bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in cervical cancer incidence rates among demographic groups: A SEER database analysis.
Authors: Thierheimer Marisa , Alkrekshi Akram , Al Zubaidi Anas , Al Armashi Abdul Rahman 
Published: June 2023

e17524 Background: Cervical cancer (CC) is the fourth most common cancer in women worldwide, with most cases caused by human papillomavirus (HPV) infection. The incidence of CC has decreased since the mid-1900s due to effective cytological screening, treatment of precancerous lesions, and vaccinations against HPV. Nonetheless, over ten thousand women in the US are diagnosed with CC yearly. Up-to-date data on the trends in cervical cancer incidence rates (IR) among different racial and age groups is lacking. Here we present an in-depth analysis of these IR trends between 1975-2018. Methods: The National Cancer Institute SEER 9 database was used to generate CC IR from 1975 to 2018 as they relate to age, race, histopathology, and county classification. Joinpoint modeling was used to incidence trends and annual percent changes (APC) with 95% confidence intervals (CI) using Monte Carlo permutation analysis to generate best-fit models with a 2-tailed t-test (p<0.05). Patients with CC were identified using ICD-O-3 primary site codes. Results: Overall, age-adjusted primary CC IR declined significantly between 1975 and 2018. Black individuals had the highest IR throughout the study period. When compared to the other racial groups, Black experienced a steeper decline in IR between 1975 and 2018. By 2018, the disparity in IR between Black individuals and White/Other individuals had nearly vanished. Of the two histopathologies studied, squamous cell carcinoma IR declined, while the IR of adenocarcinoma increased slightly. Among age groups, the IR among individuals aged 50-64 and 65+ decreased most dramatically over time. The two groups had the highest IR in 1975, but by 2018 the IR in both age groups had dropped below that of individuals aged 35-49 years. Patients in urban counties experienced similar IR decreases to those in urban and rural areas. Conclusions: Although screening and HPV vaccination initiatives have been successful at decreasing IR of CC, disparities in IR trends among racial and demographic groups persist. Examining age, racial, and community-specific CC IR trends at the population level will help prioritize resource allocation to reduce CC IR in all groups and minimize the existing gap. [Table: see text]
Risk factors for lymph node metastasis and clinical outcomes in cervical cancer patients following primary radical hysterectomy: A single-center analysis of 1495 patients.
Authors: Qian Lili , Yin Weiqi , Zhao Xingkun , Shen Zhen , Zhu Jing , Li Min , Zhang Tianjiao , Zhou Ying 
Published: June 2023

e17525 Background: Histopathological information obtained from surgical specimen is important to identify patients at increased risk for disease relapse and mortality. Lymph node metastasis (LNM) carries the highest impact on decreased survival in suspected early-stage cervical cancer. To further identify risk factors for LNM and prognosis in early stage cervical cancer patients is definitely necessary owing to the findings from different centers are inconsistent. Methods: A total 1495 cervical cancer patients were diagnosed with stage IA2-IIA cervical cancer according to clinical stage and underwent radical hysterectomy between April 2009 and December 2020. The stage of all the patients were reclassified after surgery according to FIGO 2018. We analyzed their clinicopathologic data to identify the risk factors for LNM. Among all the patients, the progression-free survival (PFS) and overall survival (OS) of 1109 patients between 2015 and 2020 were collected and analyzed. Results: The incidence of LNM is 18.8% in all 1495 patients, which increases with depth of cervical stromal invasion, tumor size, lymphovascular space involvement (LVSI) and vaginal wall invasion in univariate analysis. Multivariable analysis shows only stromal invasion (OR, 3.0; 95% CI, 1.7–5.3; P < 0.001) and LVSI (OR, 4.9; 95% CI, 3.6-6.7; P<0.001) are to be independent risk factors for LNM. In addition, the clinical parameters age is a protective factor against LNM in both univariate and multivariable analysis(P<0.001). Among the 1109 patients, the median follow-up time is 49.7 months. Multivariate analyses using the Cox proportional hazards model show that LNM (HR, 8.5; 95% CI, 3.0-23.9; P<0.001), stromal invasion (HR, 3.4; 95% CI, 2.2-5.4;P<0.001) and special histologic type (HR, 3.2; 95% CI, 1.4-7.6; P=0.006) are independent prognostic factors for OS as well as PFS in early stage cervical cancer. Conclusions: The pattern of cervical stromal invasion and presence LVSI, but not the primary tumor size, predict risk of nodal metastasis. Cervical stromal invasion, LNM and special histologic type (non-squamous cell carcinoma; non-Adenocarcinoma) are independent prognostic factors for OS as well as PFS in early stage cervical cancer. [Table: see text]
Impact of hemoglobin on survival of young women with cervical cancer treated with concurrent chemoradiotherapy.
Authors: Castro-Mollo Melanie Wendy , Galvez-Nino Marco , Ruiz Rossana , Roque Katia , Coanqui Ofelia , Valdivieso Natalia , Olivera Hurtado de Mendoza Mivael , Mas Luis 
Published: June 2023

e17529 Background: Cervical cancer is a global public health problem, with higher impact in many low-income and middle income countries. In Peru, cervical cancer is the leading cause of cancer deaths among women. The aim of this study is to investigate the prognostic factors affecting long-term survival in locally advanced cervical cancer young patients treated with concurrent chemoradiotherapy. Methods: This is a retrospective study of young women with locally advanced cervical cancer who underwent radiotherapy with concurrent platinum-based chemotherapy at the national cancer peruvian institute (INEN), from 2008 to 2012. The clinicopathological factors of all patients were collected. To explore the relationship between factors and prognosis, survival rates were estimated by the Kaplan–Meier method. Results: A total of 192 patients under 35 years old . Among all patients, 167 were diagnosed with SCC, 19 with AC, and 5 with ASC. Most of the patients were IIB and IIIB FIGO stage, 69% and 22% respectively. 38 cases had no metastatic lymph nodes and 42 cases were diagnosed of lymph node metastases, of which 30 were positive for pelvic lymph nodes only, and 12 were positive for para-aortic lymph nodes. We obtained pretreatment hemoglobin levels for all patients and found a median of 111 g/L, also we calculated the Prognostic nutritional index (PNI) with a median of 41.87 that correlates with a moderate to severe malnutrition in patients prior treatment. Response to chemoradiotherapy was not available in 13 patients, 136 achieved complete response, 30 patients with persistent disease and 12 with disease progression. Estimated median OS of all patients was 114.1 months [101.8-126.4] and median DFS was 112.3 months [98.9-125.7]. Exploratory analysis was performed to determine potential prognostic factors, only hemoglobin ≤ 100 g/L was statistically significant (p = 0.007). Conclusions: In young patients undergoing chemoradiation for cervical carcinoma, the hemoglobin prior treatment is prognostically significant.
A phase I dose-finding trial of hyperthermic intraperitoneal docetaxel combined with cisplatin in patients with advanced-stage ovarian cancer.
Authors: Li Jing , You Zhi-yao , Wu Miao-fang , Lin Zhong-qiu , Chen Qing 
Published: June 2023

e17532 Background: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods: In this single-center Phase I trial, time-to-event Bayesian Optimal Interval Design (TITE-BOIN) was used. The starting dose for docetaxel was 60 mg/m2, with escalation in 5 mg/m2 increments until the MTD was determined or the maximum dose level of 75 mg/m2 was reached. The target dose-limiting toxicity (DLT) rate was 25%, and the total sample size was 30 patients. HIPEC was delivered immediately following the debulking surgery using the closed technique with a target temperature of 43 ℃ for 90 minutes. Results: A total of 30 patients were enrolled from August 2022 to November 2022. Among patients who received a docetaxel dose level ≤ 65 mg/m2, no DLT was reported. DLTs were observed in one patient at 70mg/m2 docetaxel (grade 3 anemia) and three patients at 75mg/m2 docetaxel (one grade 3 anemia, one grade 3 hepatic impairment and one grade 4 thrombocytopenia). When patients were treated with docetaxel at a dose of 75 mg/m2 in combination with 75 mg/m2 cisplatin, the estimated DLT rate was 25% which was closest to the target DLT rate and therefore selected as the MTD. Conclusions: For ovarian cancer patients who receive HIPEC following debulking surgery, docetaxel, in combination with a fixed dose of cisplatin (75 mg/m2), can be safely used at intraperitoneal doses of 75 mg/m2(ClinicalTrials.gov identifier, NCT05410483).
Single cell multiomic profiling of high-grade serous carcinoma.
Authors: Assad Maia Sandoval Leticia , Dumbrava Mihai , Mohammed Ismail Wazim , Mazzone Amelia , Hou Xiaonan , Weroha Saravut John , Gaspar-Maia Alexandre 
Published: June 2023

e17535 Background: High-grade serous ovarian carcinoma (HGSOC) is the most frequent and deadliest type of ovarian cancer (OC). With the recent advances in transcriptomic and epigenomic profiling of cancer at single cell resolution, it has become clear that intra-tumor heterogeneity driven by genetic and epigenetic factors may be the basis of drug resistance. Current treatments are not homogeneously effective against all the cancer cell subpopulations, thus enabling resistance. With single cell sequencing technology, characterization of cell signatures and regulatory mechanisms may translate to prognostic markers and novel drug targets. Methods: The transcriptomic and epigenomic landscape of HGSOC was mapped for five tumor samples from debulking surgeries and one tissue patient-derived xenograft (PDX) using the 10X genomics sequencing platform. This strategy permits the combination of single cell ATAC-seq and single cell RNA-seq within the same nucleus (Multiome). Isolation of nuclei, library preparation and sequencing were performed following 10X genomics protocols. Sample quality and library quality were assessed by nuclear morphology and fragment size analysis, respectively. Sequenced reads were mapped to the human genome and downstream analysis including copy number variant prediction, pathway enrichment, motif enrichment and gene regulatory network analysis were performed. The sampled patients continue to be followed for clinical outcomes, such as response to therapy. Clinical data including patient age, grade, and stage of cancer, debulking status, CA-125 levels, and neoadjuvant status, were used in conjunction with the genomics data to characterize patient specific molecular regulatory signatures. Results: Cells from the six samples (total N= 26,421) were projected via UMAP. Immune and stromal cells were shown to cluster by cell-type while cancer cells clustered by patient. Cancer cells were identified as cycling cells, ciliated cells, cells with enrichment of the JAK-STAT signaling pathway, and cells exhibiting cancer stemness signatures. Transcription factor motifs and binding-site enrichment in open chromatin regions reveal transcription regulation-based subpopulations. Using the combined gene expression and open chromatin information from these cells, there is potential to uncover the genetic regulatory network(s) that drives treatment resistance. Conclusions: With single cell technology, specific clusters of cancer and tumor microenvironment cells can be classified. Beyond characterizing patient specific signatures, multiome enables the discovery of genomic, transcriptomic and epigenomic signatures that provide insight in tumor progression and treatment resistance.
Different disease progression patterns based on RECIST and CA-125 criteria and the impact on prognosis in patients with ovarian cancer treated with PARP inhibitors.
Authors: Song Kun , Ma Yana , Bu Hualei , Zhang Yawen 
Published: June 2023

e17536 Background: We aimed to assess the clinical features of disease progression (PD) based on Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 criteria, and analyse the impact on prognosis in ovarian cancer patients treated with poly (ADP-ribose) polymerase (PARP) inhibitors. Methods: All epithelial ovarian cancer patients included in this retrospective analysis were admitted to the Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University between January 2011 and July 2021. All enrolled patients were treated with PARP inhibitor monotherapy or combination therapy with antiangiogenic agents and regularly assessed with RECIST and CA-125 criteria until disease progression confirmed by RECIST criteria. Patients were divided to RECIST PD group and CA-125 PD group based on regular assessment: RECIST PD group comprised patients who were first confirmed with RECIST-assessed PD and did not achieve PD according to CA-125 criteria during the subsequent 28 days; CA-125 PD group comprised as follows: (i) patients who were first diagnosed with RECIST-assessed PD and defined as consistent if CA-125 PD occurred within the following 28 days; (ii) patients who had doubled CA-125 levels for the first time, confirmed after at least 1 week, and defined as consistent if subsequent RECIST progression occurred within 28 days of the initial doubling of CA-125; (iii) patients in whom the first occurrence of CA-125 was doubled and confirmed after at least 1 week, defined as priority PD of CA-125 provided there was no progression in RECIST assessment during the subsequent 28 days. Results: A total of 124 patients were included, with 64 (51.6%) in RECIST PD group and 60 (48.4%) in CA-125 PD group. Forty-three patients (34.7%) had disease progression consistent with RECIST and CA-125 criteria, 64 patients (51.6%) had priority PD with RECIST criteria, and 17 patients (13.7%) had priority PD with CA-125 criteria. The median interval between disease progression as determined by priority CA-125 criteria and subsequent RECIST criteria was 55 days (range 29–192 days). Patients in CA-125 PD group had a higher proportion of lymph node progression (40.0% vs. 17.2%, p = 0.005), multi-site disease progression (41.7% vs. 21.9%, p=0.018), and a worse prognosis with a median overall survival (OS) of 70.5 vs. 87.2 months (hazard ratio (HR)=2.01, p=0.015). In multivariate analysis, residual lesions after primary surgery (no vs. yes, HR=0.493, p=0.015), duration of PARP inhibitor treatment (≤ 6 vs. > 6 months, HR=2.262, p=0.006), priority criteria for PD (RECIST vs. CA-125, HR=0.441, p=0.006), and BRCA1/2 mutation status (wild-type vs. mutation, HR=2.150, p=0.028) were significantly associated with OS. Conclusions: Priority disease progression based on CA-125 criteria in ovarian cancer patients treated with PARP inhibitors might suggest a poor prognosis.
Comparison of bevacizumab plus doublet chemotherapy regimens in patients with metastatic or recurrent ovarian cancer.
Authors: Khanmammadov Nijat , Dogan Izzet , Saip Pinar , Aydiner Adnan 
Published: June 2023

e17537 Background: Ovarian cancer is the most common cause of death due to gynecological malignancies. Although the primary treatment is surgery, there are different chemotherapy regimens that can be used in metastatic disease. In this study, it was aimed to compare doublet chemotherapy regimens in combination with bevacizumab in patients with metastatic ovarian cancer. Methods: Our study was designed as a retrospective observational study. The clinical, pathological, radiological, and treatment characteristics of the patients were recorded. Survival analyzes were performed using the Kaplan-Meier method, and multivariate analysis using cox regression analysis. Results: 198 patients were included in the study. Median follow-up period after bevacizumab was 18.7 months. The most common pathological subtype was serous carcinoma (%85.9). Before bevacizumab treatment, 96% of patients received perioperative chemotherapy. The most common sites of metastasis were the peritoneum (94.5%), liver (43.9%), lung (18.7%), bone (4.5%), and brain (3%). In combination with bevacizumab, 92 (46.4%) patients used gemcitabine + carboplatin, 76 (38.4%) patients used paclitaxel + carboplatin, and 30 (15.2%) patients used gemcitabine + cisplatin. In the whole patient group, the rate of complete response was 18.7%, partial response 56.1%, stable disease 6.6%, and progressive disease 18.7%. The patients received a median of 9 cycles of bevacizumab and a median of 7 cycles of doublet chemotherapy. Median progression-free survival was 11.9 (95% CI, 9.2-14.5) months, and median overall survival was 24.7 (95% CI, 19.9-29.4) months. History of surgery before bevacizumab (p=0.006) and type of doublet chemotherapy (p=0.024) were found to be statistically significant factors affecting overall survival. The presence of brain metastases (p=0.062) had borderline significance. Conclusions: Doublet chemotherapy regimens with bevacizumab have been found to be effective and safe in the treatment of metastatic ovarian cancer in terms of survival. The combination of bevacizumab with gemcitabine + carboplatin was superior to other doublet chemotherapy regimens in terms of overall survival.
Molecular profile of SWI/SNF complex in Chinese patients with ovarian cancer.
Authors: Li Jianmin , Han Tiantian , Guo Didi , Kong Rongrong , Chen Siqi , Wang Mengjuan , Dong Yuwei , Ding Ran , Deng Wanglong , Bu Fanfeng , Chen Yang 
Published: June 2023

e17538 Background: The SWI/SNF chromatin remodeling complexes are involved in cancer initiation and progression. ARID1A, ARID1B, and SMARCA4, the essential ATPase subunit of the SWI/SNF chromatin remodeling complex, play important roles in altering chromatin structure for various cellular functions, including transcription, DNA synthesis, and repair. In ovarian cancer (OC), mutations in several SWI/SNF complexes were found, but the molecular and clinical characteristics of SWI/SNF complexes in Chinese ovarian cancer patients have never been reported. Herein, we explored the profiles of SWI/SNF mutation in the Chinese population. Methods: Genetic mutations were reviewed in OC patients who underwent hybridization capture-based next-generation sequencing (NGS). SWI/SNF mutant tumors (MT) were compared to wild-type (WT), and other co-mutations were also evaluated. The pathogenicity of germline mutations was categorized based on American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Among 461 OC patients, mutation in at least one evaluated SWI/SNF gene was identified in 23% of cases. The higher frequency of SWI/SNF alterations were ARID1A (41.03%), ARID1B (13.33%), SMARCA4 (11.28%). The co-mutated genes mainly were TP53, PIK3CA, PTEN. In addition, the MT group tended to have more BRCA1/2 somatic mutations (16.34% vs. 7.84%, χ2＝5.42, p < 0.05) and less BRCA1/2 germline pathogenic mutations (8.7% vs. 17.2%, χ2＝4.40, p < 0.05) compared to WT group. There was a significant statistical difference in TMB value that the MT group was higher than the WT group (11.1 vs. 2.7, p < 0.001). In the MT group, the TMB of patients co-mutated with TP53, PIK3CA, or PTEN mutations were 10.2, 17.3, and 32.3, respectively. The proportion of SWI/SNF alterations in MSI-H tumors was higher than those without mutations (10.0% vs. 0.8%, χ2＝19.29, p < 0.001). Conclusions: SWI/SNF mutant tumors tended to be associated with higher TMB (11.1 vs. 2.7), a higher proportion of MSI-H (10% vs. 0.8%), and more BRCA1/2 somatic mutations ( 16.34% vs. 7.84%) in OC patients. Patients with SWI/SNF alterations combined with PTEN mutation have extremely high TMB (TMB=32.3), indicating they may benefit more from immunotherapy.
Effects of the baseline prognostic factors on efficacy of the p62/SQSTM1-encoding plasmid combined with gemcitabine in patients with recurrent platinum-resistant ovarian cancer.
Authors: Shneider Alexander , Polyakov Sergey , Baranau Yauheni , Gabai Vlad , Zharkova Ekaterina , Streltsova Olga , Filimonava Aliona , Siarheyeva Volha , Kazlouskaya Sviatlana , Khorau Anton , Pothuri Bhavana , Krasny Sergei 
Published: June 2023

e17540 Background: We recently reported on the efficacy of the p62/SQTM1-encoding plasmid in patients with advanced, recurrent platinum-resistant ovarian cancer (PROC) receiving gemcitabine chemotherapy. Here we analyze the effects of baseline prognostic factors on efficacy. Methods: A prospective multicenter randomized study took place between 01/2020 and 08/2023. Cohort A (n=20) consisted of Gemcitabine 1000 mg/m2 days 1,8 every 3 weeks and Cohort B (n=20) consisted of Gemcitabine (Gem) 1000 mg/m2 days 1,8 every 3 weeks plus p62-plasmid 2.5 mg i.m. weekly. We stratified the patients into subgroups according to their baseline CA-125 level (normal vs high), number of lines of chemo (1 vs 2-3) received by a platinum-sensitive ovarian cancer (PSOC) patient before they became PROC, platinum-free interval (PFI) (up to 3 mo vs more than 3 mo), and presence or absence of peritoneal effusion. Cox proportional hazards regression analysis was utilized to determine effect of progression free survival (PFS). Results: The median follow-up was 13.8 months (mos). The median PFS was 2.8 mos in Gem (Arm A) and 7.2 mos in Gem + Plasmid (Arm B) respectively (p = 0.03). The overall response rate (ORR) by RESIST 1.1 was higher in the Gem +Plasmid arm: partial response (PR) - 5.0% and 20.0%, stable disease (SD) - 40.0% and 60.0%, and disease control rate 41.2 and 80% in Chemo and Plasmid arms respectively). In cohort A, all patients have progressed, whereas in Cohort B (Gem +Plasmid) 9 patients (45%) remained progression-free with the longest duration of response being 30 mo. Overall survival cannot be assessed yet. Analyzing prognostic factors with Cox Proportional Hazards Regression Analysis identified that the following factors increase p62 sensitivity: initial high CA-125 level PFS 2.5 and 6.5 (p = 0.01) in Arm A vs B, 1 line chemo vs 2 or 3 lines for PSOC, PFS 2.3 and 7.1 (p = 0.008) in Arm A vs B, and presence of peritoneal effusion PFS 2.4 and 7.6 (p = 0.008) in Arm A vs B (Table ). Conclusions: We observed maximal effect on PFS when combining the p62-encoding plasmid with Gem in the patients with the most dismal prognosis PROC: rapid progression (relapse as PROC after the first line of treatment and/or short PFI), in patients with an initial high level of CA-125, and/or pleural effusion. [Table: see text]