Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM10).

Exposure to ambient air particulate matter (particles less than 10µm or PM10) has been shown to be an independent risk factor for the development and progression of atherosclerosis. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have well-established anti-inflammatory properties. The aim of this study was to determine the impact of statins on the adverse functional and morphological changes in blood vessels induced by PM10. New Zealand White rabbits fed with a high fat diet were subjected to balloon injury to their abdominal aorta followed by PM10/saline exposure for 4weeks±lovastatin (5mg/kg/day) treatment. PM10 exposure accelerated balloon catheter induced plaque formation and increased intimal macrophages and lipid accumulation while lovastatin attenuated these changes and promoted smooth muscle cell recruitment into plaques. PM10 impaired vascular acetylcholine (Ach) responses and increased vasoconstriction induced by phenylephrine as assessed by wire myograph. Supplementation of nitric oxide improved the impaired Ach responses. PM10 increased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in blood vessels and increased the plasma levels of endothelin-1 (ET-1). Incubation with specific inhibitors for iNOS, COX-2 or ET-1 in the myograph chambers significantly improved the impaired vascular function. Lovastatin decreased the expression of these mediators in atherosclerotic lesions and improved endothelial dysfunction. However, lovastatin was unable to reduce blood lipid levels to the baseline level in rabbits exposed to PM10. Taken together, statins protect against PM10-induced cardiovascular disease by reducing atherosclerosis and improving endothelial function via their anti-inflammatory properties.

Endobronchially Implanted Real-Time Electromagnetic Transponder Beacon-Guided, Respiratory-Gated SABR for Moving Lung Tumors: A Prospective Phase 1/2 Cohort Study.

Purpose: Endobronchial electromagnetic transponder beacons (EMT) provide real-time, precise positional data of moving lung tumors. We report results of a phase 1/2, prospective, single-arm cohort study evaluating the treatment planning effects of EMT-guided SABR for moving lung tumors. Methods and Materials: Eligible patients were adults, Eastern Cooperative Oncology Group 0 to 2, with T1-T2N0 non-small cell lung cancer or pulmonary metastasis ≤4 cm with motion amplitude ≥5 mm. Three EMTs were endobronchially implanted using navigational bronchoscopy. Four-dimensional free-breathing computed tomography simulation scans were obtained, and end-exhalation phases were used to define the gating window internal target volume. A 3-mm expansion of gating window internal target volume defined the planning target volume (PTV). EMT-guided, respiratory-gated (RG) SABR was delivered (54 Gy/3 fractions or 48 Gy/4 fractions) using volumetric modulated arc therapy. For each RG-SABR plan, a 10-phase image-guided SABR plan was generated for dosimetric comparison. PTV/organ-at-risk (OAR) metrics were tabulated and analyzed using the Wilcoxon signed-rank pair test. Treatment outcomes were evaluated using RECIST (Response Evaluation Criteria in Solid Tumours; version 1.1). Results: Of 41 patients screened, 17 were enrolled and 2 withdrew from the study. Median age was 73 years, with 7 women. Sixty percent had T1/T2 non-small cell lung cancer and 40% had M1 disease. Median tumor diameter was 1.9 cm with 73% of targets located peripherally. Mean respiratory tumor motion was 1.25 cm (range, 0.53-4.04 cm). Thirteen tumors were treated with EMT-guided SABR and 47% of patients received 48 Gy in 4 fractions while 53% received 54 Gy in 3 fractions. RG-SABR yielded an average PTV reduction of 46.9% (P < .005). Lung V5, V10, V20, and mean lung dose had mean relative reductions of 11.3%, 20.3%, 31.1%, and 20.3%, respectively (P < .005). Dose to OARs was significantly reduced (P < .05) except for spinal cord. At 6 months, mean radiographic tumor volume reduction was 53.5% (P < .005). Conclusions: EMT-guided RG-SABR significantly reduced PTVs of moving lung tumors compared with image-guided SABR. EMT-guided RG-SABR should be considered for tumors with large respiratory motion amplitudes or those located in close proximity to OARs.

Optical scan and 3D printing guided radiation therapy - an application and provincial experience in cutaneous nasal carcinoma.

BACKGROUND: Single field Orthovoltage radiation is an acceptable modality used for the treatment of nasal cutaneous cancer. However, this technique has dosimetric pitfalls and unnecessary excessive exposure of radiation to organs at risk (OAR). We present the clinical outcome of a case series of cutaneous nasal tumours using a novel technique incorporating an optical scanner and a 3-dimensional (3D) printer to deliver treatments using parallel opposed (POP) fields. MATERIALS AND METHODS: The POP delivery method was validated using ion chamber and phantom measurements before implementation. A retrospective chart review of 26 patients treated with this technique between 2015 and 2019 was conducted. Patients' demographics and treatment outcomes were gathered and tabulated. These patients first underwent an optical scan of their faces to collect topographical data. The data were then transcribed into 3D printing algorithms, and positive impressions of the faces were printed. Custom nose block bolus was made with wax encased in an acrylic shell; 4 cm thick using the printed face models. Custom lead shielding was also generated. Treatments were delivered using 250 KeV photons POP arrangement with 4 cm diameter circle applicator cone and prescribed to the midplane. Dose and fractionation were as per physician discretion. RESULTS: Phantom measurements at mid-plane were found to match the prescribed dose within ±0.5%. For the 26 cases in this review, the median age was 78.5 years, with 15 females and 11 males. 85% of cases had Basal cell carcinoma (BCC); 1 had squamous cell carcinoma (SCC), one had synchronous BCC + SCC, and 1 had Merkel cell carcinoma. Twenty-one cases had T1N0 disease, 4 had T2N0, and 1 had T3N0. Dose and fractionation delivered were 40Gy in 10 fractions for the majority of cases. The complete response rate at a median follow-up of 6 months was 88%; 1 patient had a refractory tumour, and one patient had a recurrence. Toxicities were minor with 81% with no reported side effects. Three patients experienced grade 3 skin toxicity. CONCLUSIONS: Utilization of optic scanner and 3D printing technology, with the innovative approach of using POP orthovoltage beams, allows an effective and efficient way of treatment carcinomas of the nose with a high control rate and low toxicity profiles.