bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the CD47/TSP-1 axis: A promising strategy for patients with ovarian cancer (OC) that relapses on PARP inhibitors (PARPi).
Authors: Leary Alexandra , Jeanne Albin , Etiennot Marion , Henry Aubéri , Drelon Coralie , Schneider Christophe , Moniot Aurélie , Dedieu Stéphane 
Published: June 2024

5568 Background: There is an urgent need for novel therapies for patients relapsing post-PARPi. CD47 is an attractive target due to its overexpression in OC, particularly under PARPi treatment, and its association with shorter survival and immune evasion. While most studies have focused on the CD47/SIRPa interaction (“don’t eat me” signal), our recent data from the randomized CHIVA trial (NCT01583322) uncovered the relevance of TSP-1, a matrix glycoprotein associated with poor prognosis, as a primary CD47-interacting ligand [ASCO 2023]. The TAX2 peptide selectively disrupts TSP-1 binding to CD47. Our aim was to investigate whether inhibiting the CD47/TSP-1 axis with TAX2 could overcome PARPi resistance in a syngeneic mouse model of BRCA2 mutant OC. Methods: Biodistribution studies of fluorescent TAX2 peptide were carried out in mice bearing ovarian tumors tracked through fluorescence molecular tomography. To assess the efficacy of TAX2 and/or PARPi (olaparib) treatment, we used ID8 cells harboring Trp53-/- and Brca2-/- mutations, as a pertinent syngeneic representation of intraperitoneal high-grade serous TP53 and BRCA2 mutated OC. Olaparib was administrated at 50 mg/kg orally daily, while TAX2 was administrated at 30 to 100 mg/kg intravenously thrice weekly. Survival curves were compared using the Gehan-Breslow-Wilcoxon's test. Results: We confirmed that TAX2 peptide binds directly to human TSP-1 with KD of 11 µM. In mice bearing tumors, TAX2 correlated with TSP-1 expression with prolonged accumulation at tumor sites, but none in healthy tissues. Using a relevant peritoneal carcinomatosis model exhibiting PARP inhibitor resistance, we demonstrated that administration of TAX2 alone significantly extended survival. Interestingly, post-olaparib administration of TAX2 substantially reduced tumor burden, even at the lowest TAX2 dosing, and prolonged survival (median survival: 44 vs 38 days). Remarkably, sequential use of TAX2 increased animal survival even under treatment conditions allowing olaparib efficacy. Indeed, post-olaparib discontinuation, mice survival increased from 10.6 to 15.7 days with administration of TAX2. This sequential approach improved the median survival to 56 days. Conclusions: Our findings propose TAX2 as a promising strategy for patients relapsing on PARP inhibitors. TAX2 displayed a selective biodistribution pattern in mice, concentrating at tumor sites. Our study showcased that while TAX2 alone exhibited significant but modest activity in PARPi-naive mice, its efficacy significantly increased post-PARPi exposure, irrespective of PARPi duration. A first in human trial in the post-PARP setting is planned.
Real-world biomarker testing, treatment patterns and outcomes in a US cohort of patients with advanced ovarian cancer.
Authors: Veljovich Dan Steven , Penson Richard T. , Birrer Michael J. , Luo Linlin , Pyrih Nick , Pack Simon , Iu Crystal , Hada Manila 
Published: June 2024

5571 Background: Olaparib, a poly(ADP-ribose) polymerase inhibitor (PARPi), has shown efficacy as monotherapy for the treatment of BRCA mutated (BRCAm) advanced ovarian cancer (AOC) and in combination with bevacizumab for Homologous Recombination Deficient (HRD+) AOC. This study describes real-world (RW) characteristics, testing and treatment patterns in patients (pts) with AOC, including outcomes with olaparib first-line maintenance (1LM) therapy. Methods: A retrospective observational study utilizing the electronic health record-derived de-identified US-based Flatiron Health database was performed including women aged ≥18 y at AOC diagnosis (Jul 2018–Dec 2022) with ≥1 clinical visit. Pts were followed from diagnosis until Aug 31, 2023, cessation of dataset coverage, or death, whichever occurred first. Biomarker testing was defined as evidence of a test for BRCAm or HRD (inclusive of BRCAm). Estimated RW time to first subsequent therapy or death (TFST) and time to treatment discontinuation or death (TTD) are reported. Results: Demographic and clinical characteristics are shown in the Table. Of 1503 pts included, 80.8% (n=1214) were BRCAm tested and 36.3% (n=546) were HRD (inclusive of BRCAm) tested. Among pts who were either BRCAm or HRD tested (n=1220), 58.0% (n=708) were tested between AOC diagnosis and initiation of 1LM therapy. No 1LM therapy was recorded in 61.9% (n=931/1503) of pts. In both BRCAm and HRD+ pts, olaparib, either as monotherapy (44.5% [n=69/155] and 33.6% [n=100/298], respectively) or in addition to bevacizumab (7.1% [n=11/155] and 9.4% [n=28/298], respectively), was the most frequently used PARPi for 1LM therapy (Table). Median (95% CI) TFST and TTD was 44.7 (27.0, NA) and 22.7 (17.0, 47.0) mos, respectively in BRCAm pts receiving olaparib 1LM (n=69), and 29.1 (22.1, NA) and 22.1 (13.1, NA) mos, respectively in HRD+ pts receiving olaparib + bevacizumab 1LM (n=28). Conclusions: While most pts received BRCAm testing, a majority did not receive HRD (inclusive of BRCAm) testing. A sizeable proportion of pts with actionable biomarker results did not receive PARPi as 1LM therapy highlighting the need for education on the importance of genetic testing to guide AOC treatment. Time-to-event outcomes were comparable with those from the SOLO1 and PAOLA-1 clinical trials, thus supporting the real-world effectiveness of olaparib. [Table: see text]
Hospital challenges faced by frail patients with ovarian cancer and the adverse outcomes: A nationwide study.
Authors: Ortega Yaguachi Nataly , Javaid Saad , Frasier Kelly , Li Vivian , Vinagolu-Baur Julia , Rodriguez Evadne , Del Castillo Olivia , Batista Raquel , Jonas Kenlee , Palma Laura 
Published: June 2024

5572 Background: Ovarian cancer is a leading cause of gynecological cancer-related deaths and one of the most common causes of cancer-related fatalities among women. Frailty has been identified as a predictor of unfavorable outcomes for cancer patients, but there is limited research on its impact on individuals with ovarian cancer. We examined the effects of Frailty in hospitalized ovarian cancer patients and the associated outcomes. Methods: National Inpatient Sample (NIS) 2020 was used to identify the patients with a primary diagnosis of ovarian cancer (local/regional and advanced metastatic) and was stratified into patients with and without Frailty. The primary outcome was mortality, and secondary outcomes included length of stay, the total cost of hospitalization, and other in-hospital adverse outcomes. Multivariate logistic regression analysis was used to calculate the outcomes after adjusting for confounding variables. Results: A total of 19790 patients were hospitalized with a primary diagnosis of Ovarian cancer, among which 3215 (16.24%) patients had the concurrent diagnosis of Frailty. The mean age of patients with and without Frailty was 65.76 (+/-13.10) and 60 (+/-14.45),p<0.001, respectively. After adjusting for confounding variables, Frailty was associated with an increased risk of mortality in patients with ovarian cancer (OR=3.01(1.83-4.95); p<0.001). Patients with Frailty were also at risk of increased length of stay (+3.80 Days (3.09-4.50; p<0.001) and total cost of hospitalization (+ $ 34662 (22973-46351); p<0.001). Frail patients also had an increased likelihood of Acute respiratory failure (OR=1.72 (1.22-2.42); p=0.002), Acute kidney injury (OR=2.40 (1.88-3.05); p<0.001), Sepsis (OR=4.97 (3.19-7.75); p<0.001), ICU admission (OR=2.23 (1.44-3.45); p<0.001), Pneumonia (OR=2.63 (1.69-4.10); p<0.001), total parenteral nutrition (OR=14.20 (7.80-25.83); p<0.001) and Intubation (OR=2.11 (1.21-3.69); p=0.008). However, there was no difference in the risk of noninvasive mechanical ventilation (OR=2.07 (0.95-4.52); p=0.48) or enteral feeding (OR=32.73 (0.63-1696); p=0.08). Conclusions: Frailty in ovarian cancer patients is considered an independent predictor of mortality. It is also associated with increased healthcare resource utilization and adverse in-hospital outcomes.[Table: see text]
Efficacy of niraparib in patients with advanced ovarian cancer: A meta-analysis of randomized controlled trials.
Authors: Marinho Alice , Lambert Fossen Eduardo , Caldeira de Freitas Maria Carolina , Coelho Itaya Gabriela , Da Costa Larissa Maria , Dias Yasmin , Celso Davi Said Gonçalves , Bonalumi Dos Santos Marcela , De Souza Mariana , Vilbert Maysa 
Published: June 2024

5587 Background: Niraparib is a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor that has shown clinical benefits as a maintenance therapy for patients with advanced ovarian cancer. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy of niraparib as maintenance therapy after platinum-based chemotherapy for patients with advanced ovarian cancer. PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for RCTs published up to January 17, 2024. Hazard ratios (HR) and Odds ratio (OR) with 95% confidence intervals (CI) were pooled using a random-effects model. The endpoints of interest were time to first subsequent therapy (TFST) and progression-free survival (PFS). We performed subgroup analyses for BRCA-mutation, HRD-positive, HRD-negative, response to platinum therapy, and newly diagnosed disease. Results: Four RCTs were included, comprising a total of 1,935 patients of whom 1,291 received niraparib and 644 received placebo. Niraparib significantly improved PFS in the overall population (HR 0.45; 95% CI 0.31-0.66; p < 0.0001; I2= 82%), in patients with BRCA mutation (HR 0.32; 95% CI 0.25-0.43; p < 0.00001; I2= 21%), HRD positivity (HR 0.39; 95% CI 0.30-0.51; p < 0.00001; I2= 40%), HRD negativity (HR 0.45; 95% CI 0.36-0,57; p < 0.00001; I2= 0%), and newly diagnosed cancer (HR 0.59; 95% CI 0.39-0.73; p < 0.0001; I2= 68%). The TFST was longer in the niraparib group (HR 0.48; 95% CI 0.33-0.68; p < 0.0001; I2= 80%). There was no statistical difference between complete and partial response to platinum therapy (OR 1.00; 95% CI 0.87-0.1.16; p = 0.98; I2= 0%). Conclusions: Niraparib improves PFS and lowers the time to first subsequent therapy in patients with advanced ovarian cancer. Outcomes and results by studies. [Table: see text]
Exploring the tumor microenvironment (TME) in patients with mismatch repair-deficient (MMRd) endometrial cancer (EC) undergoing immune checkpoint inhibitor (ICI) therapy: Proteomic insights into immune resistance mechanisms.
Authors: Grau Béjar Juan Francisco , Zeng Qinghe , Mehnert Martin , Colomba Emeline , Genestie Catherine , Le Formal Audrey , Edmond Elodie , Lachaud Antoine Amaury , Pautier Patricia , Michels Judith , Gouy Sebastien , Maulard Amandine , Yaniz Elisa , Leary Alexandra 
Published: June 2024

5609 Background: MMRd status is a robust predictive biomarker for ICI in EC, however half of these pts do not respond. Most studies exploring biomarkers of response to ICI have focused on tumor or immune cell factors. We aimed to explore the tumor microenvironment (TME) in ICI-Responder (R) versus Non-Responder (NR) MMRd EC pts to identify new predictive biomarkers of response. Methods: Clinical data and outcomes of metastatic MMRd EC pts, treated with ICI at Gustave Roussy Institute (2016-2023), were retrospectively collected. Pts were classified as Rs (CR, PR, or SD ≥12 months) or NRs (PD or SD <12 months). Pre-ICI FFPE tumor samples were subjected to Biognosys UltraDeep TrueDiscovery™ Mass Spectrometry (MS) for the identification of differentially regulated protein expression between R and NR. Criteria for protein candidates’ selection were p-value < 0.01 and average absolute log2 fold change (absolute average Log ratio) > 0.58. CD8+ T cells were quantified in the intratumoral area and expressed as number of cells per mm2. Spearman correlation test (r) was used for lineal correlation calculations. Functional enrichment analysis was conducted to elucidate differentially expressed molecular signatures (Odds ratio; adjusted p-value) in Rs vs NRs, utilizing GO_Biological Process database. Results: Twenty-three tumor samples were included in the analysis: 15 from Rs and 8 from NRs. Overall, 11,187 proteins were quantified. Only 72 were found to be differentially abundant between Rs and NRs. Protein candidates present within the tumor microenvironment that were significantly UP-regulated in NRs related to: non-specific inflammation (CRP), arachidonic acid metabolism (LOX15, PTGR3), extracellular matrix synthesis (COL5A2, COL22A1, PXDN), and TGF-b (TFBR1). CRP, LOX15, PXDN and COL5A2, were negatively correlated with CD8+ T cell infiltration (r -0.23, r -0.33, r -0.51, r -0.21). Based on functional enrichment analysis, collagen fibril organization (OR 21.4; p 1.1 e-6), extracellular structure organization (OR 10.2; p 1.2 e-6), extracellular matrix (ECM) organization (OR 7.5; p 1.1e-6), supramolecular fiber organization (OR 3.4; p 0.03), and TGFBR signaling pathway (OR 6.4; p 0.08) were among the top 30 biological process upregulated in NRs. Conclusions: Our preliminary data on high throughput proteomic analysis identified the arachidonic acid pathway, ECM structural organization and TGF-b signaling as potential mediators of ICI resistance in MMRd EC, all of which may be actionable in an effort to enhance sensitivity to ICI.
Rising trends in HPV (+) & HPV (-) vulvar cancers among US non-Hispanic White and Hispanic White females 50 years and older.
Authors: Mata Zetina Ana Paola , Rajupet Sritha , Strange Theodore , Dhar Meekoo , Dhulipalla Lohitha , Mokhtar Asmaa , Castellanos Mario R 
Published: June 2024

5620 Background: Our prior studies show that vulvar cancer in older females is increasing in the US, aligning with lengthened USPSTF cervical cancer screening intervals. Most medical societies do not recommend genital exams post-cervical cancer screening, and data on vulvar cancer is lacking to make comprehensive screening strategies. We utilized the SEER database to examine vulvar cancer, HPV status, and race/ethnicity to better understand the characteristics of patients who develop cancer. Methods: We examined vulvar cancer cases & data from 2000-2020, as reported in the SEER database. Estimations of HPV-positive vulvar cancer rates by age were derived using HPV attribution percentages from the HPV Centre Information United States Full Report, with younger females defined as < 54 years. Correspondingly, cases not within this percentage were classified as HPV-negative. Results: From 2000 to 2020, vulvar cancer incidence in the US increased by 14%, with rates rising from 2.18 to 2.40 per 100,000. This rise was most pronounced in Non-Hispanic White females over 50, whose rates grew from 2.41 in 2000 to 2.87 in 2020, more than any other race and ethnicity. For HPV-positive vulvar cancer, there was a 1.5% decrease in cases among females under 54. In contrast, there were significant increases in the 55-64 and 65+ age groups, with 53% and 14% rises, respectively. Additionally, the 55-64 age group experienced a notable 23% increase in HPV-negative cases, and those 65+ had a 9% rise. Conclusions: This study is the first to show a significant increase in vulvar cancer among non-Hispanic White females, particularly those aged above 50 years. Surprisingly, we observed that HPV (+) cancers, typically associated with younger demographics, are continuing to occur in older females. This is concerning since the HPV vaccine, introduced in 2007, wasn't available for HPV prevention in females now over 50. Concurrently, there is a rise in HPV-negative vulvar cancers within these older age groups. The current guidelines don't recommend routine genital exams for females over 65, indicating that there may be an opportunity to reexamine this recommendation given the US vulvar cancer trends in older females.
Treatment patterns of metastatic urothelial cancer in the United States.
Authors: Wang Xue , Chin Andi , Popadic Lyuba , Devine Francesca , Poretta Tayla , Schmidt Kerstin , Sierecki Mitch , Hoffman-Censits Jean H. 
Published: June 2024

e16500 Background: Bladder cancer is the sixth most prevalent malignancy in the United States, of which urothelial carcinoma (UC) is the predominant histologic type. The prognosis of metastatic UC (mUC) is generally poor with standard platinum-based chemotherapy (PBC) regimens. With approvals of immunotherapy (IO) and antibody drug conjugates (ADCs) in recent years, the treatment landscape has been evolving substantially. This study aimed to describe current, real-world treatment patterns of mUC. Methods: This retrospective study used de-identified, open and closed administrative claims data from Komodo’s Healthcare Map between 1/1/2016 and 5/31/2023. Adult patients were required to have ≥2 claims for UC diagnosis and ≥2 secondary neoplasm claims (within 30 days before or any time after the first UC claim). In closed claims, patients were required to have continuous enrollment during the 6-month baseline period, whereas patients in open claims were required to have at least the median number of claims among all patients in open claims. Index date was defined as the earliest date of a secondary neoplasm claim following UC diagnosis. Patients were observed until death or end of study, whichever occurred first. Treatment patterns, including duration of treatment (DOT), were evaluated in patients who initiated first line (1L) treatment on or after 1/1/2020. A sensitivity analysis was conducted in closed claims alone. Results: Among 38,557 patients who were diagnosed with mUC, 44% received at least one line of treatment at any time. After removing patients who started 1L before 1/1/2020, 28,576 patients meeting eligibility criteria were included at baseline. Median age was 74 years; 77% patients were male; 38% had diabetes or hyperglycemia at baseline; 67% had de novo mUC. PBC with or without IO maintenance, were the most common 1L treatment regimens (47%). IO (39%) and enfortumab vedotin (EV, 21%) were the dominant regimens in 2L. Sacituzumab govitecan (SG) was predominantly administered in 3L (17%). Median DOT was generally longer in earlier versus later lines for most therapies, including PBC followed by IO maintenance, ADCs, FGFR targeted therapy and EV+Pembrolizumab (P), and were similar for other therapies (Table). Findings were similar in the sensitivity analyses. Conclusions: Novel therapies, such as IO and ADCs, have provided additional treatment options for patients diagnosed with mUC. Future studies with longer follow-up are needed to characterize the shifting treatment paradigm, as EV+P becomes a standard of care in 1L mUC. [Table: see text]
Perceptions and expectations: A study on prognostic perception and quality of life in patients with metastatic renal and bladder cancer.
Authors: Bolek Hatice , Arslan Cagatay , Basaran Mert , Cicin Irfan , Özgüroğlu Mustafa , Tural Deniz , Ürün Yüksel 
Published: June 2024

e16505 Background: In metastatic cancers, treatments are aimed at palliation, focusing on life extension and quality of life (QoL) improvement rather than cure. This study aims to investigate the alignment between patient expectations and the realistic outcomes of treatment in metastatic renal cell carcinoma (mRCC) and metastatic bladder cancer (mBC). Methods: Between 15.03.2023-15.01.2024, an online survey was conducted targeting patients with mRCC and mBC. The primary objective was to evaluate the patients’ understanding and expectations concerning curability and the anticipated outcomes of their treatments in a metastatic setting. Additionally, the study aimed to explore the impact of patients' QoL and levels of optimism on their perceptions of cure and treatment outcomes. EORTC 30.3 QoL questionnaire and Life Oriented Test (LOT) were administered. Results: A total of 169 patients participated, with a median age of 63 years.72.2% of patients assessed their general health state as "good", 13.6% as "excellent", 11.8% as "fair", and 2.4% as "poor." Out of the patients surveyed, 40.2% considered cure as "very likely," 45% as "likely," 4.7% as "a little likely," and one as "not possible." The table shows patients' perspectives on improving disease symptoms, doing daily tasks easier, and living longer with treatment. Patients' perception of cure was not affected by gender, age, treatment modality, or general health status. While only 9 patients perceived cure as "a little likely" or "not possible," this group has lower median QoL and LOT scores than those who believed cure was "very likely" or "likely." This pattern is observed in their perceptions regarding the improvement symptoms, ability to make daily life activities easier, and expectations of living longer. Conclusions: Patients with mRCC and mBC have expectations of cure from treatments that may not align with clinical realities. Prioritizing clear communication and patient participation in treatment planning, particularly around palliative care is essential for effective care delivery. [Table: see text]