bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of BRCA mutation on metastasis-free survival in a localized/locoregional high-risk real-world prostate cancer population.
Authors: Brito Frances , Song Rebecca , Rajan Aditya , Shami Jessica , Barnicle Alan , Zhao Jimmy , Dow Jessica , Khosla Sajan , Roy David , Dempster Sara 
Published: June 2024

e17104 Background: Understanding the prognostic impact of BRCA mutation status across prostate cancer (PCa) patient segments is critical to deploying the right therapies at the right time in a patient’s journey. Prior studies have shown that germline BRCA mutations are associated with poorer outcomes in an all-risk localized PCa population. To examine whether this association extends to a high-risk PCa population with either somatic or germline BRCA mutations, we evaluate the prevalence and independent prognostic impact of BRCA mutations in a real-world (RW), high-risk, localized/locoregional PCa population. Methods: A retrospective study (2016-2023) was performed using a de-identified multimodal RW dataset of patients undergoing Tempus xT next-generation sequencing. Eligible patients had localized/locoregional PCa at primary diagnosis (pDx), were biopsied prior to metastatic diagnosis, received adjuvant radiotherapy and/or had a prostatectomy, and had an evaluable Gleason score (GS). Risk groups were categorized as low/intermediate (low/int)-risk (total GS <8) and high-risk (total GS ≥8). BRCA status was defined as BRCAm if the patient had a short variant that was predicted or known to be pathogenic or a copy number loss in BRCA1 or BRCA2 and BRCAwt if no mutation was detected. Median real-world metastasis-free survival (rwMFS), defined as time from primary intervention to first metastatic diagnosis, was estimated using Kaplan-Meier methods and stratified by combined BRCA status and risk group (BRCAm high-risk, BRCAm low/int-risk, BRCAwt high-risk, BRCAwt low/int-risk). To assess the independent prognostic value of BRCA status among all patients and within a high-risk subset, two multivariate Cox models were performed adjusting for risk group, age at pDx, baseline PSA, primary intervention type, and T and N stage at pDx. Results: Among 607 eligible patients, 67 (11%) had a BRCA mutation (11 germline, 27 somatic, 29 tumor/unknown). Median rwMFS was longest in the BRCAwt low/int-risk group (n=147) at 50 mos (95% CI: 41, NA), followed by the BRCAwt high-risk group (n=393) at 36 mos (95% CI: 31, 42), and the BRCAm high-risk group (n=61) at 22 mos (95% CI: 11, 45). Median rwMFS estimates in the BRCAm low/int-risk group were unreliable due to a small sample size (n=6). From the adjusted Cox model, BRCAm patients had higher risk of metastasis compared to BRCAwt patients in the all-risk group (HR=1.48, 95% CI: 1.06, 2.09) and in the high-risk subset (HR=1.50, 95% CI: 1.04, 2.17). Conclusions: Our findings show that BRCAm is independently prognostic of metastasis in a RW, localized/locoregional, high-risk PCa population. We identify high-risk BRCAm patients as a subgroup with significantly elevated risk of developing metastasis; clinical trials with targeted therapeutic intervention may be needed to address the clinical unmet need.
Efficacy and safety of envafolimab plus lenvatinib combined with etoposide in recurrent ovarian, peritoneal, and fallopian tube cancer: An open-label, single-arm study—The ENLEN-OC-001 study.
Authors: Yu Tianxiang , Ding Bo , Xu Jingyun , Liu Sicong , Shen Yang 
Published: June 2024

e17570 Background: Previous studies have shown that combination therapy of immune checkpoint inhibitors (ICIs) may demonstrate more satisfactory efficacy in patients with ovarian cancer compared to monotherapy. Envafolimab is the first globally approved subcutaneously administered PD-L1 monoclonal antibody, which means there is less hospitalization is required, providing the possibility of live-in care. We aim to assess the efficacy and safety of the combination therapy of envafolimab plus lenvatinib combined with etoposide in patients with platinum-resistant recurrent ovarian cancer. Methods: In this single-arm, open-label study, we recruit patients with platinum-resistant ovarian cancer at the Zhongda Hospital, Southeast University (China). The specific regimen consists of subcutaneous envafolimab at a dose of 400mg, oral lenvatinib (12mg per day for patients weighing ≥60kg; 8mg per day for patients weighing <60kg) once daily on a continuous basis, and oral etoposide at a dose of 50 mg once daily on days 1–14 of a 21-day cycle. Oral etoposide is administered for six to ten cycles. The treatment will continue until disease progression or adverse event. The primary endpoint is objective response rate (ORR) assessed by investigators according to RECIST 1.1 criteria. Disease control rate (DCR), duration of response (DoR), progression free survival (PFS), overall survival (OS) and safety are evaluated as secondary endpoints . Data are summarized by descriptive statistics; time-to event endpoints are analyzed using Kaplan-Meier method. Results: From Jun 18, 2022, to Oct 31, 2023, we screened 16 and enrolled 12 patients. At the data cutoff date (Nov 30, 2023), 5 (41.7%) patients had discontinued the study, and 7 (58.3%) patients remained on treatment. Median follow-up was 8.6 months (IQR: 3.3-17.7). Based on the data collected, Objective responses were achieved in 4 (36.3%; 95% CI 10.9–69.2) of 11 patients who had at least one post-baseline efficacy assessment. DCR was 81.8%( 95% CI 48.2–97.7) and median duration of response was 7.4 months (95% CI 4.2–NA). Median progression-free survival was 9 months (95% CI 5.5–NA) and median OS was not reached. The most common grade 3 or 4 adverse events were leukopenia (2 [16.7%]) and thrombocytopenia (2 [16.7%]). No serious adverse events and treatment-related deaths were recorded. Conclusions: The combination of envafolimab plus lenvatinib combined with etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant ovarian cancer. Clinical trial information: NCT05422183 .
Identification of prognostic indicators and markers of endometrial carcinoma based on shared metabolism-related genes in gynecological tumors.
Authors: Zheng Liuqing , Wang Yanwei , Wang Li , Meng Yiran 
Published: June 2024

e17589 Background: Aberrant metabolism is a major characteristic of cancer and it is important to determine whether there is a common metabolic genetic signature among gynecological cancers. Endometrial cancer, as one of the gynecological tumors, has shown increasing morbidity and mortality rates annually. Investigating shared metabolic molecular markers in gynecological tumors can enhance our understanding of endometrial cancer. Methods: Transcriptome data for gynecological tumors, including ovarian cancer (OV), endometrial cancer (UCEC) and cervical cancer (CESC) were obtained from The Cancer Genome Atlas database. Transcriptome data for normal cervix uteri, uterus and ovary tissues were downloaded from the Genotype-Tissue Expression Project. Metabolism-related gene sets were sourced from the Kyoto Encyclopedia of Genes and Genomes for subsequent analysis (KEGG) for subsequent analysis. Weighted gene co-expression network analysis (WGCNA) was employed to identify gene modules associated with OV, UCEC and CESC. The intersection of three cancer-related modules and metabolism-related gene sets yielded shared SMRGs (Shared Metabolism-Related Genes). UCEC samples were randomly divided into training set and testing set by caret R package in a 5:5 ratio. A risk model based on SMRGs, capable of predicting the overall survival (OS) of UCEC patients, was constructed using LASSO regression and Cox regression analyses. Results: A total of 463 genes were identified as sharing SMRGs through the intersection of modules. And 81 genes associated with OS was further selected by Univariate Cox regression analysis combined with expression and clinical data. Eventually, 8 genes (CYP11B1, SRD5A1, OTC, ACACB, ASS1, ALG3, PLA2G4F and POC1B-GALNT4) were screened out by LASSO regression analysis to construct the prognostic characteristics. The training set was divided into high and low-risk groups based on the computed risk threshold. Kaplan-Meier analysis demonstrated that patients in the low-risk group exhibited better prognosis. Similar differential survival results were observed in the testing and entire sets. Furthermore, analysis of immune and stromal infiltrates indicated increased infiltration of CD8+ T cells in the low-risk group, and PLA2G4F was identified as the core gene. The expression level of PLA2G4F increased with the progression of UCEC and was closely associated with various immune checkpoint factors, including CD48, HAVCR2, CD86, TIGIT, CTLA4 and BTLA. Conclusions: This study established a shared metabolism-related gene prognostic model applicable to gynecological cancers and analyzed its potential role in the treatment and prognosis assessment of endometrial cancer. Additionally, PLA2G4F was identified as a potential immune-related biomarker for UCEC patients.
Neoadjuvant immune checkpoint blockade in mismatch repair deficient endometrial cancer: An update on recurrence-free survival and correlative biomarkers.
Authors: de Bruyn Marco , Eerkens Anneke L. , Brummel Koen , Vledder Annegé , Paijens Sterre T. , Requesens Marta , Loiero Dominik , van Rooij Nienke , Plat Annechien , Haan Floris-Jan R. , Klok Patty , Church David , Wardenaar René , Foijer Floris , Koelzer Viktor , Bosse Tjalling , Bart Jos , Jalving Mathilde , Reyners An K.L , Nijman Hans 
Published: June 2024

e17593 Background: We recently reported 37.5% radiologic and 50% pathologic response rates in a phase I feasibility study of neoadjuvant pembrolizumab in 10 mismatch repair deficient (MMRd) endometrial cancer (EC). Based on the safety data and promising responses, a phase II study with extended neo-adjuvant treatment has been initiated. Here, we provide an update on the recurrence-free survival (RFS), and unique correlative clinicopathologic, genomic and immunologic biomarkers from the phase I trial. Methods: Tumor differentiation, (germline) mismatch repair status, immune cell distribution, presence of tertiary lymphoid structures (TLSs), T cell receptor (TCR) diversity and common driver mutations (TSO500) were analyzed. Patients were stratified by radiologic or major pathologic responses. RFS was determined from time of surgery. Results: Two recurrences have been observed in non-responding patients, with a median and longest disease-free survival of 17 and 26 months, respectively. Responding patients were characterized by dedifferentiated histology (grade 3), somatic MMRd, and a monoclonal T cell expansion, which was evaluable in the interim biopsy. Neither common driver mutations, nor variants of unknown significance from the TSO500 panel were related to response. Pre- and post-treatment T cell and B cell densities were not correlated with response, nor was the presence of TLS. Pembrolizumab-responsive T cell clones could be detected in peripheral blood prior to initiation of treatment, remained constant throughout treatment duration and were detected in post-treatment tumor-draining lymph nodes (TDLN). Conclusions: Neoadjuvant pembrolizumab is associated with monoclonal T cell expansion in responding patients, which can be evaluated using pipelle biopsy. Repeat assessment of TCR clonality during extended neoadjuvant treatment is currently being evaluated. Clinical trial information: NCT04262089 .
Demographics, pathologic characteristics, and pattern of recurrence of vulvar cancer at an academic hospital in South Africa: A 10-year retrospective review.
Authors: Sajo Adekunle Emmanuel , Mnisi Edwin , Visser Cathy , Bassa Sheynaz , Dreyer Greta 
Published: June 2024

e17602 Background: Vulvar cancer although uncommon, accounts for about 5% of all gynecologic malignancies. Globally, it accounted for over 45 000 new cases and 17 000 deaths in the Globocan 2020 cancer estimates with an age-standardized rate (ASR) for incidence and mortality of 0.9 and 0.3 respectively. Vulvar cancer shares common risk factors with cervical cancer and over 90% of these are squamous cell carcinoma. In Africa, there is paucity of data on the true prevalence and recurrent rate of vulvar cancer albeit due to its rarity or poor record keeping. The current study aimed to describe the demographics, pathological characteristics and recurrence pattern of vulvar cancer at a single academic institution in South Africa. Methods: This was a retrospective descriptive observational study of vulvar cancer cases at the Gynaecologic Oncology Unit of Steve Biko Academic Hospital, Pretoria between 1st January 2012 and 31st December 2021. Data was extracted from the participants medical records on the demographics, medical history, site of tumour, disease stage, histologic characteristic and disease recurrence. The 2009 FIGO staging was used to classify the disease stage. Results: A total of 317 patients were included for analysis. The mean age was 45±12 yrs (range: 12-87). Majority were below 50yrs (71.9%) while 28.1% were 50yrs and above, 77.9% were HIV positive (median CD4 count was 428 cells/mm3, IQR= 277-662), 19.2% were HIV negative while the HIV status of 2.9% were unknown. The mean hemoglobin level at presentation was 10.7 ± 2.4g/dl. The average interval between biopsy at local clinic and presentation at the gynaecologic oncology clinic was 80days. The average number of patients seen was 31.7 per year. The majority, 79.1%, had tumours >4cm. Only about 45% of the patients had multifocal lesions. The left vulvar was significantly more affected than the right, 57.3%, (p 0.001). The anus was the most frequent contiguous structure involved in vulvar cancer, 47.5%. Squamous cell carcinoma was diagnosed in 96.5% of the participants and the most common histological grade was grade 2, at 69.9%. A large proportion of the participants,63%, presented in advanced stage (Stage 3 & 4). The mean follow up period was 23.1±26 months. The recurrence rate was 16.4%, of which 49% were local recurrence, 10.2% occurred in the groin, 22.5% involved the local and groin sites together, and 18.3% occurred at distant sites. Conclusions: Our data showed that the demographic characteristics of local patients with vulvar cancer are different from those in the developed world. The high recurrence rate might be due to the advanced disease at presentation of the majority of the patients.
Gynecologic malignancies in women younger than 40 years of age: A SEER database review.
Authors: Shah Princy , Kela Kashyap , Hegde Upendra P. 
Published: June 2024

e17605 Background: Gynecologic malignancies are one of the most common types of cancers in women, but their Epidemiology in young women is not widely known. Here we present the demographics and comparison between uterine, cervical, ovarian, vagina, and vulvar cancers in women under age 40 years based on the Surveillance, Epidemiology, and End Results (SEER) database analysis. Methods: Information was collected from the SEER database November 2022 with the data from years 2000-2020 containing 17 registries. Site recode ICD O-3/WHO 2008 Female Genital system was applied and Primary sites labeled 51.8 to 56.9 were selected. Patient population with only one primary site of Malignancy was included, and the cases with No specific sites were excluded. Age recode 0-39 years was applied. Variables of Age group, Race, Ethnicity, Median household income, Areas of residence & survival months were selected. Data was extracted for a total of 34056 patients. The Chi-square test was used for statistical analysis. P value <0.05 was considered significant. Results: The most common site of Gynecologic cancer was Cervix (50.4%) followed by Uterus (24.2%) and Ovary (23%). Vulvar(1.9%) and Vaginal (0.6%) cancers were the rarest. Squamous cell carcinoma was the most common histology for cervical (42.9%), vaginal (26%), Vulvar (51%) cancer versus Endometrioid histology for uterine (69.2%) and teratoma for ovarian (12.5%) cancer. The most common age group affected was 34-39 (44.1%) with decreasing frequency with younger age. 30.5% of participants belonged to 30-34 years of age. A total of 14 cases were noted in patients less than 1 year of age with most cases of vaginal and ovarian cancer. Non-Hispanic whites had the highest occurrence (48.8%) followed by Hispanics (28.4%), Blacks (10.7 %), Asian/Pacific Islanders (9.7%), and Alaskan/American natives (1.2%). Compared to high household income, patients with lower household income of <75,000 US dollars (USD) comprised of 61.9% of total Gynecologic malignancies. 89% of the total cases were observed in Metropolitan cities versus non-metropolitan areas. 5-year survival rate was observed at 57% overall. Vulvar cancer had the highest survival rate of 60.1% followed by Uterine (57.9%), Vaginal (57.1%), Cervix (56.1%), and Ovarian (56%) cancer. Conclusions: Early onset Gynecologic malignancies are more common in non-Hispanic whites, in Median Household income <75,000 USD, and in Metropolitan cities. Incidence increases with age. Vulvar cancer has the best 5 years survival and Ovarian has the worst one. Cervical cancer (50.4% of total cases) screening should be continued as per current guidelines. However, with Uterine and Ovarian cancers collectively contributing to close to half the Gynecologic malignancies, Practitioners should maintain high clinical suspicion to have appropriate individualized workups based on Risk Factors for early Diagnosis and Management of these cancers in this age group.
CYP11A1 inhibitor MK-5684 versus next-generation hormonal agent (NHA) switch in patients with metastatic castration-resistant prostate cancer (mCRPC) after NHA and taxane-based chemotherapy: Phase 3 MK-5684-003 trial.
Authors: Yu Evan Y. , Song Yue , Poehlein Christian Heinrich , Schloss Charles , Antonarakis Emmanuel S. 
Published: June 2024

TPS5113 Background: Androgen receptor (AR) signaling remains a key driver of prostate cancer even after progression on androgen-directed therapies. Activating AR ligand binding domain (AR-LBD) somatic point mutations are a common mechanism of resistance to androgen-directed therapies in patients with mCRPC. MK-5684 (ODM-208) is an oral, nonsteroidal inhibitor of cytochrome P450 11A1 (CYP11A1), which catalyzes the first and rate-limiting step of steroid biosynthesis. Inhibition of CYP11A1 by MK-5684 suppresses the production of all steroid hormones and their precursors that may promiscuously activate the AR signaling pathway. In the phase 1/2 CYPIDES trial, MK-5684 showed antitumor activity in patients with heavily pretreated mCRPC, especially in those with AR-LBD mutations. The randomized, open-label, phase 3 MK-5684-003 trial (NCT06136624) is evaluating the efficacy and safety of MK-5684 versus NHA switch in patients with mCRPC previously treated with NHA and taxane-based chemotherapy. Methods: Eligible patients havemCRPC (unselected for AR-LBD mutations) that progressed on androgen deprivation therapy ≤6 months before screening and during or after treatment with 1 NHA for nonmetastatic (nm) hormone-sensitive prostate cancer (HSPC), nmCRPC, mHSPC, or mCRPC for ≥8 weeks (≥14 weeks with bone progression), and also progressed during or after 1 or 2 taxane-based chemotherapies for mCRPC. Approximately 1200 patients (300 with and 900 without AR-LBD mutations) will be randomly assigned 1:1 to receive MK-5684 5 mg PO BID (+ dexamethasone 1.5 mg and fludrocortisone 0.1 mg QD) or enzalutamide 160 mg PO QD (if prior abiraterone) or abiraterone acetate 1000 mg PO QD (+ prednisone 5 mg BID; if prior enzalutamide/darolutamide/apalutamide). Randomization to treatment will be stratified by measurable disease (yes/no), disease AR-LBD mutation status (positive/negative), and prior cabazitaxel use (yes/no). Treatment will continue until radiographic disease progression (verified per Prostate Cancer Working Group 3 [PCWG3]–modified RECIST v1.1 by blinded independent central review [BICR]), unacceptable toxicity, or other discontinuation criteria are met. Tumor assessments will be performed every 8 weeks up to week 24, then every 12 weeks thereafter. Dual primary end points are radiographic PFS (per PCWG3-modified RECIST v1.1 by BICR) and OS in patients with AR-LBD mutation-positive and -negative disease, separately. Secondary end points include time to initiation of first subsequent anticancer therapy or death; ORR and DOR per PCWG3-modified RECIST v1.1 by BICR; time to pain progression; time to prostate-specific antigen progression; time to first symptomatic skeletal-related event; and safety and tolerability. Enrollment is ongoing. Clinical trial information: NCT06136624 .
Review of contemporary sewage sludge treatment and management methods in European countries with an emphasis on Greece
Authors: ELEFTHERIADOU AIKATERINI , Akratos Christos , Vavatsikos Athanasios , Gratziou Maria Evridiki 
Published: June 2024

Municipal sewage sludge is an acute problem in both developed and developing countries. Researchers are conducting many experiments to solve this problem. There are many methods of disposal, neutralization, or reuse of sediments after neutralization. The review of contemporary sewage sludge treatment and management methods in European countries with an emphasis on Greece will provide more information about the most appropriate choice for the use of sewage sludge in Greece.
The difficulties associated with adapting sewage sludge management to the requirements of sustainable development are discussed. The article draws information from the publication of Official Gazette 2692/B/21-04-2023 as well as the projects currently implemented in Greece regarding the treatment of sludge in Urban Wastewater Treatment Units. The forecasts and directions of processing sewage sludge in Greece are also investigated, through the inspection of the commitments and forecasts of the National Waste Management Plan 2015, compared to the new/ updated National Waste Management Plan of 2020.
In Greece after the introduction of the project "Treatment and purification of urban wastewater in environmentally sensitive settlements and modernization of facilities" of the Recovery and Resilience Fund from 17/01/2023, there is a growing trend towards thermal treatment of sludge using drying methods (solar etc. etc.) which by 2025 will have reformed the facts of the disposal of treated sludge in Greece. However, the examination of the issue of managing the sludge produced by municipal urban waste treatment units and the choice of the appropriate strategy for the management of urban sewage sludge remains a complex problem.
The impact of physical exertion on the level of back pain
Authors: Kamińska Natalia , Perkowski Radosław 
Published: June 2024

Introduction: Physical activity is an inherent factor in a healthy lifestyle. Regular exercise allows you to maintain fitness with age and allows for proper functioning of everyday life. The aim of the study was to assess the impact of physical effort on the level of back pain.
Materials and methods: The study involved 113 people who were assigned to one of two groups using online surveys, taking into account the level of physical activity. The occurrence of pain was assessed on the basis of the author's questionnaire and Oswestry questionnaire.
Results: The subjects from group 2 do not undertake regular physical exercise and more often indicated the occurrence of spine pain. Group 1 showed a statistically significant lower risk of pain than group 2. On the basis of the Oswestry questionnaire, group 2 people are significantly more likely to be less able to perform daily activities than group 1 people.
Conclusions: In people undertaking regular physical exercise, less reported pain and lower risk of their occurrence compared to group 2. The group of non-training people show less ability to perform daily activities due to pain.