bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual and reproductive health of women living with HIV in Muslim-majority countries: a systematic mixed studies review
Authors: Juliastuti Dyah , Dean Judith , Fitzgerald Lisa
Published: March 2020

Background

The number of women living with the human immunodeficiency virus (WLHIV) in Muslim-majority countries has increased significantly in the last decade. These women are often marginalized and face insecure sexual and reproductive health (SRH) needs and rights. However, little is known about the multi-faceted factors influencing these women’s fertility, contraceptive, and perinatal decisions and sexual life. This systematic mixed studies review aimed to synthesize the empirical evidence on social, cultural, and structural factors influencing the SRH of WLHIV in Muslim-majority countries.

Methods

This review provides a synthesis of quantitative, qualitative and mixed-method research findings searched from PubMed, EMBASE, Scopus, CINAHL and Cochrane databases. We screened 3452 SRH studies involving WLHIV. The studies, published in English between 2008 and 2017, were from 20 Muslim-majority countries with increased numbers of WLHIV. The quality of eligible studies was appraised using a mixed-methods appraisal tool (MMAT) version 2011. Findings were thematically analysed by a hybrid deductive-inductive approach. Two independent reviewers were involved in the study selection, data extraction, quality appraisal, and data synthesis.

Results

We included 13 SRH-related studies involving 1748 WLHIV in eight Muslim-majority countries. Most of these studies explored fertility desire and sexual health, while only a small proportion related to contraceptive use and the perinatal-care experience. We identified that WLHIV faced neglect of their SRH rights. These rights were predominantly affected by the socio-cultural, religious and health-services context of the women’s lives, which directed them to unsafe sex practices and stressful perinatal experiences.

Conclusions

This study points to the need for SRH laws, policies, and interventions which stop WLHIV experiencing SRH discrimination violence and achieving their SRH rights.
Use of the lignocellulose-degrading bacterium Caldicellulosiruptor bescii to assess recalcitrance and conversion of wild-type and transgenic poplar
Authors: Straub Christopher T. , Bing Ryan G. , Wang Jack P. , Chiang Vincent L. , Adams Michael W. W. , Kelly Robert M.
Published: March 2020

Background

Biological conversion of lignocellulosic biomass is significantly hindered by feedstock recalcitrance, which is typically assessed through an enzymatic digestion assay, often preceded by a thermal and/or chemical pretreatment. Here, we assay 17 lines of unpretreated transgenic black cottonwood (Populus trichocarpa) utilizing a lignocellulose-degrading, metabolically engineered bacterium, Caldicellulosiruptor bescii. The poplar lines were assessed by incubation with an engineered C. bescii strain that solubilized and converted the hexose and pentose carbohydrates to ethanol and acetate. The resulting fermentation titer and biomass solubilization were then utilized as a measure of biomass recalcitrance and compared to data previously reported on the transgenic poplar samples.

Results

Of the 17 transgenic poplar lines examined with C. bescii, a wide variation in solubilization and fermentation titer was observed. While the wild type poplar control demonstrated relatively high recalcitrance with a total solubilization of only 20% and a fermentation titer of 7.3 mM, the transgenic lines resulted in solubilization ranging from 15 to 79% and fermentation titers from 6.8 to 29.6 mM. Additionally, a strong inverse correlation (R2 = 0.8) between conversion efficiency and lignin content was observed with lower lignin samples more easily converted and solubilized by C. bescii.

Conclusions

Feedstock recalcitrance can be significantly reduced with transgenic plants, but finding the correct modification may require a large sample set to identify the most advantageous genetic modifications for the feedstock. Utilizing C. bescii as a screening assay for recalcitrance, poplar lines with down-regulation of coumarate 3-hydroxylase 3 (C3H3) resulted in the highest degrees of solubilization and conversion by C. bescii. One such line, with a growth phenotype similar to the wild-type, generated more than three times the fermentation products of the wild-type poplar control, suggesting that excellent digestibility can be achieved without compromising fitness of the tree.
Understanding the structural characteristics of water-soluble phenolic compounds from four pretreatments of corn stover and their inhibitory effects on enzymatic hydrolysis and fermentation
Authors: Chen Xiangxue , Zhai Rui , Li Ying , Yuan Xinchuan , Liu Zhi-Hua , Jin Mingjie
Published: March 2020

Background

For bioethanol production from lignocellulosic biomass, phenolics derived from pretreatment have been generally considered as highly inhibitory towards enzymatic hydrolysis and fermentation. As phenolics are produced from lignin degradation during pretreatment, it is likely that the pretreatment will exert a strong impact on the structure of phenolics, resulting in varied levels of inhibition of the bioconversion process. Despite the extensive studies on pretreatment, it remains unclear how pretreatment process affects the properties of generated phenolics and how the inhibitory effect of phenolics from different pretreatment varies on enzymatic hydrolysis and fermentation.

Results

In this study, the structural properties of phenolic compounds derived from four typical pretreatment [dilute acid (DA), liquid hot water pretreatment (LHW), ammonia fiber expansion (AFEX) and alkaline pretreatment (AL)] were characterized, and their effect on both enzymatic hydrolysis and fermentation were evaluated. The inhibitory effect of phenolics on enzymatic hydrolysis followed the order: AFEX > LHW > DA > AL, while the inhibitory effect of phenolics on Zymomonas mobilis 8b strain fermentation followed the order: AL > LHW > DA > AFEX. Interestingly, this study revealed that phenolics derived from AFEX showed more severe inhibitory effect on enzymatic hydrolysis than those from the other pretreatments at the same phenolics concentrations (note: AFEX produced much less amount of phenolics compared to AL and DA), while they exhibited the lowest inhibitory effect on fermentation. The composition of phenolics from different pretreatments was analyzed and model phenolics were applied to explore the reason for this difference. The results suggested that the amide group in phenolics might account for this difference.

Conclusions

Pretreatment process greatly affects the properties of generated phenolics and the inhibitory effects of phenolics on enzymatic hydrolysis and fermentation. This study provides new insight for further pretreatment modification and hydrolysate detoxification to minimize phenolics-caused inhibition and enhance the efficiency of enzymatic hydrolysis and fermentation.
Schur-convexity for compositions of complete symmetric function dual
Authors: Shi Huan-Nan , Wang Pei , Zhang Jian
Published: March 2020

The Schur-convexity for certain compound functions involving the dual of the complete symmetric function is studied. As an application, the Schur-convexity of some special symmetric functions is discussed and some inequalities are established.
Barriers and facilitators to implementing priority inpatient initiatives in the safety net setting
Authors: Crable Erika L. , Biancarelli Dea , Walkey Allan J. , Drainoni Mari-Lynn
Published: March 2020

Background

Safety net hospitals, which serve vulnerable and underserved populations and often operate on smaller budgets than non-safety net hospitals, may experience unique implementation challenges. We sought to describe common barriers and facilitators that affect the implementation of improvement initiatives in a safety net hospital, and identify potentially transferable lessons to enhance implementation efforts in similar settings.

Methods

We interviewed leaders within five inpatient departments and asked them to identify the priority inpatient improvement initiative from the last year. We then conducted individual, semi-structured interviews with 25 stakeholders across the five settings. Interviewees included individuals serving in implementation oversight, champion, and frontline implementer roles. The Consolidated Framework for Implementation Research informed the discussion guide and a priori codes for directed content analysis.

Results

Despite pursuing diverse initiatives in different clinical departments, safety net hospital improvement stakeholders described common barriers and facilitators related to inner and outer setting dynamics, characteristics of individuals involved, and implementation processes. Implementation barriers included (1) limited staffing resources, (2) organizational recognition without financial investment, and (3) the use of implementation strategies that did not adequately address patients’ biopsychosocial complexities. Facilitators included (1) implementation approaches that combined passive and active communication styles, (2) knowledge of patient needs and competitive pressure to perform well against non-SNHs, (3) stakeholders’ personal commitment to reduce health inequities, and (4) the use of multidisciplinary task forces to drive implementation activities.

Conclusion

Inner and outer setting dynamics, individual’s characteristics, and process factors served as implementation barriers and facilitators within the safety net. Future work should seek to leverage findings from this study toward efforts to enact positive change within safety net hospitals.
Optimizing spatial distribution to minimize the inline directivity for a marine air-gun source
Authors: Shen Honglei , Tao Chunhui , Elboth Thomas , Wang Hanchuang , Zhou Jianping , Qiu Lei , Liu Yunlong , Chen Jiachun , Jin Xiaobing
Published: March 2020

The spatial distribution of an air-gun array and the ghost reflection from the air-water interface cause a directional pattern of the source signature and introduce notches at certain frequencies. This significantly limits the bandwidth of the seismic data and the ability to obtain high-resolution subsurface imaging. With mathematical derivation and numerical simulation, we have determined that the inline directivity relies on the number of air guns and their spacing. Furthermore, the effective width of the take-off angles for an air-gun array is highly correlated with the reciprocal of the distance variance along the inline direction, which is subsequently used for optimizing the source design. For a normal horizontal source, one could adjust the distance between two consecutive air guns to improve the source signature. We optimize the spatial distribution for air guns along the inline and depth directions, that is, by using the synchronized multidepth stimulation mode, to minimize the inline directivity. Simulated results show that a six-gun composed multidepth source could be designed to achieve nearly identical energy distribution with up to ±30° take-off angle for the high-frequency end up to 250 Hz. This represents a significant improvement compared to a normal horizontal source and is more suitable for high-resolution seismic acquisition.
Application of Backus average to simulate acoustic logs in thinly bedded formations
Authors: Maalouf Elsa , Torres-Verdín Carlos , Liu Jingxuan
Published: March 2020

Slowness logs acquired in layered formations are not only affected by spatial averaging associated with the borehole acoustic tool. Layers with thicknesses smaller than the acoustic wavelength can cause measurable effects on the associated wave propagation phenomena. While spatial averaging functions can be used to model tool averaging effects, computer-intensive numerical methods such as finite differences must be used to simulate slowness logs across formations with thin layers. We adopted Backus averaging as a faster alternative to model borehole slownesses when layer thicknesses are smaller than the acoustic wavelength (i.e., in the long-wavelength limit). Using synthetic models and numerical simulations via finite-element and finite-difference methods, we have determined that borehole slownesses of a stack of horizontal layers first approach the average slowness of the individual layers. However, as the layer thickness decreases, sonic slownesses approach the slowness of a homogeneous medium with elastic properties obtained from the Backus average. Therefore, to model acoustic logs acquired in layered formations, we first approximate thin layers as a single homogeneous layer with stiffness coefficients calculated using the Backus average. Next, we apply a spatial averaging function to reproduce the spatial averaging effect inherent to borehole acoustic tools. Results indicate that the latter method is accurate and efficient for fast modeling borehole slownesses of formations with thin layers that are isotropic and intrinsically vertical transversely isotropic. The fast simulation method decreases computation time by at least a factor of 10 and yields slowness logs with a relative error below 2% compared with finite-difference numerical simulations. We also determine that the moving Backus average that is typically applied to upscale acoustic logs for seismic applications is not accurate to model borehole acoustic logs acquired across thinly layered formations.
Controlled-order multiple waveform inversion
Authors: Liu Yike , He Bin , Zheng Yingcai
Published: March 2020

Traditional full-waveform inversion (FWI) seeks to find the best model by minimizing an objective function defined as the difference between the model-predicted and observed data in amplitude and phase. In principle, FWI should fit all wave types including direct waves, diving waves, primaries, and multiples. However, when an initial model is far from the true model, FWI will encounter difficulties in matching multiples. Physically, multiples may contain more subsurface information compared to primary and diving waves. Multiples cover a wide range of reflection angles during wave propagation and offer the advantage of imaging the shadow zones that cannot be reached or are poorly illuminated by primary reflections. We have developed a new method of waveform inversion using multiples. We first separate the multiples into different orders. The objective function we seek to minimize consists of the data difference between the modeled data using a lower order multiple as the source and the higher order multiple as data. This method is called controlled-order multiple waveform inversion (CMWI). Our numerical examples determined that the CMWI is a promising method to improve velocity updates.
Newspaper depiction of mental and physical health in Qatar
Authors: Elzamzamy Khalid , Alsiddiqi Abdulkarim , Khalil Ali , Elamin Hassan , Abdul Karim Mustafa , Wadoo Ovais
Published: March 2020

This study provides an overview of the extent, nature and quality of reporting on mental health compared with physical health in Qatari newspapers. We analysed 1274 news reports from daily newspapers in Qatar. The majority of the articles provided general information and were either positive or neutral in tone, reporting purely on physical health matters. A small proportion made associations with violence or reported on suicide or substance use. Our results highlight the underrepresentation of mental health in Qatari newspapers. A collaboration between media and health professionals is recommended to improve reporting on mental health.
Community perceptions of barriers to management of chronic psychotic disorders and knowledge and attitudes about long-acting injectable antipsychotic medication: qualitative study in Dar es Salaam, Tanzania
Authors: Blixen Carol , Lema Isaac , Mbwambo Jessie , Kaaya Sylvia , Levin Jennifer B. , Sajatovic Martha
Published: March 2020

Background

Low- and middle-income countries (LMICs) experience a disproportionate burden from chronic psychotic disorders (CPDs), which are the most disabling conditions among people aged 10–24 in Sub-Saharan Africa. Poor medication adherence is seen in approximately half of individuals with CPDs in Sub-Saharan Africa, and is a major driver of relapse. A CPD treatment approach that combines the use of long-acting injectable (LAI) antipsychotic medications with a brief and practical customised adherence-enhancement behavioural intervention (CAE-L) was recently developed and tested for use in the USA.

Aims

To use a qualitative cross-sectional analysis to gather information on potentially modifiable barriers to management of CPDs, and assess attitudes about LAIs from community participants in Tanzania. Findings were intended to refine the CAE-L curriculum for use in Tanzania.

Method

In-depth interviews and focus groups were conducted with 44 participants (patients with CPD, caregivers, mental healthcare providers). All interviews and focus groups were audiotaped, translated, transcribed and analysed using content analysis, with an emphasis on dominant themes.

Results

Findings indicated that promoting medication adherence and management of CPDs in the Tanzanian setting needs to consider the individual with CPD, the family, the healthcare setting and the broader community context.

Conclusions

Qualitative findings enabled the study team to better understand the real-time barriers to medication adherence, LAI use and management of CPDs more broadly. Refinement of the CAE-L is expected to pave the way for an intervention trial for individuals with CPDs that is culturally and linguistically appropriate to the Tanzanian setting.
Predicting survival in primary resected retroperitoneal soft tissue sarcoma: A specific nomogram built on three major sarcoma center data sets.
Authors: Gronchi Alessandro , Miceli Rosalba , Shurell Elizabeth , Eilber Frederick C. , Eilber Frederick R. , Anaya Daniel A. , Lev Dina , Colombo Chiara , Pollock Raphael E.
Published: March 2020

10000

Background: To build a specific nomogram for predicting postoperative overall survival (OS) in primary retroperitoneal soft tissue sarcoma (RPS). A few single institutions attempts are already available, but due to the rarity of the disease they are based on limited number of cases with inherent limitations. In an attempt to improve the predictive capability of such a prognostic model we utilized series from 3 major sarcoma centers. Methods: We included patients with primary localized RPS resected with curative intent between 1999 and 2009 at 3 institutions (1 European and 2 North Americans). Univariable (Kaplan Meier plots) and multivariable (Cox model) analyses were carried out. Prognostic covariates were: Age (modeled as continuous covariate using 3 knot restricted cubic spline transformation); Tumor size (modeled as continuous covariate using 3 knot restricted cubic spline transformation); Grade (I,II,III); Histological subtype (Leiomyosarcoma, DD Liposarcoma, WD Liposarcoma, MPNST, Pleomorphic Sa, SFT, Other); Multifocality (no,yes); Quality of surgery (macroscopically complete, incomplete); radiation therapy (RT, done/not done). A backward selection procedure, based on the Akaike Information Criterion (AIC), was applied to select the Cox model covariates. The model discriminative ability was estimated by means of bootstrap-corrected Harrel C statistic. Results: 526 patients were identified. At a median follow-up of 45 months (interquartile range: 22‑72 months) 174 deaths were recorded. 5-yr and 7yr OS (95% confidence interval) were 56.4% (51.1,62.2%) and 50.1% (44.1,57.0%). The backward selection procedure by AIC criterion lead to exclude RT from the covariates set. All other covariates proved to be statistically significant in the final multivariable Cox model. The Bootstrap-corrected Harrell C statistic was 0.74. Of interest, size of the tumor and age of the patient had a bimodal contribution to the risk of death and the combination of histological subtype and grade proved significant. Conclusions: A new multi-institution RPS specific nomogram is now available for prognostication in the clinic and patient selection in clinical trials.
Growth modulation index and RECIST-based STBSG-EORTC criteria for the assessment of drug activity in advanced soft tissue sarcoma (ASTS) patients (pts).
Authors: Cousin Sophie , Blay Jean-Yves , Bertucci François , Isambert Nicolas , Italiano Antoine , Bompas Emmanuelle , Ray-Coquard Isabelle , Perrot Delphine , Bui Nguyen Binh , Chaix Marie , Chaigneau Loic , Corradini Nadege , Penel Nicolas
Published: March 2020

10014

Background: Despite promising phase II trial results, most of new drugs failed to improve the overall survival (OS) in ASTS pts. The choice of the endpoint in early trials remains crucial. We have evaluated the Growth Modulation Index (GMI) as potential endpoint. The GMI is defined as the Time To Progression with the second (or n+1) line of chemotherapy (TTP2) divided by the TTP with the first (or n) line (TTP1). Methods: We have carried out a retrospective multicenter study in pts receiving second-line chemotherapy after failure/intolerance to doxorubicin-based regimens. Data collected included best response(s), TTP1 & TTP2 and OS. Treatments have been classified as "active" treatment according to the EORTC- STBSG criteria (3-month Progression-free rate >40% or 6-month PFR>14%: including trabectedin, ifosfamide, gemcitabine+docetaxel for all subtypes and weekly paclitaxel for angiosarcoma) versus non-active drugs. Comparisons used chi-2 tests and Log-rank tests. We performed a logistic regression analysis for identifying factors associated with longer GMI. Results: The study population consisted in 106 men and 121 women, the median age was 57 years. 110 pts (48.4%) have received "active drugs". The median TTP1, TTP2 and GMI were 197 days, 134 days and 0.75, respectively. The median OS was 446 days. 70 pts experienced GMI>1.33 (30.6%). There was a strong relation between best objective response and GMI (p<0.0001). The treatment with "active drug" was not associated with an improvement of the OS: 490 days 407 versus days (p=0.524). The median OS of pts with GMI<1, GMI=[1.00-1.33] and GMI>1.33 were 324, 302 and 710 days, respectively (p<0.0001). None of the following factors were associated with GMI>1.33 in logistic regression analysis: age, gender, histological subtypes, grade, metastasis locations, interval between diagnosis & metastasis, association with ifosfamide or dacarbazine in 1st-line regimen or treatment with "active drug" in second-line. Conclusions: GMI seems to be an interesting endpoint providing additional information compared to classical criteria. GMI>1.33 is associated with significant improvement of the OS.
Efficacy and safety of panobinostat (LBH-589), a histone-deacetylase inhibitor (HDACi), in patients (pts) with advanced, previously treated soft tissue sarcoma (STS) and sex cord tumors (SCT): A study from the French Sarcoma Group.
Authors: Cassier Philippe Alexandre , Lefranc Anne , Penel Nicolas , Chevreau Christine , Bui Nguyen Binh , Le Cesne Axel , Ray-Coquard Isabelle Laure , Chabaud Sylvie , Amela Eric , Berge Yann , Domont Julien , Italiano Antoine , Duffaud Florence , Cadore Anne Claire , Polivka Valentine , Blay Jean-Yves
Published: March 2020

10027

Background: Treatment options are limited for pts with advanced pretreated STS. HDACi have shown activity in preclinical models of STS and SCT Methods: Pts with advanced pretreated STS and SCT were enrolled in this open label, single arm, multicenter phase II study. Panobinostat was given orally, 40 mg thrice per week. The primary end-point was 3-month progression-free rate according to RECIST 1.1 using central review. Fleming-A’Hern single-stage design for phase II trials was used, and assuming a type I error alpha of 5% with 90% power, 15/47 pts were needed to be progression free at 3 months to reject a rate of 20%. Results: Fifty three pts were enrolled between January 2010 and January 2011. Median age was 59 (range 21-79) years, and 22 (42%) pts were males, 13 had translocation-related sarcoma (TRS) and 4 had SCT. All but 5 pts had metastatic disease. The most common sites were the lung and the liver. All but one pt had documented disease progression prior to study entry. The median number of prior lines of therapy was 2 (range 1-7). Panobinostat dose was lowered to 20 mg thrice a week after 11 pts were enrolled based on the recommendation of an independent safety committee. Fifty-two pts were evaluable for toxicity (1 pt never received treatment), 48 pts (92%) reported at least one adverse event (AE) and 22 (42%) reported at least one treatment-related grade 3 or 4 AE. The most common grade 3/4 AEs were thrombocytopenia, fatigue and anemia. Fifty pts were evaluable for the primary end-point, of these, 12 pts (24%, 95%CI[13-38%]) were progression-free at 3 months, including 4/13 pts (31%, 95%CI[9-61%]) with TRS and 2/4 pts (50%, 95%CI[7-93%]) with SCT. No CR was seen, two patients (4%) with SCT had a PR and 19 pts (37%) had SD as their best response. Seven pts were progression-free at 6 months: 2 pts with SCT, 2 with TRS, 1 with liposarcoma, 1 with malignant solitary fibrous tumor and 1 with leiomyosarcoma. Conclusions: Panobinostat was poorly tolerated at 40 mg thrice a week. Efficacy in unselected advanced STS was limited although some patients had prolonged SD. Activity in pts with SCT warrants further investigation.
Characteristics of sarcoma patients with long-term response to gemcitabine and paclitaxel.
Authors: Katz Daniela , Elyan Firas , Sonnenblick Amir , Merimsky Ofer , Ospovat Inna , Cohen Orit , Salmon Asher , Nechushtan Hovav , Edelmann David , Peretz Tamar , Peylan-Ramu Nili
Published: March 2020

10034

Background: The combination of fixed-dose-rate gemcitabine and docetaxel has demonstrated efficacy in advanced uterine leiomyosarcoma and nonleiomyosarcoma sarcomas. We evaluated the tolerability and efficacy of modified taxol-gemcitabine (GemTax) protocol for patient with advanced sarcoma. The protocol was designed on a weekly basis to reduce toxicity. The purpose of this retrospective study was to evaluate the characteristics of long term-responders (≥12 treatments) to weekly GemTax, among pre-treated advanced high-grade sarcoma patients. Methods: From May 2004 to October 2011, 48 advanced sarcoma patients were treated with combination paclitaxel (60-90 mg/m2) and gemcitabine (600-900 mg/m2 over 100 min), on days 1,8 of every 3-week cycle or on days 1, 8 and 15 of every 4-week cycle at a wide-range treatment lines. Two patients are still on the protocol. Results: Fifteen patients (6 males and 9 females) completed 12 weekly treatments or more (mean 22.3 range 12-37) of which 4 completed >30 treatments. These include 5 leiomyosarcomas (one retroperitoneal), 2 uterine leiomyosarcomas, 3 MFH, 2 spindle sarcoma, 1 osteosarcoma, 1 adamantimoma and 1 pleomorphic rhabdomyosarcoma. GemTax was administered as 1st or 2nd line treatment in 2 and 8 patients, respectively, and as 3rd -6th line in 5. Of these patients, none achieved complete response (CR), 7/15 (47%) achieved a partial response (PR) and 8/15 (53%) had stable disease (SD). Median treatment duration was 10.3 months (range 4-22) Median progression-free survival was 28.85 months (range 5-84 months), and median overall survival was 51.2 months (range 16-95 months). A lower starting dose of paclitaxel (60-70 mg/m2) and gemcitabine (600-700 mg/m2) characterized the 4 patients with responses >30 cycles. Only five patients required dose reduction ranging between 10-40% due to grade 3 hematological toxicity. None of these patients, however, had febrile neutropenia, or bleeding events, and all non-hematologic toxicities including neurotoxicity were manageable. Conclusions: GemTax is a reasonable treatment option for patients with advanced pre-treated high-grade sarcomas. The regimen is well tolerated and dose adjustments do not seem to impact response.
Effect of metastasis surgery on overall survival in patients (pts) with advanced soft tissue sarcoma (ASTS): A subanalysis of the PALSAR trials.
Authors: Kotecki Nuria , Bui Nguyen Binh , Blay Jean-Yves , Mathoulin-Pelissier Simone , Chevreau Christine , Thariat Juliette , Cupissol Didier , Bay Jacques-Olivier , Coindre Jean-Michel , Lotz Jean-Pierre , Jimenez Marta , Brouste Veronique , Guillemet Cecile , Italiano Antoine , Penel Nicolas
Published: March 2020

10035

Background: The role of surgery in pts with ASTS remains controversial. We have conducted an exploratory retrospective analysis of the role of metastasis surgery in ASTS pts receiving 1st-line chemotherapy (CT). Methods: The database includes all pts enrolled in PALSAR-1 and PALSAR-2 trials [Fayette 2009; Bui-Nguyen 2011], treated with dose-intensified MAID or high-dose CT with peripheral blood stem cells support as 1st-line treatment of ASTS. In our analysis, the primary endpoint is overall survival (OS). Log-ranks are used for univariate analysis and Cox model for multivariate analysis. Impact of treatments had been evaluated after adjustment to confounders (Cox Model). Confounders were defined as parameters with significantly different distribution in pts who underwent metastasis surgery and those who did not (p<0.05) and significantly associated with OS (p<0.05). Results: The database consists of 410 pts (160 in PALSAR-1 and 248 in PALSAR-2) with a median age of 43. Among them, 77 patients (18%) underwent metastasis surgery. At the end of the treatment, 61 pts experienced complete response (CR), 45 with CT alone and 16 with metastasis surgery and CT. The median follow-up was 29 months. The median OS was 35.7 months (29.9-41.5). The following parameters are associated with longer OS in univariate analysis: primary location (p=0.0001), performance status (p=0.010) and absence of liver metastasis (p=0.001). We identified 4 factors associated with metastasis surgery (n=76): limb/trunk primaries, young age, absence of liver metastasis and absence of progression of the target lesions after 4 cycles. The sole identified confounder was primary location. In multivariate analysis the 2 categories of patients experiencing significant longer OS are those with CR without surgery (HR=2.2, [1.7-5.8], p=0.0001) and those with CR following metastasis surgery (HR=3.8, [2.3-6.2], p=0.0001). Conclusions: Among the pts with ASTS receiving poly-CT as 1st-line treatment, the OS of pts experiencing CR with or without metastasis surgery appears similar. Metastatis surgery without CR does not offer significant OS advantage.
Palliative ambulatory 14-day infusional ifosfamide in the outpatient setting for treatment of advanced soft tissue sarcomas (STS): “Old wine in a new bottle.”
Authors: Alam Salma Moona , Benson Charlotte , Olmos David , Jones Robin Lewis , Mitchell Scott , Al-muderis Omar , Dunlop Alison , Propert-Lewis Cerys , Scurr Michelle R. , Judson Ian Robert
Published: March 2020

10039

Background: Ifosfamide (IFO) has recognised activity in soft tissue sarcomas. There is evidence for improved cytotoxicity and tolerability utilising a prolonged 14 day infusional outpatient regimen compared with the standard 3-day regimen (Loeffler et al 1990). We undertook a retrospective review of all patients treated with this regimen from September 2008 - December 2011 to determine toxicity and treatment response. Methods: Pts. were identified from our database and demographics, histological subtype, toxicity and survival outcomes were collected. IFO was given via central venous access using 2 x 7 day pumps at 1g/m2/day with mesna for 14 days q 4 weekly. Oral sodium bicarbonate was used to maintain alkaline urine with oral mesna for haematuria, and thiamine for symptoms of encephalopathy as required. Results: 29 patients (pts), with advanced sarcoma, median age 56 years (27-76 yrs), 14F 15 M, median number of cycles = 1 ( 1-9). At baseline: PS 0=1, 1=24, 2=4. 18 pts had de-differentiated liposarcoma (D-LPS), 6 synovial sarcoma, 5 had other subtypes. 12 pts received only 1 cycle, with 5 stopping due to encephalopathy. Ten patients developed encephalopathy, 9 occurring in cycle 1, other toxicity was tolerable, with Gr 2-3 nausea (15 pts) and vomiting (9pts) and only 2 Gr 3 episodes of myelotoxicity for all cycles. 4 patients achieved PR, (2 with D-LPS and 2 with Synovial sarcoma) 11 pts. had SD. Median PFS was 19 months and OS was 12.5 months. 2 pts. with D-LPS had a sustained prolonged response of 15 and 16 months. Conclusions: Infusional IFO is generally well tolerated; however a significant incidence of neurotoxicity was seen. Pts. with D-LPS demonstrated best response to treatment, a sarcoma subtype that has previously failed to respond to systemic therapy. This regime warrants further investigation.
Clinical effectiveness of recombinant adenovirus human p53 gene combined with hyperthermia in treatment of advanced soft tissue sarcoma.
Authors: Xiao Shaowen , Zhang Shanwen
Published: March 2020

10045

Background: Soft tissue sarcoma in advanced stage usually resist to both chemo- and radiotherapy. Several studies indicated that rAdp53 can reverse this resistance and enhance the effectiveness of radiotherapy, chemotherapy and hyperthermia. This study is to evaluate the efficacy and safety of recombinant adenovirus human p53 gene (rAdp53) combined with hyperthermia and radiation in treatment of advanced soft tissue sarcoma. Methods: From Nov. 2001 to July 2011, 30 patients with advanced soft sarcoma were enrolled in this study. All cases received hyperthermia treatment, once a week for total of 9 times, and intratumoral injection of rAdp53 at dose of 1x1012 virus particles (vp) for 8 times. Radiation were given 48 hours after the first rAdp53 injection at a dose of 2Gy/f, five fractions a week for a total dose 16~70Gy /8~35f/2~8w, at an average of 56.3±5.3 Gy. Patients were monitored for response and adverse events. Results: The median follow-up time was 96 months. Among these patients, one case (3.3%) achieved complete response (CR), 9 (30%) cases had a partial response (PR), and 18 (60.0%) cases had a stable disease (SD). The overall clinical effectiveness rate (CR+PR+SD > 6months) was 83.3.0% (25/30). One-year survival rate is 56.6% (17/30), 2-year survival rate is 23.3% (7/30), 3-year survival rate is 10.0% (3/30), and 5-year survival rate is 6.7% (2/30). Overall median survival time was 18.1 months and median TTP was 13 months. No significant adverse events were noted, except for transient fever associated with rAdp53 administration. Conclusions: rAdp53 combined with hyperthermia and radiation is effective and safe modalities in treatment of advanced soft tissue sarcoma.
Rechallenge with ifosfamide-containing regimen as salvage option for patients with metastatic soft tissue sarcomas progressing after multiple pretreatments.
Authors: Hoiczyk Mathias , Kuschel Petra , Grabellus Florian , Geffken Mareike , Ahrens Marit , Schuler Martin H. , Bauer Sebastian
Published: March 2020

10046

Background: Ifosfamide (I) is commonly used in first or second-line treatment of locally advanced or metastatic soft tissue sarcomas (STS). The clinical efficacy of a rechallenge with ifosfamide (IR) or I-containing regimen (ICR) is unclear. We conducted a retrospective analysis of our institutional database (n=1354) of pts who received IR or ICR. Methods: 66 STS pts were identified, who had received more than one I-based regimen. Ifosfamide retreatment was given in neoadjuvant (n=26), adjuvant (n=18) or metastatic settings (n=22) and most patient were pretreated with doxorubicin (D; 94%). PFS was determined from first administration of IR until disease progression, OS from R until last follow-up or death. ORR (RECIST) was assessed to determine the clinical benefit rate (CBR) defined as CR, PR plus SD. Covariates were age, gender, histology, pretreatment, dose intensity, response and toxicity. Results: Median age at time of first I was 45y (range: 17-74, 44% f 56% m). Median time from diagnosis until first ICR treatment was 4mo. Median time from first I until IR, which was given as median 3rd-line treatment (2-9 lines), was 17 mo. Histologies were 12 leiomyo-, 11 lipo- 13 pleomorphic,14 synovial, 4 rhabdomyosarcomas and 12 other subtypes. Pts received a median of I 9.6 g/m²/cycle and a median of 4 cycles. I was given as monotherapy (38%) or in combination (D: 45%, other 17%). Overall median PFS was 5mo with PFS-rates of 63% at 12 and 25% at 24 wks. Median PFS was 6 mo for ICR and 2 mo for IR. The median OS was 36 mo from time of first diagnosis of metastases or locally advanced disease. ORR was 29% for I/D combination (CBR 70%) and 12 % for I monotherapy (CBR: 52%). 22 pts received a second IR with a median of 2 cycles (27% PR; CBR:77%; 69% combinations). Most common toxicities for IR/ICR were neutropenia (42%), encephalopathy (21%) and neutropenic fever (18%). Dose reductions were necessary in 18% of pts and treatment was stopped in 8% due to toxicity. No significant cardiotoxicity was observed. Conclusions: Patients with soft tissue sarcomas who had at least disease stabilization after initial ifosfamide-based therapy may derive substantial clinical benefit from a rechallenge.
Geriatric high-grade soft tissue sarcoma (G-HG STS): An analysis of 116 patients (pts) evaluating prognostic factors and clinical outcomes stratified by histology.
Authors: Quek Richard Hong Hui , Harunal Rashid Mohamad Farid Rin , Pan Summer , Tan Mann Hong , Foo Leon Siang Shen , Sittampalam Kesavan , Sairi Alisa , Adam Kiraely , Hanafi Widayana , Lim Soon Thye , Tay Kevin , Soh Lay-Tin , Chin Francis , Teo Melissa , Poon Donald
Published: March 2020

10051

Background: STS in geriatric pts is not well studied. We evaluated prognostic factors and clinical outcomes in elderly pts with HG STS. Methods: Single centre retrospective study. G-HG STS pts defined as age > 65 yrs seen in our centre from 2002 - 2011 with complete medical records were identified. Charlson age-comorbidity score was assessed for each pt. Results: 116 pts from 4 most common HG STS histo-types representing 69% of pts in the geriatric STS cohort were analysed; leiomyosarcoma (LMS, 14%), non well-differentiated liposarcoma (nWD-LPS, 9%), angiosarcoma (AS, 30%), and undifferentiated pleomorphic sarcoma (UPS, 47%). Median age was 72 yrs, 81% presented with localised disease; of 78% of these localised pts who had curative surgery, 49% received adjuvant therapy, of whom 92% had radiotherapy (RT) only. AS arises more commonly from the head/neck region (p<0.001) and fewer receive curative surgery (p=0.006). In 43 pts who had metastases either at diagnosis or relapse, 33% received first-line palliative chemotherapy with a response rate of 27% in evaluable pts. At a median follow-up of 15.8 mths, overall survival (OS) for the entire cohort was 25.1 mths, 30.5 vs 3.9 mths in pts presenting with localised vs metastatic disease respectively (p<0.0001). In pts who had curative surgery for localised disease, overall relapse-free survival (RFS) was 17.7mths; 26.8 mths vs 16.0 mths vs 7.3 mths vs 12.5 mths in LMS, nWD-LPS, AS and UPS respectively. In univariate analysis, adjuvant RT, non-head/neck primary and sarcoma subtype were associated with improved RFS. In multivariate analysis, adjuvant RT (p<0.001), sarcoma subtypes AS (p=0.011) and UPS (0.012) vs LMS remained significant. In pts with metastatic HG STS either at diagnosis or relapse, overall median OS was 5.9 mths; 5.9 mths (LMS), 30.5 mths (nWD-LPS), 6.4 mths (AS) and 4.3 mths (UPS). In univariate analysis, presence of bone metastases was significantly associated with inferior OS (p=0.0029). Charlson score did not correlate with RFS or OS. Conclusions: Prognosis of G-HG STS appears poor particularly in AS and UPS. Adjuvant RT improves outcomes in this group of pts and should not be omitted based on age alone.
Prospective web-based collection of sarcoma cases diagnosed and treated in France: Experience of the NetSarc network of the French Sarcoma Tumor Boards.
Authors: Ducimetiere Francoise , Blay Jean-Yves , Le Cesne Axel , Bui Nguyen Binh , Penel Nicolas , Bompas Emmanuelle , Gouin Francois , Duffaud Florence , Coindre Jean-Michel , Rios Maria , Chevreau Christine , Kurtz Jean-Emmanuel , Isambert Nicolas , Anract Philippe , Piperno-Neumann Sophie , Bertucci François , Kerbrat Pierre , Guillemet Cecile , Lebbe Celeste , Ray-Coquard Isabelle ,   on behalf of the NetSarc Network
Published: March 2020

10056

Background: The management of sarcomas, as for all rare tumors, is hampered by the limited dissemination of medical knowledge. Management within a specialized multidisciplinary sarcoma tumor board (STB) improves compliance to clinical practice guidelines. Since 2010, a national network with a dedicated system for referral, gathering the 26 regional STBs, is supported by the French NCI. Its objectives are to monitor the management of sarcomas and give equal access to expertise and innovative treatments to all patients with sarcoma. We report here the first experience of a web-based data collection from these STBs. Methods: The expected incidence of sarcoma in France is 6.1/105/year, ie 4000 new cases per year. A website collecting all files discussed in the 26 STBs was generated from Jan 2010 ( www.netsarc.org ). The prospective collection of clinical data, STB decision and patient follow-up was implemented in the national database (40 items). Results: 7472 patients were accrued during 2 years, 6202 (83%) had sarcoma, 2860 (46%) were new cases, representing 36% of expected incident cases. The number of new cases discussed in STB increased between 2010 and 2011 (+38%). Patients were referred to the STB (2010-2011; % of cases) prior 1) to biopsy (9%-15%), 2) to first surgery (34%-39%), 3) to adjuvant treatment (35%-34%), after treatment (14%-8%) and at time of relapse (8%-4%). 15% had a metastases at initial diagnosis. The R0+R1 resection rates for primary surgery were 55% vs 42% within vs outside the STB centers of NetSarc. 8% of declared patients were proposed to inclusion into a clinical trial. Conclusions: This web-based tool enabled the description of the activity of the STB at the national level. Clinical practices improved between 2010 and 2011, but 64% of new cases of sarcoma were not discussed in the referent STB prior to surgery. The yearly follow-up of the database will help to monitor evolution of clinical practices.
Neoadjuvant chemoradiotherapy for patients with high-risk extremity and truncal sarcomas: A 10-year follow-up study.
Authors: Look Hong Nicole Jannelle , Hornicek Francis J , Harmon David C. , Choy Edwin , Chen Yen-Lin , Yoon Sam S. , Nielsen G. Petur , Szymonifka Jackie , Yeap Beow Yong , DeLaney Thomas F. , Mullen John Thomas
Published: March 2020

10058

Background: Patients with high-risk extremity and truncal soft tissue sarcomas (STS) are at considerable risk for recurrence. A regimen of preoperative mesna, doxorubucin hydrochloride (Adriamycin), ifosfamide, and dacarbazine (MAID), interdigitated with radiotherapy (RT), followed by resection and postoperative chemotherapy with or without RT, has demonstrated high rates of local and distant control. The goal of this series is to study outcomes of our most recent cohort of patients treated on this regimen. Methods: We retrospectively reviewed records of 55 consecutive patients with STS of the extremity or superficial trunk who completed all phases of treatment at our institution from January 2000–July 2011. Clinicopathologic characteristics and patient outcomes were analyzed. Results: Fifty-five patients were analyzed and had a median age of 53 years (range 18-73). The median tumor size was 10.1cm (range 2.5-35.5 cm). Twenty-seven (49%) and 28 (51%) patients had grade 2 and 3 tumors, respectively. Margins were negative in 49 (89%) patients, and positive in 6 (11%) patients. At a median follow-up of 43 months, there were 7 (13%) locoregional, and 17 (31%) distant recurrences. The local and distant 5-year recurrence-free survival (RFS) rates were 92% and 64%, respectively. The 5-year overall (OS) and disease-specific survival rates were 86% and 89%, respectively. There were no treatment-related deaths or secondary myelodysplasias. There were no significant predictors of OS or RFS. Conclusions: Outcomes of a contemporary cohort of patients with extremity and truncal STS treated with an intense regimen of neoadjuvant chemoradiotherapy and surgery are consistent with previous reports from our institution and better than reports of chemotherapy alone. [Table: see text]
Effect of anti-β1 integrin antibody on lung seeding of osteosarcoma cells in live mice visualized by single-cell in vivo imaging.
Authors: Kimura Hiroaki , Tome Yasunori , Momiyama Masashi , Hayashi Katsuhiro , Bouvet Michael , Tsuchiya Hiroyuki , Hoffman Robert M.
Published: March 2020

10072

Background: Integrins play a role in tumor growth and metastasis (Int. J. Cancer 129, 2905-2915, 2011). However, the effect of integrin inhibition has not been visualized on single cancer cells in vivo. In this study, we used a powerful subcellular in vivo imaging model to demonstrate how an anti-integrin antibody affects seeding and growth of osteosarcoma cells on the lung. Methods: The 143B human osteosarcoma cell line expressing red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nucleus was established. Using the double-labeled osteosarcoma cells, single cancer-cell seeding in the lung after i.v. injection of osteosarcoma cells was imaged in live mice. Results: The anti-b1 integrin monoclonal antibody, AIIB2, greatly inhibited the seeding of cancer cells on the lung while a control antibody had no effect. To image the efficacy of the anti-integrin antibody on spontaneous metastasis, mice with orthotopically-growing 143B-RFP cells in the tibia were also treated with AIIB2 or control anti-rat IgG1 antibody. After 3 weeks treatment, mice were sacrificed and primary tumors and lung metastases were evaluated with fluorescence imaging. AIIB2 significantly inhibited spontaneous lung metastasis but not primary tumor growth. In a separate experiment, the anti-β1 integrin antibody increased survival in the orthothopic osteosarcoma model. Conclusions: The efficacy of the anti-β1 integrin antibody against metastasis may be due to inhibition of lung seeding of the cancer cells. The increased survival of mice with orthotopically-growing 143B-RFP treated with AIIB2 may be due to inhibition of metastasis, which in turn may be inhibited by effect of the anti-β1 integrin on cancer-cell seeding in the lung.