Proton therapy in the palliative setting.

Given its sharp dose fall off and ability to spare healthy surrounding tissue, proton beam therapy (PBT) has traditionally been used to treat various types of malignancies in the definitive setting, with strong, empirical data supporting its utility and safety. In the palliative setting, however, photon therapy has generally remained the standard of care in radiation treatment delivery due to lower cost, and greater availability. However, recent data suggest that the use of PBT may provide benefit in terms of symptom management and disease control in patients with locally advanced or recurrent disease who do not qualify for definitive therapy or with metastatic disease. Additionally, due to its unique dosimetric properties, PBT may confer less overall toxicity, thus helping preserve or improve the quality of life in this patient population, especially for those who are nearing end of life. While there is a need for further study, initial data analyzed from both retrospective and prospective single-institution and multi-institution trials are promising. This review aims to explore the efficacy and safety of PBT in the palliative setting among adults and to summarize pertinent studies that support its usage. To the authors' knowledge, this is the first review of the literature pertaining to PBT used in the palliative setting across multiple disease sites.

A Pilot Study of Galunisertib plus Stereotactic Body Radiotherapy in Patients with Advanced Hepatocellular Carcinoma.

TGFß is a pleiotropic cytokine with immunosuppressive activity. In preclinical models, blockade of TGFß enhances the activity of radiation and invokes T-cell antitumor immunity. Here, we combined galunisertib, an oral TGFß inhibitor, with stereotactic body radiotherapy (SBRT) in patients with advanced hepatocellular carcinoma (HCC) and assessed safety, efficacy, and immunologic correlatives. Patients (n = 15) with advanced HCC who progressed on, were intolerant of, or refused sorafenib were treated with galunisertib (150 mg orally twice a day) on days 1 to 14 of each 28-day cycle. A single dose of SBRT (18-Gy) was delivered between days 15 to 28 of cycle 1. Site of index lesions treated with SBRT included liver (9 patients), lymph node (4 patients), and lung (2 patients). Blood for high-dimensional single cell profiling was collected. The most common treatment-related adverse events were fatigue (53%), abdominal pain (46.6%), nausea (40%), and increased alkaline phosphatase (40%). There were two instances of grade 2 alkaline phosphatase increase and two instances of grade 2 bilirubin increase. One patient developed grade 3 achalasia, possibly related to treatment. Two patients achieved a partial response. Treatment with galunisertib was associated with a decrease in the frequency of activated T regulatory cells in the blood. Distinct peripheral blood leukocyte populations detected at baseline distinguished progressors from nonprogressors. Nonprogressors also had increased CD8+PD-1+TIGIT+ T cells in the blood after treatment. We found galunisertib combined with SBRT to be well tolerated and associated with antitumor activity in patients with HCC. Pre- and posttreatment immune profiling of the blood was able to distinguish patients with progression versus nonprogression.

Raman spectroscopy of TiO2 thin films formed by hybrid treatment for biomedical applications.

The paper presents the results of the investigations of the surface layer obtained after application of the combined hybrid method of oxidation in a fluidized bed (FB) and deposition of the oxide coating by PVD technique. The material used in the study was Ti Grade 2. The process of diffusive saturation was carried out in a fluidized-bed reactor at the temperature of 640°C for 8h in air while the top oxide layer was obtained through PVD method - magnetron sputtering using TiO2 target and argon atmosphere with the pressure of 3×10(-2)mbar and the distance between the substrate to the target of 60mm. In order to determine changes in the properties that occur as a result of modification of the Ti surface, the following examinations were carried out by SEM-EDX, X-ray diffraction methods, Raman spectroscopy, Glow Discharge Optical Spectroscopy (GDOS) and Secondary Ion Mass Spectrometry (SIMS). The coatings obtained were characterized by zonal structure comprising the solution zone of Tiα(O) and oxide zone of TiO2 with modifications of rutile and anatase, depending on the oxidation method. It was found that formation of oxide layers using the hybrid method (FB+PVD) leads to limitation of defects in the oxide layer after fluidized-bed thermal treatment and obtaining a uniform, tight coating with improved corrosion properties which are important from the biomedical standpoint.

Fabrication and characterization of oxygen - diffused titanium using spectroscopy method.

A thin native oxide film that forms on the titanium surface makes contact with the bone tissue has been considered to be of great importance to successful osseointegration. The study investigated oxygen-diffused grade 2 titanium obtained by introducing oxygen into the titanium crystal lattice using thermal treatment in fluidized bed performed at 610°C and 640°C in 6, 8, 12h. The thermal treatment at different temperatures and different times led to the formation of a TiO2 rutile film on the titanium surface and a concentration gradient of oxygen into titanium (XRD/GID analyses and GDOS results). Moreover Raman spectroscopy results showed that the TiO2 film on the surface titanium was composed of two oxides (TiO2), i.e. anatase and rutile, for the analyzed variants of heat treatment. The aim of the present study was to establish the optimum conditions for obtaining oxygen-diffused TiO2 film. The results obtained in the study demonstrated that the use of a fluidized bed for titanium oxidation processes allows for obtaining uniform oxide layers with good adhesion to the substrate, thus improving the titanium surface to suit biomedical applications.

Molecular characterization of capsular polysaccharides and surface protein genes in relation to genetic similarity of group B streptococci isolated from Polish pregnant women.

Serotyping, subtyping and genotyping are important tools for epidemiological studies of group B streptococci (GBS). We investigated the genotype distribution of 353 GBS isolates originating from vaginal or rectal carriage to identify capsular serotypes and subtypes based on the surface protein genes of the alpha-like protein (Alp) family. GBS were recovered from 30% of 1176 pregnant women during the period 2007-2009, with a predominance of capsular genotypes III (35%), Ia (20%), V (17%), II (15%), Ib (8%) and IV (5%). The most common Alp gene was epsilon (26%), followed by rib (22%), alp2 (21%), bca (17%) and alp3 (14%). Several protein genes were significantly associated (G(2)=249·635, P<0·0001) with particular serotypes: epsilon with Ia, Ib, IV; bca with Ib, II; rib with II, III; alp3 with V; alp2 with III. High genetic diversity within GBS strains was observed using DNA macrorestriction. Serotypes Ib, II and III demonstrated the greatest genetic heterogeneity and serotype V the lowest heterogeneity (relative frequency coefficient ≥0·03 vs. -0·46, respectively). Macrolide-resistant strains with serotype V and alp3 gene, showed higher uniformity in genetic profile. The distribution of serotypes and surface proteins of GBS strains are necessary data to inform the design and formulation of new GBS vaccines for use in Poland and other countries.