bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell analysis to study the longitudinal changes in systemic tumor immune environment in cervical cancer after radiochemotherapy.
Authors: Zhao Caining , Xu Zhiyuan , Zhang Yan , Ye Bin , Zheng Danyang , Yu Hao , Kong Feng-Ming Spring 
Published: June 2023

e17530 Background: Chemoradiation is the mainstay treatment for cervical cancer, which affects not only tumor immune microenvironment (TIME) but may also the systemic tumor immune microenvironment (STIE). Improved understanding of STIE beyond the tumor may enhance improving treatment strategies for cervical cancer. With these motivations, we applied single-cell RNA-sequencing (SCRNA-seq) to investigate longitudinal dynamics of a comprehensive set of immune cells in cervical cancer patients receiving chemoradiation (RCT). Methods: Two patients diagnosed with cervical squamous cell carcinoma at a locally advanced stage and received 45Gy/25f, with concurrent cisplatin, were enrolled. Peripheral blood was collected for SCRNA-seq using the 10× Genomics. Fresh blood samples were obtained at baseline 1-week, 2-week, 3-week, 5-week (end of external beam radiotherapy) and after Chemoradiation. Seurat 4.0 was used to cluster and annotate cell clusters. Results: A total of 90862 cells were clustered into 3 main subsets, including NK&T, B, and myeloid subsets. Then NK&T subset was extracted and further annotated into 10 clusters, including CD8+T naive, CD8+T effector, CD8+T effector memory, mucosal-associated invariant T (MAIT), cycling CD8+T, CD4Tem, CD4+T naive/central memory, regulatory T (Treg), natural killer (NK), and NKT cells. After plotting the dynamic changes of different cell types, MAIT and cycling CD8+T cell steadily increased with time or RT dose accumulation, suggesting that RCT could induce their proliferation. MAIT highly expressed CD69 and CXCR4 much like CD8+T effector memory cell, and cycling CD8+T cell expressed CX3CR1 like CD8+T effector cell. Besides, pseudotime analysis revealed that the differentiation process started from naive CD8+T cell towards cycling CD8+T cell passing through effector memory CD8+T cell, and effector CD8+T cell. In this process, the transcriptionally distinct MAIT cell belong to a different branch of the Pseudotime trajectory compared to the rest of the T cells, albeit mapping close to effector memory CD8+T cell, in line with their shared phenotypic identity. Enrichment was employed to explore their function and MAIT was enriched with genes involving cytokine-cytokine receptor interaction. Moreover, MAIT cell with increased antigen process and presentation function was note, and PD-1 checkpoint pathway was up-regulated during RCT. Conclusions: Chemoradiation induced the accumulation of MAIT cell which has increased antigen process and presentation features and cycling CD8+T cell with a higher PD-1 checkpoint pathway gene expression signature. Taken together, we provide insight into the peripheral immune remodeling induced by RCT, which will help optimize and improve treatment strategies for cervical cancer. Clinical trial information: NCT05061342 .
Start so young? Defense of the primary HPV test as a screening test for cervical cancer in women aged 25 and over in Brazil.
Authors: Costa Jose Iran , Telles O. Lima Jurema , Sales Mozart J. T. , Katz Leticia 
Published: June 2023

e17531 Background: Cervical cancer (CC) is the most frequent type of cancer on woman at reproductive age and on the puerperal pregnancy cycle in Brazil. It is a disease that can be prevented with the resources already available at Brazil’s public healthcare system.The most important risk factor for developing cervical cancer is infection with human papillomavirus (HPV). With the covid 19 pandemic, there was an advance in the possibility of carrying out an HPV test by PCR by through the government initiative "uterus is life" and we was asked what age should start the HPV test in the proposed screening organized. Methods: Descriptive, observational, cross sectional study Carried two cancer centers( using an adapted form, between 2020 2021 Sociodemographic data, cancer characteristics. Descriptive statistics were used to analyze the data and evaluation of secondary data from the ministry of health (DATASUS) This study was approved by the institution’s ethics committee. Recife, Brazil. Results: From 2021 -2022, 240 patients with CC mean age 50,48y (SD ± 13.8; range 24-87), 15, 8 % < 35 y, age of first sexual intercourse: mean age 16,7 (SD ± 3.2, range 11- 30) and 79,6 % < 18y. age of first pregnancy mean 18 (SD ± 6.54; range 12- 36) 77,4 % < 18 y.In the year 2019 of the number of patients undergoing treatment in the Brazilian public system (SUS), by age group, 14.076 patients <35 y (58%). $821,000 was spent in 2019 on anticancer chemotherapy for CC in women < 35 y. Conclusions: With a view to establishing an organized screening policy using the HPV test, considering the window of opportunity to diagnose the non-invasive cervical cancer stage, the onset of sexual activity and the age of first pregnancy among patients with invasive cervical cancer and the representativeness of patients with < 35 years undergoing treatment for advanced CC. The "Utero é Vida" initiative recommended starting the screening of the HPV test from the age of 25 y, in addition to intensifying vaccination coverage against HPV.
Homologous recombination deficiency (HRD) status and response to platinum-based chemotherapy and PARP inhibitors in Chinese patients with ovarian cancer.
Authors: Yuan Hua , Li Ning , Wu Lingying , Yao Hongwen 
Published: June 2023

e17533 Background: The association between platinum-based chemotherapy and PARPis response and HRD status in Chinese epithelial ovarian cancer patients has not been fully elucidated. Methods: We assessed homologous recombination deficiency (HRD) score using genomic scar analysis (GSA) algorithm of Beijing Genomics Institute (BGI) assay. The definitive HRD status were determined by combining HRD score tested with the BGI assay and homologous recombination repair (HRR) gene mutation status. We then tested the association of HRD with response to platinum-based chemotherapy and PARP inhibitors in Chinese patients with ovarian cancer. Results: In total, 209 patients with definitive HRD status were included: 66.0% (138 of 209) for HRD and 34.0% (71 of 209) for non-HRD. Patients with HRD tumors were more likely to have a larger tumor (73.9% vs 59.2%, P = 0.029), and less likely to receive neoadjuvant chemotherapy (48.6% vs 67.6%, P = 0.009). No differences were found between patients with HRD and non-HRD tumors in age at diagnosis, histology, stage, postoperative residual disease status. In the entire cohort, patients with HRD tumors were more likely to be platinum sensitive with a platinum-free interval (PFI) of > 6 months than those with non-HRD (79.6% vs 65.7%, P=0.030). Patients with HRD had a significantly better PFS and OS than patients with non-HRD in the entire study population (PFS: unadjusted HR = 0.54, 95% CI: 0.38–0.77, P = 0.001; and OS: unadjusted HR = 0.44, 95% CI: 0.26–0.75, P = 0.002). Multivariate analysis showed that patients with HRD was an independent predictor of increased PFS and OS (PFS: HR = 0.56, 95% CI: 0.39-0.82, P = 0.002; OS: HR = 0.50, 95% CI: 0.29-0.86, P = 0.012). In patients who received PARPis as first-line maintenance (n=55), the median duration of PARPis was 23.3 months (1.2-40.0 months) and 11.0 months (1.4-39.1 months) in HRD and non-HRD subgroup, respectively. Patients with HRD had a significantly better PFS than non-HRD patients (median PFS: NR vs 22.5 months, unadjusted HR = 0.39, 95% CI: 0.16-0.97, P = 0.035). Multivariate analysis showed that patients with HRD was an independent predictor of increased PFS (HR = 0.22, 95% CI: 0.07-0.68, P = 0.008). Conclusions: Patients with HRD tumors are more likely to respond to platinum-based chemotherapy and PARPis when compared with those who are non-HRD. HRD tumors associate with a better survival in Chinese ovarian cancer patient.
Diagnostic model of low-grade serous ovarian cancer and borderline serous ovarian tumor: Model development and validation based on radiomics.
Authors: Song Kun , Chen Zhongshao , Wang Fang , Han Jiamin 
Published: June 2023

e17534 Background: Evidence to date indicates that there is a close relationship between low-grade serous ovarian cancer (LGSOC) and serous borderline ovarian tumor, but there is a significant difference in prognosis. Preoperative imaging and clinical information to assess the nature of lesions as accurately as possible is beneficial to the surgical management of patients. Methods: A total of 104 patients who underwent CT examination and surgical treatment for pelvic masses in Qilu Hospital of Shandong University from 2013 to 2021 were included in the study, including 25 patients with low-grade serous ovarian cancer, 34 patients with serous borderline ovarian tumor, and 45 patients with serous cystadenoma. Quantitative image features were extracted from CT and combined with clinical information to construct a diagnostic model. The diagnostic performance was evaluated by ROC and AUC. Results: The diagnostic model was constructed by RFECV (recursive feature elimination and cross validation) together with SVM (support vector machine), random forest and XGBoost (eXtreme Gradient Boosting) algorithms, among which the RFECV combined random forest algorithm model showed the optimal accuracy (0.78) and AUC (0.92). Combined with clinical features, a new diagnostic model was constructed again by RFECV and random forest, and the accuracy (0.91) and AUC (0.96) were further improved. Conclusions: Through the combination of CT image-based radiomics and clinical features, the clinical diagnosis model was successfully constructed, which can accurately evaluate and predict the pathological types of patients, and is expected to be used in clinical practice and guide surgical decision-making.
Clinical remission rates in patients with epithelial ovarian cancer in the pandemic versus the pre-pandemic period.
Authors: Shammas Natalie , Mukherjee Amrita , Xu Lanfang , Cannavale Kimberly L. , Szamreta Elizabeth A. , Monberg Matthew , Hodeib Melissa , Chao Chun 
Published: June 2023

e17541 Background: The COVID-19 pandemic presented challenges for patients with ovarian cancer (OC). The objectives of this study were to compare patient remission outcomes following first-line treatment before and after the onset of the pandemic, and to evaluate potential racial/ethnic disparities in remission outcomes during the pandemic. Methods: This retrospective cohort study was conducted at Kaiser Permanente Southern California (KPSC), a large, integrated healthcare delivery system. Patients diagnosed with Stage I-IV epithelial ovarian cancer 01/01/2017-06/30/2021 were included. Pre and post pandemic periods were designated using 03/04/2020 as the cut-off. Data on cancer characteristics and treatment were obtained from KPSC’s electronic medical records. Chart review was conducted to collect data on complete and clinical remission (complete + partial remission) after first course of treatment. Imaging showing no evidence of disease and normal CA 125 values were used to define complete remission. Partial remission was defined as an incomplete response to therapy documented by the treating physician. Other variables included age and stage at diagnosis, race/ethnicity, Charlson’s comorbidity index, neighborhood deprivation index and prior membership. Modified Poisson regression with robust error variance was used to evaluate the association for the pandemic period and race/ethnicity with the remission outcomes. Results: Of 728 patients included, 531 and 197 patients were diagnosed in the pre-pandemic and pandemic periods, respectively. The distributions of the patients’ age, race, and stage were similar between the pre-pandemic and pandemic period. The cohort was racially/ethnically diverse: 46.0% White, 33.5% Hispanic, 7.4% Black, and 13.1% Asian. Complete remission was observed in 406 (76.5%) patients in the pre-pandemic period compared to 149 (75.6%) patients in the pandemic period (p=0.82). Clinical remission was observed in 473 (89.1%) patients in per-pandemic and 176 (89.34%) patients in pandemic period (p=0.92). No statistically significant associations were found between the remission outcomes and the pandemic in the adjusted models. Black patients had lower complete remission rates (but not lower clinical remission rates) compared to White patients in the pandemic period (p=0.06). Of note, Black patients had 67.6% complete remission rate in the pre-pandemic period whereas only 35.3% achieved complete remission in the pandemic period (p=0.01). However, the number of Black patients in the pandemic period was small (N=17). Conclusions: Overall, patients diagnosed with ovarian cancer achieved similar complete and clinical remission rates between the pre-pandemic and pandemic period. Complete remission varies across subgroups of patients. This finding needs to be further investigated with a larger sample.
Spatial profiling of ovarian clear cell carcinoma (OCCC) and identification of immune-hot features.
Authors: Tai Ya-Ting , Lin Wei-Chou , Wang Duncan Yi-Te , Ye Jieru , Tan Tuan Zea , Wei Lin-Hung , Huang Ruby Yun-Ju 
Published: June 2023

e17543 Background: OCCC is an ovarian cancer subtype with high incidence in Asia. Despite its frequent occurrence as an early-stage disease, optimal therapeutic options for high-risk patients are limited. Recently, immune-hot features have been proposed as an indicator for poor prognosis for early-stage OCCC. Specific patterns of intra-tumoral heterogeneity (ITH) associated with these immune-hot features have yet to be defined. Methods: Formalin-fixed paraffine embedded (FFPE) tumor sections from 10 early-stage primary OCCC patients were included. Digital Spatial Profiling (DSP) of 18 protein targets from the Human Protein Core Panel was conducted by using the nanoString GeoMx system to profile selected regions of interest (ROIs) based on the reference H&E staining morphology. Areas of illumination (AOIs) were defined according to ROI segmentation by the fluorescence signals of pan-cytokeratin (PanCK), CD45, or DNA. The digital signals were quantified by the nanoString nCounter system. Results: Unsupervised hierarchical clustering of 252 AOIs from 229 ROIs showed 5 distinct clusters. PanCK+ AOIs distributed in 5 clusters were found to express combinations of markers suggestive of immune mimicry: granzyme B (GZMB) high epithelial cells (C1-a), immune signal high epithelial cells (C1-b), immune-like cells (C1-c), fibronectin-high epithelial cells (C2-a), and signal-cold epithelial cells (C2-b). CD45+ AOIs were mostly clustered in C1-c. Tumor cells with C1-c and C2-a features were associated with recurrence while those in C1-a were associated with no recurrence (Chi-square p=2.8E-04). Tumor infiltrating immune cells (TIIs), which were found to be more enriched of the macrophage lineage (stronger CD68 expression, p=4.5E-03), were associated with recurrence (66.7% in recurrence vs 14.3% in no recurrence, Chi-Square p=0.098). TIIs appeared in PanCK segments of C1-b and C1-c with higher frequencies (45% in C1-b, 25% in C1-c, Chi-square p=0.046) and in PanCK segments of C1-a with extremely low frequency (0%). Correlating with morphology, tumors with recurrence showed higher frequency of papillary pattern (54.7%, Chi-Square p=1.01E-04) and lower frequency of tubulocystic pattern (18.9%, Chi-Square p=7.21E-03). Plus, TIIs were found with high frequency in ROIs with papillary pattern (65.2%, Chi-Square p=4.99E-04) and low frequency in ROIs with tubulocystic pattern (8.7%, Chi-Square p=6.43E-03). Papillary ROIs, which showed macrophage lineage immune mimicry, high CD68 intensity and low PanCK intensity, were found to have very low frequency of PanCK segments of C1-a (6.2%, Chi-Square p=1.26E-04), but extremely high frequency (100%) of PanCK segments of C1-c. Conclusions: Spatial profiling of early-stage OCCC tumors revealed immune-hot tumor features associated with recurrence. These features included immune mimicry of tumor cells, the presence of TIIs, and a papillary pattern in morphology.
A real-world study of US patients with metastatic ovarian, fallopian tube, and peritoneal cancer (mOFPC) using integrated electronic health records (EHR) and claims datasets.
Authors: P B Avinash , Funingana Gabriel , Singh Neeraj , George Rohini , Sowa Anna , Chakkrapani Sangavai , Priya Vandana , Vaidya Vivek Prabhakar , Vidal Laura , Saini Kamal S. , Agrawal Smita 
Published: June 2023

e17548 Background: Ovarian cancer is the most lethal gynecologic cancer. Detailed epidemiologic descriptions from a real-world database of a large population of ovarian and related cancer patients can provide insights into the characteristics, treatment patterns, and outcomes of these patients, and could serve as a useful benchmark while developing new therapies. Methods: This retrospective analysis uses the ConcertAI RWD360 dataset which is a real-world de-identified dataset of more than 6 million patients from across the United States derived from various EHR systems and integrated with a large administrative open claims dataset (>90% overlap). 60429 patients in this dataset had OFPC out which 12406 patients had metastatic cancer. We present here the key characteristics of this mOFPC cohort including histology, biomarkers and top treatment patterns. We also performed overall survival (OS), time to treatment discontinuation (TTD) and time to next treatment (TTNT) analyses starting from initiation of 1st line of therapy (LoT) for all patients who received systemic treatment after metastatic diagnosis (8308 patients). Results: The top 5 histologies and biomarkers tested in this mOFPC cohort are presented in Table. The median OS from start of 1st LoT for this cohort was 2.45 years. The median TTD and TTNT across all 1st line therapies were 2.5 months and 5.5 months respectively. Top 2 treatments given as 1st LoT after metastatic diagnosis are also presented in Table. Chemotherapy (cis/carboplatin + pacli/docetaxel) and chemotherapy + bevacizumab were the most common 1st LoTs and there was no difference in the OS of patients treated with these two LoTs. Conclusions: This study describes the characteristics of a large US real-world cohort of mOFPC patients. Here we have presented data on the overall cohort, but further analysis of outcomes stratified by treatment arms, biomarkers and histology can be performed to better inform best treatments for specific sub-cohorts. [Table: see text]
Genetic counseling referral frequency and attrition for newly diagnosed epithelial ovarian cancer at Grady Memorial Hospital from 2012-2022.
Authors: Wood Sarah Jeanne , Cao Yichun , Canning Madison , Vemuru Shalini , Paysour Jamie , Murphy Danielle , Liu Yuan , Meisel Jane Lowe 
Published: June 2023

e17549 Background: Ovarian cancer is the most lethal gynecologic cancer with roughly 20% of cases attributable to mutations in BRCA 1 or BRCA 2. In 2018, the SOLO-1 study, comparing PARPi to placebo in BRCA 1/2 mutated ovarian cancers following first-line chemotherapy showed an unprecedented 70% reduction in the hazard to progression or death. Consequently, in 2020, ASCO published a consensus statement recommending germline testing for all women with epithelial ovarian cancer. Currently, our understanding of the improvement, or lack thereof, in germline testing for ovarian cancers following these changes are not well described, and research is needed to determine the real-world frequency of and barriers to genetic testing. Methods: We retrospectively reviewed 115 patients’ charts with newly diagnosed ovarian cancer from 2012-2022 at Grady Memorial Hospital. An assessment of genetic testing was acquired, including genetic counseling referral frequency, attrition, somatic tumor testing, and mutated genes identified. Additional characteristics including age, race, histology, grade, and stage were obtained. Univariate association (Chi-square or Fisher’s exact test) was performed to correlate the above variables with germline testing. Results: Of 115 patients diagnosed with ovarian cancer from 2012–2022, 33% received a genetic counseling referral and 16.5% received an evaluation. Germline testing, in lieu of referral, was ordered by the physician in 20% of cases. Among patients who completed germline testing, a pathogenic mutation was found in 9.8% of patients. Patients who were ≤ 48 years old were more likely to be referred for genetic counseling (50% vs. 26.5%, p = 0.016), and those with earlier stage disease (stage 1 or 2 versus stage 3 or 4) were more likely to be referred for genetic counseling (46.5% vs. 25%, p = 0.018). There was a significant difference in those receiving genetic counseling referral pre and post October 2018 (when SOLO-1 was published) with 50% of patients being referred after October 2018 versus 18% of patient before referred prior (p = 0.005), and in 2021 (following the ASCO consensus statement), an impressive 63.6% of patients were referred with attrition rate of 54.5%. Conclusions: Our real-world data demonstrates improvement in germline testing for newly diagnosed ovarian cancers at our institution over the past decade, with significant increases in both genetic counseling referral and attrition since 2018. Despite these improvements, we continue to be deficient in testing patients who are older and with more advanced-stage disease, which may be due to the gravity of their presentation and prioritized focus of treatment initiation. System-wide changes, including the option of having genetic testing ordered by the oncologist in the clinic with genetic counseling performed after results are available, are being explored.