bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of bone modifying agents in patients with metastatic castrate-sensitive prostate cancer.
Authors: Mitchell Aaron Philip , Mishra Akriti A. , Bach Peter B , Morris Michael J. 
Published: March 2021

68 Background: Bone modifying agents (BMAs) do not prevent skeletal related events (SREs) among patients with metastatic, castration-sensitive prostate cancer (mCSPC). Within this population, BMAs are recommended for prevention of osteoporotic fractures but not for SRE prevention. Utilization patterns of BMAs among patients with mCSPC have not been described, and it is unknown whether these patients may receive BMAs intended for SRE prevention unnecessarily. We conducted this study to measure BMA use among mCSPC patients who are unlikely to have an indication for osteoporotic fracture prevention. Methods: We used linked SEER-Medicare data. Our cohort included men newly diagnosed with de-novo stage IV prostate adenocarcinoma during 2007-2015. We included those age > = 66 at diagnosis, who lived at least 60 days after diagnosis, had continuous enrollment in Medicare Parts A and B from 180 days prior to diagnosis through the outcome period and Part D from diagnosis through outcome period, and who received androgen deprivation or antiandrogen therapy after diagnosis. We excluded patients who had previously received BMAs, or who had existing osteoporosis, osteopenia, hypercalcemia, or prior bone fracture. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of prostate cancer diagnosis, during which time the development of castrate-resistant disease is unlikely to arise. We also assessed receipt of BMAs within 90 days of diagnosis as a secondary outcome. We used multivariable logistic regression to assess patient factors associated with BMA use. Results: Our sample included 2,998 patients. Median age at diagnosis was 77. 77% of patients were white, 12% were Black, and 11% were of other race/ethnicity. 77% of patients were treated in the physician office setting and 23% the hospital outpatient setting. Overall, 24% received a BMA within 180 days of diagnosis; 18% did within 90 days. BMA therapy was more common among patients treated in the hospital outpatient vs. physician office setting (OR 1.25, 95%CI 1.03-1.52). Age, race/ethnicity, comorbidity, and renal disease were not associated with likelihood of BMA therapy. There was substantial variation across the study period: 19% of patients received BMAs from 2007-2009 (19% zoledronic acid, 0% denosumab), and 29% from 2012-2015 (9% zoledronic acid, 21% denosumab). Conclusions: Use of BMAs among patients with mCSPC is common. In this cohort of mCSPC patients, who were unlikely to have a BMA indication for osteoporotic fracture prevention based on the absence of history of osteoporosis, osteopenia, or fracture, nearly one-quarter received BMAs. The increase in BMA use which occurred during the 2007-2015 study period appears to have been driven by increased utilization of denosumab following its approval in 2010. Use of BMAs in patients with mCSPC without a need for osteoporotic fracture prevention may constitute overuse.
TALAPRO-1: Phase II study of talazoparib (TALA) in patients (pts) with DNA damage repair alterations (DDRm) and metastatic castration-resistant prostate cancer (mCRPC).
Authors: De Bono Johann S. , Mehra Niven , Higano Celestia S. , Saad Fred , Buttigliero Consuelo , van Oort Inge M. , Mata Marielena , Chen Hsiang-Chun , Healy Cynthia G. , Czibere Akos , Fizazi Karim 
Published: March 2021

93 Background: Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) show antitumor activity in mCRPC/DDRm pts treated with novel hormonal therapy (NHT). TALAPRO-1 is an open-label study evaluating TALA (a potent PARP inhibitor/trapper) in men with mCRPC/DDRm. We report a planned interim analysis (IA; Dec 2019). Updated results at a Sep 4 2020 cut-off, available in November 2020, will be presented at the meeting. Methods: TALAPRO-1 (NCT03148795) is enrolling pts (N ≈ 100) with measurable soft tissue disease, progressive mCRPC, and DDRm likely to sensitize to PARPi ( ATM, ATR, BRCA1/2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C), who received 1–2 chemotherapy regimens (≥1 taxane-based) for metastatic disease and progressed on ≥1 NHT (enzalutamide/abiraterone acetate) given for mCRPC. DDRm are defined as known/likely pathogenic variants or homozygous deletions. Pts receive oral TALA 1 mg/day (moderate renal impairment 0.75 mg/day) until radiographic progression, unacceptable toxicity, consent withdrawal, or death. Primary endpoint is objective response rate (ORR). Secondary endpoints: time to objective response; response duration; prostate-specific antigen (PSA) decrease ≥50%; circulating tumor cell (CTC) count conversion (to CTC = 0 and <5 per 7.5 mL blood); time to PSA progression; radiographic progression-free survival (rPFS); overall survival; safety. A planned efficacy/safety IA was done when 60 pts with DDRm and measurable disease completed ≥6 months of TALA/no longer followed. Radiographic responses are based on investigator assessments. Results: 113 pts received TALA (cut-off Dec 12 2019); 75 pts were evaluable for IA, with DDRm, had measurable disease, received ≥16 weeks’ treatment, and were assessed for ORR (54.7% BRCA1/2, 4.0% PALB2, 22.7% ATM; 18.7% other DDRm).All pts evaluable for IA had prior docetaxel; 45.3% cabazitaxel. Confirmed ORR, rPFS, and composite response (investigator-assessed) in pts who received TALA for ≥16 weeks are in the table. Most common treatment-emergent adverse events: anemia (42.5%); nausea (32.7%). Conclusions: TALA monotherapy has encouraging antitumor activity in docetaxel-pretreated mCRPC pts with BRCA1/2 alterations and was generally well tolerated. Funding: Pfizer Inc. Clinical trial information: NCT03148795. [Table: see text]
Open-label, phase II study of ladiratuzumab vedotin (LV) for castration-resistant prostate cancer (SGNLVA-005, trial-in-progress).
Authors: Sher Amna Falak , Bruce Justine Yang , Gabrail Nashat Y. , Anderson Ian Churchill , Patrikidou Anna , Sanborn Rachel E. , Cho Jae Yong , Lee Arielle Shebay , Lee Jong-Seok , Nott Louise M. , Oh Do-Youn , Oh Sang Cheul , Oh Sung Yong , Wang Yinghui , Wang Zejing , Guthrie Troy H. 
Published: March 2021

TPS185 Background: LIV-1 is a transmembrane protein expressed in a variety of cancer types. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel investigational humanized IgG1 antibody-drug conjugate (ADC) directed against LIV-1. LV mediates delivery of monomethyl auristatin E (MMAE), which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death. In a phase 1 study, LV was tolerable and active in heavily pretreated patients with metastatic breast cancer (Modi 2017). This study is currently evaluating the safety and efficacy of LV in different advanced solid tumors with various LIV-1 expression, including metastatic castration-resistant prostate cancer (mCRPC), advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (squamous and nonsquamous), head and neck squamous cell carcinoma, and melanoma. Methods: SGNLVA-005 (NCT04032704) is an open-label, phase 2 study evaluating LV monotherapy in patients with previously treated, locally advanced unresectable or metastatic advanced solid tumors, including mCRPC. Patients with mCRPC will receive LV administered as a 30 minute intravenous infusion (IV) at 1.25 mg/kg every 1 week. Up to 30 patients with mCRPC will be enrolled. Patients in the mCRPC cohort must have metastatic castration-resistant disease, have received no more than 1 prior line of androgen receptor-targeted therapy, have ≥28 days between androgen receptor-targeted therapy and start of study treatment, an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1, and adequate organ function. In addition, mCRPC patients with measurable and non-measurable disease are eligible if the protocol-defined criteria are met. mCRPC patients must not have BRCA gene mutations, prior cytotoxic chemotherapy in the metastatic mCRPC setting, prior radioisotope therapy, or radiotherapy to ≥30% of bone marrow. Patients are not preselected based on tumor LIV-1 expression. Their tumor samples will be analyzed for correlation between LIV-1 expression and response. Safety and efficacy will be monitored throughout the study. Study objectives include objective tumor response rate per RECIST 1.1 and prostate-specific antigen (PSA) response rate per Prostate Cancer Clinical Trials Working Group 3 (both primary); safety and tolerability, disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics and immunogenicity (all secondary); and pharmacodynamics. Study accrual is ongoing in the USA, Italy, South Korea, Taiwan, Australia, and the UK. Clinical trial information: NCT04032704.
Clinical-pathological characterization and outcomes of metastatic urothelial cancer in Latin America: Retrospective and translational multicenter database (LACOG 1518).
Authors: Souza Vinicius Carrera , Luz Murilo , Bastos Diogo Assed , Freitas Marcelo Roberto Pereira , Dauster Pereira E Silva Breno , Monteiro Fernando Sabino M. , Fernandes Roni , Caitano Manuel , Trindade Karine , Nogueira Lucas , Herchenhorn Daniel , Sade Juan , Nunes Galvão de Oliveira Fernando , Fay Andre P. , Werutsky Gustavo , Maluf Fernando C. , Fabricio Vanessa Carvalho , Gidekel Rosemarie , Pacheco Patricia , Soares Andrey 
Published: March 2021

TPS497 Background: There is lack of high-quality and comprehensive data on advanced urothelial cancer in Latin America. Pathological and clinical outcomes information of this cancer can help the scientific community to understand the current standard of treatment and identify possible gaps for optimal care. Very few translational studies were performed in advanced urothelial cancer in developing countries describing the prevalence of key biomarkers for targeted agents and immunotherapy. Methods: LACOG 1518 is a large multi-institutional retrospective study that will collect information about sociodemographic data, treatment and outcome of patients diagnosed with recurrent/ metastatic urothelial cancer in Latin America between January 2016 and December 2019. Socio-demographic characteristics, clinical-pathological features, treatment patterns and outcomes will be extracted from medical charts. Tumor tissue will be collected for fibroblast growth factor receptor (FGFR) gene mutation or fusion test in a central laboratory. A biorepository will be built for future translational research including PD-L1 test and next generation sequencing. Primary endpoint consists on characterize demographic, socioeconomic factors, medical and oncological history of patients diagnosed with recurrent/metastatic urothelial cancer. This study aim to describe treatment sequence, duration, best response and progression time in each line of therapy as well as survival at 1 and 2 years. Translational research endpoints are biomarkers prevalence and association with treatment responses and outcomes.
TROPiCS-04: Study of sacituzumab govitecan in metastatic or locally advanced unresectable urothelial cancer that has progressed after platinum and checkpoint inhibitor therapy.
Authors: Grivas Petros , Tagawa Scott T. , Bellmunt Joaquim , De Santis Maria , Duran Ignacio , Goebell Peter-Juergen , Necchi Andrea , Sridhar Srikala S. , Sternberg Cora N. , Aziz M Usman , Pichardo Cabilia C. , Loriot Yohann 
Published: March 2021

TPS498 Background: Treatment options are limited for patients with locally advanced unresectable or metastatic urothelial carcinoma (mUC) who progress following prior platinum-based and checkpoint inhibitor (CPI) therapy. Sacituzumab govitecan (SG) is an antibody-drug conjugate consisting of an anti–Trop-2 monoclonal antibody coupled to SN-38 (an active metabolite of irinotecan, a topoisomerase-I inhibitor) via a unique hydrolyzable linker. A phase II registrational study, TROPHY-U-01 study, confirmed the initial positive efficacy signal in mUC. SG demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.5 months in patients with mUC (median 3 prior lines of therapy and 87% with ≥1 Bellmunt risk factors) who progressed after prior platinum-based and CPI therapies (n=113; Loriot ESMO 2020). The results compared favorably with historic single-agent chemotherapy (ORR ~10%; OS ≤7 months). A phase III trial has been initiated to confirm these findings. Methods: TROPiCS-04 (NCT04527991) is a global, multicenter, open-label, randomized, controlled trial in patients with locally advanced unresectable or mUC who progressed after prior platinum-based and CPI therapies (with Eastern Cooperative Oncology Group performance status 0–1 and adequate hematologic, hepatic, and renal function). Patients will be randomized 1:1 to receive SG 10 mg/kg intravenously (IV) on day 1 and 8 of 21-day cycles or single-agent treatment of physician’s choice (paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine 320 mg/m2 IV on day 1 of 21-day cycles) until progressive disease, unacceptable toxicity, or withdrawal of consent. Treatment beyond progressive disease may be permitted in patients deemed to be receiving clinical benefit per investigator assessment. Approximately 482 patients will be enrolled to provide 90% power on the primary endpoint of OS. Secondary endpoints include progression-free survival, ORR, clinical benefit rate, duration of response (all per Response Evaluation Criteria in Solid Tumors v1.1), safety, and quality of life. Study initiation is ongoing and enrollment begins in Q4 2020 across ~90 sites. Clinical trial information: NCT04527991.
Sub-urothelial durvalumab injection-1 (SUBDUE-1): A novel approach to immunotherapy for bladder cancer.
Authors: Viswambaram Pravin , Moe Andrew , Liow Elizabeth Chien Hern , Redfern Andrew David , Swarbrick Nicole , Ferguson Tom , Davis Ian D. , Hayne Dickon 
Published: March 2021

TPS503 Background: Bladder cancer progression may be influenced by the host immunological response to the tumour. Cells strongly associated with this immunological response include Tumour Infiltrating Lymphocytes (TILs) and Tumour-Associated Macrophages (TAMs). Several solid tumours, including bladder cancer can demonstrate good responses to systemic immuno-oncology (IO) agents, however, the efficacy of IO agents in localised bladder carcinoma remains less clear, although numerous trials are underway. One such IO agent is durvalumab, an antibody against the immune checkpoint protein programmed cell death ligand 1 (PD-L1). The sub-urothelial administration of immune therapeutic agents has not been reported. This method of administrating other agents such as Botulinum toxin has shown excellent feasibility and efficacy. Local delivery could have a number of therapeutic advantages and aligns more closely with the intra-vesical therapies commonly adopted in this clinical scenario. It remains unknown whether systemic effects (both beneficial and adverse) of PD-L1 blockade would be reduced by this mode of delivery. Our aim was to establish: a protocol for the sub-urothelial administration of durvalumab. the safety and tolerability of sub-urothelial administration of durvalumab to identify an appropriate dose for future phase II studies the local immunological efficacy of sub-urothelial administration of durvalumab by assessing the quantity and distribution of TILs and TAMs in pre- and post-administration biopsies Methods: This dose-finding Phase Ib trial is currently recruiting patients with invasive, high-grade bladder cancer (≥pT1) already scheduled for radical cystectomy. Cystoscopy under general anaesthesia and sub-urothelial injection of durvalumab will be performed a minimum of 2 weeks prior to cystectomy, utilising a 3+3 dose escalation design (25mg, 75mg, 150mg). The selected dose of durvalumab is diluted into 25mL of normal saline, and administered to the bladder using a 5Fr Bonee needle via 22Fr rigid cystoscope. PROMS, blood specimens, and tumour histopathology and immunohistochemistry at allocated times pre- and post-cystectomy are being collected for translational end-points. Analysis of safety and tolerability will be primarily descriptive in nature. This trial is registered with the Australian Clinical Trials Registry (ACTRN12620000063910, funded by ANZUP Below the Belt and has been approved by the appropriate institutional HREC. To date, four patients have been recruited. This study has a two-year recruitment target and is expected to finish recruiting in 2022. Clinical trial information: ACTRN12620000063910.
European Health Care Systems and the Emerging Influence of European Union Competition Policy
Authors: Morton Andrew J. B. 
Published: March 2021

AbstractContext: Since the 1990s, the EU's influence over national health care policy has been limited to European internal market law or social policy coordination mechanisms. The introduction of EU competition law into health care is more recent and underdeveloped; however, its introduction would potentially be much more far-reaching and disruptive.Methods: Three EU competition law (state-aid) cases are used and comprise both Court of Justice and European Commission decisions. One is from Ireland, one is from the Netherlands, and the third is from Belgium.Findings: The Belgian (Iris-H) case sees EU institutions scrutinize a clearly “social” (nonmarket) health care model with EU competition law for the first time. This is a highly significant development. It is clear, however, that the European Commission is more reluctant to use EU competition law to scrutinize health care systems than the European courts are.Conclusions: This intent on the part of EU institutions will have to be assessed in future cases, as considerable uncertainty about its shape and outer contours remains. However, EU competition law, and the EU's state-aid investigation apparatus, encroaching into the national health care systems for the first time is highly significant.
High-dimensional immunotyping of tumors grown in obese and non-obese mice
Authors: Wogsland Cara E. , Lien Hilde E. , Pedersen Line , Hanjra Pahul , Grondal Sturla M. , Brekken Rolf A. , Lorens James B. , Halberg Nils 
Published: March 2021

ABSTRACT
Obesity is a disease characterized by chronic low-grade systemic inflammation and has been causally linked to the development of 13 cancer types. Several studies have been undertaken to determine whether tumors evolving in obese environments adapt differential interactions with immune cells and whether this can be connected to disease outcome. Most of these studies have been limited to single-cell lines and tumor models and analysis of limited immune cell populations. Given the multicellular complexity of the immune system and its dysregulation in obesity, we applied high-dimensional suspension mass cytometry to investigate how obesity affects tumor immunity. We used a 36-marker immune-focused mass cytometry panel to interrogate the immune landscape of orthotopic syngeneic mouse models of pancreatic and breast cancer. Unanchored batch correction was implemented to enable simultaneous analysis of tumor cohorts to uncover the immunotypes of each cancer model and reveal remarkably model-specific immune regulation. In the E0771 breast cancer model, we demonstrate an important link to obesity with an increase in two T-cell-suppressive cell types and a decrease in CD8 T cells.
Theory of change: Drama and arts-based community engagement for malaria research and elimination in Cambodia
Authors: Ean Mom , Sanann Nou , Callery James J. , Pell Christopher , Peto Thomas J. , Tripura Rupam , Cheah Phaik Yeong 
Published: March 2021

Background: Across the Greater Mekong Sub-region, malaria persists in isolated communities along international borders. Arts and drama have been used to reach to communities in Cambodia to engage them in malaria research, prevention and control. The “Village Drama Against Malaria” (VDAM) project was conducted in north eastern and western Cambodia: Stung Treng; Battambang and Pailin provinces during 2016 to 2019. In total, VDAM reached 55 rural villages, 2,378 student participants and 43,502 audience members. Methods: This article presents the results of two stakeholder-led evaluation workshops in which participants collaboratively developed theories of change to better understand the potential and actual impact of arts and drama-based activities on malaria in these communities. The workshops had a particular focus on identifying areas for monitoring and evaluation so that impact can be measured. Workshop participants included village malaria workers, community leaders, professional and student drama performers, and representatives from the local health authorities and the national malaria control programme. Results: Five broad areas were identified as relevant for monitoring and evaluation: logistical and practical challenges; embeddedness and reach of engagement; health knowledge and confidence of young people; community-level malaria outcomes; impact on malaria. These areas align well with the monitoring and evaluation conducted to date and point to additional opportunities for data collection. Conclusions: The findings from these workshops will inform future engagement strategies, for example, we may engage a smaller number of young people but over a longer period and more in-depth.
Stability of Vocal Variables Measured During the Early Communication Indicator for Children With Autism Spectrum Disorder
Authors: McDaniel Jena , Yoder Paul , Estes Annette , Rogers Sally J. 
Published: March 2021

Abstract
The Early Communication Indicator (ECI) was designed to measure expressive communication progress in young children. We evaluated using the 6-min ECI procedure for a new purpose—a sampling context for stable measures of vocal development of young children with autism spectrum disorder (ASD). We evaluated how many ECI sessions were required to adequately stabilize estimates of volubility, communicative use, and phonological complexity of vocalizations at two periods (average of 10 months apart). Participants included 83 young children with ASD (M age = 23.33 months). At study initiation, two phonological complexity variables required two sessions; other variables required three. At study endpoint, all variables required fewer sessions. Findings support the feasibility and stability of using the ECI for the new purpose.
Phase noise of the near-infrared single-mode fiber Mach–Zehnder
interferometer and its stabilization technology
Authors: Bai Yunrui , Yu Haijuan , Zhang Yong , Miao Zhangwang , He Chaojian , Dou Rui , Zhang Yuting , Lin Xuechun 
Published: March 2021

We present an estimation method and an investigation on the phase-noise
stabilization for a near-infrared fiber Mach–Zehnder interferometer
(MZI) using a laser diode at 1530 nm as the light source. Based on the
theoretical analysis, the phase noise is mainly produced by the tiny
fluctuations of external temperature, whose amplitude is proportional
to the optical path difference (OPD) between two arms of optical
fibers in the interferometer. By minimizing the length difference
between two fibers in the MZI and specifying the compensation signal
applied to the piezoelectric transducer (PZT) modulator actively, the
interferometer worked stably at different phase differences. When the
interferometer was working at the 90° phase difference, which is
usually necessary for practical application, the RMS noise was
minimized to 0.47°. By quantitative analysis, the magnification ratio
of noise amplitude at room temperature per unit OPD of the MZI was
132.29°/m (

=

0.73

r
a
d

/

m

). In this experiment, a good linear
correlation between the initial OPD and the phase signal intensity was
successfully observed. Using this estimation method, an optical fiber
interferometer of different wavelengths can be built more conveniently
in practical engineering applications.