bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporating mpMRI and biomarkers in active surveillance protocols: The prospective Stockholm3 Active Surveillance trial (STHLM3AS).
Authors: Lantz Anna , Olsson Henrik , Nordström Tobias , Jäderling Fredrik , Egevad Lars , Annerstedt Magnus , Gronberg Henrik , Eklund Martin 
Published: February 2020

TPS379 Background: Level one evidence shows that men with low-risk prostate cancer undergoing active surveillance (AS) with repeated PSA tests and systematic biopsies have low mortality. However, monitoring sometimes misses significant cancer progression and causes patient morbidity. The objective of this study is to evaluate a new proposed protocol for AS using the combination of the Stockholm3 test and MRI targeted biopsies in comparison to conventional follow-up using PSA and systematic biopsies. Methods: A prospective multicenter study with paired design was used to evaluate our proposed protocol (Stockholm3, MRI, targeted biopsies) compared with the conventional protocol according to Swedish National Guidelines (PSA, systematic biopsies) for follow-up of men on AS. The STHLM3 study was performed between 2012-2014. In the study 1 374 men were diagnosed with ISUP grade 1 disease. Out of these, 541 men currently on AS were invited to the STHLM3AS study. Eligible individuals had to be alive without any severe comorbidity, without contraindications for MRI and without a history of initiating prostate cancer treatment. The primary endpoint ISUP grade ≥2 cancer and the secondary endpoint number of performed biopsies will be evaluated using relative sensitivity (RS). At baseline a blood test for PSA and Stockholm3 test as well as a bi-parametric MRI was performed. For men with PIRADS ≥ 3 targeted and systematic biopsies were performed. For men with PIRADS < 3 only systematic biopsies were performed. The study is registered at ClinicalTrials.gov (NCTNCT03956108). Results: 301 men on AS have been included in the study. Since this is a trial in progress, no results will be presented. Conclusions: To our knowledge, this is the largest prospective multicenter study evaluating the performance of MRI for disease monitoring in an AS-cohort. Prediction models using biomarkers and MRI will likely both have an increasing role in the monitoring of AS patients in the future. We hypothesise that the sequential use of first Stockholm3 test followed by MRI will decrease the number of biopsies, while retaining the sensitivity to detect ISUP grade ≥2 cancer compared with using systematic biopsies in all men. Clinical trial information: NCTNCT03956108.
A phase Ib/II trial of perioperative intratumoral MVA-BN-brachyury (MVA) plus systemic PROSTVAC and atezolizumab (Atezo) for intermediate-risk and high-risk localized prostate cancer (AtezoVax).
Authors: Maughan Benjamin Louis , Sanchez Alejandro , O'Neil Brock B. , Lowrance William Thomas , Dechet Christopher B. , Albertson Daniel Joseph , Sirohi Deepika , Gupta Sumati , Swami Umang , Agarwal Neeraj 
Published: February 2020

TPS382 Background: Many patients with intermediate or high-risk localized prostate cancer relapse after prostatectomy, identifying an unmet need. Cancer vaccines increase the infiltrating lymphocyte concentration in localized and metastatic prostate cancer (PMID 25255802, 29858218). We hypothesize that treatment with a combination of two vaccines plus PD-L1 inhibition will be safe and significantly stimulate immune infiltration within the tumor microenvironment. MVA is a modified vaccinia virus that is replication-deficient, inducing the generation of tumor antigen-specific killer T-cells. PROSTVAC is a poxviral based cancer vaccine using a vaccinia virus prime and fowlpox based boost along with co-stimulatory molecules B7.1, leukocyte function-associated antigen-3, and intercellular adhesion molecule-1. Methods: This study is a single-arm,, phase I/II investigator initiated trial (NCT04020094). Primary objectives: 1) Safety, 2) Quantitative change in infiltrating CD8+ lymphocytes between the biopsy and prostatectomy as measured by immunofluorescence. Secondary endpoints: 1) 6- and 12-month undetectable PSA rate; 2) PSA-PFS compared to institutional historic control. Inclusion criteria: unfavorable intermediate to very high-risk prostate adenocarcinoma (per NCCN). Exclusion criteria: non-adenocarcinoma histology and metastatic disease (including regional nodal metastasis). A total of 22 patients will be enrolled starting with a 6 patient safety lead in. Prostate MRI will be obtained prior to treatment. Treatment schema: 2 neoadjuvant cycles (Atezo + MVA + PROSTVAC), followed by prostatectomy then 6 additional adjuvant cycles (Atezo + PROSTVAC). Neoadjuvant cycle 1: atezolizumab (1200mg IV Q3wks), PROSTVAC-V (Prime, 2x108 Inf.U subcutaneous), MVA (2 x 108 Inf.U/0.5 ml, intra-tumoral injection, volume determined by MRI). Neoadjuvant cycle 2: atezolizumab, PROSTVAC-F (Boost, 1x109 Inf.U, subcutaneous), MVA. Adjuvant: atezolizumab and PROSTVAC-F. Clinical trial information: NCT04020094.
INTREPId (INTermediate Risk Erection PreservatIon Trial): A randomized trial of radiation therapy and darolutamide for prostate cancer.
Authors: King Martin T. , Wise David R. , Scala Lawrence M. , Mariados Neil M. , Whitbeck Amanda , Pomerantz Mark , Bober Sharon , Davicioni Elai , Bubley Glenn , Nguyen Paul L. 
Published: February 2020

TPS384 Background: Men with intermediate risk prostate cancer are often recommended external beam radiation therapy (EBRT) with or without 4-6 months of androgen deprivation therapy (ADT). However, ADT can be associated with prolonged erectile dysfunction due to delayed testosterone recovery. Darolutamide is a second-generation androgen receptor with low blood-brain barrier penetration. We hypothesize that men who receive Darolutamide with RT rather than ADT with RT are able to achieve surrogate PSA endpoints indicative of long-term disease control while preserving erectile function. Methods: This is an open label, phase 2B, multi-center, randomized controlled trial. Eligibility criteria include intermediate risk prostate cancer, good erectile quality per the EPIC-26 questionnaire, and archival tissue suitable for submission to Decipher Biosciences (San Diego, CA). Men will be stratified by Decipher score (low/intermediate vs high), RT modality (EBRT vs Brachytherapy/stereotactic body radiation therapy/combination RT), and age (>65 vs <65). Men with a Decipher high score will be strongly encouraged to undergo extreme RT dose-escalation. The primary endpoint is PSA nadir ≤ 0.5 within 6 months from end of treatment (EOT). The hierarchical endpoint is maintenance of good erectile quality at 3 months from EOT. The key secondary endpoint is interval to PSA failure at 3 years from EOT. Endpoints will be analyzed in a fixed-sequence hierarchical method. 220 patients will be accrued over 3 years. Non-inferiority margins for the primary and key secondary endpoints are 9% (90% power) and 4.9% (80% power), respectively. Men will be randomized to 6 months of GnRH agonist plus bicalutamide 50 mg daily with RT or 6 months of darolutamide 600 mg twice daily with RT. Assessments will occur at baseline, during treatment, EOT, and at regularly scheduled intervals up to 36 months from EOT. Correlative endpoints include discovering transcriptomic and radiomic predictors of response. Clinical trial information: NCT04025372.
P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for adult and pediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).
Authors: Subramaniam Shalini , Toner Guy C. , Stockler Martin R. , Martin Andrew James , Pashankar Farzana D. , Frazier A. Lindsay , Mazhar Danish , Ford Kate , Walpole Euan Thomas , Stevanovic Amanda Gwendolyn , Wyld David , Troon Simon , Hanning Fritha J. , Birtle Alison Jane , Wheater Matthew James , Huddart Robert A. , White Jeff D. , Spunt Sheri L. , Grimison Peter S. ,   Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: February 2020

TPS425 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is the achievement of a favourable response, and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives > 80% power to detect a 20% improvement in the favourable response rate and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV D1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF SC D6 or filgrastim daily; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 13 sites open in UK (led by Cambridge Clinical Trials Unit), 67 sites open in the USA (led by Children’s Oncology Group). As of September 2019, 98 patients have been recruited triggering the first formal interim analysis. Clinical trial information: NCT02582697.
Phase III study of perioperative pembrolizumab (pembro) plus cystectomy versus cystectomy alone in cisplatin-ineligible patients (pts) with muscle-invasive bladder cancer (MIBC): KEYNOTE-905.
Authors: Galsky Matt D. , Necchi Andrea , Shore Neal D. , Witjes Fred , Nam Kijoeng , Sbar Eric , Homet Moreno Blanca , Plimack Elizabeth R. 
Published: February 2020

TPS593 Background: Pts with MIBC ineligible for neoadjuvant cisplatin-based chemotherapy who only receive the standard radical cystectomy+pelvic lymph node dissection (RC+PLND) have a high rate of recurrence and poor prognosis. PD-1/PD-L1 inhibition is an effective first-line option for cisplatin-ineligible pts. Neoadjuvant single-agent pembro, a PD-1 inhibitor, has shown activity in pts with MIBC, with a pathologic complete response (pCR) rate of 42% for all pts and 54% for PD-L1+ pts (PURE-01; NCT02736266). Methods: KEYNOTE-905 (NCT03924895) is a randomized phase 3 trial of preoperative pembro plus RC+PLND versus RC+PLND alone in cisplatin-ineligible pts with MIBC. An estimated 610 pts will be enrolled and randomly assigned 1:1 to either neoadjuvant pembro (3 cycles) followed by RC+PLND and adjuvant pembro (14 cycles) or RC+PLND alone and observation. Pembro 200 mg will be administered IV every 3 weeks. Pts in the RC+PLND group will proceed directly to RC+PLND within 8 weeks from randomization. Pts will be stratified by clinical T stage (T2 vs T3 or T4), PD-L1 expression (combined positive score [CPS] ≥10 vs <10), and geographic region (United States vs Europe vs most of world). Adults (≥18 years) ineligible to receive cisplatin with histologically confirmed MIBC (T2-T4aN0M0), clinically nonmetastatic disease (N0M0), and an ECOG PS score of 0-2 are eligible. Previous systemic anticancer therapies for MIBC are not permitted. CT/MRI will be performed before and after cystectomy. Pts disease free after imaging for cystectomy will continue to undergo serial imaging until disease progression or discontinuation from the study; all imaging will be assessed by blinded independent central review. Coprimary end points are pCR (based on central pathology review) and event-free-survival in all pts and in pts with tumor PD-L1 CPS ≥10. Secondary end points are OS, disease-free survival, and pathologic downstaging in all pts and in pts with tumor PD-L1 CPS ≥10, and safety. Exploratory end points include patient-reported outcomes and biomarkers. Accrual began July 24, 2019. Clinical trial information: NCT03924895.
Window of opportunity trial to characterize the safety, pharmacokinetics, and pharmacodynamics of fosciclopirox (CPX-POM) in cisplatin-ineligible muscle invasive bladder cancer patients.
Authors: Taylor John Arthur , Wood Robyn , Ham Tammy , Casey Crista , Dandawate Prasad , Reed Greg , Woolbright Benjamin L. , Baltezor Michael Jay , Jensen Roy A. , Dalton Michael , Zhukova-Harrill Valentina , McCulloch William , Anant Shrikant , Weir Scott James 
Published: February 2020

TPS604 Background: Fosciclopirox (Ciclopirox Prodrug, CPX-POM) is being developed for the treatment of non-muscle invasive and muscle invasive (MIBC) bladder cancer. CPX-POM selectively delivers its active metabolite, ciclopirox (CPX), to the entire urinary tract following systemic administration. In a validated, chemical carcinogen mouse model of bladder cancer, CPX-POM treatment results in significant decreases in bladder weight, a clear migration to lower stage tumors, dose-dependent reductions in Ki67 and PCNA staining, and inhibition of Notch 1 and Wnt signaling. The safety, dose tolerance, pharmacokinetics and pharmacodynamics of IV CPX-POM have recently been characterized in 19 patients with advanced solid tumors (CPX-POM-001, NCT03348514). The safety and dose tolerance of IV CPX-POM was characterized across a dose range of 30 to 1200 mg/m2. The CPX-POM Recommended Phase 2 Dose (PR2D) of 900 mg/m2 administered IV over 20 minutes on Days 1-5 every 21 days was selected. Methods: Twelve cisplatin ineligible MIBC patients (Stage >T2, NO-N1, M0), scheduled for radical cystectomy (RC) will be enrolled in this window of opportunity study. Patients will receive two 21-day treatment cycles followed by RC within 14 days of completion of the second cycle. Safety and tolerability assessments will be made based on observed adverse and serious adverse events, physical examination, vital signs, electrocardiogram, clinical laboratory tests, and concomitant medications. Assessment of complete and partial pathologic response will be determined at RC. Ki67, Notch and Wnt signaling, and CD8+ lymphocyte tumor infiltration will be determined by immunohistochemistry. An unbiased approach to characterizing CPX-POM mechanisms of action will also be employed using RNAseq and ChIPseq. Serial blood (plasma) and complete urine specimens will be collected on Days 5-6 of Cycle 1 for determination of drug and metabolite concentrations by LC-MS/MS. Plasma and urine steady-state pharmacokinetics of CPX-POM, CPX and ciclopirox glucuronide will be characterized. Urine ß-glucuronidase activity is also being determined by ELISA. Clinical trial information: NCT03348514.
Nutrition of Children With Cancer in Brazil: A Systematic Review
Authors: Viani Karina , Albuquerque Luiza , Barr Ronald D. , Ladas Elena J. 
Published: February 2020

PURPOSEThe objective of this systematic review was to describe nutrition-related publications on children and adolescents diagnosed with cancer in Brazil.METHODSThe methodology followed that of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Medline, LILACS (the Latin American & Caribbean Health Sciences Literature), and Embase were searched in April 2019, and data extraction and rating of methodologic study quality (according to the National Institutes of Health quality score assessment) were performed independently by reviewers.RESULTSTwenty-seven studies met the inclusion criteria, reporting on 3,509 patients from 1994 to 2018. Most of the studies (74%) were of poor quality in methodology and reporting. Different cancer diagnoses were included in 52% of studies, whereas acute leukemia was the exclusive focus in 41%. The majority of the articles (70%) were from institutions in the Southeast Region of Brazil, mainly the state of São Paulo (74%); no publications were from the North Region of the country. Twelve studies addressed nutritional status and body composition, reporting an abundance of malnourished patients in the Brazilian population of children and adolescents with cancer. Six studies on micronutrients pointed to possible deficiencies in this population, with a yet unclear but promising role for supplementation during treatment.CONCLUSIONEvidence indicates that there is great interest in the impact of nutrition on childhood cancer treatment and clinical outcomes in Brazil. However, there is a need to focus on high-quality research, particularly with multicentric/national studies. This will help establish research priorities and better planned clinical interventions, adapted to each region of the country.
Evaluating Patients’ Perception of the Risk of Acute Care Visits During Systemic Therapy for Cancer
Authors: Phillips Cameron M. , Deal Ken , Powis Melanie , Singh Simron , Dharmakulaseelan Laavanya , Naik Harsh , Dobriyal Aditi , Alavi Nasrin , Krzyzanowska Monika K. 
Published: February 2020

PURPOSE: Unplanned emergency department (ED) visits and hospitalizations are common during systemic cancer therapy. To determine how patients with cancer trade off treatment benefit with risk of experiencing an ED visit or hospitalization when deciding about systemic therapy, we undertook a discrete choice experiment. MATERIALS AND METHODS: Patients with breast, colorectal, or head and neck cancer contemplating, receiving, or having previously received systemic therapy were presented with 10 choice tasks (5 in the curative and 5 in the palliative setting) that varied on 3 attributes: benefit, risk of ED visit, and risk of hospitalization. Preferences for attributes and levels were measured using part-worth utilities, estimated using hierarchical Bayes analysis. Segmentation analysis was conducted to identify subgroups with different preferences. RESULTS: A total of 293 patients completed the survey; most were female (76%), had breast cancer (63%), and were currently receiving systemic therapy (72%) with curative intent (59%). Benefit was the most important decision attribute regardless of treatment intent, followed by risk of hospitalization, then risk of ED visit. Two segments were observed: one large cluster exhibiting logical and consistent choices, and a smaller segment exhibiting illogical and inconsistent choices. Patients in the latter segment were more likely to have metastatic head and neck cancer, be male, were older, and reported fewer prior ED visits. CONCLUSION: Although the risk of ED visit or hospitalization contributes to patient treatment preferences, benefit was the most important attribute. Segmentation suggests that a subset of patients may lack cognitive abilities, engagement, or literacy to consistently evaluate treatment choices. Understanding this subset may provide insight into patients’ decision making and understanding of treatment options.
A LIBERDADE DE EXPRESSÃO NAS DECISÕES DE PRIMEIRA INSTÂNCIA DO TJ-RJ
Authors: Hartmann Ivar Alberto Martins 
Published: February 2020

O objetivo deste trabalho é avaliar a prática judicial da primeira instância na resolução de conflitos entre a liberdade de expressão e a proteção da imagem e da honra, geralmente com pedidos de danos morais formulados. A pergunta de pesquisa é: os juízes de primeira instância, quando confrontados com o conflito entre esses direitos constitucionais, utilizam qual método de decisão? Há o recurso à proporcionalidade, razoabilidade ou ponderação a partir do caso concreto, conforme prescrito pelo Supremo e pela doutrina? A hipótese é de que as decisões de primeira instância destoam daquilo que exige a Constituição, segundo a interpretação do Supremo e da doutrina brasileira. A partir de análise de uma amostra aleatória de 30% das decisões de primeira instância do TJ-RJ no período de 2013 a 2015, constata-se que 34% das decisões não realizam ponderação e nem citam qualquer jurisprudência ou doutrina. Já 43% das decisões não realizam ponderação e nem citam qualquer jurisprudência. Existe uma desconexão entre, de um lado, a doutrina constitucionalista teórica, que descreve a aplicação de métodos sofisticados para a solução de conflitos de direitos fundamentais, e, de outro, a realidade das decisões judiciais que ignoram esses métodos ao tratar do exercício da liberdade de expressão. Mais estudos empíricos são necessários para testar se a situação da justiça estadual do Rio de Janeiro se repete em outros estados brasileiros.
CONTROLE DE CONVENCIONALIDADE NA JUSTIÇA DO TRABALHO BRASILEIRA: ANÁLISE JURISPRUDENCIAL QUANTITATIVA E QUALITATIVA
Authors: Beltramelli Neto Silvio , Marques Mariele Torres 
Published: February 2020

O artigo examina o perfil do exercício do controle de convencionalidade pela Justiça do Trabalho brasileira. Para tanto, procedeu-se a pesquisa jurisprudencial que intentou constatar como, com que frequência e em que casos o Tribunal Superior do Trabalho e os Tribunais Regionais do Trabalho (TRTs) das 1ª, 2ª e 15ª Regiões praticam o controle de convencionalidade. O exame realizado debruçou-se sobre um espectro amostral de decisões selecionadas a partir de acórdãos do TST e dos três TRTs de maior porte do país. Conclui-se que a Justiça do Trabalho, à semelhança dos demais ramos do Poder Judiciário brasileiro, faz uso do controle de convencionalidade de modo pontual e seletivo, inexistindo uma atitude hermenêutica de decisão que considere, sistematicamente, o possível exercício de tal controle na prática jurisdicional. A investigação realizou-se com emprego do método indutivo de abordagem e do método bibliográfico de procedimento.
Developing new health technologies for neglected diseases: a pipeline portfolio review and cost model
Authors: Young Ruth , Bekele Tewodros , Gunn Alexander , Chapman Nick , Chowdhary Vipul , Corrigan Kelsey , Dahora Lindsay , Martinez Sebastián , Permar Sallie , Persson Johan , Rodriguez Bill , Schäferhoff Marco , Schulman Kevin , Singh Tulika , Terry Robert F , Yamey Gavin 
Published: February 2020

Background: Funding for neglected disease product development fell from 2009-2015, other than a brief injection of Ebola funding. One impediment to mobilizing resources is a lack of information on product candidates, the estimated costs to move them through the pipeline, and the likelihood of specific launches. This study aimed to help fill these information gaps. Methods: We conducted a pipeline portfolio review to identify current candidates for 35 neglected diseases. Using an adapted version of the Portfolio to Impact financial modelling tool, we estimated the costs to move these candidates through the pipeline over the next decade and the likely launches. Since the current pipeline is unlikely to yield several critical products, we estimated the costs to develop a set of priority “missing” products. Results: We found 685 neglected disease product candidates as of August 31, 2017; 538 candidates met inclusion criteria for input into the model. It would cost about $16.3 billion (range $13.4-19.8B) to move these candidates through the pipeline, with three-quarters of the costs incurred in the first 5 years, resulting in about 128 (89-160) expected product launches. Based on the current pipeline, there would be few launches of complex new chemical entities; launches of highly efficacious HIV, tuberculosis, or malaria vaccines would be unlikely. Estimated additional costs to launch one of each of 18 key missing products are $13.6B assuming lowest product complexity or $21.8B assuming highest complexity ($8.1B-36.6B). Over the next 5 years, total estimated costs to move current candidates through the pipeline and develop these 18 missing products would be around $4.5B (low complexity missing products) or $5.8B/year (high complexity missing products). Conclusions: Since current annual global spending on product development is about $3B, this study suggests the annual funding gap over the next 5 years is at least $1.5-2.8B.