bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of serial serum chromogranin A (CGA) and CGA/PSA ratio and treatment response with abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Lewis Akeem Ronell , Costello Brian Addis , Quevedo Fernando , Pagliaro Lance C. , Weinshilboum Richard M. , Wang Leiwei , Kalari Krishna Rani , Kohli Manish , Tan Winston , Giridhar Karthik 
Published: June 2022

e17036 Background: Elevated serum CGA is associated with an intrinsic or treatment-related neuroendocrine differentiation in men with mCRPC. We previously demonstrated that elevated serum CGA was negatively associated with OS in men with mCRPC. Fluctuations in serum CGA during mCRPC therapy is not well known. We analyzed the impact of (i) rising serum CGA and (ii) baseline CGA/PSA ratio during treatment to identify associations with AA therapy. Methods: Between June 2013 and August 2015, 92 men with mCRPC were enrolled in a prospective trial (“PROMOTE”; NCT#01953640) with uniform serum processing performed prior to initiating abiraterone acetate/prednisone (AA/P) and serially after 12 weeks of AA/P treatments. Serum CGA was measured using a homogenous automated immunofluorescent assay. Patients (pts) receiving proton pump inhibitors or with abnormal renal function were excluded due to possible false elevations of serum CGA (n = 21 excluded). All patients underwent a composite response assessment at 12-weeks with imaging/PSA/QOL questionnaires. Kaplan Meier estimates, and Cox Regression models were used to calculate association with time-to-treatment failure (TTF) analyses, defined as time from treatment initiation to AA/P discontinuation based on disease progression (BlueSky Statistics, Chicago, IL, USA). Results: Of the 71 eligible pts, 67/71 had paired baseline and 12-week CGA and 70/71 pts had a baseline and a 12-week PSA available. The median baseline CGA was 83.0ng/ml (range: 53.0 - 127.0 ng/ml), median baseline PSA was 14.4 ng/ml (range: 6.4-40.2 ng/ml), and the median TTF was 10 months (range: 6-25 months). The median CGA after 12 weeks of AA/P was 98.0 ng/ml (58.0 -148.0 ng/ml) and we observed a CGA rise in 41/67 (61.2%) pts. An increase in chromogranin was associated with a lower risk of treatment failure (HR: 0.52, p = 0.0181). The median CGA/PSA ratio was 7.8 (2.6 -16.0). An elevated pretreatment CGA/PSA ratio above the median was associated with a lower risk of treatment failure (HR: 0.54 p value = 0.0185). Conclusions: We show that an increasing chromogranin on AA/P and an elevated baseline CGA/PSA in pts with mCRPC were associated with a favorable response to AA/P. Further studies are needed to assess if rising CGA during therapy reflects neuroendocrine differentiation and may indicate a sign of treatment effect targeting the androgen susceptible cells. Clinical trial information: NCT#01953640.
Survival benefit of postoperative adjuvant chemotherapy for patients in poor-differentiated early-stage cervical cancer: A multicenter, cohort study.
Authors: Lu Huaiwu , Xu Miaochun , Zhou Ying , Zhao Bingbing , Ren Fang , Wei Luwei , Chen Qing , Zhang Bingzhong , Lin Zhongqiu 
Published: June 2022

e17509 Background: Postoperative adjuvant therapy decisions for early-stage cervical cancer (ESCC) without high risk factor, including parametrial extension, positive nodes and positive margins, now depend on Sedlis criteria, which do not mention the degree of differentiation. In this study, we aimed to explore the benefit of adjuvant chemotherapy for patients of ESCC with poor differentiation but without positive Sedlis criteria after radical hysterectomy, and develop a score to predict the recurrence risk in these patients, so as to further improve the indications of postoperative adjuvant therapy for patients of ESCC. Methods: Patients of ESCC with pathologically proven poor differentiation after radical hysterectomy were prospectively included in a multicenter study. Univariate Cox proportional hazards regression were developed to evaluate the independent risk factors for recurrence. The log-rank test was performed to compare the progression-free survival (PFS) and overall survival (OS) of adjuvant chemotherapy (ACT) and no further treatment (NFT) groups. Selected variables were analyzed in a Multivariate Cox Regression Model and used to build a nomogram for ESCC to predict the survival probabilities. Results: In total, 352 patients were randomly assigned to two groups, a training group and a validation group, at a ratio of 1:1 (176 patients: 176 patients). In both of training and validation cohort, the ACT groups had longer PFS than the NFT groups ( P= 0.007 and 0.016, respectively), while the differences of OS were not statistically significant ( P= 0.922 and 0.107, respectively). In the multivariate analysis, ACT was proved an independent prognostic factor for the PFS (P = 0.048), and the strongest predictor of PFS even analyzing with other potential independent prognostic factors (HR 0.116, 95%CI 0.014-0.981). Five factors, including postoperative treatment, histologic type, isthmus uteri involvement, FIGO stage, SCCA level, were included in the nomogram to predict survival probabilities in the training cohort and performed well in the validation cohorts. Conclusions: For the patients of ESCC who don't meet to Sedlis criteria but with poor differentiation, ACT after radical hysterectomy can reduce the recurrence rate.
To conquer cervical and breast cancer in little charted waters: Synergistic and integrated approaches to identify early breast and cervical cancer in Cameroon.
Authors: Okwen Patrick Mbah , Mbangsi Maryanne Zithem , Okwen Kinlabel Tetamiyaka Tezok 
Published: June 2022

e17510 Background: Across Africa, several governments have put in place policies to promote prevention of cervical and breast cancers. (Njunguna 2020, Njiru 2013, WHO 2017) These include routine screening at consultations, sensitization programs, HPV vaccination programs, and creation of cancer treatment centers. However there still exists a policy to practice gap and clinicians do not routinely screen for cancers and sensitization messages are not reaching those who need it most. Therefore, on the one hand the clinicians are not supplying these services and the women who need the services are not demanding for them. Methods: We used existing guidance for cervical and breast cancer screening and treatment including local policies and ASCO guidelines. We screened 64 women in the Ntasen and Ntanka communities of Cameroon. We then used the results to create sensitization and education programmes for community members using culturally relevant approach of storytelling. Results: We reported 11 out of 64 positive cervical conditions (VIA pos = 8; VILI pos = 10; both VIA/VILI pos = 7) making a 17.2% prevalence. The median age for VIA/VILI positive was 35.5 years (Range 21-60 years). 3 out of 11 (27.3%) were HIV positive. We reported 4 out of 64 positive breast conditions (BIRADS 2 (2); BIRADS 3 (1); BIRADS 4 (1)). We reported 12 out of 64 STIs (gonorrhea (4); Syphilis (2); HPV (6)). Treatment could not be initiated for breast and cervical conditions due to lack of health technologies needed. Patients were therefore referred for treatment. All participants with gonorrhea and syphilis were immediately initiated treatment. Conclusions: Considering the high burden of disease from cervical and breast cancer in Cameroon, Africa, and LMIC, exploring cost effective approaches for screening like VIA/VILI will be helpful in reducing disease burden. However, access to low-cost health technologies to provide treatment for positive cases, use of culturally relevant approaches to sensitize communities to uptake these health technologies, inclusion of patient representatives in decision making, and capacity building for clinicians and community health workers for diagnosis and treatment are needed to complete the recipe for conquering cancers in LMIC. A combined approach of routinely screening for breast, cervical, and STIs is useful for integrating a common cause for these conditions.
Whole exome sequencing facilitated diagnosis of patients with multiple mucinous neoplasms of the female genital tract.
Authors: Zhang Fang , Shi Min , Zhao Na , Guo Peng , Hou Jun , Liu Yang 
Published: June 2022

e17513 Background: The differential diagnosis is challenging in clinical practice, especially among gastric-type AD of the cervix with ovarian metastases, multiple primary mucinous neoplasm in cervix and ovary, and synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT). Previous studies have revealed that next-generation sequencing might be a feasible tool in identifying the origin of tumor. Herein, whole exome sequencing (WES) was performed to distinguish patients with metastatic disease. Methods: WES analysis was performed on 28 tumors and 7 normal tissues derived from 8 patients. Each patient had one lesion of the cervix uteri. Most of them had lesions at other anatomical sites, including corpus uteri, ovary, oviduct, vermiform appendix and omentum. Mutations signatures and clonal evaluation inferred from single-nucleotide/copy number variants were explored. Results: Previous studies of multiple types of cancer have identified more than 40 single-base substitution (SBS) signatures. SBS3/6 referring to defective DNA mismatch repair and SBS10 reported in both uterus and colorectal AD were significantly enriched in this study. Next, we found no significant distribution of SBS3/6/10 among tumors at different anatomical sites. These findings indicate that primary cervical/ovarian AD with metastases other than multiple primary cancers was the predominant histology in 8 patients. The association of genomic alterations in POLE/ POLD1/HRR pathway with the distribution of SBS signatures was explored. SBS3 had a trend of significant distribution (p = 0.01) in four patients who had germline alterations in HRR pathway. Furthermore, SBS10 was significantly enriched (p = 0.009) in 2 patients with germline POLE/POLD1 alterations. Clonal evolution analyses revealed that 2 patients were identified as having SMMN-FGT, and other 6 patients had dominant clones in different tumors, which suggested a . Notably, besides the dominant clones and subclones, some tumors also exhibited extra independent clones, which might be the mixed histology of primary and metastatic tumor. In addition, we found the difference of overall survival in patients having gastric-type AD of the cervix with ovarian metastases and cervical AD patients with different FIGO stage disease based on SEER database data. Conclusions: Our study demonstrated that WES might be a feasible tool to distinguish patients having primary cervical AD with multiple metastases from those with multiple primary cancers of the female genital tract, which suggests that WES proved valuable in facilitating the diagnostic workup. A prospective, multi-center, large cohort study is needed to investigate the performance of WES in identifying the origin of tumors in patients with multiple tumors of the FGT.
Productivity losses under various second-line recurrent or metastatic cervical cancer treatment scenarios in the United States.
Authors: Ting Jie , Ayer Turgay , Dalgic Ozden Onur , Erdogan Melisa , Yaylali Emine , Chhatwal Jagpreet 
Published: June 2022

e17520 Background: Recent data showed that a substantial proportion of second-line (2L)-eligible recurrent or metastatic cervical cancer (r/mCC) patients do not receive therapy. Additionally, although higher direct medical costs has been demonstrated with increasing r/mCC disease severity, there is no data on the impact of 2L treatment choices on societal costs. This study aims to estimate productivity loss due to untreated r/mCC and reduction in productivity losses associated with various 2L therapy options in the United States. Methods: We simulated the natural history of r/mCC by developing a Markov model with three stages: progression-free (PF), progressive (P), and death (D) for the course of r/mCC patients (average age: 50 years) during 2L treatment. We considered four treatment scenarios for patients who progressed on 1L systemic therapy: no 2L therapy, chemotherapy, overall 2L treatments (including option of cytotoxic monotherapy, immunotherapy, or other combination therapies), and tisotumab vedotin (TV). The model was parameterized and calibrated to match the overall survival and progression-free survival reported in recent clinical studies. Productivity loss associated with each disease stage was estimated by time spent at each stage, activity performance rate, and annual market and non-market productivity. Model outcomes included cumulative time spent in each stage and per patient 1-year and 5-year productivity losses. Results: Within a 1-year period, patients spend an estimated 6.1 months in the P stage under the no 2L treatment scenario; 4.4 months in PF and 4.3 months in P under 2L chemotherapy; 4.4 months in PF and 4.8 months P under overall 2L treatments scenario; and 5.7 months in PF and 4.3 months in P under TV scenario. Per person 1-year productivity under no 2L therapy was between $11.7K-$16.8K. As compared with no 2L therapy, 1-year per-person productivity improved by $5K-$14.6K under chemotherapy, by $5.8K-$15.6K under overall 2L treatments, and by $7.3-$19.9K under TV. When extending to a 5-year horizon, the projected cumulative per patient productivity improvement relative to that of patients with no 2L therapy ranged by $9.2K-$20.7K under chemotherapy, by $12.9K-$25.3K under overall 2L treatments, and by $19K-$36.9K under TV. Conclusions: Societal costs of 2L r/mCC in terms of lost productivity is substantially less in patients receiving 2L treatment vs. no treatment, within a 1-year period of becoming eligible for 2L therapy. Among patients receiving treatment (chemotherapy only or overall 2L treatment), we projected that society still incurs potentially meaningful lost productivity, relative to being treated with TV. TV’s 2021 approval in 2L r/mCC offers additional treatment option for patients, and continued efforts should be directed toward providing more treatment options in this setting.
Patterns of care in Medicaid-enrollees with recurrent or metastatic cervical cancer.
Authors: Leath Charles A. , Nysenbaum Jessica , Fiori Anthony , Ting Jie , Zhang Jenny , Pauly Nathan 
Published: June 2022

e17525 Background: Cervical cancer remains a disease with high unmet need, and a large proportion of patients are insured through Medicaid (̃30%). Previous real-world studies demonstrated significant variability in treatments for recurrent or metastatic cervical cancer (r/mCC) patients following doublet chemotherapy ± bevacizumab, despite the 2018 approval of pembrolizumab in PD-L1+ r/mCC. As r/mCC treatment landscape continues to evolve, there is a need to understand current real-world unmet need among Medicaid r/mCC patients. This study aims to evaluate treatment patterns and healthcare resource utilization (HCRU) among Medicaid-insured r/mCC patients. Methods: This is a retrospective analysis of nationwide Medicaid claims to assess patient characteristics, treatment patterns, and HCRU among r/mCC patients between 2016-2019 (most recent Medicaid data available). First line treatment (1L) for r/mCC was identified as the first administration of systemic therapy without concomitant radiation or surgery. Patient characteristics, treatment patterns, and HCRU were characterized by line of therapy. Results: A total of 2,741 adult females initiated systemic treatment for r/mCC between 2016–2019, mean age was 52.8 (SD = 12.8), and most patients were enrolled in comprehensive managed care plans (58%). Over 41% (N = 1,145) had evidence of second line treatment (2L), with over one third (N = 385) of those also having evidence of third line treatment (3L). Consistent with treatment guidelines, the majority (61%) of 1L regimens were doublet chemotherapy ± bevacizumab. In contrast, no clear standard of care was observed among patients receiving 2L or 3L therapy. Notably, immunotherapy accounted for 22% of treatment regimens in 2L/3L overall, with its use increasing significantly over time (< 6% in 2016 to 41% in 2019; p-value < 0.001); however, despite availability of immunotherapy, most patients did not remain on treatment for a prolonged duration (immunotherapy median duration 2.2 months vs. 2.5 months for non-immunotherapy, p-value = 0.9). Across all HCRU measures (inpatient admissions, outpatient visits, emergency visits, and pharmacy claims), 2L/3L patients had less utilization per patient, compared with 1L patients. Conclusions: There was no clear standard of care for 2L+ r/mCC patients enrolled in Medicaid treated between 2016-2019. Although immunotherapy use is increasing, there is still high medical unmet need based on short durations of treatment and poor historical outcomes. New therapies should provide meaningful clinical benefit without significant increase in HCRU.
Inhibition of the mToR pathway with everolimus can modulate heat shock genes and ERCC1 gene expression and improves outcomes on serous ovarian cancer in HIPEC in vitro model.
Authors: Andrade Warne Pedro , Gonçalves Bryan Ôrtero Perez , Silva Luciana Maria , Peixoto Iago Oliveira , Andrade Tatiana Torres Lisboa , Silva-Filho Agnaldo Lopes da 
Published: June 2022

e17541 Background: Worldwide, epithelial ovarian cancer accounts for a significant percentage of malignancies and is the most lethal neoplasm of the gynecological system, mainly due to silent manifestation and late diagnosis. Predominantly, around 70% of newly diagnosed women with epithelial ovarian cancer have the locally advanced or metastatic stage (III/IV). The extensive peritoneal dissemination of epithelial ovarian cancer might occur at the time of primary tumor diagnosis or related to disease relapse after previous treatment. Therefore, understanding the dynamic of peritoneal dissemination is of utmost importance, as peritoneal carcinomatosis is frequently associated with disease morbidity and mortality. Methods: In this study, we cultivated ovarian cancer cells using the OV-90 cell line (high-grade serous) and assessed citoxicity using MTT assay. Initially, the ovarian cancer cells were treated with everolimus 18 nM (37˙C) for 24 hours for both experimental and control groups. Subsequently, two experimental groups were treated with cisplatin in normothermia (Group 1) and hyperthermia (Group 2) (37˙C and 41˙C, respectively) while the control group was treated with phosphate-buffered saline solution 1X at 37˙C (Group 3) and 41˙C (Group 4) for 24 hours. After the first treatment, we re-supplemented each group under the same beforementioned conditions and incubated it for three additional hours. Moreover, the RNA extracts of each sample set were submitted to RT-PCR for the obtention of the qRT-PCR material. Lastly, we compared the expression of the ERCC1 gene and heat shock genes amongst the different intervention groups. Results: There statistical difference concerning cytotoxicity between treatment with everolimus and heated cisplatin versus treatment with everolimus and cisplatin in normothermia. We observed that the ERCC1 and TRAP 1 genes were downregulated in OV-90 cell lines under heated conditions compared to the normothermia group. Conclusions: The use of everolimus in HIPEC in vitro model increases the cytotoxic response and suggest that inhibition of the mTOR pathway modulates the expression of heat shock genes e ERCC1 gene improving outcomes. Nevertheless, there is still a need for studies evaluating the effectiveness of everolimus in preclinical trials under hyperthermic conditions.
Anti-cancer effects of high-dose selenium via lipid peroxidation in ovarian cancer.
Authors: Choi Jung-A , Lee Elizabeth Hyeji , Kim Hyosun , Cho Hanbyoul , Kim Jae-Hoon 
Published: June 2022

e17547 Background: Selenium is an essential trace element and act as a regulator in the oxidation-reduction system. Selenium deficiency is observed in various cancers. Therefore, we investigated the relevance of high-dose selenium with the anticancer effect of ovarian cancer. Methods: We evaluated cytotoxicity and cell death by MTT assay and Annexin V-FITC/PI-labeled flow cytometry and biological function by invasion assay, ROS assay, immunoblotting, and FACS analysis. Using SKOV3-bearing xenograft mouse models, we evaluated the anti-cancer effect of high-dose selenium. Selenium toxicity was evaluated by the amount of ALT, AST, BUN and creatinine in the serum of C57BL/6 mice. Results: We observed that high-dose selenium, which was exposed to ovarian cancer cells, significantly increases the generation of reactive-species oxygen (ROS), leading to more significant cell death and cytotoxicity compared to low doses. We found that high-dose selenium triggers lipid peroxidation-mediated cell deaths and causes a reduction of glutathione peroxidase (GPX) systems. As a result of examining the lethal dose of selenium to the C57BL/6 nude mouse, it occurred in the concentration range of 3000 μg/Kg or more. SKOV3-bearing mouse models revealed the high-dose selenium administration (2000 μg/Kg) significantly reduced the ovarian tumor growth (p < 0.05). Moreover, we confirmed that high-dose selenium inhibited the expression of increased GPX in SKOV3-bearing mice. Conclusions: Our results suggest that high-dose selenium induces an anticancer effect through lipid peroxidation regulation according to the GPX redox system. Furthermore, we can suggest that chemotherapy based on high-dose selenium may have the effect of maximizing therapeutic efficacy and reducing anticancer drug resistance in ovarian cancer.
BRCA1/2 genes mutations frequency in patients with various histological types of ovarian cancer (data for South of Russia).
Authors: Timoshkina Natalya N. , Petrusenko Natalia A. , Gvaldin Dmitry Yu. , Gappoeva Madina A. , Kavitskiy Sergey E. , Cherkes Maria A. , Verenikina Ekaterina V. , Kutilin Denis S. 
Published: June 2022

e17548 Background: About 10-15% of malignant ovarian tumors (OC) are associated with hereditary diseases, and about 65-85% of hereditary OC have a mutation in BRCA1/2 genes. The aim of the study was to analyze BRCA1/2 genes hereditary mutation spectrum in patients in the South of Russia diagnosed with OC. Methods: We used EDTA venous blood and FFPE-blocks of 324 patients with histologically verified epithelial OC (T1-3cNx-1Mx-1, stage I-IV). BRCA1 gene mutations (185delAG, 300T > C, 2080delA, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT) and BRCA2 gene mutations (6174delT) were determined by real-time PCR. Results: The most common types of OC were poorly differentiated serous carcinoma (high degree of malignancy) - 75.6%, well-differentiated serous carcinoma (low degree of malignancy) - 13%, mucinous tumors - 2.8%, endometrioid tumors - 4.3%, clear cell adenocarcinomas - 4.3%. BRCA1/2 genes mutations were found in 52 (16%) patients with OC. The frequency of detected BRCA1/2 genes mutations was: 5382insC - 53.8%, 4153 delA - 9.6%, 300T > G - 21.2%, 2080delA - 7.7%, 185delAG - 3.8%, 6174delT - 3.8%. 3819delGTAAA and 3875delGTCT mutations were not found in the BRCA1 gene. All carriers were confirmed to have the same mutations in the tumor. There were no cases of sporadic changes in BRCA1/2. BRCA1 mutation carriers prevailed in the group of high-grade serous carcinoma patients (11.1%), where all cases of BRCA2 gene mutations were identified. In the group of low-grade serous carcinoma patients, the mutation rate was 1.5%, in the endometrioid adenocarcinomas group - 0.6%, in the mixed epithelial tumors group - 2.8%. In the group of patients with mucinous tumors, mutations were not detected. Conclusions: Thus, frequency of BRCA1/2 gene mutations in OC patients living in the South of Russia was 16.0%. Distribution of mutation types in the BRCA1 gene, with a predominance of 5382insC (53.8%) and 300T > G (21.2%), corresponded to their occurrence ratio in the European populations. BRCA1/2 gene mutations were registered more often in the group of high-grade serous carcinoma patients.