bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated results of a phase II trial of AP23573, a novel mTOR inhibitor, in patients (pts) with advanced soft tissue or bone sarcomas
Authors: Chawla S. P. , Tolcher A. W. , Staddon A. P. , Schuetze S. M. , D’Amato G. Z. , Blay J. Y. , Sankhala K. K. , Daly S. T. , Rivera V. M. , Demetri G. D. 
Published: March 2020

9505 Background: AP23573 is an mTOR inhibitor that has shown anti-tumor activity in phase 1 clinical trials, particularly in patients with advanced sarcomas. Given this observation, this phase 2 trial was undertaken to assess further the efficacy and safety of AP23573 across various sarcoma subtypes. Methods: Advanced sarcoma pts, with no restrictions on prior therapies, were enrolled into 4 cohorts based on histologic subtype, in a phase 2 trial with Simon’s 2-stage design. AP23573 (12.5 mg, i.v.) is administered for 5 days every 2 wks. Efficacy is assessed using RECIST guidelines, with clinical benefit response (CBR) defined as complete or partial response (PR) or stable disease (SD) for at least 16 wks duration. For each cohort, treatment was defined as successful if the proportion of patients with CBR was ≥ 25%. Studies of potential predictive markers of response include 18FDG-PET imaging, analysis of mTOR pathway proteins in tumoral tissue, and measurement of plasma cytokines and angiogenic factors. Results: In total, 216 pts were enrolled as all cohorts met criteria to enter Stage 2 of the trial. Of these pts, 213 were treated (106 M/107 F) (age 17–79 yrs, median 50 yrs). Most frequent related adverse events included mucositis, rash, hyperlipidemia, fatigue, and thrombocytopenia. Preliminary response data for 193 evaluable pts are available: overall 54 (28%) had CBRs, including 5 PRs (3 pts with osteo, 1 with spindle cell of bone, and 1 with MFH). Twenty of 76 pts (26%) imaged with PET had rapid induction of partial metabolic responses following 3 to 5 days of study treatment. Conclusions: Initial assessments from this trial show that single-agent AP23573 is well tolerated and has efficacy in pts with advanced sarcomas that warrants evaluation in phase 3. Analysis of the potential utility of FDG-PET and a broad set of candidate biomarkers continues. Enrollment is complete, and pt treatment and follow-up are ongoing. [Table: see text] [Table: see text]
Updated results from a phase III trial of sunitinib in GIST patients (pts) for whom imatinib (IM) therapy has failed due to resistance or intolerance
Authors: Casali P. G. , Garrett C. R. , Blackstein M. E. , Shah M. , Verweij J. , McArthur G. , Judson I. , Li J. , Baum C. M. , Demetri G. D. 
Published: March 2020

9513 Background: Sunitinib malate (previously known as SU11248) is an oral multitargeted tyrosine kinase inhibitor with both antitumor and antiangiogenic effects due to blockade of KIT, PDGFRs, VEGFRs, FLT3, and RET. Initial results from this phase III trial showed sunitinib was associated with significantly longer TTP than placebo in IM-resistant GIST pts. Methods: This double-blind, placebo-controlled, phase III trial compared sunitinib 50 mg/day (N=207) to placebo (N=105) in IM-resistant or -intolerant GIST pts. Treatment was administered in 6-week cycles (4 weeks on, 2 weeks off treatment). The primary endpoint was TTP. Secondary endpoints included PFS, OS, ORR, and pain and health status (HS) measures. Pain relief response rate (PRRR) was defined as the proportion of pts who had ≥1 pain relief response event (based on weekly changes in present pain index of MPQ and analgesic consumption). HS was measured using the EQ-5D questionnaire. Results: A planned interim analysis showed significantly longer median TTP with sunitinib versus placebo (27.3 vs 6.4 weeks; HR, 0.33; P<0.001), which led to unblinding of the study and crossover of all placebo pts to open-label sunitinib. OS was also significantly longer with sunitinib (median OS will be presented). Sunitinib therapy induced PRs in 14 pts (6.8%) and durable SD (≥22 weeks) in 36 (17.4%) vs. 0% PR and SD ≥22 weeks in 2 (1.9%) pts on placebo. Four of 9 IM-intolerant pts achieved PR with sunitinib therapy versus 0 of 4 IM-intolerant pts treated with placebo. There was a trend for higher PRRR with sunitinib versus placebo in the ITT population (17.4% vs 9.5%, P=0.064) and in 174 pts who reported pain or analgesic use at baseline (31.0% vs 17.2%, P=0.052). The most common treatment-related AEs were fatigue, diarrhea, skin discoloration, and nausea, which were usually grade 1/2 and easily managed. Updated survival and tumor-control efficacy measures, tolerability, and HS results will be available for presentation. Conclusions: Sunitinib significantly prolonged TTP and OS in GIST pts for whom IM therapy had failed due to resistance or intolerance. This trial demonstrated major clinical benefit from a multitargeted tyrosine kinase inhibitor in pts resistant to a different kinase inhibitor. [Table: see text]
Sunitinib for patients (pts) with advanced imatinib (IM)-refractory GIST: Early results from a “treatment-use” trial
Authors: Morgan J. A. , Garrett C. R. , Schutte H. J. , Hurwitz H. , Rosen L. S. , Ruka W. , Picus J. , Kaiser P. , Baum C. M. , Demetri G. D. 
Published: March 2020

9540 Background: Pts with advanced or metastatic GIST are typically treated first with IM, but many GISTs develop resistance to IM over time or are initially resistant this agent, and a small fraction of GIST pts are intolerant of IM therapy. Sunitinib malate (previously known as SU11248) is an oral, multitargeted tyrosine kinase inhibitor of KIT, PDGFR, VEGFR, FLT3, and RET that has demonstrated efficacy in extensive prior trials involving IM-refractory GIST pts. Since GIST pts who were ineligible for participation in sunitinib clinical trials might derive significant benefit from this therapy, a treatment-use program was implemented for this purpose. Methods: This on-going, multicenter, open-label trial was designed to grant access to sunitinib for treatment use in pts who were ineligible for other sunitinib trials and who had advanced IM-resistant GIST or documented intolerance to IM. Pts on sunitinib are monitored closely to assess clinical benefit as judged by the investigator. Sunitinib is administered at a starting dose of 50 mg/day on a 4/2 schedule (4 consecutive weeks on, 2 weeks off treatment). Clinical endpoints include safety and tolerability, as well as disease control (TTP), response rates, and survival. Results: Of 268 GIST pts enrolled in this treatment-use trial at the time of this analysis, 247 had received at least one dose of sunitinib. The median number of cycles completed was 2 (range, 0–9), and the median number of days on treatment was 83 (range, 1–385). The most frequently reported treatment-related AEs were fatigue (36%), diarrhea (31%), nausea (27%), and hand-foot syndrome (15%), which were generally grade 1/2. At the time of analysis, preliminary efficacy data were available for 152 pts. Of these, 123 pts remain on therapy and have received a median of 3 (range, 2–7) cycles of sunitinib. Based on initial investigator assessments, one pt achieved a CR, 14% achieved PR and 63% have noted SD as best response. Conclusions: Sunitinib was associated with acceptable tolerability in this population of IM-refractory GIST pts enrolled in this treatment-use trial. Consistent with previous results, promising clinical activity was seen, and expanded tolerability and efficacy data will be presented. [Table: see text]
reGISTry: An observational registry of gastrointestinal stromal tumor (GIST) patients (pts) in the USA
Authors: Trent J. C. , Blanke C. D. , Pisters P. W. , Von Mehren M. , Davis D. S. , Ruxer R. , McWhorter L. T. , Salvado A. J. 
Published: March 2020

9543 Background: The management of pts with GIST dramatically changed after the discovery of the biologic role of dysregulated KIT and PDGFR receptor tyrosine kinases. However, published data on the epidemiology and patterns of diagnosis and management of GIST are limited. To fill this gap, the reGISTry, an observational, internet-based database designed to understand evolving patterns of care for pts with GIST, overall and by pt and provider characteristics, was established. Methods: Up to 200 physicians are expected to participate; recruitment of centers is stratified by geographic area and institution size/type. The reGISTry will be active for at least 4 years with expected accrual of 1800 pts. Pts must have a diagnosis of GIST and give written informed consent. Collected data include pt demographics, clinical characteristics, clinical/economic outcomes and medical care provided to treat GIST. Data analyses are performed every 6 months. Results: The first pt was enrolled in Jan 2005. As of Nov 2005 there were 108 pts enrolled from 39 centers. Eighty five pts (79%) were from community-based practices and 23 (21%) from university/academic centers. Fifty-five pts (51%) were male. Median age was 62 years (range 37–85). At diagnosis, 84 pts (78%) had a primary tumor and 24 (22%) metastatic disease. At diagnosis, 101 pts (94%) had immunohistochemical KIT testing, 95% with positive results. Only 2% of pts had genotyping performed. Surgery was the most common first-line treatment (85 pts, 79%). Eighty-nine percent of those with primary disease and 42% of those with metastatic disease underwent surgical resection as their initial therapy. Fifty percent of pts with metastatic disease and 7% of pts with primary disease underwent systemic therapy as their initial treatment. Forty-seven pts (44%) had imatinib mesylate therapy with 400 mg daily the most commonly prescribed dose. Therapeutic efficacy was more commonly assessed by CT size with radiodensity (55.6%) than positron-emission tomography (0%). Conclusions: The reGISTry is a useful tool for determining evolving practice patterns in the management of GIST. Iterative data analyses over the next 4 years will allow for comparison of management patterns as advances in the understanding of GIST evolve. [Table: see text]
Angiosarcoma of the breast
Authors: Sher T. , Hennessy B. T. , Valero V. , Trent J. , Broglio K. , Woodward W. A. , Hunt K. K. , Hortobagyi G. N. , Gonzalez-Angulo A. M. 
Published: March 2020

9554 Background: The purpose of this analysis is to describe the characteristics and clinical outcomes of female patients with primary breast angiosarcoma. Methods: The M. D. Anderson Cancer Center Breast Medical Oncology database was searched to identify breast angiosarcoma patients between 1965–2002. Survival outcomes were estimated by the Kaplan-Meier method. The log-rank statistic was used to compare groups. Cox proportional hazards models were used for multivariate analysis. Results: The 69 patients had a median follow up of 40 months (range, 0–413 months). Median age at diagnosis was 46. Median tumor size was 5.5 cm. Thirteen patients had received prior chest radiation (18.8%) for invasive breast carcinoma and were older than other patients (p<0.0001). Most patients underwent a simple mastectomy with (41%) or without (45%) axillary dissection. Regional metastasis to axillary lymph nodes was rare (2/28 patients). Fifteen patients (22%) received neoadjuvant chemotherapy, of whom two had a complete clinical response and 3 a partial response to doxorubicin/ifosfamide (AI); 44% received adjuvant chemotherapy, one patient received neoadjuvant and 31% adjuvant radiotherapy. There have been 38 recurrences [locoregional (20), distant (16), or combined (2)] and 27 deaths. The 5-year overall and recurrence-free survival (RFS) rates were 61% (95% CI 49–76%) and 44% (95% CI 33–58%) with estimated medians of 100 and 37 months, respectively. Survival and RFS were significantly associated with T stage (p=0.03) but not with patient age or prior radiation. Survival was also significantly worse in patients who received neoadjuvant chemotherapy administration (p=0.01) likely due to more advanced disease when this approach was used. In Cox proportional hazards models, only age at diagnosis was associated with RFS. Of 29 patients treated with chemotherapy at relapse, there were 4 complete and 10 partial responses (48% responses) with AI or a gemcitabine-taxane combination. Conclusion: Breast angiosarcoma is frequently advanced at diagnosis with a tendency for locoregional recurrence. In light of this and its observed chemosensitivity, a multidisciplinary therapeutic approach with chemo- radiotherapy and surgical resection should be considered. Initial chemotherapy for neoadjuvant and metastatic disease is effective. No significant financial relationships to disclose.
ABV (doxorubicin [Adriamycin], bleomicin and vincristine) polychemotherapy regimen in HIV Kaposi’s Sarcoma: Uruguaian 10-year experience
Authors: Krygier G. , Sosa A. , Blanco A. , Lombardo K. , Castillo C. , Dutra A. , Cabrera S. , Savio E. , Muse I. , Sabini G. 
Published: March 2020

9559 Background: Kaposi’s sarcoma is the most common malignancy among HIV patients and is considered to be one of the AIDS defining conditions. This abstract illustrates our 10 year experience with the treatment of 32 Kaposi’s sarcoma HIV patients with the same therapeutic approach. Methods: Between 04/95 and 03/05 we recruited 32 previously untreated patients that were diagnosed with Kaposi’s sarcoma and treated at the Servicio de Oncologia Clinica (Universitary Clinicas Hospital) in Montevideo. All of them received the same iv polychemotherapy plan (Adriamycin 10mg/m2, Bleomycin 10 U/m2 and Vincristine 1.4 mg/m2, every two weeks until tumor progression or severe toxicity). Results: 21 of the patients were good risk ones and the remaining 11 were poor risk patients (AIDS Clinical Trials Group staging classification). CD4 levels varied from 6 to 780/ml and the viral load ranges were 240 to 89000 copies. The patients received an average of 10.2 (4–21) polychemotherapy cycles. Grade 3–4 myelotoxicity was reported in 5 patients delaying the onset of the subsequent cycles. Grade 2 neurotoxicity was seen in 7 patients after 4, 5, 6, 8, 10, 11 and 13 cycles of ABV, changing vincristine for vinblastine (4mg/m2 every two weeks) in these patients. All the patients achieved a partial response with improvements in CD4 levels and viral load. 13/32 patients experienced a relapse (3–29 months after last chemotherapy cycle). 3 patients were retreated with paclitaxel 135 mg/m2 with 2/3 new partial responses of shorter duration. 5 patients received 4 additional ABV cycles achieving a new partial response. 5 patients refused further treatment dying due to progressive disease. One relapsed patient developed a second malignancy (High grade Non Hodgkin lymphoma) dying three months later. Conclusions: These data suggest that ABV regimen is still an effective treatment option for HIV-Kaposi’s sarcoma, specially in the undeveloped countries in which the cost of other better internationally approved options (liposomal doxorubicin and daunorubicin) makes them unaccesible for the majority of the population. No significant financial relationships to disclose.
Sequential epirubicin-docetaxel-CMF as adjuvant therapy of early breast cancer: Results of the Taxit216 multicenter phase III trial
Authors: Bianco A. R. , De Matteis A. , Manzione L. , Boni C. , Palazzo S. , Di Palma M. , Iacono C. , De Placido S. , Papaldo P. , Cognetti F. 
Published: March 2020

LBA520 Background: Docetaxel is among the most active drugs for advanced breast cancer and it has recently shown efficacy in the adjuvant setting too. This trial is aimed at comparing the efficacy and tolerability of a sequential approach of a chemotherapy combination regimen containing docetaxel to a standard anthracycline-based regimen as adjuvant therapy in node-positive (N+) early breast cancer. Methods: Between July 1998 and July 2002, 972 N+ early breast cancer patients were randomized to either arm A (E→CMF): Epirubicin (E) 120 mg/m2 iv d1 q21 × 4 cycles followed by Cyclophosphamide 600 mg/m2 iv, Methotrexate 40 mg/m2 iv and Fluorouracil 600 mg/m2 iv (CMF) d1,8 q28 × 4 cycles; or armB (E→T→CMF) in which Docetaxel 100 mg/m2 iv (T) d1 q21 × 4 cycles was administered after the 4th cycle of E and before the 1st cycle of CMF. Treatment allocation was performed by a computer program using a dynamic balancing algorithm. Balancing factors were: center, lymph node involvement (1 to 3, 4 to 9, >10), estrogen receptor status (negative/positive/unknown), menopausal status (pre/post). During chemotherapy pts were subjected to physical examination and blood chemistry tests every 3 wks, hematology was repeated weekly. At the completion of treatment pts were followed up every 3 months for the first 2 years, every 6 months for years 3–5 and every 12 months for years 6–10. Primary endpoint was disease free survival (DFS) and secondary endpoints were tolerability and overall survival (OS). The study was designed to detect a hazard ratio of 0.70, assuming an α of 0.05 (two sided), a power of 0.80 and an expected DFS in Arm A of 0.65 at 5 years. This required 480 pts per Arm and 250 events. Results: As of March 27th 2006, 486 pts were enrolled in arm A and 486 in arm B, 252 primary events were recorded and the median follow up was 53 months. DFS at 5 years was 0.67 in arm A vs 0.74 in arm B with an estimated Hazard Ratio (HR) of 0.80 (95% CI: 0.62–1.03, p = 0.079). After adjustement by predefined balancing factors (ER, Nodal and menopausal status) the HR was 0.78 (95% CIs: 0.61–1.00; p = 0.05). As for OS, 117 deaths were observed with HR of 0.74 (95% CIs: 0.51–1.07, p = 0.10). Conclusions: Sequential E→T→CMF yields a borderline significant improvement of DFS. Follow up update is still ongoing. [Table: see text]
The Virtuosity of Langston Hughes: Persona, Rhetoric, and Iconography inThe Weary Blues
Authors: Skansgaard Michael 
Published: March 2020

AbstractPrevious historical studies of The Weary Blues have focused on the racial symbolism of Langston Hughes’s technique, which (as the consensus goes) authenticates the voice of the persona through its deliberate simplicity. This orthodox view is wrongheaded from the outset. The essay uses a new system of rhetorically driven scansion to identify elaborate rhetorical symmetries and polyrhythms that shape the cognition of Hughes’s persona and the recognition of his readers in ways that prose language cannot. Hughes employs rhetoric and iconography as alternative modes of historical narration. This recuperation of his persona intervenes in an ongoing dispute in the field of historical poetics about the value of formalism and cognitivism. The essay aims to show that the concept of thinking in verse is valuable where it has been least applied: in reclaiming the value of traditionally marginalized literatures such as those of the African American vernacular tradition.
Great potential of ultrasound elastography for the assessment of the masseter muscle in patients with temporomandibular disorders. A systematic review
Authors: Olchowy Anna , Wieckiewicz Mieszko , Winocur Efraim , Dominiak Marzena , Dekkers Ilona , Łasecki Mateusz , Olchowy Cyprian 
Published: March 2020

Objective: To summarize the available evidence on the use of elastography in the assessment of the masseter muscle in healthy individuals and patients with masseter muscle disorders. Methods: Systematic literature review has been performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: 16 of 142 studies identified were analyzed. Elastography was used in seven studies. Heterogeneity was observed in terms of study protocols, devices, patients, units of measure, and results. Elasticity values showed a correlation between the left and right masseter muscle side in healthy people, but not in patients with temporomandibular disorders (TMDs). Elasticity values increased in TMD and were correlated with the severity of TMD symptoms. Phantom studies proved the high reliability of elastography. Conclusion: Elastography is a promising tool for the assessment of the masseter muscle elasticity, but the evidence is insufficient. Studies on larger groups are needed to determine the accuracy of elastography to characterize masticatory muscle disorders.
Clinical manifestation of norovirus infection in children aged less than five years old admitted with acute diarrhea in Surabaya, Indonesia: a cross-sectional study
Authors: Fardah Athiyyah Alpha , Shigemura Katsumi , Kitagawa Koichi , Agustina Nazara , Darma Andy , Ranuh Reza , Raharjo Dadik , Shirakawa Toshiro , Fujisawa Masato , Marto Sudarmo Subijanto 
Published: March 2020

Background: The objective of this study was to investigate the clinical manifestation of norovirus infection between norovirus genogroup and severity of acute diarrhea in pediatric patients at the Dr. Soetomo Hospital, Surabaya, Indonesia. Methods: This cross-sectional study involved 31 participants aged 1-60 months admitted to the hospital with acute diarrhea from April 2012 to March 2013. Norovirus genogroups (GI and II) were identified from patient stool using reverse transcription polymerase chain reaction (RT-PCR). Severity was measured using the Ruuska and Vesikari scoring system. Results: In total, 94 stool samples were obtained, of which 31 (19%) were norovirus positive. Norovirus GI was found in one sample with mild diarrhea. Norovirus GII was found in 30 samples (96.8%); one sample with mild diarrhea (3.3%), 20 samples with moderate diarrhea (66.7%), and nine samples with severe diarrhea (30%). Conclusion: Norovirus GII was the most prevalent cause of acute diarrhea and 30% of the cases manifested as severe diarrhea.
Renminbi Internationalization: Domestic Challenges and External Implications
Authors: Lopes Marra de Sousa Ana Tereza 
Published: March 2020

En este trabajo se investiga el proceso de inserción de la moneda china, el renminbi (rmb), en el Sistema Monetario Internacional (smi). Al analizar el histórico de internacionalización del rmb y los instrumentos que el gobierno chino ha utilizado para esto, se observó que China impulsa su moneda por medio de acciones que in­tentan evitar una sobreexposición de la cuenta capital y financiera, y, por lo tanto, el impacto negativo que los mercados, dominados por los agentes de Wall Street, pueden producir sobre su economía. De este modo, el proceso de internacionalización del rmb es diferente del de todas las monedas que pasaron por internacionalización durante la égida del Dollar Wall Street Regime (dwsr), pues no puede ser sustancialmente controlado por los mercados internacionales. Se interpreta así que esa inserción mo­netaria puede ser vista como una forma de contestación a los mercados financieros globales, al papel del dólar y al ejercicio del poder de Estados Unidos en el sistema financiero y monetario.
Organisational empowerment and speaking up against unsafe practice: the case for newly qualified nurses in Saudi Arabia
Authors: Mansour Mansour , Al-Madani Maha , Al-Anati Abdelrahman , Jamama Aysar 
Published: March 2020

Background/aims Nurses' sense of empowerment and ability to speak up against unsafe clinical practice are crucial to patient safety and staff wellbeing. However, research examining these attitudes among newly qualified nurses is lacking. This study aimed to investigate perceptions of organisational empowerment and willingness to speak up against perceived unsafe practice among newly qualified nurses in Saudi Arabia. Methods A questionnaire was completed by a convenient sample of 83 newly qualified nurses in the Eastern Province of Saudi Arabia. Descriptive statistics and Spearman's correlation coefficient (rho) were used for data analysis. Findings The nurses reported moderate levels of both empowerment and willingness to speak up against unsafe practice. There was a statistically significant correlation between the participants' total structured empowerment score and their speaking up score. Willingness to speak up against potentially unsafe practice was also correlated with participants' perceived access to support at work. Conclusions These findings highlight the need to support newly qualified nurses to develop their level of empowerment and assertive communication skills. Nurse managers, educators and peers must therefore consider practical strategies to help build and sustain newly qualified nurses' sense of work empowerment and assertiveness.