Stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer - Acute toxicity and patient-reported outcomes in the prospective, multicenter SMILE phase II trial.

Background: Due to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methods: A total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. Results: There were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. Conclusion: Daily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

Radiation therapy facility risk analysis in Brazil with SEVRRA software.

Risk assessment deals with processes, accident-initiating events, barriers and risk ratings to unveil the fragility and weakness of some processes; within this study, specifically related to radiation therapy facilities. Barriers are technical or organizational safety measures put in place to avoid, prevent, detect, control, reduce or mitigate the consequences of an accident once an initiating event has occurred. In this work, radiological risk analysis was performed for a set of 20 Brazilian radiotherapy facilities making use of the freeware sevrra risk-management software. The objective of this study was to define parameters that could be useful in creating an overall risk profile. This profile would be helpful for establishing priorities for decision making and support a risk-informed regulatory process. The most relevant missing barriers in facilities were identified according to three parameters: the 'importance index', 'impacted facilities index' and the 'barrier-effectiveness index'. Barriers such as 'in vivo dosimetry in the first treatment session', 'weekly in vivo dosimetry to detect errors in the dose delivering process', 'annual external audit for the control of reference dose rate' and 'independent verification of calibration by various medical physicists with a different dosimetry equipment' were found to be the most effective in reducing the risk level of the facilities. The present investigation reinforces the need to strengthen the mechanisms that guarantee the effectiveness of such barriers in radiation therapy procedures.

A new chemical etching process to improve endosseous implant osseointegration: in vitro evaluation on human osteoblast-like cells.

The development of novel mechanical and chemical surface modification treatments to improve the osteointegration properties of osseointegrated dental implants is nowadays a topic of great applicative interest. The aim of the present study was to analyse the role of surface topography and chemistry of four different surface treatments on titanium by an in vitro human osteosarcoma immortalised cell line model (MG63). The surface treatments considered were (a) machined titanium, (b) chemical etched on machined titanium, (c) sandblasted titanium and (d) chemical etching on sandblasted titanium. Chemical and physical surface properties were investigated by Scanning Electron Microscopy, Thin Film-X ray Diffraction and by Laser Profilometry. The in vitro biological response was characterised using the MG63 cell line by elution cytotoxicity tests, cell morphology, adhesion, proliferation activity, alkaline phosphatase activity and total DNA content in order to show a relationship between osteoblast response and surface features. Chemical and physical characterisation showed that the considered treatments differently modify the surface morphology in the micro and sub-micrometric scale. Although some differences in alkaline phosphatase activity were observed in the biological characterisation, depending on the specific material's surface finishing, the results showed that cells were well responsive on all the tested materials and grew and differentiated with similar proliferation rate.

Titanium for osteointegration: Comparison between a novel biomimetic treatment and commercially exploited surfaces.

The objective of this preliminary in vitro biological study was to assess the effect of the surface physicochemical and topographical properties of a novel bioactive titanium (BSP) obtained by BioSpark treatment. A short-term study was per-formed to evaluate the bone cell response to BSP and compare it to two commercially available materials: no treated (TI) and chemically etched (ETC) titanium. Material characterization was carried out using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), non-contact laser profilometry (LPM), and Thin Film X-ray Diffraction (TF-XRD). Surface analysis showed ETC to have the highest rough surface, followed by TI surface and then BSP being the smoothest material at micro level, but showing a sub micrometer porous structure covered with a ""net-like"" rough structure. The BSP surface was found to consist of a layer of amorphous calcium and phosphorus and crystalline titanium oxide, not detected in the other materials tested. Indirect biological cytotoxicity studies were performed to determine cell viability following incubation with the eluted extract of the materials. Results indicated no remarkable deterioration in cell viability. In particular, no detectable effect was observed on cellular viability as a result of the chemical interaction between the BSP bioactive surface and the surrounding culture medium. Direct cellular studies showed that the material surface resulted in good cell adhesion on BSP samples. This could be related to both the nano-roughness, and also the crystallinity of the superficial layer of titanium oxide coupled with bioactive Ca- and P-chemical enrichment. The cellular proliferation analysis demonstrated a remarkably higher activity for the cells cultured on BSP, with values significantly higher than the other test materials and the control for all time points. These findings are highly suggestive that the surface properties of the BioSpark treated titanium significantly increases cell proliferation rate. In conclusion, this study has demonstrated that the novel bioactive treatment shows potential as a method for improving osteointegration properties of titanium for orthopaedic and dental implants. (Journal of Applied Biomaterials & Biomechanics 2004; 2: 35-44).

A novel biomimetic treatment for an improved osteointegration of titanium.

Direct osteointegration of titanium and titanium alloys implants is one of the main goals of biomaterials research for dental and orthopedic applications. Chemical, mechanical or biological treatments are investigated searching for fast and durable implant to bone bonding. The aim of the present work is to assess the in vitro mineralisation capabilities and to investigate the mechanical and physico-chemical properties of a new biomimetic treatment on titanium. The new surface treatment was obtained using Anodic Spark Deposition technique, and consists of a first ASD treatment performed in solutions containing phosphate ions followed by a second ASD treatment in a solution rich in calcium ions. The resulting surface is finally treated by alkali etching. The physio-chemical and mechanical properties of this material are analyzed and the mineralization potential is considered by surface analysis after soaking it in different solutions of simulated body fluid (SBF). The developed biomimetic treatment was then compared to other treatments from the literature. The proposed treatment was found to possess a very high mineralization capaci-ty, that makes its application very interesting in terms of speed and strength of direct implant osteointegration. (Journal of Ap-plied Biomaterials & Biomechanics 2003; 1: 33-42).