bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes with systemic therapy given after progression on prostate specific membrane antigen radioligand therapy (PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Labidi Soumaya , Salehi Aida , Fallah Parvaneh , Morin Vincent G. , Li Meredith , Probst Stephan , Ferrario Cristiano , Rose April A. N. 
Published: January 2024

78 Background: PSMA-RLT is a novel therapeutic modality that improves overall survival in mCRPC. However, outcomes for systemic therapy given after progression on PSMA-RLT are not well described. We investigated treatment choices and outcomes in patients (pts) with mCRPC who experienced disease progression after PSMA-RLT. Methods: We performed a single center retrospective cohort study of pts with mCRPC, who received PSMA-RLT at the Jewish General Hospital between 2020 and 2023. Clinical characteristics, PSA50, further lines of therapy post PSMA-RLT and survival were abstracted from chart review. A log-rank test was used to assess overall survival (OS). Post-PSMA-RLT specific OS (Post-RLT-OS) was defined from the date of first systemic treatment after PSMA-RLT failure to death or last follow up. Results: We identified 42 pts who received PSMA-RLT for mCRPC. The median age was 63 years (47-89) and the majority (56.1%) of pts received PSMA-RLT as a 3rd or later line of therapy in mCRPC setting. Amongst these pts, 15/42 (35.7%) achieved a PSA50 response to PSMA-RLT; 36 pts experienced disease progression, and 25/36 with disease progression (69.4%) received subsequent active systemic therapy. Post-PSMA-RLT systemic therapy included chemotherapy (n=17), PARP inhibitors (PARPi) (n=3), bipolar androgen therapy (BAT) followed by androgen receptor-axis targeted agent (ARAT) (BAT+ARAT) (n=2), Radium (n=2), BAT (n=1), and different PSMA-RLT agent (n=1). Amongst the pts who received post-PSMA-RLT therapy, 5/25 (20%) achieved a PSA50 response. PSA50 responses were observed in pts who received chemotherapy (n=2), BAT+ARAT (n=2) and PARPi (n=1). After a median follow-up of 10 months, the median Post-RLT-OS in the entire cohort was 11.7 months. Post-RLT-OS was significantly associated with PSA levels at the time of post-PSMA-RLT systemic therapy. The median Post-RLT-OS for pts with PSA < 100 (n=11), 100 ≤ PSA < 1000 (n=5) PSA ≥ 1000 (n=5) was 15, 15.7, and 8.6 months respectively (P = 0.014). Conclusions: Some pts derive benefit from post-PSMA-RLT systemic therapy; however, the overall response rate is low and therapeutic options are limited. More research is needed to define mechanisms of resistance to PSMA-RLT, and to identify novel therapeutic opportunities in this patient population.
HRR testing and PARPi utilization among patients with metastatic castration resistant prostate cancer treated in the real-world setting.
Authors: Vasudevan Anupama , Katzen Harvey I. , Gart Mike , Blanc Simon 
Published: January 2024

91 Background: HRR mutations (HRRm) have prognostic value in metastatic castration-resistant prostate cancer (mCRPC). Treatment with poly (ADP-ribose) polymerase inhibitors (PARPi) has shown better outcomes among patients with HRR mutations. This study aimed to understand the HRR testing rates among mCRPC patients and utilization of PARPi(s) among HRRm mCRPC patients treated in the real world. Methods: A random sample of 480 mCRPC patients from the Integra Connect PrecisionQ de-identified database were included in this retrospective observational analysis with additional information supplemented by curation. The database contains ~80% community oncology and ~20% academic practices with over 2 million cancer patients across 500 sites of care. Eligible male patients were those aged ≥18 years, diagnosed with mCRPC, and who received treatment between 2020 and 2023. HRR testing rates and utilization of PARPi use were assessed and presented for this study. Results: The mean (SD) age of 480 mCRPC patients was 76.9 (8.3) years; 78.3 % reported being White, 7.9% as African American, 1% as Asian, and 12.7% as Other. Most of the patients reported a payer type of Medicare/Medicaid (69.2%) followed by 15.6% Commercial and 15.2% as Self-Pay/Other. Testing for HRR was reported in 235 (48.9%) of the mCRPC patients and 59 (25.1%) of those patients were HRRm. The mean (SD) age of 59 HRRm mCRPC patients was 77.1 (7.2) years; 88.1% were white, 6.8% African/American, and 5.1% Other. Payer type was reported as being Medicare/Medicaid in 72.9% followed by 18.6% Commercial and 8.5% as Self-Pay/Other. BRCA and ATM mutations were reported among 22/59 (37.2%) and 15/59 (25.4%) patients, respectively. Among the 59 HRRm mCRPC patients, 53 (90%) were noted to have received prior NHA (novel hormone agents) while only 36/53 (67.9%) were noted to have received PARPi. Conclusions: Fewer than half of those patients with mCRPC were tested for HRR. This highlights the lack of testing among those receiving care in a real-world setting. The underutilization of PARPi in these patients is a missed potential opportunity for improving their outcomes.
Secondary primary malignancies among patients with GU cancer.
Authors: Tripathi Nikita , Ayaz Ahsan , Naqvi Syed Arsalan Ahmed , Khan Muhammad Ali , Saxena Akshat , Bibi Arifa , Channar Aneeta , Tyson Mark , Riaz Irbaz Bin , Cobran Ewan Kemar , Bryce Alan Haruo , Abdul-Muhsin Haidar , Singh Parminder 
Published: January 2024

98 Background: The risk of secondary primary malignancies (SPM) among the survivors of GU cancer is not well-established. In this study, we attempt to describe the patterns of SPMs in patients diagnosed with GU cancers. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (SEER*Stat 8.4.2) was searched to obtain data on the incidence of SPM in adult patients (age >18 years) diagnosed with GU cancers, including prostate, renal, and bladder cancer. Standardized incidence ratios (SIRs) with a 95% confidence interval (CI) were calculated. SIR was defined as the observed SPMS from each category divided by the expected number of SPMs in the age-matched US population for the same period. The data was further stratified by age (<50y, 50-70y, >70y), race (White, Black, Asian/Pacific Islander), ethnicity (Hispanic, non-Hispanic), chemotherapy, and radiotherapy exposure. Results: A total of 1,041,217 patients were included in this analysis. In patients diagnosed with GU cancer, the incidence of overall SPM was 11%. Particularly, patients with GU cancers were observed to have a high incidence of Endocrine system SPM (1.52; 1.45-1.59), and urinary system SPM (1.51; 1.49-1.53) These results were consistent by different sociodemographic groups. In patients diagnosed with prostate cancer, the incidence of thyroid SPM was increased (1.31; 1.23-1.39). Particularly, prostate cancer patients treated with radiation therapy had increased incidence rates of SPM in the peritoneum, omentum and mesentery (1.57; 0.79-2.81) and urinary bladder (1.36;1.32-1.40) was higher as compared to those with no exposure to radiation therapy (1.11;1.08-1.13 and 1.03;1-1.06 respectively). Bladder cancer patients had an overall increased incidence of SPM in the esophagus (1.21; 1.08-1.35), lung, bronchus, trachea, and other respiratory organs (1.97;1.92-2.01), prostate (3.50;3.4-3.6) and kidney (1.86;1.76-1.97). A higher incidence of renal pelvis, ureter and other urinary organ SPM (11.08;10.48-11.07) was also notable in this population. Similarly, kidney cancer patients had a higher incidence of the endocrine system (3.00;2.74-3.27), prostate (1.24;1.2-1.29) and bladder 1.78;1.68-1.79 SPMs. Conclusions: This population-based study shows an increased risk of SPM development in GU cancer survivors compared to the general population. Clinicians should keep a high index of suspicion for SPMs and initiate appropriate workups at early warning signs.
COMBAT: A study of 64Cu-SAR-BBN and 67Cu-SAR-BBN for identification and treatment of GRPr-expressing metastatic castrate-resistant prostate cancer.
Authors: Nordquist Luke T. , Lengyelova Eva , Almaguel Frankis , Mancini Brandon Robert , Song Hong , Armstrong Andrew J. , Zurita Amado J. , Anderson Monique , Parker Michelle , Miller Robert M. , Iagaru Andrei 
Published: January 2024

TPS247 Background: Metastatic castrate resistant prostate cancer (mCRPC) is an advanced and lethal form of prostate cancer. Prostate-specific membrane antigen (PSMA)-targeted theranostic agents, 68Ga-PSMA-11 and 177Lu-PSMA-617, have been approved by the FDA for patient selection and therapy for patients with mCRPC, respectively. Approximately 25% of patients with mCRPC show low or no PSMA expression. Consequently, these patients are unlikely to benefit from PSMA-targeted agents and represent a significant unmet need for both imaging and therapy. The Gastrin Releasing Peptide receptor (GRPr) is a transmembrane G-protein coupled receptor that is upregulated in many human cancers, including PC. A promising new theranostic pair, consisting of 64Cu-SAR-BBN (imaging) and 67Cu-SAR-BBN (therapy), targets the GRPr. This may offer a potential imaging and treatment option for patients with low or no PSMA expression. Methods: COMBAT is a multi-center, open-label, phase I/IIa dose-escalation and cohort expansion study of 64Cu-SAR-BBN and 67Cu-SAR-BBN administered to patients with mCRPC. Eligible patients will have progressive mCRPC, prior exposure to at least one androgen receptor pathway inhibitor, will be ineligible for 177Lu-PSMA-617 therapy, and show a positive 64Cu-SAR-BBN PET. This study is being conducted in 2 phases: a Dose Escalation Phase (n=up to 24) and a Cohort Expansion Phase (n=14). The primary and key secondary objectives include assessment of safety of 64Cu- and 67Cu-SAR-BBN, determining the maximum tolerated dose (MTD) or maximum feasible dose (MFD) and anti-tumor efficacy of 67Cu-SAR-BBN. The 67Cu-SAR-BBN dose levels investigated in the escalation phase include: 6 GBq (cohort 1, single dose with dosimetry assessment), 10 GBq (cohort 2, single dose), 14 GBq (cohort 3, single dose), and up to 28 GBq across two doses (cohort 4, two doses at MTD/MFD). Additional doses may be administered during the Dose Escalation Phase (maximum of 4 doses in each cohort). The Dose Expansion Phase of the study will allow the administration of up to 4 doses of 67Cu-SAR-BBN at the MTD/MFD. Response measurements include reduction in PSA levels, radiological progression-free survival, duration of response, and overall survival. Radiological response will be assessed by RECIST 1 V1.1 and PCWG3. At the time of submission of this abstract, cohort 1 is open for enrollment. Clinical trial information: NCT05633160 .
A randomized phase I/II study of neoadjuvant treatment with 177-Lutetium-PSMA-617 with or without ipilimumab in patients with very high-risk prostate cancer who are candidates for radical prostatectomy (NEPI trial).
Authors: Krafft Ulrich , Grünwald Viktor , Fendler Wolfgang P. , Herrmann Ken , Reis Henning , Roghmann Florian , Rahbar Kambiz , Heidenreich Axel , Giesel Frederik , Niegisch Guenter , Hadaschik Boris A. 
Published: January 2024

TPS352 Background: High-risk prostate cancer accounts for approximately 15% of newly diagnosed prostate cancers. For patients with high-risk, locally advanced prostate cancer, prostatectomy alone may be insufficient therapy. Cure rates from radical prostatectomy alone are less than 25%. Ipilimumab increases overall survival in men with post-docetaxel mCRPC who received radiotherapy to bone metastases followed by ipilimumab in comparison to placebo. Final results of the VISION trial (NCT03511664), a phase III study designed to assess the efficacy of [177Lu]Lu-PSMA-617 in patients with PSMA-positive mCRPC, show a significant prolongation of survival in a setting without established therapy. Since both ipilimumab combined with radiation and [177Lu]Lu-PSMA-617 have been proven to be effective in the treatment of mCRPC, we hypothesize, that CTLA-4-inhibitors exert synergistic effects on [177Lu]Lu-PSMA-617 RLT-induced tumor damage and immune priming. Methods: Patients diagnosed with highest risk prostate cancer (ISUP-GG 4+5 and cT3 plus cN+ or PSA > 20ng/ml) who are candidates for radical prostatectomy receive 12 weeks of neoadjuvant treatment with ADT plus [177Lu]Lu-PSMA-617 (LuPSMA) with randomized allocation with or without ipilimumab. Prior to initiation of the randomized set, we will conduct a Safety-Run-In-Phase. The initial 3-6 patients will receive a reduced dose of 3.7 Gb [177Lu]Lu-PSMA-617 and 3 mg/kg Ipilimumab, which will be increased to the target dose of 7.4Gb [177Lu]Lu-PSMA-617 and 3 mg/kg Ipilimumab in the following 3-6 patients if sufficiently well tolerated. The safety and feasibility of the combination will be assessed after 6-12 patients based on toxicity or delay of prostatectomy (max. 3 weeks). In the absence of serious toxicity signals a total of 46 patients will be randomized 1:1 (ipilimumab + ADT + LuPSMA vs. ADT + LuPSMA) to receive 2 cycles of 7.4 GBq LuPSMA with or without 4 cycles of ipilimumab 3mg/kg prior to prostatectomy. Scheduled Imaging with mpMRI and PSMA PET CT is performed prior to neoadjuvant therapy and prior to radical prostatectomy. Co-primary endpoints of the study are feasibility of radical prostatectomy after neoadjuvant therapy, and complete pathologic response. Secondary endpoints are evaluation of the safety profile of neoadjuvant treatment according to "National Cancer Institute Common Terminology Criteria for Adverse Events" (NCI CTCAE) v5.0 and disease-free survival. Enrollment of the first patient in NEPI Trial is expected to be completed in late September 2023. A total of up to 3 German centers will participate. Clinical trial information: EudraCT-Nr.: 2021-004894-30.
SWOG S2210: A phase II study of neoadjuvant carboplatin for localized, high-risk prostate cancer with germline BRCA1/2 mutations.
Authors: Cheng Heather H. , Callis Samuel , Lin Daniel W. , Yu Evan Y. , Dorff Tanya B. , Kase Adam McLain , Tangen Catherine , Petrylak Daniel P. , Lerner Seth P. 
Published: January 2024

TPS354 Background: Carriers of germline pathogenic variants or mutations in BRCA2 and BRCA1 (referred to here as gBRCA1/2m) are enriched in metastatic prostate cancer (PrCa), and now have FDA-approved options for PARP inhibitors in late-stage disease. The NCCN guidelines recommends germline genetic testing for PrCa patients with metastatic, node positive and high risk localized prostate cancer. Prior studies have shown that gBRCA1/2m carriers with PrCa are more likely to have high-risk disease (6,7) and to develop lethal disease even after curative intent treatment (8,9). In other gBRCA1/2m-related cancers (breast, ovarian and pancreas), platinum-based regimens are part of neoadjuvant and front-line metastatic therapy options. Carboplatin is a well-tolerated, widely available and inexpensive DNA-damaging alkylating agent that is familiar to oncologists. The study hypothesis is that 4 cycles of neoadjuvant carboplatin, followed by radical prostatectomy for patients with localized high/very high risk PrCa and g BRCA1/2m will result in a meaningful pathologic complete response (pCR) rate. Methods: S2210 is a single-arm, open label study of 12 wks neoadjuvant carboplatin (4 cycles of AUC 5 every 21 days), followed by radical prostatectomy. Key eligibility criteria include people with high/very high-risk disease: cT3a or Grade Group 4-5 PrCa and/or PSA>20 ng/mL, have no evidence of distant metastases by conventional imaging (PSMA-PET-detected mets permitted if conventional imaging is negative and surgeon deems PSMA-detected sites resectable), who are candidates for radical prostatectomy and carboplatin, and have documented evidence of gBRCA1/2m through testing in a CLIA-certified lab. ADT prior to registration is permitted but must be discontinued on study. The study hypothesis is that the study treatment will result in ³30% rate of pathologic complete response (pCR, primary endpoint). A two-stage design will be used such that if ³1 of first 20 eligible patients achieves pCR, 20 further evaluable patients will be enrolled. This design has a significance level of 4.7%, and a power of 99%. Secondary endpoints include biochemical recurrence-free (at 2-, 3-, 5-yrs), metastasis-free and overall survival. Translational/correlative studies include analysis of 2nd allele inactivation in tumor, HRD signature, and ctDNA signature for monitoring of recurrence. S2210 was activated in August 2023. Clinical trial information: NCT05806515 .
A phase 1, first-in-human, dose-escalation and expansion study of FX-909 in patients with advanced solid malignancies, including advanced urothelial carcinoma.
Authors: Iyer Gopa , Gao Xin , Rasco Drew W. , Milowsky Matthew I. , Garmezy Benjamin , Rodriguez Rivera Ildefonso I , Tepper Jennifer , Moles Melissa Ann , Gjini Evisa , Bowden Michaela , Meyers Michael L. , Bellmunt Joaquim , Galsky Matt D. 
Published: January 2024

TPS709 Background: High Expression of Peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor-family transcription factor, drives the initiation and development of UC in luminal molecular subtype tumors. Genetic profiling of UC has identified recurrent oncogenic alterations in the PPARG transcriptional complex, including focal amplification, missense mutations, and fusions in the heterodimeric partner of PPARG, the retinoid X receptor alpha (RXRA). High levels of PPARG expression and recurrent oncogenic alterations are observed in other solid malignancies including colorectal, gastroesophageal, pancreatic and lung cancers. FX-909 is an oral, first-in-class, new molecular agent that specifically, potently, and covalently modifies PPARG to mediate basal and ligand-activated transcription. Treatment of genetically defined UC xenografts with FX-909 has shown an 84% tumor growth inhibition (TGI) at a dose expected to be equivalent to 50 mg dose in humans, which is the starting dose in this clinical study. Methods: FX-909-CLINPRO-1 (NCT05929235) is a first-in-human, multicenter, open-label Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FX-909 given orally in patients with advanced solid malignancies. Patients enrolled in the trial must have ECOG performance status ≤2 and must be ≥ 18 years of age. Initially, FX-909 will be given once daily to patients with any advanced solid malignancy in a dose-escalation phase (Part A) utilizing a 3+3 design. Five dose cohorts of 3 to 6 patients are planned. At the time of submission, three patients are enrolled in Part A- cohort one, 50mg. Additional patients will be allowed to backfill to previously cleared dose levels that demonstrate therapeutically relevant exposures or evidence of clinical activity. Once a RP2D has been determined, a monotherapy expansion phase (Part B) will proceed in a Simon 2-stage design in patients with locally advanced (unresectable) or metastatic UC with measurable disease and tumors harboring defined genetic alterations in PPARG, RXRA and FGFR3 (Motley et al, 2022). In stage 1, up to 19 evaluable patients will be enrolled. If ≥4 objective responses are observed, enrollment will continue into Stage 2 with an additional 14 evaluable patients. One treatment cycle is 28 days. Dose expansion will evaluate the safety, PK/PD profile, and antitumor activity of FX-909 at the RP2D. Exploratory objectives include the evaluation patient selection biomarkers from tissue and blood samples. FX-909 clinical activity will be assessed using RECIST v1.1 criteria. The study is currently enrolling patients in the US. Clinical trial information: NCT05929235 .
Antagonistic Activities of Endophytic Fungi from Chili Pepper (Capsicum frutescens L.) Stems and Leaves against Colletotrichum sp.
Authors: Puspitarini Sofia , Aji Oktira Roka 
Published: January 2024

Colletotrichum sp. is one of the type pathogenic fumgi that can cause antachnose diseases. One of the plants that can be attacked by antrachnose is cayenne pepper (Capsicum frutescens L.). This study attempts to determine the ability of endophytic fungi from the stems and leaves cayenne pepper (Capsicum frutescens L.). Methods: This study used dual culture method to determine the percentage of resistence to patogen Colletotrichum sp. and the area of growth endophytic fungi planted on PDA (Potato Dextrose Agar). Results:. There are 3 isolates from the stems and leaves of cayenne pepper that is JE-B4-C, JE-D5-C, dan JE-B1-C. Among all the isolates, the largest percentage of inhibition and growth area endophytic fungi were found in isolate JE-B4-C with each of 29,41% dan 58,04 cm2. Conclusions: Expected isolates JE-B4-C derived from the genus eupenicillium, while isolates JE-D5-C and JE-B1-C respectively derived from the genus Aspergillus and Neoscytalidium.
Developing and Evaluating the Fidelity and Understandability of Plain Language Summaries of Position Statements
Authors: Nygren Margaret A. , Linscott Robyn , Nagel Mike , Atkins Michael , Ward Julie , Alexander Jenny 
Published: January 2024

Abstract
The American Association on Intellectual and Developmental Disabilities (AAIDD) and The Arc of the United States (The Arc) have a long history of taking jointly held positions on matters of public policy that affect people with intellectual and developmental disabilities (IDD). This article describes the methods used to develop and evaluate the understandability and fidelity of written plain language summaries of the organizations’ joint position statements for an audience of people with IDD who read. Implications for adapting source material for nonreading audiences are discussed.
A Tanítási Környezetet (TE) és a Tanári Oktatási Hatásrendszert (TASCQ) vizsgáló kérdőívek magyar nyelvű adaptációja kelet-közép-európai mintán
Authors: Csordás-Makszin Ágnes , Karsai István , Hamar Pál , Soós István 
Published: January 2024

Vizsgálatunk tárgyát az oktatási stratégiákat kiváltó előzmények megismeréséhez alkalmazható Tanítási Környezetet (TE) és a Tanári Oktatási Hatásrendszert (TASCQ) vizsgáló angol nyelvterületeken alkalmazott kérdőívek magyar nyelvre történő adaptálása és pszichometriai elemzése képezte. Adatokat Kelet-Közép-Európában Szlovákia, Románia, Szerbia és Magyarország területén élő magyar ajkú testnevelő tanárok bevonásával gyűjtöttünk. A felmért adatokkal a pedagógusok köznevelésben tapasztalt tanítási környezetét és az önmeghatározás elméletben (Deci & Ryan, 2000) megnevezett motivációs stratégiák kialakításának hátterét kívántuk megismerni. A tanítási környezetben három területet vizsgáltunk: a tanóra időkorlátja, az iskolamenedzsment általi nyomás és az intézményben történő szakmai fejlődés lehetősége (Taylor, Ntoumanis & Standage, 2008). Az önmeghatározás elmélet három, a tanárok viselkedésén keresztül testet öltő, fő motivációs stratégiát határoz meg (autonómiatámogatás, struktúra és személyes odafigyelés). 2018 és 2021 között 376 testnevelő tanár (195 nő, 181 férfi) töltötte ki a Tanítási Környezet (Taylor, Ntoumanis & Standage, 2008), valamint a Tanár Oktatási Hatásrendszere (TASCQ – Belmont, Skinner, Wellborn és Connel, 1988) kérdőívet. A megerősítő faktoranalízis eredményei alapján az eredti Tanítási Környezet kérdőív faktorszerkezetét módosítottuk, illetve a kérdéssort két itemmel lerövidítettük. Így a módosítások után az illeszkedési mutatók: χ2TE-H= 95,70, az χ2/dfTE-H=2,33; CFITE-H=0,96; RMSEATE-H =0,06; IFITE-H=0,96. A belső konzisztencia - Cronbach α - értékei 0,66 és 0,85 között változnak, ekképpen megfelelnek az elvárt kritériumoknak. A Tanár Oktatási Hatásrendszere kérdőív faktorain nem változtattunk, viszont annak érdekében, hogy az illeszkedési mutatók elérjék a megkívánt értékeket, az eredeti angol nyelvű változatot nyolc itemmel csökkentettük. Így az illeszkedési mutatók: χ2TASCQ-H=44,18; χ2/dfTASCQ-H=2,59; CFITASCQ-H=0,96; RMSEATASCQ-H=0,06; IFITASCQ-H=0,96. Ebben a kérdőívben a belső konzisztencia értékei 0,66 és 0,73 között változnak, ami szintén megfelel az elvárt kritériumoknak.
Elemzésünk eredményei alapján megállapítható, hogy a kérdőívek alkalmazásával nyert adatok alkalmasak tudományos igényű következtetések levonására.