bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pegylated liposomal doxorubicin and carboplatin versus paclitaxel and carboplatin as first-line treatment for Chinese patients with ovarian cancer: A multi-center, randomized, open-label trial.
Authors: Shen Yuanming , Kong Beihua , Xia Bairong , Wang Fei , Yin Rutie , Li Qingshui , Yue Ying , Kang Shan , He Liping , Wang Ke , Meng Yuanguang , Wang Shixuan , Qu Pengpeng , Huang Xianghua , Guo Ruixia , Yan Ping , Pan Mei , Lou Ge , Cheng Wenjun , Xie Xing 
Published: June 2023

5556 Background: Paclitaxel combined with carboplatin is a standard first-line chemotherapy regimen for ovarian cancer. This study was designed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) plus carboplatin (CD) compared with paclitaxel plus carboplatin (CP) as first-line treatment for epithelial ovarian cancer (EOC). Methods: Patients with stage IC to IV EOC, fallopian tube cancer, or primary peritoneal cancer were eligible for enrolment in this open-label, randomized controlled trial at 20 centers in China. Patients were randomly assigned 1:1 to CD group (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) or CP group (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for 3-6 cycles. The primary end point was progression free survival (PFS); secondary end points were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: Between March, 2019 to December, 2021, 395 patients were enrolled, of whom 391 patients were analyzed (195 assigned to CD, 196 to CP). Baseline characteristics were balanced between the two treatment groups. The median follow-up was 21.6 months for the CD group and 22.5 months for the CP group. There was no significant difference in PFS between the two arms (P=0.516); the median PFS was 28.1 months and 30.1 months in the CD and CP arms, respectively. OS data were immature at data cutoff, with a total of 26 deaths in the two treatment groups. In patients with at least one measurable lesion at baseline, ORR was 65.5% in the CD arm and 66.2% in the CP arm (P= 0.941); DCR was 74.1% and 73.8% in the CD and CP arms, respectively (P= 0.971). Among patients who were evaluable by GCIG CA125 criteria, CA125 response was obtained in 86.0% and 88.5% of patients in the CD and CP arms, respectively (P=0.560). More frequent grade 1 to 3 alopecia (32.1% vs 12.3%) and neurotoxicity (20.4% vs 0%) were observed in the CP arm; more hand-foot syndrome (grade 1 to 3, 10.8% vs 2.6%), and oral mucositis (grade 1-3, 12.8% vs 5.1%) in the CD arm. Conclusions: The efficacy of CD regimen is comparable to that of CP, with less alopecia and neurotoxicity. CD may be an alternative first-line treatment for EOC. However, survival data are not yet mature, and longer follow-up is needed. Clinical trial information: NCT03794778 .
The role of innate immune system in modulating CHK1 inhibitor (CHK1i) response in BRCA wild-type (BRCAwt), platinum-resistant high-grade serous ovarian cancer (PR-HGSOC): Exploratory analysis from a phase II study of CHK1i prexasertib.
Authors: Giudice Elena , Nair Jayakumar , Huang Tzu-Ting , Lee Min-Jung , Trepel Jane B. , Lee Jung-Min 
Published: June 2023

5557 Background: Immune checkpoint blockade, e.g., anti-PD-1/PD-L1, demonstrated limited efficacy in HGSOC despite high levels of tumor-infiltrating lymphocytes, suggesting the innate, rather than adaptive, immune system may play a prominent role in anticancer response. Preclinical studies suggest CHK1i modulates the innate immune milieu. We previously showed clinical activity of prexasertib in BRCAwt, PR-HGSOC patients (pts). Here, we investigated the association of innate immunogenic features with CHK1i response. Methods: Prexasertib was given at 105 mg/m2 IV every 14 days in a 28-day cycle. Baseline (BL) fresh core biopsies were collected from pts enrolled in the biopsy (Bi) cohort for RNA sequencing. Computational immunogenomic analysis (CIBERSORT) was used for immune cell fractions quantification. Blood samples (BS) were obtained at BL and cycle 1 day 15 (C1D15) from pts enrolled in both Bi and non-Bi (nBi) cohorts for multiparametric flow cytometry (FC) analysis to evaluate dynamic changes in immune cell subsets. Mann-Whitney and Wilcoxon tests were used to compare unpaired and paired data, respectively. Results: 49 BRCAwt, PR-HGSOC pts were enrolled in the Bi cohort (n=25) and nBi cohort (n=24). 39 were evaluable per RECIST v1.1. 18/39 pts (46.2%) had a clinical benefit (CB), defined as progression-free survival≥6 months. Transcriptomic profiles of BL biopsies (n=15) met the quality control and assurance (Gene Similarity Index, Principal Component Analysis) for further in silico analysis. CIBERSORT analysis did not exhibit any differences in the immune cell fractions between CB and non-CB (NCB) groups at BL. FC analysis on paired BS (BL and C1D15) showed an increase of immunosuppressive monocytic myeloid-derived suppressor cells (M-MDSCs, p<0.001) and classical monocytes (CM, p=0.003) in the NCB group (18 paired BS). In the CB group (19 paired BS), CD141+ and CD1c+ dendritic cells (DCs) express higher rates of CD83, a marker of maturity and functionality (p<0.001 and p<0.001, respectively), despite no increase in the absolute number of DCs. At C1D15, a higher rate of M-MDSCs (median 7.8% vs. 5.52%; p=0.03) and CM (median 40.7% vs. 31.7%; p=0.03) were found in the NCB group (n=18) compared to the CB group (n=19); also, CM showed lower expression of HLA-DR in the NCB group (median 19.25% vs. 27.8%; p=0.02). Conclusions: Collectively, our data suggest the possible involvement of innate immunity in modulating CHK1i response. Increasing peripheral immunosuppressive cells and lower immunocompetence of the innate immune system may contribute to CHK1i resistance, whereas the functionality of DCs may be involved in the response. Enhancing innate immunity may represent a strategy to increase CHK1i response in this hard-to-treat population. Clinical trial information: NCT02203513 .
DNA methylation patterns between tissue and blood samples in ovarian cancer.
Authors: Wen Hao , Feng Zheng , Ge Huijuan , Wang Yanan , Wang Jingshu , Sun Xiaoran , Yang Bo , Quan Chenlian , Zhou Xiaoyan , Wu Xiaohua 
Published: June 2023

5558 Background: Altered DNA methylation pattern, with functional consequences in the activity of key carcinogenic pathways, has been shown to be involved in the carcinogenesis of ovarian cancer. Tumor DNA is released into the blood via apoptosis or necrosis. Therefore, cell-free DNA (cfDNA) methylation alteration can also be detected in blood, which has shown promising performance in ovarian cancer early detection and prognostication. However, the difference of DNA methylation patterns between the tissue and blood samples of ovarian cancer is still unclear. Methods: PERCEIVE-I study (NCT04903665) is a prospective study aimed at the early detection of gynecological malignancies. Blood and paired tissue samples from this study were collected at the Fudan University Shanghai Cancer Center. Blood samples from age-matched non-cancer controls were also collected. All the blood and paired tissue samples were sequenced by a target methylation panel covering ~490,000 CpG sites. Finally, The ovarian cancer methylation patterns were analyzed based on 11 paired cancer-adjacent tissue samples and 170 blood samples (cancer, n=48; non-cancer control, n=122). Results: In total, 7,225 differentially methylated blocks (DMBs) were identified by comparing cancer and adjacent tissues, with 5,093 hypomethylated and 2,132 hypermethylated. By contrast, there were 5,853 hypomethylated and 8,685 hypermethylated DMBs in cancer blood samples compared with non-cancer controls. Among the 7,225 DMBs in tissues, 3,962 (54.8%) blocks were also observed to be altered in blood samples, including 2,354 hypomethylated blocks and 1,114 hypermethylated blocks. GO analysis revealed that these hypomethylated blocks were mainly associated with functions such as regulation of synaptic membrane and DNA-binding transcription activator activity, while the hypermethylated blocks were mainly enriched in the pattern specification process, transcription factor complex, and the DNA-binding transcription activator activity. The alteration of the above 3,962 DMBs in tissue were highly correlated with the alteration in blood (correlation coefficient of 0.71, 0.50, 0.73 and 0.73 for stage I-IV, respectively). Furthermore, in patients carrying germline BRCA1/2 mutations (n=11), most of the above DMBs were not significantly different from those without germline BRCA1/2 mutations (n=37). Conclusions: In this study, we demonstrated that blood DNA methylation alteration was highly consistent with tissue DNA methylation alteration in ovarian cancer, indicating the sustained release of DNA methylation signals from the primary cancer sites. These results suggest that cfDNA methylation can be used as reliable biomarkers for the early detection of ovarian cancer. Clinical trial information: NCT04903665 .
Detection of homologous recombination deficiency (HRD) using a novel genomic and epigenomic liquid biopsy assay in patients with breast cancer.
Authors: Barbacioru Catalin , Yen Jennifer , Tolkunov Denis , Safabakhsh Pegah , Wang Hao , Gross Andrew , Overstreet Brooke , Jenkins Colby , Drusbosky Leylah , Kiedrowski Lesli Ann , Eagle Craig , Chuang Han-Yu 
Published: June 2023

556 Background: Homologous recombination and repair (HRR) deficiency (HRD) is characterized by genomic instability associated with dysfunction in BRCA1/2 or other HRR genes. Patients with breast cancer harboring an HRD phenotype with or without HRR mutations have derived clinical benefit from PARPi therapy. We have previously shown that GuardantINFINITY, a novel genomic and epigenomic liquid biopsy assay, can identify HRR SNVs, indels, rearrangements, copy number loss, reversions, and BRCA1 promoter methylation for patient selection and resistance monitoring, a major challenge for PARPi treatment. Here, we present a method of predicting HRD status by cfDNA using GuardantINFINITY in patients with advanced breast cancer. Methods: We developed a probabilistic genomic model to predict HRD status, inferred from genome-wide somatic SNV, indel, and CNV signatures indicative of BRCA1/2 deficiency, including large-scale state transitions (LST), whole-genome tumor loss of heterozygosity (LOH), telomeric allelic imbalance (TAI). A second probabilistic model, based on targeted measurements of genomic and epigenetic changes was learned from a subset of clinical samples to enhance the genomic model. The model was trained and tested on a cohort of over 12,000 GuardantOMNI and GuardantINFINITY clinical breast cancer samples to assess the sensitivity of accurately detecting deficiency in select HRR-genes ( BRCA1/2, PALB2, RAD51D). The aggregated predictive model was validated on an independent cohort of breast cancer samples. Results: The model based on genomic and epigenetic signals identified HRR-gene deficiency in a breast cancer cohort with a estimated 95% LoD of 22.5% tumor fraction and an AUC of 0.75 across all tumor fractions, an improvement in sensitivity over when only the genomic model is used (AUC of 0.7, 95% LoD of 28%). Specificity remained high for both models (100%, n = 83) in cancer free samples. Application of this model in a cohort of 1,101 patients with unselected breast cancer identified 390 patients with an HRD phenotype, of whom 192 patients had a known HRR-gene mutation. Of the 201 patients with a known pathogenic mutation in an HRR gene, 49 also had co-occurring LoH in the same gene, indicating biallelic loss. Conclusions: In this analysis, we demonstrate that a probabilistic model of genomic and methylation predictors can detect HRD status in patients with breast cancer from cfDNA using GuardantINFINITY. Additional analytical and clinical studies to further evaluate this model are ongoing. With HRD prediction, GuardantINFINITY provides a comprehensive minimally-invasive solution for PARPi and DNA damage treatment selection, longitudinal monitoring, and an exploratory platform for investigating epigenetic signals that may underpin resistance.
Efficacy and safety of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer who had measurable residual disease: A post-hoc subgroup analysis of the PRIME study.
Authors: Kong Beihua , Wu Lingying , Zhu Jianqing , Yin Rutie , Wang Jing , Pan Lingya , Zheng Hong , Liu Jihong , Wu Xiaohua , Wang Li , Huang Yi , Wang Ke , Zou Dongling , Zhao Hongqin , Wang Chunyan , Lu Weiguo , Lin An , Zhen Xiaoa , Hang Wenzhao , Hou Jianmei 
Published: June 2023

5562 Background: Niraparib maintenance therapy significantly prolonged progression-free survival (PFS) versus placebo in patients with newly diagnosed advanced ovarian cancer (aOC), but its antitumor activity remains unclear in those with measurable residual disease (MRD) after first-line platinum-based chemotherapy (1LCT). This study aims to report the efficacy, including antitumor activity, and safety of niraparib maintenance therapy in patients with MRD after 1LCT from the phase 3 PRIME trial (NCT03709316). Methods: In PRIME, adults with newly diagnosed aOC who had received cytoreductive surgery and responded to 1LCT were randomized 2:1 to receive niraparib or placebo with stratification by receipt of neoadjuvant chemotherapy, response to 1LCT, status of germline BRCA mutations, and tumor homologous recombination deficiency status. Tumor assessment was conducted at baseline and every 12 weeks thereafter by blinded independent central review (BICR) according to RECIST, version 1.1. Between 29 June 2018 and 11 November 2019, 384 patients were randomized (255 niraparib, 129 placebo). The data cut-off date was 30 September 2021. This post-hoc analysis reports BICR-assessed objective response rate (ORR) and PFS in patients with MRD at baseline. An initial response was confirmed ≥4 weeks later. Results: In total, 73 (19.0%) patients (47 niraparib, 26 placebo) had MRD at baseline. Baseline characteristics were well balanced between the two MRD groups. Complete and partial responses, both confirmed, were observed in 12 (25.5%) and 15 (31.9%) niraparib-treated patients and 3 (11.5%) and 5 (19.2%) placebo-treated patients, respectively, leading to a confirmed ORR of 57.4% with niraparib and 30.8% with placebo (odds ratio, 3.20; 95% confidence interval [CI], 1.11–9.11). ORRs by biomarker status are provided in the table. Median PFS (95% CI) was 22.3 (8.7–not estimable) months with niraparib versus 8.3 (5.6–11.0) months with placebo (hazard ratio, 0.36; 95% CI, 0.19–0.71). Treatment-emergent adverse events (TEAEs) of grade ≥3 occurred in 28 (59.6%) niraparib-treated patients and 7 (26.9%) placebo-treated patients. TEAEs led to treatment discontinuation in three (6.4%) niraparib-treated patients and one (3.8%) placebo-treated patient. Conclusions: In patients with newly diagnosed aOC who had MRD after 1LCT, niraparib maintenance therapy tended to induce additional antitumor activity and led to a clinically meaningful increase in PFS versus placebo. Clinical trial information: NCT03709316 .[Table: see text]
The effect of maintenance hormone therapy on overall survival in advanced-stage low-grade serous ovarian carcinoma: A risk-set matched retrospective study.
Authors: Barakzai Syem , Bregar Amy , del Carmen Marcela G. , Eisenhauer Eric L , Goodman Annekathryn , Rauh-Hain Jose Alejandro , Gockley Allison Ann , Melamed Alexander 
Published: June 2023

5568 Background: Low-grade serous ovarian carcinoma (LGSOC) is a rare malignancy often treated similarly to high-grade serous ovarian carcinoma (HGSOC) despite differences in clinical behavior and carcinogenesis. Observational studies suggest that, among patient with advanced-stage LGSOC, maintenance hormonal therapy (HT) following primary treatment is associated with improved progression free survival. We conducted a multi-institutional observational study to investigate whether HT is associated with an overall survival advantage in this setting. Methods: We included patients with histologically confirmed stage III or IV LGSOC diagnosed between Jan 1, 2004, and Dec 31, 2019, treated in Commission on Cancer accredited cancer programs in the US. Patients who received HT within 6 months of diagnosis were matched to controls who did not initiate HT during this timeframe. The primary outcome was risk of death from any cause, within five-years of initiation of HT or observation. For each treated patient, we employed risk-set propensity score matching to identify a control in a manner that avoided the introduction of immortal-time-bias, and balanced groups with respect to year of diagnosis, upfront treatment strategy, age, stage, race/ethnicity, comorbidity index, insurance status, zip-code median income, and cancer program type. Results: There were 296 patients who initiated HT within 6 months of diagnosis, and 2,805 potential controls. Patients who received HT were more often treated in academic medical centers (55% vs 44%), diagnosed later in the study period (62% vs 23% diagnosed in 2018-2019), and received upfront chemotherapy less frequently (55% vs 83%). After risk set and propensity score matching, we identified 204 patients treated with HT and 204 untreated controls, who were otherwise similar with respect to measured covariates. In the matched cohort, maintenance HT was associated with a reduction in the risk of death (hazard ratio 0.61; 95% CI 0.37-0.99), corresponding to a 60-month survival of 71% compared with 61%, and an improvement in 5-year life expectancy of 3.6 months (95% CI 0.004-7.2). Conclusions: Maintenance hormone therapy following primary management of LGSOC is associated with an overall survival benefit compared with observation.
Trends and outcomes of systemic therapy in hormone receptor-positive early-stage male breast cancer: A propensity score analysis.
Authors: Yu Liuwen , Zeng Bangwei , Chen Minyan , Huang Meng , Guo Wenhui , Chen Lili , Lin Yuxiang , Li Jing , Li Yan , Fu Fangmeng , Jacobs Lisa K. , Wang Chuan 
Published: June 2023

557 Background: Male breast cancer (MBC) is a rare disease. Research on trends and survival outcomes in systemic treatment for MBC is limited. This study aims to describe trends and survival outcomes of different systemic treatments in hormone receptor-positive (HR+) early MBC and to assess the factors related to treatment selection. Methods: We identified stage I-III HR+ invasive MBC patients who have undergone surgery and systemic therapy diagnosed during 2004-2014 from the National Cancer Database (NCDB). Treatment groups include: endocrine therapy (ET), chemotherapy (ET), combination therapy (ET+CT), and None. Using Cochran-Armitage trend tests to describe the temporal trends of different treatments. Performing propensity score models to evaluate overall survival. Conducting a logistic regression to analyze factors associated with ET+CT. Results: Among 6217 patients included (median follow-up 50.1months), 1290 (20.7%) patients received no systemic therapy (None), 705 (11.3%) patients only received CT, 2358 (37.9%) patients only received ET, and 1864 (30.0%) patients received ET+CT. From 2004 to 2013, there was a significant increase in the use of ET ( P(trend) < .001), which was accompanied by a decrease in CT and no treatment (all P(trend) < .001). And the use of ET+CT showed no significant change. After using overlap weighting (OW) to control confounders, multivariable cox regression analysis showed that ET+CT was associated with improved survival compared with ET (hazard ratio [HR], 0.46; P< .001). Sensitivity analyses (including the inverse probability of treatment weighting (IPTW) (HR,0.49; P < .001), IPTW with stabilized weight (HR,0.49; P< .001), propensity score matching (PSM) (HR,0.51; P < .001), PS regression adjustment (HR,0.47; P < .001), and PS stratification (HR 0.44; P < .001)) and exploratory subgroup analyses (except for well-differentiated, stage I, and breast conservation + radiotherapy subgroups) indicated similar outcome. Factors associated with receiving ET+CT include younger age, private insurance, Charlson Comorbidity Index was 0, poorer differentiation, higher stage, mastectomy and radiotherapy, estrogen receptor-positive and progesterone receptor-negative, and HER2-positive. Conclusions: ET+CT was associated with improved survival compared with ET in HR+ early MBC patients, except for some low-risk subgroups.
Patterns of ovarian cancer care in an elderly population in Australia: A prospective cohort study from the National Gynaecology Oncology Registry (NGOR).
Authors: Naidoo Mahendra , Scott Clare L. , McNally Orla , Rome Rob , Perera Sharnel , Zalcberg John Raymond ,   NGOR Steering Committee & Ovarian, Tubal and Peritoneal (OTP) Cancer Working Group
Published: June 2023

5572 Background: Elderly women with ovarian cancer are often undertreated in comparison to best practice. The National Gynae-Oncology Registry (NGOR) is Australia’s first country-wide clinical quality registry (CQR) measuring compliance with optimal care defined by a set of clinical quality indicators (CQIs). Objectives: To assess compliance with a predefined set of CQIs for elderly women with newly diagnosed ovarian cancer aged > 75 compared to non-elderly women aged <75 years of age from the NGOR sites. Methods: All women with newly diagnosed ovarian cancer from May 2017 – July 2022 were eligible for inclusion. Data were collected from medical records and relevant hospital linked databases by expert data managers. Results: A total of 1590 women were eligible for inclusion from 21 hospitals across 5 Australian states. The CQI data were subsequently aggregated and are summarised in the table. The proportion of elderly women receiving first-line chemotherapy with a platinum and taxane doublet was significantly lower compared to non-elderly (60% vs 89%, p < 0.001). The proportion of women with sub-optimally debulked or Stage IV cancer who received first-line chemotherapy with a platinum/taxane doublet and bevacizumab was significantly lower in elderly women compared to non-elderly (10% vs 30%, p < 0.001) . Enrolment in clinical trials or translational research was significantly lower in elderly women compared to non-elderly (13% vs 21%, p=0.002). The remaining CQIs showed no significant differences between the age groups. Conclusions: In this cohort, most measures of best practice were not significantly different between elderly and non-elderly women, with the exception of elderly women receiving less first line doublet chemotherapy, less doublet chemotherapy with bevacizumab in sub-optimally debulked or Stage IV cancer, and less likely to be enrolled in clinical trials or translational research. While these 3 CQIs represent a minority of the overall list of CQIs, such lack of compliance may result in significant differences in quality of life and overall survival for elderly women with ovarian cancer. Subsequent investigation is therefore warranted to confirm and explain these findings. [Table: see text]