bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative real-world (RW) evidence on darolutamide (Daro), enzalutamide (Enza), and apalutamide (Apa) for patients (Pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the United States: DEAR.
Authors: Morgans Alicia K. , Shore Neal D. , Khan Nasreen , Constantinovici Niculae , Khan Javeed , Chen Guifang , Xu Julie , Ortiz Jorge A. , George Daniel J. 
Published: June 2023

5097 Background: Novel androgen receptor inhibitors (ARIs) are recommended for pts with nmCRPC. Daro has a distinct structure with low blood-brain barrier penetration which may lead to a lower risk of central nervous system-related adverse events (AEs) and minimal risk of AEs commonly associated with ARIs. DEAR is the first study comparing RW utilization, outcomes, and AEs between daro and enza/apa in nmCRPC pts. Methods: This retrospective chart review cohort study uses electronic medical records from the PPS network of US urology practices. Eligible pts had nmCRPC, no prior novel hormonal therapy, and initiated first ARI treatment (index date) between 8/2019-3/2022. We describe the % of pts who discontinued initial ARI treatment (DISC), % who progressed to metastasis (PROG), and % with AEs. A comparative analysis was performed between daro and enza/apa using Cox proportional hazards models for time to DISC/time to PROG, adjusting for observed baseline (BL) factors. Results: 870 pts were included (daro/enza/apa, n=362/382/126). Median age (80/79/80 y), median BL prostate-specific antigen (PSA) doubling time (6.8/6.4/7.4 mo), other BL characteristics, and median follow-up (22.2/22.7/23.3 mo) were similar for daro/enza/apa. A lower % of pts had a DISC event on daro vs enza/apa (30.4 vs 40.8/46.0) or a PROG event (17.7 vs 28.3/27.8) during the study period. Multivariate analyses adjusting for BL factors showed that pts on daro had a lower risk of DISC and PROG over time vs enza/apa. A lower % of pts on daro had AEs vs enza/apa (24.9 vs 29.3/30.2). Conclusions: Overall, a lower % of pts discontinued initial ARI treatment, progressed to metastasis, or had AEs on daro vs enza/apa. In analyses adjusting for observed BL factors, pts on daro had considerably lower risk of DISC and PROG vs enza/apa. This study confirms daro’s strong efficacy and favorable tolerability profile in a RW setting. The longer treatment duration seen with daro may be associated with a lower risk of progression to mCRPC vs enza/apa. [Table: see text]
Differences of prediction performances by multigene assays in patients with breast cancer with distinct genetic backgrounds.
Authors: Xing Fei , Chen Ting-Hao , Wang Huimin , Ma Xuejiao , Ding Ran , Lu Zhongyu 
Published: June 2023

526 Background: The 21-gene (Oncotype Dx), PAM50 (Prosigna) and Chinese-based 28-gene (RecurIndex) are validated genomic assays that provide prognostic information for distant recurrence risk in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer (EBC). In this study, we aim to compare the differences in prediction performance by different multigene assays and gene expression profiles between the Eastern and the Western. Methods: Under the Affymetrix U133 platforms, the differences in gene expressions and risk scores from the Eastern population comprised of GSE20685 (n = 327) and part of GSE45255 (n = 95), and the Western population GSE25066 (n = 508) and the European in GSE45255(n = 44) were analyzed respectively. Patients were stratified by 21-gene Recurrence Scores (RS) of low (0-10), intermediate (11-25) and high (26-100) and categorized by ROR-S score of PAM50 of low (0-40), intermediate (41-60) and high (61-100). For 28-gene, a recurrence index for distant recurrence (RI-DR) cutoff of 33 was used to classify patients into high- and low-risk groups. Wilcoxon rank test was used to test for continuous variables and the chi-square test was used for categorical variables. Results: The Western population has significantly higher RS (85.9 vs. 65.5, p < 0.001) and ROR-S (57.4 vs.53.7, p = 0.034) scores than the Eastern population. The distribution of 28-gene risk groups was significantly different between races with a higher proportion of high-risk in the Western (10.5% vs. 6.6%, p = 0.035). The low-risk patients in the Eastern stratified by 28-gene assay had significantly higher distant metastasis-free survival (DMFS) rates than high-risk (80% vs. 52%, p < 0.001), which compared with Oncotype Dx RS (96% vs. 76%, p < 0.001) and PAM50 ROR-S (93% vs. 72%, p < 0.001). At the same time, the analysis of gene expressions revealed significantly high expressions of YWHAB, SF3B5, CKAP5, and DDX39A in the Eastern than that in the Western. However, most genes from 21-gene and ROR-S were more highly expressed in the Western than that in the Eastern. Conclusions: 21-gene and PAM50 provide the good performance and show similar patterns in the prognosis of EBC; However, the DMFS rate of the high-risk in the Eastern population determined by 28-gene was much lower than 21-gene and PAM50, which means there are bigger chemo-benefit in the high-risk from 28-gene. In conclusion, 28-gene has better performance in the prognosis of the Eastern population and is a more suitable tool for Eastern breast cancer patients.
Pulsed electrical fields in combination with anti-PD1 and survival of mice with TNBC (EMT6) murine breast tumor.
Authors: Nafie Ebtesam , Pastori Chiara , Wagh Mukta , Murad Fatima , Trikha Mohit , Neal Robert 
Published: June 2023

540 Background: Delivery of pulsed electric field (PEF) energy is used to destabilize cells through multiple biochemical processes. We questioned whether a specific PEF treatment type could synergize with anti-PD1 in an orthotopic Triple Negative Breast Cancer (TNBC) EMT6 mouse model. Our previous studies have demonstrated that PEF treatment induces neo-antigen presentation and triggers an innate and adaptive immune response. Anti-PD1 therapy is ineffective at blocking growth of (TNBC) EMT6 tumors that are orthotopically implanted in mice. We evaluated whether a biphasic monopolar form of PEF could synergize with anti-PD1 when it was administered intraperitoneally or intra-tumorally, and whether there was a change in immune response post treatment. Methods: Forty-eight female Balb/c mice were implanted with 200,000 EMT6 cells into the mammary fat pads. Once tumor diameter reached 5 mm they were randomized into 6 groups of 8 animals: 1) Sham/IgG; 2) intra-tumoral (IT) anti-PD-1; 3) intra-peritoneal (IP) anti-PD-1; 4) PEF + anti-PD-1(IP); 5) PEF + anti-PD-1(IT) 6) 2X PEF on day 0 and day 7 + anti-PD-1(IT administered weekly). Sham-PEF mimicked the same procedure but without PEF. Anti-PD1 was administered weekly, IT or IP at 200 µg/mouse and PEF was delivered once on day of randomization. Tumors were measured three times per week, and animal survival was monitored until tumor volume necessitated euthanasia (≥2000mm3). Blood was collected on day 14 for flow cytometric analysis of systemic immune response which included quantifying CD3 positive T cells, B cells and NK cells. Results: Anti-PD1 treatment (IT or IP) did not reduce tumor growth, nor did it prolong survival compared to Sham/IgG treated animals. All anti-PD1 alone (IT or IP) as well as Sham treated animals had to be euthanized by day 35. In contrast, PEF combined with anti-PD1 given IT and IP significantly reduced tumor growth by 83% and 70%, respectively, on Day 14 compared to anti-PD-1 only treated animals (p = 0.03). Interestingly, EMT6 bearing mice treated with double PEF + IT administered anti-PD1 survived longer compared to mice treated with single PEF + IT administered anti-PD1. On day 65, 71% of double PEF + IT administered anti-PD1 were still alive compared to 12.5% of mice treated with PEF + IT administered anti-PD1 (p = 0.002). Flow cytometry analysis on day 14 indicated an increase in circulating adaptive (T- and B-cells) and innate (NK cells) immunocytes in the PEF + anti-PD1 treated animals compared to the control. Conclusions: Collectively, these results indicate that some types of PEF ablation synergize with weekly anti-PD1 in stimulating an increase of CD3+ T cells, B cells and NK cells, reducing tumor growth and prolonging survival of tumor bearing mice. These results suggest the synergistic potential of combining Immunotherapy with some forms of PEF, which warrants further study in patients.
Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers.
Authors: Myers Sara P. , Sevilimedu Varadan , Barrio Andrea Veronica , Tadros Audree , Mamtani Anita , Robson Mark E. , Morrow Monica , Lee Minna 
Published: June 2023

544 Background: Distinct pathological characteristics and mutational signatures in BRCA-associated breast cancers may result in differential response to chemotherapy but understanding of treatment response after neoadjuvant chemotherapy (NAC) is limited. We describe a single-institutional experience to compare rates of pathologic complete response (pCR) after NAC in BRCA carriers (g BRCA1/2) and noncarriers. Methods: From 11/2013 to 01/2022, 1426 consecutive women with clinical stage I-III breast cancer were treated with NAC followed by surgery. Baseline disease characteristics were compared between g BRCA1/2 and noncarriers using two-sample non-parametric tests. Conditional logistic regression was used to evaluate the association between BRCA status and pCR (i.e., ypT0/is pN0) adjusting for variables selected using backward elimination. Results: 92 (6.5%) and 73 (5.1%) had deleterious mutations in BRCA1 and BRCA2, respectively. Compared to noncarriers, g BRCA1/2 were younger (p<0.001) with clinical T1 (p=0.002) and triple negative disease (TN) (57% vs 25% noncarriers, p<0.001). Almost all patients received doxorubicin/cyclophosphamide/paclitaxel therapy (93%) with g BRCA1/2 more likely to receive carboplatin (p<0.001). pCR rate was 42% of g BRCA1, 21% of g BRCA2, and 26% of noncarriers (p=0.001). Among clinically node positive (cN+) patients, nodal pCR was higher in g BRCA1/2 compared to noncarriers (53/96 (55%) vs 371/856 (43%), p=0.012). This difference was seen in ER+/HER2- (36% gBRCA1/2 vs 20% noncarriers; p=0.027) and TN subtypes (79% g BRCA1/2 vs 45% noncarriers; p<0.001). Poorly differentiated tumors (p<0.001), cN+ (p=0.010), lower cT stage (p=0.028), ductal histology (p<0.001), TN and HER2+ receptor status (p<0.001), absence of lymphovascular invasion (p<0.001), carboplatin receipt (p=0.041), and BRCA1 status (p=0.001) were also associated with pCR on univariate analysis. After adjusting for differentiation and molecular subtype, BRCA1 status remained independently associated with pCR. Conclusions: g BRCA1 undergoing NAC have higher pCR rates relative to g BRCA2 and patients with sporadic disease. Across breast cancer subtypes, g BRCA1/2 more frequently converted to pN0. Defining biological mechanism for these findings would allow customization of treatment based on germline genetics. [Table: see text]
Prognostic role of HER2 expression in patients with ER-positive/HER2-negative breast cancer: Results from a population-based cancer registry study.
Authors: Musolino Antonino , Serra Olga , Pellegrino Benedetta , Tommasi Chiara , Zanoni Daniele , Cortesi Laura , Canino Fabio , Piacentini Federico , Sgargi Paolo , Michiara Maria 
Published: June 2023

547 Background: Estrogen Receptor (ER)-positive (+)/Human Epidermal Growth Factor Receptor 2 (HER2)-negative (-) breast cancers (BCs) express variable protein levels of both ER and HER2, which can influence prognosis. Methods: We evaluated all invasive ER+/HER2- BCs (n = 3633) that were diagnosed and systematically collected by the Parma Province Cancer Registry, Italy, from 2004 to 2018. Tumors were classified by HER2 (IHC score of 0, 1+ or 2+ with negative FISH) and ER status (ER-low [1-9%], ER-moderate [10-79%] or ER-high [80-100%]). Comparisons of clinicopathologic characteristics and disease outcome were performed. Results: BCs with late-stage diagnosis ( P = 0.04), high histologic grade ( P < 0.0001), or high proliferative rate ( P < 0.0001) were more likely HER2 2+/FISH-. The rate of ER-high BCs did not change from 2675 of 2938 (91%) HER2 0 tumors to 508 of 560 (90.7%) HER2 1+, and 124 of 135 (91.9%) HER2 2+/FISH- tumors. Correspondingly, ER-low BCs were not enriched among HER2 0 tumors compared to the other tumors with different HER2 expression ( P = 0.6). The 5-year overall survival (OS) for HER2 2+/FISH- BCs was lower than that for HER2 0 or 1+ tumors ( P = 0.03). ER-low/moderate tumors were associated with poorer OS in comparison with ER-high BCs ( P < 0.0001). HER2 2+/FISH- status was detrimental to OS among patients (pts) with ER-high tumors ( P = 0.04), while this finding was not observed among ER-low/moderate BCs ( P = 0.21). An interaction between HER2 2+/FISH- expression and ER-high status was found for poorer OS after adjusting for prognostic variables (HR = 1.7; 95% CI: 1.1-2.9). Conclusions: The prognostic role of HER2 expression in pts with ER-positive/HER2-negative BCs seems to be restricted to ER-high tumors, while the worse prognosis of tumors with lower ER expression is not associated with HER2 status. These findings may help identify optimal patient inclusion criteria for clinical trials with novel anti-HER2 therapies in ER-positive/HER2-negative disease.
An analysis of breast cancer index scores predicting benefit of extended endocrine therapy by race.
Authors: Siu-Li Nicholas , Pagano Ian , Fukui Jami Aya 
Published: June 2023

549 Background: Patients with early-stage hormone receptor-positive (HR+) breast cancer have a good prognosis. Prior studies have shown that extending endocrine therapy beyond the first 5 years reduces the risk of late distant recurrence. The Breast Cancer Index (BCI) is a gene expression assay that provides both a prognostic risk of late distant recurrence in addition to a yes/no prediction of benefit from receiving extended endocrine therapy. To date, no studies have examined the relationship between race and BCI score. This study aims to investigate the interaction between race and BCI scores in women with early-stage HR+ breast cancer. Methods: We analyzed BCI scores, demographics, and tumor characteristics from 89 women diagnosed with early-stage HR+ breast cancer. Univariate logistic regression analysis was run using race, BCI recurrence risk, hormone status, tumor size, or tumor grade as predictor variables. BCI prediction of benefit was used as the outcome variable. Results: Compared to Caucasians, Native Hawaiians had significantly greater odds of having a BCI score predicting benefit from receiving extended endocrine therapy (OR = 7.00, p = 0.04). Additionally, there were significantly greater odds of having a score predicting benefit among those who had a recurrence risk of 5-10% (OR = 3.84, p = 0.04), or ≥10% (OR = 9.16, p < 0.001) compared to a recurrence risk < 5%. Conclusions: Our findings highlight the utility of characterizing differences in BCI predictive and prognostic scores by race among breast cancer patients with early-stage HR+ tumors. Notably, Native Hawaiian women had 7.0 times increased odds of having a score predicting benefit of extended endocrine therapy compared to Caucasians. This result is salient given the high incidence of breast cancer among Native Hawaiians. Though not statistically significant, our data also demonstrated Filipinos had increased odds of a score predicting benefit as well. Furthermore, our findings show a direct correlation between prognostic risk of late distant recurrence and predictive benefit of extended endocrine therapy with a higher odds ratio associated with higher recurrence risk. Our study shows notable differences in BCI findings when stratifying patients by race. However, our sample size is relatively small, and we lack sufficient data from patients representing other races such as Hispanic and Black. Future studies may expand the sample size and adjust for known breast cancer risk factors. The goal is to identify trends that may improve our usage of the BCI as a tool to effectively guide hormone therapy recommendations in patients with early-stage HR+ breast cancer. [Table: see text]
Patient-reported outcomes (PROs) in primary advanced or recurrent endometrial cancer (pA/rEC) for patients (pts) treated with dostarlimab plus carboplatin/paclitaxel (CP) as compared to CP in the ENGOT-EN6/GOG3031/RUBY trial.
Authors: Mirza Mansoor Raza , Powell Matthew A. , Lundgren Caroline , Sukhin Vladyslav , Pothuri Bhavana , Gilbert Lucy , Gill Sarah , Ronzino Graziana , Nevadunsky Nicole , Kommoss Stefan , Willmott Lyndsay , Boere Ingrid , Mathews Cara Amanda , Buscema Joseph , Teneriello Michael , Shahin Mark S. , Meyers Oren , Garside Jamie , Coleman Robert L. , Slomovitz Brian M. 
Published: June 2023

5504 Background: In RUBY, a phase 3, global, randomized, double-blind, placebo (PBO)-controlled trial, dostarlimab+carboplatin/paclitaxel demonstrated significant and clinically meaningful improvement in PFS compared with PBO+CP in pts with pA/rEC. PROs are reported here. Methods: 494 pts with pA/rEC were randomized 1:1 to dostarlimab (D)+CP or PBO+CP Q3W for 6 cycles followed by D or PBO monotherapy Q6W ≤3 yrs or to disease progression. EORTC QLQ-C30 and EN24 were prespecified secondary endpoints. PROs were administered on Day 1 of each treatment (tx) cycle (C), end of tx (EOT), and at safety and survival follow-ups and reported here for C7, the end of chemotherapy (chemo) and C13, and the end of 1 yr of study. Change (chg) from baseline (BL) to C7/C13 was calculated for all scales assessed. Mixed model for repeated measures analysis was conducted to generate least-squares means (LSM), adjusting for correlations across multiple time point assessments within a pt and controlling for the BL value for the global, pain, fatigue, and physical function (PF) scores. Results: PRO outcomes were similar for D+CP and PBO+CP through the chemo period (C7). The table shows selected scores at C7 and C13 for mean (SD) and chg from BL. Further, no differences across the 3 yr period between the 2 arms were reported; LSM (standard error) for global QoL was 0.5 (1.42; P=0.72), PF was −0.7 (1.39; P=0.63), fatigue was 0.2 (1.75; P=0.91) and pain was −1.0 (1.99; P=0.62). Mean chg from BL to EOT showed improvement in back/pelvic pain for D+CP and deterioration in global QoL/GHS, social functioning, body image, and chg in taste for pts on PBO+CP. Conclusions: Dostarlimab + CP significantly improved PFS while maintaining HRQoL, further supporting its use as a standard of care in pA/rEC. Clinical trial information: NCT03981796 . [Table: see text]
Hyperthermic intraperitoneal chemotherapy in platinum-sensitive relapsed epithelial ovarian cancer: The CHIPOR randomized phase III trial.
Authors: Classe Jean-Marc , Meeus Pierre , Leblanc Eric , Wernert Romuald , Quenet Francois , Marchal Frédéric , Houvenaeghel Gilles , Bats Anne-Sophie , Ferron Gwenael , Brigand Cecile , Berton Dominique , Gladieff Laurence , Joly Florence , Ray-Coquard Isabelle Laure , Durand-Fontanier Sylvaine , Liberale Gabriel , Brument Emilie , Asselain Bernard , Campion Loic , Glehen Olivier 
Published: June 2023

5510 Background: Standard treatment for patients with first platinum-sensitive relapse of epithelial ovarian cancer (EOC) is based on surgery and second-line systemic chemotherapy (CT). The role of hyperthermic intra-peritoneal chemotherapy (HIPEC) remains uncertain. Methods: The CHIPOR multicentric randomized phase III trial (NCT01376752), conducted in 31 institutions, enrolled patients with a first platinum-sensitive relapse (platinum-free interval of ≥6 months) of EOC. Patients were treated with 6 cycles of platinum and taxane based CT ± bevacizumab, and those amenable to a complete cytoreductive surgery at the end of CT were enrolled and randomly assigned to receive HIPEC (cisplatin 75 mg/m² at 41°C for 60 min) or not. Randomization was performed during complete cytoreductive surgery, stratified by center, surgical outcome (no residual disease vs residual <0.25 cm), chemotherapy-free interval before relapse, and PARP inhibitor use (yes vs no). The primary endpoint was overall survival (OS). The target sample size was 404 evaluable patients, providing 80% power at 5% alpha after 268 deaths. Secondary endpoints included progression-free survival (PFS), peritoneal PFS, patient-reported outcomes, safety, and postoperative morbidity and mortality (≤60 days after surgery). Results: Between May 11, 2011, and May 14, 2021, 415 patients were randomized. Baseline characteristics were balanced between treatment arms. At the data cutoff (Jan 8, 2023), with a median follow-up of 6.2 years, 268 patients (65%) had died. Efficacy results are summarized below. Conclusions: HIPEC significantly improves OS and peritoneal PFS of women with first platinum-sensitive relapse of EOC treated with second-line platinum-based CT followed by secondary complete cytoreductive surgery. Ongoing analyses, including patient reported outcome, BRCA status, bevacizumab exposure, and subsequent therapy, will be presented. Clinical trial information: NCT01376752 . [Table: see text]
Advanced cervical cancer therapy: Comparison of contemporary expert and healthcare professional recommendations from an online treatment decision tool.
Authors: Prescott Lauren S. , Constanzo Jerfiz , Salani Ritu , Urban Renata R. , Westin Shannon Neville , Quill Timothy A. , Duska Linda R. 
Published: June 2023

5528 Background: Practice patterns for the management of advanced cervical cancer are rapidly evolving given the emergence of novel treatment options. We developed an online Interactive Decision Support Tool (IDST) for advanced cervical cancer to provide expert guidance to healthcare professionals (HCPs). Methods: With input from 5 experts, an IDST was developed for patient scenarios with newly diagnosed (ND) and recurrent/second-line (2L) advanced cervical cancer. The IDST included expert insights on 352 scenarios based on criteria such as adenopathy, disseminated disease status, previous therapy, and actionable biomarkers (PD-L1, MMR/MSI, TMB). Users were asked to enter specific patient criteria and their intended management approach. The IDST then showed the 5 expert recommendations for that specific scenario and HCPs were asked to indicate whether the recommendations changed their intended treatment plan. Expert recommendations vs user-selected therapy for different scenarios were analyzed. We present self-reported practice patterns in this disease setting and the impact of expert recommendations on treatment choice. Results: At this interim analysis, 141 unique learners used the IDST, entering 232 unique patient scenarios. Data from the IDST also showed areas of consensus and controversy in treating patients with advanced cervical cancer. For locally advanced, ND, no adenopathy and no metastases, all experts recommended pelvic chemoradiation with or without brachytherapy vs only 61% of HCPs; 16% and 3% of those entering cases for the locally advanced ND setting indicated expert recommendation changed their treatment choice and that barriers impeded the recommendations, respectively. For advanced ND, with adenopathy, metastatic, PD-L1–positive cervical cancers, all experts vs 50% of HCPs chose an immunotherapy-containing platinum-based chemotherapy regimen with/without bevacizumab; 9% of those indicated barriers to implementing expert recommendations. In 2L recurrent disease, all experts chose either single-agent immunotherapy (if PD-L1 positive) or tisotumab vedotin (if PD-L1 negative) vs 45% and 40% of HCPs, respectively; 19% of those selecting 2L therapy in the recurrent setting said the expert recommendations had changed their intended choice. Conclusions: Analysis from this IDST indicates differences in practice patterns between experts and HCPs for various case scenarios of advanced cervical cancer. Online decision support tools may increase the number of HCPs making optimal treatment decisions for advanced cervical cancer, particularly when new data, indications, and guideline updates must be considered. Updated and detailed analyses from the IDST will be presented.