography.

BACKGROUND: For breathing adapted radiotherapy, the same motion monitoring system can be used for imaging and triggering of the accelerator. PURPOSE: To evaluate a new technique for prospective gated computed tomography (CT) and four-dimensional CT (4DCT) using a laser based surface scanning system (Sentinel(™), C-RAD, Uppsala, Sweden). The system was compared to the AZ-733V respiratory gating system (Anzai Medical, Tokyo, Japan) and the Real-Time Position Management System (RPM(™)) (Varian Medical Systems, Palo Alto, CA, USA). MATERIAL AND METHODS: Temporal accuracy was evaluated using a moving phantom programmed to move a platform along trajectories following a sin(6)(ωt) function with amplitudes from 6 to 20 mm and periods from 2 to 5 s during 120 s while the motion was recorded. The recorded data was Fourier transformed and the peak area at the fundamental and harmonic frequencies compared to data generated using the same sinusoidal function. For verification of the 4DCT reconstruction process, the phantom was programmed to move along a sinusoidal trajectory. Ten phase series were reconstructed. The distance from the couch to the platform was measured in each image. By fitting the function sin(ωt-ϕ) to the values measured in the images corresponding to each slice, the phase of each image was verified. RESULTS AND CONCLUSION: In the recorded data, the peak area at the fundamental frequency covered on average 104 ± 4%, 102 ± 4% and 91 ± 27% of the peak area in the generated data for the Sentinel(™), RPM(™) and AZ-733V systems, respectively. All systems managed to resolve both harmonic frequencies. The second experiment showed that all images were sorted into the correct series using breathing data recorded by each system. The systems generated very similar results, however, it is preferable to use the same system both for imaging and treatment.

Radiation-induced platelet-endothelial cell interactions are mediated by P-selectin and P-selectin glycoprotein ligand-1 in the colonic microcirculation.

BACKGROUND: Antiplatelet reagents have been reported to protect against intestinal damage associated with abdominal radiotherapy, but the mechanisms behind radiation-induced platelet-endothelium interactions are not known. We sought to define the adhesive mechanisms that regulate radiotherapy-induced platelet-endothelial cell interactions in the colon. METHODS: All mice except the controls were exposed to abdominal radiation with a single dose of 20 Gray. Mice were pretreated with an isotype-matched control antibody or a monoclonal antibody directed against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1). Platelet and leukocyte rolling and adhesion in the colon were determined by use of inverted intravital fluorescence microscopy 16 hours after radiation. Radiation-induced intestinal leakage of fluorescein isothiocyanate-conjugated dextran was examined in separate experiments. RESULTS: Immunoneutralization of P-selectin decreased radiation-provoked platelet rolling by 87% and adhesion by 63%. Moreover, inhibition of PSGL-1 decreased platelet rolling and adhesion by 77% and 83%, respectively, in animals exposed to radiation. Similarly, inhibition of P-selectin and PSGL-1 decreased radiation-induced leukocyte rolling and adhesion by more than 84% and 90%, respectively, in the colon. In contrast, inhibition of P-selectin or PSGL-1 had no impact on radiation-induced intestinal leakage. In addition, systemic depletion of platelets and leukocytes did not affect intestinal barrier dysfunction in radiated animals. CONCLUSION: This study demonstrates that radiation-provoked platelet and leukocyte accumulation are mediated in part by P-selectin and PSGL-1. Radiation-induced gut leakage, however, is independent of accumulation of platelets and leukocytes in the intestinal microvasculature.

Local radiotherapy of exposed murine small bowel: apoptosis and inflammation.

BACKGROUND: Preoperative radiotherapy of the pelvic abdomen presents with complications mostly affecting the small bowel. The aim of this study was to define the features of early radiation-induced injury on small bowel. METHODS: 54 mice were divided into two groups (36 irradiated and 18 sham irradiated). Animals were placed on a special frame and (in the radiated group) the exteriorized segment of ileum was subjected to a single absorbed dose of 19 or 38 Gy radiation using 6 MV high energy photons. Specimens were collected for histology, immunohistochemistry (IHC) and ELISA analysis after 2, 24 and 48 hours. Venous blood was collected for systemic leucocyte count in a Burker chamber. RESULTS: Histology demonstrated progressive infiltration of inflammatory cells with cryptitis and increased apoptosis. MIP-2 (macrophage inflammatory protein) concentration was significantly increased in irradiated animals up to 48 hours. No significant differences were observed in IL-10 (interleukin) and TNF-alpha (tumour necrosis factor) levels. IHC with CD45 showed a significant increase at 2 hours of infiltrating leucocytes and lymphocytes after irradiation followed by progressive decrease with time. Caspase-3 expression increased significantly in a dose dependent trend in both irradiated groups up to 48 hours. CONCLUSION: Acute small bowel injury caused by local irradiation is characterised by increased apoptosis of crypt epithelial cells and by lymphocyte infiltration of the underlying tissue. The severity of histological changes tends to be dose dependent and may affect the course of tissue damage.

Critical role of P-selectin and lymphocyte function antigen-1 in radiation-induced leukocyte-endothelial cell interactions in the colon.

PURPOSE: Radiation therapy is frequently used in treating different types of tumors, although associated with serious side effects, such as fibrosis and complicated diarrhea. This study was designed to define the adhesive mechanisms behind radiotherapy-induced leukocyte recruitment in the colon. METHODS: All mice, except control animals, were radiated with a single dose of 20 Gy. Mice were pretreated with an isotype-matched control antibody or a monoclonal antibody directed against P-selectin. In separate experiments, lymphocyte function antigen-1-deficient animals were used. Leukocyte rolling and firm adhesion were determined by use of inverted intravital fluorescence microscopy 16 hours after radiation. RESULTS: It was found that immunoneutralization of P-selectin reduced leukocyte rolling by 83 percent and adhesion by 87 percent in radiated mice. Moreover, radiation-induced leukocyte adhesion in LFA-1-deficient mice was decreased by 94 percent compared with wild-type animals. CONCLUSIONS: This study demonstrates that leukocyte rolling is mediated by P-selectin and that firm leukocyte adhesion is supported by lymphocyte function antigen-1 in radiation-induced enteritis. Moreover, P-selectin-dependent leukocyte rolling is a precondition for subsequent leukocyte adhesion in radiation-induced intestinal injury. Thus, targeting P-selectin and/or lymphocyte function antigen-1 may protect against pathologic inflammation in the colon induced by radiotherapy.

Radiation enteropathy and leucocyte-endothelial cell reactions in a refined small bowel model.

BACKGROUND: Leucocyte recruitment and inflammation are key features of high dose radiation-induced tissue injury. The inflammatory response in the gut may be more pronounced following radiotherapy due to its high bacterial load in comparison to the response in other organs. We designed a model to enable us to study the effects of radiation on leucocyte-endothelium interactions and on intestinal microflora in the murine ileum. This model enables us to study specifically the local effects of radiation therapy. METHOD: A midline laparotomy was performed in male C57/Bl6 mice and a five-centimetre segment of ileum is irradiated using the chamber. Leucocyte responses (rolling and adhesion) were then analysed in ileal venules 2 - 48 hours after high dose irradiation, made possible by an inverted approach using intravital fluorescence microscopy. Furthermore, intestinal microflora, myeloperoxidase (MPO) and cell histology were analysed. RESULTS: The highest and most reproducible increase in leucocyte rolling was exhibited 2 hours after high dose irradiation whereas leucocyte adhesion was greatest after 16 hours. Radiation reduced the intestinal microflora count compared to sham animals with a significant decrease in the aerobic count after 2 hours of radiation. Further, the total aerobic counts, Enterobacteriaceae and Lactobacillus decreased significantly after 16 hours. In the radiation groups, the bacterial count showed a progressive increase from 2 to 24 hours after radiation. CONCLUSION: This study presents a refinement of a previous method of examining mechanisms of radiation enteropathy, and a new approach at investigating radiation induced leucocyte responses in the ileal microcirculation. Radiation induced maximum leucocyte rolling at 2 hours and adhesion peaked at 16 hours. It also reduces the microflora count, which then starts to increase steadily afterwards. This model may be instrumental in developing strategies against pathological recruitment of leucocytes and changes in intestinal microflora in the small bowel after radiotherapy.