bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overall survival in treated ovarian cancer patients in Argentina: OCEANIA study.
Authors: Abreu Gabriela , Queiroz Juliana , Nogueira Thiago , Soares Claudia , Menezes Patricia , Carrizo Mariano Nicolas , Criniti Juan , Felice Rosana , Scibona Paula , Simonovich Ventura , Riggi Maria Cecilia , Cravero Florencia , Odetto Diego , Saadi José , Jotimliansky Laura Fabia 
Published: June 2023

e17595 Background: OCEANIA is a retrospective, real-world database study that evaluated treatment patterns and outcomes in a cohort of patients diagnosed with ovarian cancer (OC) in private healthcare settings in Latin America. The present analysis focused on evaluating up to five-year overall survival (OS) in a cohort of treated patients with OC in Argentina. Methods: Patients with an OC code diagnosed from 2010 to 2019 and with a cancer-related treatment claim (antineoplastics, surgery, and/or radiotherapy) were selected from a private healthcare provider’s database (Hospital Italiano de Buenos Aires) in Argentina. Patients were followed from diagnosis until the end of observation period or death. Frequency of OC patients by FIGO (International Federation of Gynecology and Obstetrics) stage was described. Cumulative treatment type was described through the whole follow-up period. One- to five-year survival Kaplan–Meier curves were built; patients who were lost to follow-up were censored. Results: 741 patients with OC were identified in the database with a mean (standard deviation) follow-up time of 31.7 (30.6) months; 539 (72.7%) were treated during this period. Among this population, 76.3% had information about FIGO staging: 73 (17.8%) were stage 1; 36 (8.8%) stage 2; 259 (63.0%) stage 3; and 43 (10.5%) stage 4. Cumulative distribution across treatment types revealed 355 (65.9%) patients received antineoplastics (321 [90.4%] received platinum-based treatment), 496 (92.0%) surgery and 18 (3.3%) radiotherapy. During a five-year observation window, 111 patients died (more than one half within two years of diagnosis). The adjusted cumulative OS for all treated patients in years 1–5 was 93.2%, 87.2%, 80.9%, 74.1%, and 69.0%, respectively (Table). Conclusions: OS is a key outcome in assessing the impact of current standards of care. Based on the results, although most (69.0%) of the patients survived after 5 years of follow-up, further improvement in OS presents a challenge. However, recent drug releases for OC management in Latin America may change this scenario. [Table: see text]
Circulating tumor DNA-based molecular residual disease detection for the monitoring of high-grade serous ovarian cancer.
Authors: Ying Xiang , Zheng Xiaocui , Wang Yizhi , Li Jiarui , Li Xing , Lin Guomin , Wang Kai , Wang Xipeng 
Published: June 2023

e17600 Background: The current standard treatment of epithelial ovarian cancer includes surgery and platinum-based chemotherapy. Most of the patients are sensitive, but still over 70% of patients have recurrence or disease progression. Post-operative circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) test can be a potential biomarker for monitoring the disease. Methods: Stage II-IV high-grade serous ovarian cancer (HGSOC) patients were recruited in this study. Tumor tissues were collected for whole exome sequencing (WES; 300x). Germline mutations were excluded by paired white blood cell test. Proprietary algorithm was used to select 30-40 single nucleotide variants (SNV) for each patient. Blood samples were collected at diagnosis, after surgery, after chemotherapy, and during adjuvant treatment, and MRD was detected by multiplex polymerase chain reaction (PCR)-based sequencing (100,000x) using the customized panel. Results: At the time of analysis, WES was performed in 20 patients, of which 11 of them harbored HRR pathway-related mutations, including 5 BRCA1, 4 BRCA2, 1 ATM, and 1 FANCL. 7 patients had completed MRD monitoring for 3 times (pre-surgery, post-surgery, and post-chemotherapy). 71.4% (5/7) of patients were positive for MRD at baseline, with a median variant allelic frequency (VAF) of 2.79%. The VAF at baseline was positively associated with CA125 level at baseline (Pearson R = 0.937，p = 0.002). 2 patients were positive for MRD after surgery (VAF = 0.09% and 0.04%). One of them presented with multiple diverse lesions and the CA125 level returned normal after surgery and 8 cycles of chemotherapy. Another patient had an abnormal CA125 level of 1597 U/ml after surgery. All the 7 patients were negative for MRD after completion of chemotherapy. Follow-up is ongoing. Conclusions: We preliminary proved the feasibility of dynamic monitoring with MRD in epithelial ovarian cancer patients. Over 70% of HGSOC patients were MRD-positive at baseline. The MRD status was generally consistent with the clinical status of the patients. The performance of MRD in predicting recurrence of HGSOC is still under investigation. Clinical trial information: NCT05027828 .
GD2 and GD3 gangliosides as diagnostic biomarkers for all stages and subtypes of ovarian cancer.
Authors: Jeter Anna , Galan Alba , Papaluca Arturo , Nejatie Ali , Matanes Emad , Brahimi Fouad , Yasmeen Amber , Carmona Euridice , Klein Kathleen Oros , Billes Sonja , Dawod Ahmed E. , Gawande Prasad , Mes-Masson Anne-Marie , Greenwood Celia , Gotlieb Walter H. , Saragovi H. Uri 
Published: June 2023

e17604 Background: Ovarian cancer (OC) is the deadliest gynecological cancer, often diagnosed at advanced stages. A fast and accurate diagnostic method for early-stage OC is needed. The tumor marker gangliosides, GD2 and GD3, exhibit properties that make them ideal potential diagnostic biomarkers but they have never before been quantified in OC. We investigated the diagnostic utility GD2 and GD3 for diagnosis of all subtypes and stages of OC. Methods: This retrospective study evaluated GD2 and GD3 expression in biobanked tissue and serum samples from patients with invasive epithelial OC, healthy donors, non-malignant gynecological conditions, and other cancers. GD2 and GD3 levels were evaluated in tissue samples by immunohistochemistry (n=299), and in two cohorts of serum samples by quantitative ELISA. A Discovery Cohort (n=379) showed feasibility of GD2 and GD3 quantitative ELISA for diagnosing OC, and a subsequent Model Cohort (n=200) was used to train and cross-validate a diagnostic model. Results: GD2 and GD3 were expressed in tissues of all OC subtypes and FIGO stages but not in surrounding healthy tissue or other controls. In serum, GD2 and GD3 were elevated in patients with OC. A novel diagnostic model that included serum levels of GD2 and GD3 was superior to the standard of care (CA125, p<0.001) at detecting OC, as well as, in early-stage (I/II) OC samples. Conclusions: GD2 and GD3 are high value candidates for building a novel diagnostic panel. A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early-stage. Further research exploring the utility GD2 and GD3 for diagnosis of OC is warranted. Future work will aim to validate these biomarkers in independent prospective studies. [Table: see text]
Development of a microbead based immunoassay to detect circulating soluble HLA-E: Application in cancer immunobiology.
Authors: Kanangat Varun , Auger Claire , Tarhoni Imad , Marshalla Megan K. , Gerard David , Abdelkader Ahmed , Borgia Jeffrey Allen 
Published: June 2023

e17606 Background: The Human Leukocyte Antigens [HLA] gene complex is subdivided into classical (HLA-A, B, and C) and non-classical (HLA-E, F, G, and H) loci. These genes are associated with immune modulation and immunopathogenesis in cancer, though the roles of non-classical HLA molecules are poorly understood. Here, we explored potential expression patterns of soluble HLA-E (sHLA-E) in patient sera across a range of common malignancies to identify potential disease applications for future study. Methods: Quantitative Luminex immunobead assay were developed for sHLA-E using methods we previously defined. In the first phase of this study, we assessed sHLA-E protein levels across a range of treatment-naïve metastatic malignancies (n=5 each), including breast, lung adenocarcinoma, lung squamous cell carcinoma, colorectal, head and neck, ovarian, melanoma, and sarcoma. Based on these results, we refocused our efforts on a second cohort surgically treated by gynecologic oncology for either non-malignant (n=13) or malignant (n=42) lesions of ovarian origins. One-way ANOVA or Independent sample t tests, with normality confirmed via Levene's Test for Equality of Variances, were used to identify statistical relationships. Results: There were significantly (p<0.05) higher levels of sHLA-E protein in ovarian cancer relative to other cancer types surveyed. In the second phase of the study, serum specimens from patients undergoing surgery for a suspected gynecological malignancy were tested for sHLA-E. This study also showed the significantly high expression of sHLA-E in ovarian cancer relative to those with nonmalignant lesions of ovarian origins (p=0.035) that was independent of FIGO grade (p>0.05). For comparison, levels of sHLA-E were not significantly elevated for tumors of endometrium/ endomyometrium origins (n=76; p=0.270) relative to baseline of benign cases. Conclusions: We identified a highly specific statistical relationship for a circulating isoform of HLA-E in ovarian cancer in our cohorts. The significance of these findings in relation to clinical outcomes or treatment response will be explored in future studies. [Table: see text]
Multivariate index assay (MIA3G) to reduce preventive surgery for ovarian cancer.
Authors: Ghosh Srinka , Pappas Todd C. , Reilly Gerard P , Phan Ryan 
Published: June 2023

e17607 Background: Ovarian cancer (OC) – most lethal gynecologic malignancy - is rare among women with adnexal mass. Preventive adnexal surgery is a common practice, despite pathology confirming malignancy in only 10-15% of these cases. This motivates a surveillance-based clinical management paradigm to prognosticate the risk for malignancy and channel appropriately for surgery. We recently developed a multivariate index assay -MIA3G[1] - to assess risk for OC in women with adnexal mass. In a multi-center prospective surveillance trial, we assessed the concordance between preventive surgery and clinical management using MIA3G. Methods: MIA3G risk prediction uses a DNN algorithm which models 7 serum biomarkers (CA125, HE4, BM2, APO, FSH, TFR, PreAlbumin), age and menopausal status. With NPV of 99.7% (CI:99.2–99.9) it risk stratifies patients into low probability of malignancy or indeterminate. Across 11 centers, the MIA3G cohort comprised of 546 women (IQR:41-61yo) with symptomatic or asymptomatic masses and/or presence of HBOC variants. Serial blood draws were timed with clinic-visits and the ultimate one coincident with surgery. The objectives were: 1) prognosticate the MIA3G based preventive surgery pool and 2) establish concordance between the MIA3G probabilistic risk and the pathology-based outcome of malignancy versus benign. Results: In the study cohort of 546 patients, 20.3% (111) underwent preventive surgery. Conservatively, at a 12.8% FPR[1], MIA3G would have stratified approximately 70 patients, a projection of 37% less for surgery. Partitioning by clinical characteristic: (i) symptomatic: In comparison to 27.8% (73/263) of patients referred to surgery, MIA3G projections would have resulted in a 54.8%(33/263) reduction. (ii) asymptomatic: 22.5%(31/138) of patients were referred to surgery; MIA3G projections would have resulted in a 45.2% (17/138) reduction. In the 111 preventive surgeries, pathology confirmed a malignancy rate of 6.3% (7/111). The overall concordance of MIA3G with pathology was 84.68% (94/111) which increased to 91.98% (102/111) in the pre-menopausal (PRE) sub-cohort. The malignant discordancy (MIA3G:FN), all in PRE, comprised of early-stage epithelial: endometreoid, Leiomysarcoma and Sertoli-Leydig cell where the masses were characterized as cystic benign/indeterminate by ultrasound. These findings underscore the power of MIA3G when preventive surgery is considered for patients with ovarian cancer risk. Conclusions: The multivariate index assay MIA3G reduces numbers of preventative surgery for ovarian cancer risk. The high concordance establishes that MIA3G non-invasive surveillance-based clinical management can be effective for the risk assessment of ovarian cancer in patients presented with adnexal mass. Surgical management should be reserved for high probability of malignancy. [1]: DOI 10.3389/fmed.2023.1102437.
Multivariate index assay MIA3G vs other assessment tools for the ovarian cancer risk assessment of indeterminate masses.
Authors: Ghosh Srinka , Pappas Todd C , Phan Ryan 
Published: June 2023

e17609 Background: Estimated 10% of women with adnexal masses will undergo preventive surgery for ovary removal to mitigate malignancy risk. This is significant, compared to the 15% rate of ovarian cancer (OC) confirmed by pathology. On the other hand, a women’s lifetime risk of getting OC is estimated at 1 in 78, with death at 1 in 108. This predicament motivates a surveillance paradigm for assessment of malignancy risk. ROMA (Roche) is a multi-marker assay intended to assess the cancer risk of adnexal masses in women already scheduled for surgery. We recently characterized the clinical performance of MIA3G[1], to assess OC risk for women with adnexal mass clinically characterized as benign or indeterminate. Here we present the comparative analysis for MIA3G and ROMA in a multi-site study. Methods: MIA3G -a 7-biomarker assay with a DNN-based risk prediction algorithm – was tested for clinical management of women (median: 51yo, IQR:41-61) across 11 centers. Data is presented for 206 patients with adnexal mass (286 unique samples), who follow an admix of surgical and clinical management. The continuous MIA3G probabilistic scores and dichotomized risk classification were used for the analyses. The primary objective was to compare MIA3G with ROMA assays. The secondary objective was to validate – via a pair-wise approach – the correlation of the biomarkers, age and menopausal status(MENO) - with the predicted risk stratification. Results: MIA3G stratified 13% [CI:0.096-0.174] and 87% [CI:82.6-90.4] of the 286 samples as indeterminate and low risk of malignancy respectively (p-value<2.2e-16, Welch’s t-test). In comparison, ROMA stratified 11.3% with a high likelihood of finding a malignancy on surgery. In the pre-menopausal sub-cohort MIAG3 risk-stratified only 7% as indeterminates, whereas for ROMA and CA125 the analogous estimates increased to 15% and 20% respectively. For the post-menopausal population, the converse trend was observed. In MIAG3 with increasing risk, the inhibitive effect of APO was signaled (R2:-24%, p:0.0006) and potential implication of iron metabolism was observed in TFR (R2:-31%,p:9.76e-5). B2M indicated inflammation with increasing risk (R2:28%, p:0.052. In addition to being a clinical attribute, MENO status was confirmed with FSH and age (R2 >80%,p<2.2e-16). A strong correlation of risk with HE4 (R2:38%) and CA125 (R2:32%) was observed and a HE4-CA125 pairwise-correlation of >85% confirmed. Additionally, the positive association of PRE with APO( R2 :33%) and negative association with CA125 and HE4 (R2~:-20%) rounded out the comprehensive nature of the MIA3G assay for characterizing the nuanced evolution of the masses. Conclusions: This real-world study established the efficacy of MIA3G as the most clinically validated tool for the risk assessment of ovarian cancer of indeterminate masses. 1: DOI 10.3389/fmed.2023.1102437.
The predictive value of CA-125 for radiologic evidence of metastatic disease in type 2 endometrial cancers.
Authors: Miller Madison Ellis , Pham Tra , Kole Monica , Elshaikh Mohamed A. , Dimitrova Irina 
Published: June 2023

e17610 Background: Type 2 endometrial cancers encompass histologic variants that are more aggressive and have a higher incidence of extrauterine disease at the time of presentation than their type 1 counterparts. For high grade endometrial carcinomas, current National Comprehensive Cancer Network (NCCN) guidelines propose the "consideration of chest, abdomen and pelvis CT to evaluate for metastatic disease." We sought to investigate the predictive value of serum CA-125 for radiographic evidence of metastatic disease in patients with type 2 endometrial cancers. Methods: An IRB-approved, retrospective study investigating patients diagnosed with endometrial cancers between 2000-2020 at an urban, multi-site health system was conducted. Only patients with type 2 endometrial cancers and both pre-operative computed tomography scans of the chest, abdomen, and pelvis (CT CAP) and serum CA-125 results were included. A Youden’s index was used to calculate the optimal CA-125 cutoff. The sensitivity and specificity of CA-125 in predicting radiographic evidence of extrauterine disease was then calculated using this pre-determined CA-125 cutoff. Results: In total, 2,227 patients diagnosed with endometrial cancer (types 1 and 2) between 2000-2020 were identified. 1,932 cases were excluded due to low grade disease and/or the absence of pre-operative imaging and CA-125 results. Ultimately, 295 cases were included in analyses. A receiver operating characteristic (ROC) curve was used to generate Youden’s index which established the optimal CA-125 cutoff as 68 U/mL (P=0.0005). Using this cutoff, the specificity and sensitivity were determined to be 92.45% and 63.86%, respectively. The positive predictive value was 76.81% and the negative predictive value was 86.73%. Conclusions: According to current NCCN guidelines, pre-operative imaging and CA-125 should be considered if extrauterine disease is suspected in the setting of endometrial cancer. Although the role of serum CA-125 in monitoring clinical response is well documented, the utility of this test in stratifying patients who should undergo further radiologic evaluation is uncertain. Our results suggest that a CA-125 cutoff of > 68 U/mL is predictive of radiographic evidence of metastatic disease and, thus, can be used to determine which patients should receive pre-operative CT CAP.
The association of progesterone receptor and abnormal p53 expression in endometrioid endometrial cancer.
Authors: Chang Ting-Chang , Wu Ren-Chin , Jung Shih-Ming , Ueng Shir-Hwa , Chang Wei-Yang , Chou Hung-Hsueh , Huang Kuan-Gen , Huang Huei-Jean , Chao Angel , Tang Yun-Hsin , Lynn Perera , Lai Chyong-Huey 
Published: June 2023

e17611 Background: Based on the TCGA endometrial cancer study results, a clinically applicable classification that identifies distinct subgroups with prognostic signature, the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), has been built and validated. It shows that those with abnormal expression of p53 (p53abn) are the group with the worst prognosis. We attempted to explore the association of p53abn and progesterone receptor (PR) in endometrioid endometrial cancer. Methods: We included 397 consecutive endometrial cancer cases of endometrioid histology with adequate tumor tissue in the formalin-fixed, paraffin-embedded (FFPE) block and available follow-up information. This study was granted by Chang Gung Medical Foundation IRB 201702242B0D001. Sanger sequencing to assess the POLE exonuclease domain hotspot mutations of exon 9-14 and immunohistochemical staining on FFPE tumor tissue sections for p53, ER, PR, and mismatch repair proteins were performed. Immunohistochemical p53 expression of cancer cell nucleus was recorded as completely negative (0%), weakly positive (1-59%), and diffusely strong positive (>60%). Tumors with weak positive p53 staining were defined as p53 wild type (p53wt), while the other two were defined as p53 abnormal (p53abn). PR scores were calculated by multiplying the average staining intensity by the tumor cell nucleus stained percentage. We arbitrarily defined a progesterone receptor score of 100 or higher as positive (PR+). Progression-free and endometrial cancer-specific overall survivals starting at the date of diagnosis were evaluated using Kaplan-Meier method and compared by log-rank test between groups. Results: PR was positive in 82% of all studied cases. Of the 48 cases with p53abn tumor, 35(73%) were PR (+). With a median follow-up of 74 months, the progression-free survival and cancer-specific survival of patients with PR+ tumors (N = 310) were 93% and 96.8%, respectively, compared with 75% and 85.7% of those with PR- tumors (N = 70) (both p < 0.001, log-rank test). Among those with P53abn, PR expression was associated with a favorable progression-free survival ( p = 0.081) and better cancer-specific survival ( p = 0.044). POLEmut, POLE mutated; dMMR, deficient mismatch repair PR+, progesterone receptor score ≥100, ER+, estrogen receptor score ≥100; p53abn, abnormal p53 expression. MMR was undetermined in 32 cases, PR in 17 cases, ER in 17 cases, and p53 was undetermined in 10 cases. POLE status was detected in all cases. Cases with POLE wild type, proficient mismatch repair, progesterone score < 100, estrogen score < 100 and wild type p53 were not listed in this table. Conclusions: Our study showed that incorporating PR into prognostic molecular markers for endometrioid endometrial cancer might provide further risk stratification. [Table: see text]
Development and validation of prediction models for coexisting adnexa malignancy in patients with endometrial cancer using machine learning algorithm: A population-based cohort study.
Authors: Wang Qiannan , Song Kun 
Published: June 2023

e17617 Background: As the rate of ovarian conservation in endometrial cancer patients declined over the course of a decade, the study was to build and validate prediction models based on machine learning algorithms using preoperative predictors to evaluate the risk of coexisting adnexa malignancy, in order to guide decision-making for patients and clinicians before the surgery. Methods: Patients surgically treated for endometrial cancer from 30 medical center which forming the Chinese Endometrial Carcinoma Consortium (CECC) between 2010 and 2019 were enrolled. These patients were randomly divided at ratio of 7:3 into development cohort and validation cohort. Preoperative clinical and histopathological features were included as predictors, and least absolute shrinkage and selection operator (LASSO) was used for selecting candidate predictors. Machine learning (ML) algorithms including logistic regression (LR) analysis, support vector machine (SVM), random forest (RF), AdaBoost, decision tree (DT), naïve Bayes (NB), and multilayer perceptron (MP) were applied to develop the models. The best final model was selected by integrating area under the receiver operating characteristic curve (AUC) value as well as the relative sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy into account. Results: Among 3108 patients in the study cohort, 212 (6.7%) coexisted with adnexal malignancy. Data from 2226 female patients were divided into the cohort for model development. Ultimately the model included 10 predictors selected by LASSO: personal cancer history, age, CA-125, neutrophil lymphocyte ratio (NLR), tumor grade, myometrial involvement, cervix involvement, lymph node involvement, adnexal involvement, and extrauterine involvement. Among all ML algorithms, LR model outperformed the other algorithms, with an AUC of 80% and an accuracy of 85% in the validation cohort. Further evaluation proved that the model was well-calibrated and showed satisfied clinical utility. Based on LR, an online calculator was created for enhancing the clinical interpretability. Conclusions: This model provides individualized estimates of risk of adnexa malignancy in patients with endometrial cancer, with all model inputs available at the time before the surgery. A prospective feasibility study will be needed prior to implementation in the clinic.