Anthocyanin suppresses CoCrMo particle-induced osteolysis by inhibiting IKKα/β mediated NF-κB signaling in a mouse calvarial model

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Yamin Li, Juehong Li, Bin Li, Hui Qin, Xiaochun Peng, Yaochao Zhao, Yunsu Chen
Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model. One hundred and twelve male BALB/c mice were divided randomly into four groups: sham group (sham operation and injection with PBS), vehicle group (CoCrMo particle treatment and injection with PBS), low-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.1mg/g/day), and high–dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.4mg/g/day). Mice were sacrificed after two weeks, harvesting the calvariae tissue for in depth analysis by micro-CT, histomorphometry, immunohistochemical and molecular biology analysis. As expected, anthocyanin markedly inhibited CoCrMo particle–induced inflammatory infiltration and decreased bone loss in vivo. Anthocyanin also reversed the increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoproteger (OPG) and suppressed osteoclast formation in CoCrMo particle–stimulated calvaria. Additionally, anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the calvaria of CoCrMo-stimulated mice. Furthermore, we confirmed that anthocyanin attenuated osteolysis by blocking NF-κB pathway via inhibiting inhibitor of nuclear factor kappa-B kinase α/β (IKKα/β) phosphorylation. In conclusion, our study demonstrated that anthocyanin can protect against CoCrMo particle–induced inflammatory osteolysis via inhibiting the IKKα/β-NF-κB pathway, and have a potential therapeutic effect on the treatment of wear particle–induced osteolysis.



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Identification of triosephosphate isomerase as a novel allergen in Octopus fangsiao

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Yang Yang, Zhong-Wei Chen, Barry K. Hurlburt, Gui-Ling Li, Yong-Xia Zhang, Dan-Xia Fei, Hai-Wang Shen, Min-Jie Cao, Guang-Ming Liu
Octopus is an important mollusk in human dietary for its nutritional value, however it also causes allergic reactions in humans. Major allergens from octopus have been identified, while the knowledge of novel allergens remains poor. In the present study, a novel allergen with molecular weight of 28kDa protein was purified from octopus (Octopus fangsiao) and identified as triosephosphate isomerase (TIM) by mass spectrometry. TIM aggregated beyond 45°C, and its IgE-binding activity was affected under extreme pH conditions due to the altered secondary structure. In simulated gastric fluid digestion, TIM can be degraded into small fragments, while retaining over 80% of the IgE-binding activity. The full-length cDNA of O. fangsiao TIM (1140bp) was cloned, which encodes 247 amino acid residues, and the entire recombinant TIM was successfully expressed in Escherichia coli BL21, which showed similar immunoreactivity to the native TIM. Different intensity of cross-reactivity among TIM from related species revealed the complexity of its epitopes. Eight linear epitopes of TIM were predicted following bioinformatic analysis. Furthermore, a conformational epitope (A71G74S69D75T73F72V67) was confirmed by the phage display technology. The results revealed the physicochemical and immunological characteristics of TIM, which is significant in the development of hyposensitivity food and allergy diagnosis.



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Temporal regulation of Wnt/β-catenin signaling is important for invariant NKT cell development and terminal maturation

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Kalyani Pyaram, Jyoti Misra Sen, Cheong-Hee Chang
The Wnt/β-catenin signaling pathway plays important roles during various cellular functions including survival and proliferation of immune cells. The critical role of this pathway in conventional T cell development is established but little is known about its contributions to innate T cell development. In this study, we found that β-catenin level, an indication of the strength of Wnt/β-catenin signaling, is regulated during invariant NKT (iNKT) cell development. β-catenin levels were greatly increased during iNKT cell selection from double positive thymocytes to Stage 0 of iNKT cell development and during subsequent development to Stage 1. Thereafter, β-catenin levels decrease from Stage 2, which is essential for the terminal maturation of iNKT cells. Failure to dampen Wnt/β-catenin signaling as in mice expressing a stabilized active form of β-catenin (CATtg) resulted in increased Stage 2 and decreased Stage 3 iNKT cells. Inefficient transition from Stage 2 to 3 in CATtg iNKT cells seems to be contributed by poor expression of IL-15R (CD122) and transcription factor T-bet, both of which are necessary for terminal maturation of iNKT cells in the thymus. Consequently, IFN-γ+ iNKT cells were greatly reduced in CATtg mice. Together, our findings reveal that proper regulation of β-catenin and in turn Wnt signaling plays an important role in the terminal maturation and function of iNKT cells.



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CD47 limits antibody dependent phagocytosis against non-malignant B cells

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Sandra Gallagher, Sean Turman, Kristen Lekstrom, Susan Wilson, Ronald Herbst, Yue Wang
Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and −CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP. We show that CD47 is expressed on all B cells in mice, with the highest level on plasma cells in bone marrow and spleen. Although its expression is dispensable for B cell development in mice, CD47 on B cells limits antibody mediated phagocytosis. B cell depletion following in vivo anti-CD19 treatment is more efficient in CD47-/- mice than in wild type mice. In vitro, both naïve and activated B cells from CD47-/- mice are more sensitive to ADCP than wild type B cells. Lastly, we show in an ADCP assay that blocking CD47 can enhance anti-CD19 antibody mediated phagocytosis of wild type B cells. These results suggest that in addition to its already demonstrated benefit in cancer, targeting CD47 may be used as an adjunct in combination with B cell depletion antibodies for treatment of autoimmune diseases.



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Lactobacillus buchneri S-layer as carrier for an Ara h 2-derived peptide for peanut allergen-specific immunotherapy

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Julia Anzengruber, Merima Bublin, Eva Bönisch, Bettina Janesch, Angelika Tscheppe, Matthias L. Braun, Eva-Maria Varga, Christine Hafner, Heimo Breiteneder, Christina Schäffer
Peanut allergy is an IgE-mediated severe hypersensitivity disorder. The lack of a treatment of this potentially fatal allergy has led to intensive research on vaccine development. Here, we describe the design and initial characterization of a carrier-bound peptide derived from the most potent peanut allergen, Ara h 2, as a candidate vaccine. Based on the adjuvant capability of bacterial surface (S-) layers, a fusion protein of the S-layer protein SlpB from Lactobacillus buchneri CD034 and the Ara h 2-derived peptide AH3a42 was produced. This peptide comprised immunodominant B-cell epitopes as well as one T cell epitope. The fusion protein SlpB-AH3a42 was expressed in E. coli, purified, and tested for its IgE binding capacity as well as for its ability to activate sensitized rat basophil leukemia (RBL) cells. The capacity of Ara h 2-specific IgG rabbit-antibodies raised against SlpB-AH3a42 or Ara h 2 to inhibit IgE-binding was determined by ELISA inhibition assays using sera of peanut allergic patients sensitized to Ara h 2. IgE specific to the SlpB-AH3a42 fusion protein was detected in 69% (25 of 36) of the sera. Despite the recognition by IgE, the SlpB-AH3a42 fusion protein was unable to induce β-hexosaminidase release from sensitized RBL cells at concentrations up to 100ng per ml. The inhibition of IgE-binding to the natural allergen observed after pre-incubation of the 20 sera with rabbit anti-SlpB-AH3a42 IgG was more than 30% for four sera, more than 20% for eight sera, and below 10% for eight sera. In comparison, anti-Ara h 2 rabbit IgG antibodies inhibited binding to Ara h 2 by 48% ±13.5%. Our data provide evidence for the feasibility of this novel approach towards the development of a peanut allergen peptide-based carrier-bound vaccine. Our experiments further indicate that more than one allergen-peptide will be needed to induce a broader protection of patients allergic to Ara h 2.



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Caring for children with intellectual disabilities part 1: Experience with the population, pain-related beliefs, and care decisions

Publication date: March 2017
Source:Research in Developmental Disabilities, Volume 62
Author(s): Lara M. Genik, C. Meghan McMurtry, Lynn M. Breau
Some children with intellectual disabilities (ID): experience pain more frequently than children without ID, express their pain differently, and are incapable of providing self-reports. No research has examined disability and pain-related beliefs of respite workers (RW) and their relations to pain assessment and management decisions for children with ID.Objectives(1) compare disability and pain-related beliefs between RW and a sample with little experience in ID; (2) determine whether individuals' beliefs and personal characteristics are related to pain assessment and management decisions.ParticipantsFifty-six RW (aged: 18–67 years, Mage=33.37, 46 female) and 141 emerging adults (aged: 18–31 years, Mage=19.67, 137 female).Procedure/measuresIn an online survey, participants responded to six vignettes depicting pain in children with ID, and completed measures of pain and disability-related beliefs.Results/discussionCompared to those without experience, RW held more positive disability-related beliefs, t(192)=4.23, p<0.001. Participants' pain-related beliefs (e.g., sensitivity to pain) differed depending on severity of the child's ID and participant group. Participants' pain-related beliefs predicted care decisions. Results provide initial insight into RW pain-related beliefs about children with ID, and a basic understanding of the relations among pain beliefs, personal characteristics and pain-related decisions.



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How have evolutions in strategies for the treatment of relapsed/refractory multiple myeloma translated into improved outcomes for patients?

Publication date: Available online 14 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Pieter Sonneveld, Edwin De Wit, Philippe Moreau
Although multiple myeloma (MM) remains incurable, the introduction of novel agents has improved clinical outcomes dramatically over the past 15 years. Response rates have risen from ∼30% with single agents to up to 90% with combination therapies. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, form the foundations for treatment of relapsed and/or refractory MM (RRMM). Newer agents, such as the IMiD pomalidomide, the histone deacetylase inhibitor panobinostat and the proteasome inhibitors carfilzomib and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab, have further improved overall response rates in these patients. Importantly, increased response rates have been observed in heavily pretreated patients. The availability of highly effective and tolerable drugs may offer alternative treatment strategies to those who are unsuitable for treatment with thalidomide, lenalidomide or bortezomib. Improving tolerability of treatment regimens and lengthening progression‐free intervals has been shown to significantly improve health-related quality of life for patients living with RRMM.



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Asparaginase pharmacology: challenges still to be faced

Abstract

Purpose

The benefits of asparaginase (ASNASE) in the treatment of ALL and NHL are indisputable and new ASNASE preparations are under clinical development to overcome limitations of the actual ASNASE therapy, especially immunogenicity. Apart from ALL and NHL further indications of ASNASE are preclinically and clinically evaluated.

Methods

We reviewed ASNASE literature and especially focused on the mechanism of action, on biomarker, which determine ASNASE sensitivity and resistance, and on ASNASE pharmacodynamics in vivo.

Results

More than 40 years after the clinical introduction of ASNASE its mechanism of action is yet not fully understood. Studies on asparagine synthetase (ASNS) as biomarker for ASNASE resistance are contradictory and complicated by methodological obstacles. The role of glutamine hydrolysis for ASNASE efficacy is still debated, other mechanisms are possibly not yet identified. In addition, individual pharmacokinetic/-dynamic relationships cannot be properly addressed because of methodological limitations.

Conclusion

More sophisticated preclinical models and suitable methods for monitoring of ASNASE pharmacodynamics are urgently needed (1) to understand the mechanism of action, (2) to establish valid biomarkers for ASNASE sensitivity and resistance, (3) to evaluate the pharmacokinetics/-dynamics of ASNASEs in individual patients, and (4) to compare the bioequivalence of clinically established, as well as new ASNASE preparations.

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Age-related reduction of dermal fibroblast size up-regulates multiple matrix metalloproteinases as observed in aged human skin in vivo

Summary

Background

Fragmentation of collagen fibrils, the major structure protein in skin, is a hallmark of dermal aging. Matrix metalloproteinases (MMPs) are largely responsible for fragmentation of collagen fibrils. However, the alteration of all known mammalian MMPs and the mechanism underlying altered expression of MMPs in chronologically aged human skin are less understood.

Objectives

To quantify gene expression of all 23 known mammalian MMPs in sun-protected young and aged human skin in vivo, and investigate the potential mechanism underlying age-related alteration of multiple MMPs.

Methods

MMPs mRNA expression levels and MMPs activity in sun-protected young and aged human skin in vivo were determined by real-time RT-PCR and in situ zymography, respectively. The relative contributions to elevated MMPs in epidermis and dermis were quantified by laser capture microdissection (LCM) coupled real-time RT-PCR. Dermal fibroblast morphology and collagen fibrils fragmentation in human skin in vivo were assessed by second harmonic generation microscopy and atomic force microscopy, respectively. In vitro cell morphology was assessed by CellTracker^® fluorescent dye and Phalloidin staining. Protein levels were determined by ProteinSimple capillary electrophoresis immunoassay.

Results

Among all 23 known mammalian MMPs, multiple MMPs are elevated in aged human skin dermis. Consistent with this finding, increased MMPs activity and collagen fibrils fragmentation were observed in aged skin dermis. As dermal fibroblasts are the major MMPs producing cells in the dermis, reduction of dermal fibroblast size, which is observed in aged human skin, contributes to elevation of age-related multiple MMPs. Reduction of fibroblast size up-regulates c-Jun/c-Fos and activates AP-1, the major regulator of multiple MMPs.

Conclusions

Combined actions of the wide variety of MMPs that are constitutively elevated in aged dermis may be involved in progressive degradation of dermal collagen fibrils. Age-related elevations of multiple MMPs are likely resulted from the reduction of fibroblast size via activation of AP-1.

This article is protected by copyright. All rights reserved.

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Detection of human parvovirus B19 DNA in 22% of 1,815 cutaneous biopsies of a wide variety of dermatologic conditions suggests viral persistence after primary infection and casts doubts on its pathogenic significance

Summary

Background

Human parvovirus B19 (B19V) has been associated with a number of dermatologic and systemic conditions, including myocarditis and autoimmune syndromes.

Objectives

To determine the frequency of B19V deoxyribonucleic acid (DNA) detection in a large dermatopathology practice, and to characterize the histopathologic patterns involved.

Methods

We selected for polymerase chain reaction (PCR) detection of B19V a total of 1,815 skin biopsies pertaining to entities allegedly related to Parvovirus B19, as well as cases suspected clinically of representing paraviral exanthemas. Immunohistochemical detection of B19V viral protein 2 (VP2) was performed in 92 PCR-positive cases.

Results

B19V DNA was found by PCR in 402 out of 1,825 biopsy specimens (22%). VP2 protein was identified by immunohistochemistry only in three instances of papular purpuric "gloves and socks" syndrome.

Conclusions

Since the virus has the capacity to persist in different tissues (including the skin) for long periods, it could represent merely an innocent bystander, so no pathogenetic significance can be inferred from the PCR positivity for B19V in the vast majority of dermatologic conditions studied.

This article is protected by copyright. All rights reserved.

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Properties and evolution of dissolved organic matter during co-composting of dairy manure and Chinese herbal residues

Abstract

Composting is an effective method in treating solid organic wastes, in which dissolved organic matter (DOM) plays an important role in transformation of organic matter and microbial activity. Therefore, an understanding of the properties and evolution of DOM during composting is crucial. In this study, DOM was studied using elemental analysis, spectroscopic analysis (UV-vis, FTIR, and pyrolysis-GC/MS), and colloidal analysis during a 120-day composting. Results showed that the content of N and O in DOM increased while C and H content declined progressively over the composting time. Aliphatic C–H stretching, aromatic C=C or C=O stretching of amide groups, and C–O stretch (carbohydrates) showed an obvious decrease, while COO– and C–N groups had a significant increase. The evolution of DOM indicated a gradual decrease of the lipid and polysaccharide fractions, whereas an increase of aromatic and nitrogenous compounds was observed. The DOM also showed a more stable status, and an accumulation of small molecular compounds occurred with composting proceeded. Taken together, these results shed a good insight into the properties and evolution of DOM during a composting process.

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Influences of chromium and cadmium on the development of black soldier fly larvae

Abstract

The black soldier fly Hermetia illucens is a good candidate for waste management. The harvested insects are rich in protein and have the potential to be used in animal feed. However, people are wary about heavy metals in waste. Therefore, it is necessary to understand how the uptake of heavy metals could affect H. illucens and where and to what extent metals are accumulated by the black soldier fly. Based on these considerations, developmental parameters were investigated in the different life stages of H. illucens fed an increasing concentration gradient of cadmium (Cd) and chromium (Cr); additionally, Cd and Cr distribution in the body parts of H. illucens at the different life stages was monitored. We found that Cd and Cr have no effects on larvae survival and eclosion rate, but they do have effects on larvae duration and pupation rate. Both Cd and Cr were transferred into larvae, prepupae, and pupae. While the concentrations of Cd in larvae and prepupae were much higher than that in their diets, the opposite case was observed with Cr. The concentrations of Cd and Cr in H. illucens decreased in later development stages. In individual larva and prepupa, Cd and Cr were mainly included in the body and not in the integument. In the pupa, the puparium contained higher Cd and Cr concentrations than the pupa body. The distribution of Cd and Cr in the different life stages and body parts may present a potential strategy for how H. illucens tolerate and remove heavy metal stress.

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Hydrothermal synthesized magnetically separable mesostructured H 2 Ti 3 O 7 /γ-Fe 2 O 3 nanocomposite for organic dye removal via adsorption and its regeneration/reuse through synergistic non-radiation driven H 2 O 2 activation

Abstract

Hydrogen titanate (H₂Ti₃O₇) nanotubes/nanosheets (HTN) are emerging class of adsorbent material which possess unique property of activating hydrogen peroxide (H₂O₂) to generate the reactive oxygen species (ROS), such as superoxide radical ions (O₂^.−) and hydroxyl radicals (·OH), effective in the decomposition of surface-adsorbed dye. However, HTN are non-magnetic which create hurdle in their effective separation from the treated aqueous solution. To overcome this issue, magnetic nanocomposites (HTNF) composed of HTN and maghemite (γ-Fe₂O₃) nanoparticles have been processed by subjecting the core–shell magnetic photocatalyst consisting of γ-Fe₂O₃/silica (SiO₂)/titania (TiO₂), having varying amounts of TiO₂ in the shell to the hydrothermal conditions. HTNF-5 magnetic nanocomposite consisting of 31 wt% H₂Ti₃O₇, typically having nanotube morphology with the highest specific surface area (133 m² g⁻¹) and pore-volume (0.22 cm³ g⁻¹), exhibits the highest capacity (74 mg g⁻¹) for the adsorption of cationic methylene blue (MB) dye from an aqueous solution involving the electrostatic attraction mechanism and pseudo-second-order kinetics. Very fast magnetic separation followed by regeneration of HTNF-5 magnetic nanocomposite has been demonstrated via non-radiation driven H₂O₂ activation. It has been ascertained for the first time that the underlying mechanism of dye decomposition involves the synergy effect between the constituents of HTNF magnetic nanocomposite.

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A Phase I/IIa Study of DHP107, a Novel Oral Paclitaxel Formulation, in Patients with Advanced Solid Tumors or Gastric Cancer

Lessons Learned

Ideally, patients should have access to an oral formulation of paclitaxel, as well as an intravenous formulation, to allow development of regimens exploring alternate schedules and to avoid reactions to Cremophor EL (BASF Corp., Ludwigshafen, Germany, https://www.basf.com).

DHP107 is a novel oral paclitaxel formulation that is a tolerable and feasible regimen for patients with gastric cancer, with data suggesting efficacy similar to that of intravenous paclitaxel.

Background.

We evaluated the maximum tolerated dose (MTD) of DHP107, a novel oral paclitaxel formulation, and the efficacy and safety of the agent in patients with advanced solid tumors.

Patients and Methods.

Phase I study: cohorts of 3–6 patients with advanced solid tumors received escalating DHP107 doses. Phase IIa study: patients with measurable advanced gastric cancer received DHP107, 200 mg/m² b.i.d., on days 1, 8, and 15 every 4 weeks. Pharmacokinetics, safety, and efficacy were analyzed.

Results.

Phase I: 17 patients received a dose-escalating regimen of DHP107, 150–250 mg/m² b.i.d. Dose-limiting toxicities were neutropenia and febrile neutropenia. The MTD (recommended dose) for phase IIa was 200 mg/m² b.i.d. Phase IIa: 11 patients with measurable advanced gastric cancer in whom first-line therapy failed received DHP107 (MTD). Three confirmed partial responses were observed. Median progression-free survival of gastric cancer patients (n = 16) treated at the MTD was 2.97 (95% confidence interval, 1.67–5.40) months (Fig. 1). The most frequent grade 3/4 adverse events were neutropenia (35.3%) and leukopenia (17.6%) at the MTD (phase I and IIa combined; n = 17).

Conclusion.

DHP107 showed good antitumor efficacy and was tolerable. The MTD (200 mg/m² b.i.d.) is recommended for use in further studies comparing DHP107 with standard intravenous paclitaxel therapy. The Oncologist 2017;22:000–000

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An International Vascular Registry Infrastructure for Medical Device Evaluation and Surveillance

Publication date: Available online 14 February 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): A. Sedrakyan, J.L. Cronenwett, M. Venermo, L. Kraiss, D. Marinac-Dabic, M. Björck




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Neck muscle fatigue differentially alters scapular and humeral kinematics during humeral elevation in subclinical neck pain participants versus healthy controls

Publication date: Available online 14 February 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Mahboobeh Zabihhosseinian, Michael W.R. Holmes, Samuel Howarth, Brad Ferguson, Bernadette Murphy
BackgroundScapular orientation is highly dependent on axioscapular muscle function. This study examined the impact of neck muscle fatigue on scapular and humeral kinematics in participants with and without subclinical neck pain (SCNP) during humeral elevation.MethodsTen SCNP and 10 control participants performed three unconstrained trials of dominant arm humeral elevation in the scapular plane to approximately 120 degrees before and after neck extensor muscle fatigue. Three-dimensional scapular and humeral kinematics were measured during the humeral elevation trials.ResultsHumeral elevation plane angle showed a significant interaction between groups (SCNP vs controls) and trial (pre- vs post-fatigue) (p=.001). Controls began the unconstrained humeral elevation task after fatigue in a more abducted position, (p=.002). Significant baseline differences in scapular rotation existed between the two groups (Posterior/Anterior tilt, p=.04; Internal/External Rotation, p=.001).DiscussionSCNP contributed to altered scapular kinematics. Neck muscle fatigue influenced humeral kinematics in controls but not the SCNP group; suggesting that altered scapular motor control in the SCNP group resulted in an impaired adaption further to the neck muscle fatigue.



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Individualized selection of beam angles and treatment isocenter in tangential breast IMRT

Publication date: Available online 14 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Joan Penninkhof, Sara Spadola, Sebastiaan Breedveld, Margreet Baaijens, Nico Lanconelli, Ben Heijmen
Purpose/objectivePropose a novel method for individualized selection of beam angles and treatment isocenter in tangential breast IMRT.Methods and MaterialsFor each patient, beam and isocenter selection starts with the fully automatic generation of a large database of IMRT plans (up to 847 in this study), each of these plans belongs to a unique combination of isocenter position, lateral beam angle, and medial beam angle. The imposed hard planning constraint on patient maximum dose may result in plans with unacceptable target dose delivery. Such plans are excluded from further analyses. Due to differences in beam set-up, database plans differ in mean doses in organs-at-risk (OARs). These mean doses are used to construct 2-dimensional graphs, showing relationships between 1) contralateral breast dose and ipsilateral lung dose, and 2) contralateral breast dose and heart dose (analyzed only for left-sided). The graphs can be used for selection of the isocenter and beam angles with the optimal, patient-specific trade-offs between the mean OAR doses. For 30 previously treated patients (15 left-sided and 15 right-sided tumors), graphs were generated considering only the clinically applied isocenter with 121 tangential beam angle pairs. For 20 of the 30 patients, 6 alternative isocenters were investigated as well.ResultsComputation time for automatic generation of 121 IMRT plans took on average 30 minutes. The generated graphs demonstrated large variations in trade-offs between conflicting OAR objectives, depending on beam angles and patient anatomy. For patients with isocenter optimization, 847 IMRT plans were considered. Adding isocenter position optimization next to beam angle optimization had a small impact on the final plan quality.ConclusionA method is proposed for individualized selection of beam angles in tangential breast IMRT. This may be especially important for patients with cardiac risk factors or an enhanced risk for development of contralateral breast cancer.

Teaser

A method for individualized selection of beam angles and treatment isocenter in tangential breast IMRT, based on graphical representations of mean OAR doses in a large database of automatically generated IMRT plans, is presented. The method may be especially useful for patients with cardiac risk factors or an enhanced risk for induction of a tumor in the contralateral breast.


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Salvage treatment options for recurrent seminoma? Expert Opinion Commentary

Publication date: Available online 14 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Peter Chung, Padraig Warde




http://ift.tt/2ldlQmg

Development of a Quality and Safety Competency Curriculum for Radiation Oncology Residency: An International Delphi Study

Publication date: Available online 14 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jenna Adleman, Caitlin Gillan, Amanda Caissie, Carol-Anne Davis, Brian Liszewski, Andrea McNiven, Meredith Giuliani
PurposeThe purpose of this study was to develop an entry-to-practice quality and safety competency profile for radiation oncology (RO) residency.Methods and MaterialsA comprehensive list of potential quality and safety competency items was generated from public and professional resources and interprofessional focus groups. Redundant or out-of-scope items were eliminated through investigator consensus. Remaining items were subjected to an international two-round modified Delphi process involving experts in RO, radiation therapy, and medical physics. During Round One, each item was scored independently on a 9-point Likert scale indicating appropriateness for inclusion in the competency profile. Items indistinctly ranked for inclusion or exclusion were reevaluated through web-conference discussion and re-ranked in Round Two.ResultsAn initial 1,211 items were compiled from 32 international sources and distilled to 105 unique potential quality and safety competency items. Fifteen of the 50 invited experts participated in Round One: 10 radiation oncologists, four radiation therapists, and one medical physicist from 13 centres in five countries. Round One rankings resulted in 80 items included, one item excluded, and 24 items indeterminate. Two areas emerged more prominently within the latter group: change management and human factors. Web-conference with five participants resulted in nine of these 24 items edited for content or clarity. In Round Two, 12 participants rescored all indeterminate items resulting in 10 items ranked for inclusion. The final 90 enabling competency items were organized into thematic groups consisting of 18 key competencies under headings adapted from Deming's System of Profound Knowledge.ConclusionsThis quality and safety competency profile may inform minimum training standards for RO residency programs.

Teaser

The purpose of this study was to develop an entry-to-practice quality and safety competency profile for radiation oncology (RO) residency education. An international 2-round modified Delphi process was conducted with participation from 15 experts in radiation oncology representing 13 centres in five countries. Ninety of the initial 105 items were ranked for inclusion in the final competency profile. This profile may form the basis of quality and safety training standards in RO residency programs.


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Predicting patient-specific dosimetric benefits of proton therapy for skull-base tumors using a geometric knowledge-based method

Publication date: Available online 14 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): David C. Hall, Alexei V. Trofimov, Brian A. Winey, Norbert J. Liebsch, Harald Paganetti
PurposeTo predict the organ-at-risk (OAR) dose levels achievable with proton beam therapy (PBT), solely based upon the geometric arrangement of the target volume in relation to the OARs. Comparison to an alternative therapy yields a prediction of the patient-specific benefits offered by PBT. This could enable a physician at a hospital without proton capabilities to make a better-informed referral decision, or aid patient selection in model-based clinical trials.Methods and MaterialsSkull-base tumors were chosen to test the method, owing to their geometric complexity and multitude of nearby OARs. By exploiting correlations between dose and distance-to-target in existing PBT plans, models were independently trained for six types of OAR: brainstem, cochlea, optic chiasm, optic nerve, parotid gland and spinal cord. Once trained, the models could estimate the feasible dose-volume histogram and generalized equivalent uniform dose (gEUD) for OAR structures of new patients. Models were trained using 20 patients and validated with a further 21 patients. Validation was achieved by comparing the predicted gEUD to that of the actual PBT plan.ResultsThe predicted and planned gEUD were in good agreement: considering all OARs, the prediction error was +1.4 ± 5.1 Gy (mean ± SD) and Pearson's correlation coefficient was 93%. When compared to an IMRT plan, the model could classify whether an OAR structure would experience a gain with a sensitivity of 93% (95% CI: 87% – 97%) and a specificity of 63% (95% CI: 38% – 84%).ConclusionsWe trained and validated models that quickly and accurately predict the patient-specific benefits of PBT for skull-base tumors. Similar models could be developed for other tumor sites. Such models are useful when an estimation of the feasible benefits of PBT is desired, but the experience and/or resources required for treatment planning are unavailable.

Teaser

This work aims to develop models that can predict the patient-specific benefits offered by proton therapy, solely based upon a patient's geometry. A knowledge-based method trains the models upon geometric patterns observed in a set of existing proton treatment plans for skull base tumors. The models were validated yielding a Pearson's correlation coefficient of 93%; similar models could be trained for other tumor sites and be used to make better-informed referral decisions.


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