Better compliance with hypofractionation vs. conventional fractionation in adjuvant breast cancer radiotherapy

Abstract

Background

The aim of the study was to identify factors significantly associated with the occurrence of unintended treatment interruptions in adjuvant breast cancer radiotherapy.

Patients and methods

Patients treated with postoperative radiotherapy of the breast or chest wall between March 2014 and August 2016 were evaluated. The radiotherapy regimens and techniques applied were either conventional fractionation (CF; 28 daily fractions of 1.8 Gy or 25 fractions of 2.0 Gy) or hypofractionation (HF; 15 daily fractions of 2.67 Gy) with inverse planned intensity-modulated radiotherapy (IMRT) or three-dimensional planned conformal radiotherapy (3DCRT). Logistic regression analysis was used to identify factors associated with noncompliance. Noncompliance was defined as the missing of at least one scheduled radiotherapy fraction.

Results

In all, 19 of 140 (13.6%) patients treated with HF and 39 of 146 (26.7%) treated with CF experienced treatment interruptions. Of 23 factors tested, the fractionation regimen emerged as the only independent significant prognostic factor for noncompliance on multivariate analysis (CF; p = 0.007; odds ratio, 2.3; 95% confidence interval, 1.3–4.2). No statistically significant differences concerning the reasons for treatment interruptions could be detected between patients treated with CF or HF.

Conclusion

HF is significantly associated with a better patient compliance with the prescribed radiotherapy schedule compared with CF. The data suggest that this finding is basically related to the shorter overall treatment time of HF.

http://ift.tt/2mh9tn3

Complexity in cancer stem cells and tumor evolution: towards precision medicine

Publication date: Available online 23 February 2017
Source:Seminars in Cancer Biology
Author(s): Caterina A.M. La Porta, Stefano Zapperi
In this review, we discuss recent advances on the plasticity of cancer stem cells and highlight their relevance to understand the metastatic process and to guide therapeutic interventions. Recent results suggest that the strict hierarchical structure of cancer cell populations advocated by the cancer stem cell model must be reconsidered since the depletion of cancer stem cells leads the other tumor cells to switch back into the cancer stem cell phenotype. This plasticity has important implications for metastasis since migrating cells do not need to be cancer stem cells in order to seed a metastasis. We also discuss the important role of the immune system and the microenvironment in modulating phenotypic switching and suggest possible avenues to exploit our understanding of this process to develop an effective strategy for precision medicine.



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Editorial Board

Publication date: 1 March 2017
Source:Acta Biomaterialia, Volume 50





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Biomimetic collagen/elastin meshes for ventral hernia repair in a rat model

Publication date: 1 March 2017
Source:Acta Biomaterialia, Volume 50
Author(s): Silvia Minardi, Francesca Taraballi, Xin Wang, Fernando J. Cabrera, Jeffrey L. Van Eps, Andrew B. Robbins, Monica Sandri, Michael R. Moreno, Bradley K. Weiner, Ennio Tasciotti
Ventral hernia repair remains a major clinical need. Herein, we formulated a type I collagen/elastin crosslinked blend (CollE) for the fabrication of biomimetic meshes for ventral hernia repair. To evaluate the effect of architecture on the performance of the implants, CollE was formulated both as flat sheets (CollE Sheets) and porous scaffolds (CollE Scaffolds). The morphology, hydrophylicity and in vitro degradation were assessed by SEM, water contact angle and differential scanning calorimetry, respectively. The stiffness of the meshes was determined using a constant stretch rate uniaxial tensile test, and compared to that of native tissue. CollE Sheets and Scaffolds were tested in vitro with human bone marrow-derived mesenchymal stem cells (h-BM-MSC), and finally implanted in a rat ventral hernia model. Neovascularization and tissue regeneration within the implants was evaluated at 6weeks, by histology, immunofluorescence, and q-PCR. It was found that CollE Sheets and Scaffolds were not only biomechanically sturdy enough to provide immediate repair of the hernia defect, but also promoted tissue restoration in only 6weeks. In fact, the presence of elastin enhanced the neovascularization in both sheets and scaffolds. Overall, CollE Scaffolds displayed mechanical properties more closely resembling those of native tissue, and induced higher gene expression of the entire marker genes tested, associated with de novo matrix deposition, angiogenesis, adipogenesis and skeletal muscles, compared to CollE Sheets. Altogether, this data suggests that the improved mechanical properties and bioactivity of CollE Sheets and Scaffolds make them valuable candidates for applications of ventral hernia repair.Statement of SignificanceDue to the elevated annual number of ventral hernia repair in the US, the lack of successful grafts, the design of innovative biomimetic meshes has become a prime focus in tissue engineering, to promote the repair of the abdominal wall, avoid recurrence. Our meshes (CollE Sheets and Scaffolds) not only showed promising mechanical performance, but also allowed for an efficient neovascularization, resulting in new adipose and muscle tissue formation within the implant, in only 6weeks. In addition, our meshes allowed for the use of the same surgical procedure utilized in clinical practice, with the commercially available grafts. This study represents a significant step in the design of bioactive acellular off-the-shelf biomimetic meshes for ventral hernia repair.

Graphical abstract

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The Placebo and Nocebo Phenomena: Their Clinical Management and Impact on Treatment Outcomes

Publication date: Available online 23 February 2017
Source:Clinical Therapeutics
Author(s): Victor Chavarria, João Vian, Círia Pereira, João Data-Franco, Brisa S. Fernandes, Michael Berk, Seetal Dodd
PurposeThis overview focuses on placebo and nocebo effects in clinical trials and routine care. Our goal was to propose strategies to improve outcomes in clinical practice, maximizing placebo effects and reducing nocebo effects, as well as managing these phenomena in clinical trials.MethodsA narrative literature search of PubMed was conducted (January 1980–September 2016). Systematic reviews, randomized controlled trials, observational studies, and case series that had an emphasis on placebo or nocebo effects in clinical practice were included in the qualitative synthesis. Search terms included: placebo, nocebo, clinical, clinical trial, clinical setting, placebo effect, nocebo effect, adverse effects, and treatment outcomes. This search was augmented by a manual search of the references of the key articles and the related literature.FindingsPlacebo and nocebo effects are psychobiological events imputable to the therapeutic context. Placebo is defined as an inert substance that provokes perceived benefits, whereas the term nocebo is used when an inert substance causes perceived harm. Their major mechanisms are expectancy and classical conditioning. Placebo is used in several fields of medicine, as a diagnostic tool or to reduce drug dosage. Placebo/nocebo effects are difficult to disentangle from the natural course of illness or the actual effects of a new drug in a clinical trial. There are known strategies to enhance clinical results by manipulating expectations and conditioning.ImplicationsPlacebo and nocebo effects occur frequently and are clinically significant but are underrecognized in clinical practice. Physicians should be able to recognize these phenomena and master tactics on how to manage these effects to enhance the quality of clinical practice.



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Erratum to “Pitavastatin vs Pravastatin in Reduction of Remnant Lipoprotein Cholesterol in Patients with Dyslipidemias” Clin Ther. 2016;39:1250--1251

Publication date: Available online 22 February 2017
Source:Clinical Therapeutics
Author(s): Leonardo Roever




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Interleukin-10: A Compelling Therapeutic Target in Patients With Irritable Bowel Syndrome

Publication date: Available online 23 February 2017
Source:Clinical Therapeutics
Author(s): Sunil Kumar, Ratnakar Shukla, Prabhat Ranjan, Awanish Kumar
PurposePro- and antiinflammatory cytokines are important modulators of the immune response and play a major role in conditions of intestinal inflammation, such as irritable bowel syndrome (IBS). Cytokine production is regulated genetically, and imbalances in cytokine secretion may affect disease susceptibility and clinical outcomes of various conditions. There is a rapidly growing body of evidence to support an etiologic role for gastrointestinal infection and the associated immune activation in the development of postinfectious IBS. Other factors such as psychological stress, anxiety, and depression may likely be involved in the altered profiles of pro- and antiinflammatory cytokines that lead to chronic IBS.MethodsWe searched the literature using PubMed, MEDLINE, and Google Scholar with related key terms and prepared this review article on that basis.FindingsInterleukin (IL)-10 is a regulatory cytokine that inhibits both antigen presentation and the release of proinflammatory cytokines. Therefore, it is proposed as a potent antiinflammatory biological therapy for IBS.ImplicationsRecently, a strong interest in the therapeutic potential of IL-10 for IBS has developed. The diverse roles of IL-10 in IBS are reviewed here. We conducted an in-depth review on IL-10 and IBS to address this question. Future studies of IL-10 may provide new insights into IBS therapy.



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Study on strengthening mechanism of Ti/Cu electron beam welding

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Shun Guo, Qi Zhou, Yong Peng, Xiangfang Xu, Chenglei Diao, Jian Kong, TianYuan Luo, KeHong Wang, Jun Zhu
Welding-brazing method is widely used for dissimilar metals welding. However, it is becoming increasingly difficult to further improve the connection strength by controlling the formation of the transition layer. In this study, an innovative welding method referred to as adjacent welding was addressed, which greatly improved the tensile strength of Ti/Cu dissimilar joint. The strength of new joint could reach up to 89% that of copper base metal, compared to the use of a traditional welding-brazing method which strength coefficient is within the limit of 70%. In order to determine the strengthening mechanism of adjacent welding, optical microscopy, SEM, EDS and XRD were applied for the analysis of microstructure and phase structure. Furthermore, tensile strength was also tested. The results show that due to the process of remelting and reverse solidification of intermetallic compounds (IMCs) layer, a less complex and thinner IMCs layer was formed and TiCu (553HV) with high embrittlement existing in the front of titanium substrate was changed into Ti2Cu (442HV). Performances of joints were optimized by these changes. An interpretation module was presented for the mechanism.

Graphical abstract

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Phase transformations of the L12-Ti3Al phase in γ-TiAl alloy

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Shouzhen Cao, Shulong Xiao, Yuyong Chen, Lijuan Xu, Xiaopeng Wang, Jianchao Han, Yi Jia
A new phase L12-Ti3Al was found in the Ti-46Al-6Nb alloy after rapid-cooling and then annealing at 850°C for 5h. The transformation kinetics involving the L12 phase were observed by transmission electron microscopy (TEM): The plate-like L12 phase precipitates in the massive γ (γm) phase and then partially transforms into α2 or B2 phase; the transformations of bulk α2 (αb)→L12/L12→γ were also observed to form a fine lamellar structure with an average interlamellar spacing <20nm. The orientation relationships between γ, α2 and L12 phases were confirmed by TEM observation and crystallographic calculation, which are (001)γ//(001)L12, [010]γ//[010]L12, [100]γ//[100]L12 and (0001)α2//{111}L12, 〈112¯0〉α2//〈11¯0〉L12. The L12 phase was also observed in Ti-the 47Al alloy after the quenching-annealing process. Thermodynamic analysis of the transformations indicates that the γ→L12 transformation is extremely susceptible to temperature changes while transformations between the α2 and L12 phases are not.

Graphical abstract

http://ift.tt/2lva9qy

Highly sensitive and selective ethanol and acetone gas sensors based on modified ZnO nanomaterials

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Jinxiao Wang, Jun Yang, Ning Han, Xinyuan Zhou, Shuyan Gong, Jianfeng Yang, Peng Hu, Yunfa Chen
Nowadays, highly sensitive metal oxide semiconductor gas sensors are exerting a growing important influence on the detection of target gases. It is still challenging to get both high sensitivity and selectivity to effectively distinguish gas mixtures. In this study, Mn doped ZnO (MZO) is prepared by a facile co-precipitation method and then further modified by CdO addition. The results show that 2.2mol% MZO has high responses to both acetone and ethanol, while 10 mol% CdO activated 1mol% MZO exhibits excellent sensitivity to ethanol and neglectable response to acetone. This is explained by the enhanced alkalinity of ZnO by the CdO addition expelling acetone from adsorption onto the sensor surface, which is verified by temperature–programmed CO2 desorption. Moreover, the CdO-MZO gas sensor has an optimized working temperature of 240°C, far lower than 340°C of MZO, due to the higher oxidativity as proved by the temperature-programmed H2 reduction. The MZO and CdO-MZO gas sensors are then used as a sensor array to distinguish the ethanol and acetone concentrations in mixtures with varied ratios, showing the promise of the gas sensor property tailoring approach for future high performance gas sensors.

Graphical abstract

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Defects engineering induced room temperature ferromagnetism in transition metal doped MoS2

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Yiren Wang, Li-Ting Tseng, Peter P. Murmu, Nina Bao, John Kennedy, Mihail Ionesc, Jun Ding, Kiyonori Suzuki, Sean Li, Jiabao Yi
First principle calculations are employed to calculate the electronic structure and magnetic properties of transition-metal doped MoS2 considering the effects of defect/defect complex. It shows that pure MoS2 with both Mo and S vacancy are nonmagnetic. Mn, Fe, Co and Ni substitution in Mo site all lead to spin polarized state. Considering defect complex, the results show that (TMMo+TMMo) defect complex has the lowest formation energy at high S pressure and prefers close to each other except for (CoMo+CoMo). Experimentally, we doped Mn, Co, Ni and Fe into MoS2 single crystals. The doping leads to room temperature ferromagnetic ordering and clustering, agreeing well with the first principle calculations.

Graphical abstract

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Influence of WO3 addition on the material transfer behavior of the AgTiB2 contact material

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Hangyu Li, Xianhui Wang, Yong Xi, Yanfeng Liu, Xiuhua Guo
To clarify the effect of WO3 addition on the electrical performance of Ag-4wt.%TiB2 contact material, each contact pair was made 20,000 operations at 12 V, 29 A for the Ag-4wt.%TiB2 contact materials without and with WO3 addition. The morphology and chemical composition of arc eroded contact surface were characterized by scanning electron microscope and energy dispersive spectrometer, and the mass change before and after electrical contact test was determined as well. The results show that WO3 addition not only decreases the arc duration and arc energy, but also changes the arc erosion characteristics and material transfer mode. For the Ag-4wt.%TiB2 contact material without WO3 addition, the material transfer occurs from cathode to anode. However, it has an opposite change for the Ag-4wt.%TiB2 contact material with WO3 addition. Furthermore, WO3 addition can prevent the formation of cracks on the eroded surface.

Graphical abstract

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Shear dependent electrical property of conductive shear thickening fluid

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Qian Chen, Mei Liu, Shouhu Xuan, Wanquan Jiang, Saisai Cao, Xinglong Gong
Conductive shear thickening fluid (C-STF) consisting of SiO2 particles, carbon nanotube (CNT) and ethyl glycol (EG) was developed. The shear thickening effect of C-STF was strengthened with the increasing CNT mass fraction. Different from the traditional shear thickening fluid (STF), the as-prepared C-STF showed unique electrical property due to presence of the conductive doping CNT. The initial resistance of C-STF varied from 94 kΩ to 18 kΩ at different CNT mass fractions (0.1wt%, 0.2wt%, 0.3wt% and 0.4wt%). Moreover, the resistance could be critically decreased once accounting the unexpected shear and the decrements reached to as high as 90%. Meanwhile, the shear dependent impedance spectroscopies at different shear rates were analyzed and an equivalent circuit model was proposed to investigate the microstructure dependent electrical property. This phenomenon not only gave much valuable information for understanding the detail shear thickening mechanism but also broadened their application in anti-impact sensor.

Graphical abstract

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Bone age in unilateral spastic cerebral palsy: is there a correlation with hand function and limb length?

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Individualized early death and long-term survival prediction after stereotactic radiosurgery for brain metastases of non-small cell lung cancer: Two externally validated nomograms

Publication date: Available online 23 February 2017
Source:Radiotherapy and Oncology
Author(s): Jaap D. Zindler, Arthur Jochems, Frank J. Lagerwaard, Rosemarijne Beumer, Esther G.C. Troost, Daniëlle B.P. Eekers, Inge Compter, Peter-Paul van der Toorn, Marion Essers, Bing Oei, Coen W. Hurkmans, Anna M.E. Bruynzeel, Geert Bosmans, Ans Swinnen, Ralph T.H. Leijenaar, Philippe Lambin
IntroductionCommonly used clinical models for survival prediction after stereotactic radiosurgery (SRS) for brain metastases (BMs) are limited by the lack of individual risk scores and disproportionate prognostic groups. In this study, two nomograms were developed to overcome these limitations.Methods495 patients with BMs of NSCLC treated with SRS for a limited number of BMs in four Dutch radiation oncology centers were identified and divided in a training cohort (n=214, patients treated in one hospital) and an external validation cohort n=281, patients treated in three other hospitals). Using the training cohort, nomograms were developed for prediction of early death (<3months) and long-term survival (>12months) with prognostic factors for survival. Accuracy of prediction was defined as the area under the curve (AUC) by receiver operating characteristics analysis for prediction of early death and long term survival. The accuracy of the nomograms was also tested in the external validation cohort.ResultsPrognostic factors for survival were: WHO performance status, presence of extracranial metastases, age, GTV largest BM, and gender. Number of brain metastases and primary tumor control were not prognostic factors for survival. In the external validation cohort, the nomogram predicted early death statistically significantly better (p<0.05) than the unfavorable groups of the RPA, DS-GPA, GGS, SIR, and Rades 2015 (AUC=0.70 versus range AUCs=0.51–0.60 respectively). With an AUC of 0.67, the other nomogram predicted 1year survival statistically significantly better (p<0.05) than the favorable groups of four models (range AUCs=0.57–0.61), except for the SIR (AUC=0.64, p=0.34). The models are available on http://ift.tt/2mp6oAm nomograms predicted early death and long-term survival more accurately than commonly used prognostic scores after SRS for a limited number of BMs of NSCLC. Moreover these nomograms enable individualized probability assessment and are easy into use in routine clinical practice.



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Mismatch Repair Deficiency, Microsatellite Instability, and Survival in the MAGIC Trial

This study examines the association among mismatch repair deficiency, microsatellite instability, and survival in patients with resectable gastroesophageal cancer randomized to surgery alone or perioperative chemotherapy.

http://ift.tt/2mbCkMz

Telomere Length and Risk of Cancer and Non-Neoplastic Diseases

This Mendelian randomization study evaluates the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.

http://ift.tt/2mp2fwn

Using the National Cancer Database for Outcomes Research

This review describes the use of the National Cancer Database to study cancer care, with a focus on the advantages of using the database and important considerations that affect the interpretation of National Cancer Database studies.

http://ift.tt/2mbMJrC

A Large Skin Cancer Screening Quality Initiative

This study evaluates a skin cancer screening initiative for risk level of screened population and incidence and thickness of detected melanomas in screened vs unscreened patients of primary care clinics of a large health care system.

http://ift.tt/2mp60lI

PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle

Publication date: Available online 22 February 2017
Source:Journal of Dermatological Science
Author(s): Teruki Yanagi, Hiroo Hata, Eri Mizuno, Shinya Kitamura, Keisuke Imafuku, Shinichi Nakazato, Lei Wang, Hiroshi Nishihara, Shinya Tanaka, Hiroshi Shimizu
BackgroundPCTAIRE1 (also known as cyclin-dependent kinase 16 (Cdk16) and PCTK1) is a Cdk family protein that has been implicated in spermatogenesis. We recently revealed the function of PCTAIRE1 in the tumorigenesis of malignancies, including breast and prostate cancers; however, the tumorigenic function of PCTAIRE1 in cutaneous squamous cell carcinoma (SCC) remains unclear.ObjectiveIn this study, we investigated the role of PCTAIRE1 in the tumorigenesis of cutaneous SCCs.Methods and ResultsIn cutaneous/oral SCC A431, DJM-1, HSC-3 cells, PCTAIRE1 gene-knockdown was found to diminish cell proliferation as assessed by cell counting and clonogenic assays. FACS analyses of annexin V-PI staining and DNA content showed PCTAIRE1 knockdown to cause G2/M arrest followed by apoptosis. The depletion of PCTAIRE1 was found to lead to the accumulation of tumor suppressor p27 and down-regulation of c-Myc. In tumor xenografts of A431 cells, the conditional knockdown of PCTAIRE1 restores p27 protein expression and suppresses tumor growth. Clinically, in primary tumors from patients with SCC, PCTAIRE1 is more highly expressed in malignant lesions than in adjacent normal epidermis. Conversely, expression levels of p27 are significantly lower in SCC than in normal epidermis.ConclusionsOur findings reveal a crucial function for PCTAIRE1 in regulating p27, c-Myc levels and tumor growth in cutaneous SCC cells, suggesting that PCTAIRE1 could be a novel target for skin tumor treatment.



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