bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical hair relaxer use and its potential effect on incidence of endometrial cancer in Black women.
Authors: Hedin Tosha , Haider Mahvish 
Published: June 2024

e17591 Background: Research is being conducted to determine chemical hair relaxer’s effects on women’s risk of endometrial cancer (EC). Recent studies have suggested that frequent use (>4 times/year) of chemical relaxers increases incidence of EC by a hazard ratio of 2.55. Black women purchase 60% of chemical straighteners in the United States while being 6.5% of the population. Hair relaxer can be made from sodium hydroxide, lithium hydroxide, or potassium hydroxide. These chemicals can cause a hormone imbalance with estrogen, leading to increased endometrial cancer incidence. This study aims to correlate population data of endometrial cancer and hair relaxer to explain the increased incidence of gynecologic cancer in Black women. Methods: The average rate of incidence per 100,00 per year for endometrial cancer for White and Black women were obtained from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program SEER*Stat Database: NPCR and SEER Incidence – U.S. Cancer Statistics 2001–2019 Public Use Research Database. Chemical relaxer was first commercially available in 1971. The average age of endometrial cancer diagnosis was obtained from the National Cancer Institute. Results: Nineteen years of data was collected from the SEER database. EC had 222,464 cases total. In the year 2001, EC incidence was most common in White women at a rate of 25 per 100,000. Black women were second, at a rate of 20 per 100,000. In 2017, Black women surpassed White women for most incidence with a rate of 28, in comparison to White women's rate of 27.5 per 100,000. In the year 2019, Black women increased to the rate of 29 per 100,000, which was greater than White women's rate at 27.6 per 100,000. Conclusions: Studies have shown that ever use of hair relaxer in the past 12 months is associated with higher incidence of EC. The hazard ratio increases to 2.55 when hair relaxer is used 4 or more times per year. The National Cancer Institute states that the average age to be diagnosed with EC is 60 years old for all races of women. Because hair relaxer was made commercially available in 1971, the year 2017 would be when women at the average age of diagnosis would have access to hair relaxer their entire lives. 2017 is also the year when Black women became the racial group with the highest incidence of EC in the United States. Hair relaxer could be an important variable as to why EC incidence in Black women has surpassed White women. In the future, this information could be used to risk stratify women for cancer surveillance or have warning labels placed on hair relaxer boxes.
Assessment of sociodemographic factors in timely endometrial cancer diagnosis following an abnormal transvaginal ultrasound performed for postmenopausal bleeding.
Authors: Atkins Sage , Nolin Angela , Unnithan Shakthi , Myers Evan R. , Moss Haley , Erkanli Alaattin , Havrilesky Laura J. 
Published: June 2024

e17595 Background: Postmenopausal bleeding (PMB) is the most common initial presentation of endometrial cancer. The American College of Obstetrics and Gynecology recommends evaluation of PMB with transvaginal ultrasound (TVUS) to determine the endometrial stripe (ES) thickness, followed by tissue sampling if ES >4 mm. We assessed if differences in race, ethnicity, language, or insurance status were associated with delayed endometrial sampling following an abnormal ES on TVUS, and if the timing of endometrial sampling after TVUS was associated with differences in rates of endometrial cancer diagnosis and staging. Methods: We conducted a retrospective study of consecutive patients with an intact uterus and PMB who presented to a single academic institution and underwent TVUS between January 2013-December 2022. TVUS was characterized as normal (ES ≤4 mm), abnormal (ES >4 mm), or inadequate (ES not fully visualized). Prompt sampling was defined as sampling with endometrial pathology within 3 months of abnormal TVUS. Logistic regression analyses were performed to characterize associations between race, ethnicity, preferred language, insurance status and prompt endometrial sampling. We assessed rates of endometrial cancer diagnosis and stage at diagnosis, comparing sampling at ≤3 versus 3-12 months after TVUS. Results: Among 3,369 patients meeting inclusion criteria, 1,671 (50%) had abnormal ES. Out of the total cohort, patients with an abnormal ES comprised 576/1336 (43%) of Black or African American and 946/1889 (50%) of White patients. 307/1671 (18%) of patients with abnormal ES did not receive prompt sampling. Neither race (Black OR 1.03, 95% CI 0.79-1.35 vs White), ethnicity, (Hispanic OR 1.1, 95% CI 0.54-2.27 vs. non-Hispanic), non-English primary/preferred language (OR 0.9, 95% CI 0.47-1.71 vs English), nor Medicare insurance status (OR 0.96, 95% CI 0.65-1.42 vs private insurance, age-adjusted) were associated with prompt endometrial sampling after abnormal ES. Endometrial cancer was diagnosed in 147/1227 (12%) of cases who underwent sampling for abnormal ES (143/1165 (12%) with prompt sampling and 4/62 (6%) with delayed sampling). The stage distribution of endometrial cancers diagnosed after prompt sampling was 107/133 (80%) Stage I and 26/133 (20%) stage II-IV, compared to 2/4 (50%) stage IA and 2/4 (50%) stage II-IV after delayed sampling. Conclusions: One in five patients with PMB and an abnormal appearing endometrium on ultrasound did not receive appropriate sampling within 3 months. Race, ethnicity, language, and insurance status were not associated with timely receipt of endometrial sampling following an abnormal ultrasound. With prompt endometrial sampling for abnormal TVUS, 80% of endometrial cancers are diagnosed at the earliest stage.
Development and validation of a prediction model for lymph node metastasis based on molecular classification in endometrial carcinoma.
Authors: Han Qiuyue , Jiang Quanhong , Xu Jiaqi , Zhang Yuan , Li Li , Kong Beihua , Song Kun , Bu Hualei , Dong Ruifen 
Published: June 2024

e17599 Background: The aim of this study is to develop a robust preoperative model using molecular classification to accurately predict the likelihood of occult lymph node metastasis (LNM) in patients diagnosed with early-stage endometrial cancer (EC). Such a model could help guide surgeons in choosing between systematic lymph node dissection and sentinel lymph node biopsy. Methods: Patients with clinically early-stage EC were included from Qilu Hospital of Shandong University between January 2010 and December 2017. Univariate and multivariate analyses was performed to identify the risk factors associated with occult LNM. Different machine learning (ML) algorithm models were applied to construct several prediction models, based on factors screened by the least absolute shrinkage and selection operator (LASSO). These models were evaluated by the receiver operating characteristic (ROC) derived area under the curve (AUC) values and the optimal model was established to build the nomogram. Bootstrap was used to validate of this model. The AUC, decision-curve analysis, clinical impact curves and interpretability metrics were used to determine the clinical net benefit of the model. Furthermore, risk stratification of EC patients was created based on the nomogram's threshold values. Results: Out of 363 patients with early-stage EC, 35 (9.1%) presented with LNM. Serum carbohydrate antigen 125 (CA125) and depth of myometrial invasion were independent predictive factors of LNM. An optimal ML model based on logistic regression (AUC: 0.744) was established to predict the occult LNM, including five factors screened by LASSO and they are CA125, neutrophil-to-lymphocyte ratio (NLR), histological subtype, depth of myometrial invasion and molecular classification. This model displayed good discrimination ability (AUC: 0.843) and calibration ability. Conclusions: This new preoperative LNM prediction model based on molecular classification can precisely indicate the probability of LNM in patients with early-stage EC, which could provide recommendations for the treatment of systematic lymph node dissection and sentinel lymph node biopsy based on risk stratification.
Vulvo-vaginal cancer trends during the pandemic.
Authors: Stewart Chelsea , Chan Joshua Elbridge , Tran Nathan , Johnson Caitlin Ruth , Darcy Kathleen M. , Tian Chunqiao , Kapp Daniel Stuart , Liao Cheng-I 
Published: June 2024

e17609 Background: During the COVID-19 pandemic, many patients in the United States experienced access-to-care issues. We hypothesized this may have disrupted recent trends in incidence for diseases such as vulvar and vaginal carcinoma often identified on physical exam and biopsy. In this study, we aimed to evaluate the impact of the COVID-19 pandemic on vulvar and vaginal carcinoma incidence based on age and race. Methods: Data on cancer incidence were obtained from the United States Cancer Statistics program. We employed SEER*Stat 8.4.1.2 and Joinpoint regression program 5.0.2. We compared actual vulvar and vaginal squamous cell carcinoma incidence rates in the year 2020 to estimated rates based on trends from the years 2001-2019. Results: From 2001-2020, 69,114 cases of vulvar carcinoma and 15,419 cases of vaginal carcinoma were identified. In 2019, the incidence rate was 2.14 and 0.44 per 100,000 people for vulvar and vaginal cancer, respectively. Using data from 2001-2019, there was a 1.19% increase per year in vulvar cases per year (p<0.001), while vaginal cases remained stable (average annual percent change -0.24%, p=0.179). Based on the trend noted in vulvar SCC, we expected incidence of vulvar SCC to be 2.19 per 100,000 patients in 2020, however, the reported 2020 incidence was 1.99 per 100,000. Based on these calculations, there were 9.03% fewer vulvar cases (n=246) in 2020 than expected. Assuming vaginal incidence rates remained stable, there were 9.34% fewer vaginal cases (n=70) in 2020 than expected. Based on race, non-Hispanic Asian and Pacific Islander patients experienced the largest proportional difference in actual vs expected cases of vulvar cancer, with the actual 2020 case numbers being 38% fewer (n=23) than expected based on trends. For vaginal cancer, the largest proportional difference in actual vs expected cases was among Hispanic patients, with the actual 2020 case numbers being 24% fewer than expected (n=32). Conclusions: During the 2020 COVID-19 pandemic, the incidence of vulvo-vaginal cancers was less than expected given the established trends, particularly in NHAPI and Hispanic patients. Further research is warranted to better determine if the above-described gaps were from delayed diagnosis due to access of care or other causes.
PRadR: PSMA targeted radionuclide therapy in adult patients with metastatic clear cell renal cancer, a multicentric phase I/II.
Authors: Vinceneux Armelle , Bidaux Anne-Sophie , Cropet Claire , Tatu Delphine , Bernardin Mathilde , Neymarc Séverine , Pérol David , Pouget Jean-Pierre , Constanzo Julie , Foray Nicolas , Djaileb Loic , Kelly Antony , Kryza David , Giraudet Anne-Laure 
Published: June 2024

TPS4608 Background: Prostate Specific Membrane Antigen (PSMA) is highly expressed in neovessels of various solid tumors including Renal Cell Carcinoma, especially clear cell (ccRCC), which is the most frequent sub type. In ccRCC, PSMA expression in tumor vessels is correlated with higher grade and stage as well as in match between primary tumor and metastasis. PSMA may be a target expressed in metastatic ccRCC for radionuclide therapy using PSMA Ligands Radiolabeled with Lutetium-177 (PRLT), which is already used in daily practice for prostate cancer. 177Lu-PSMA in prostate cancer with renal impairment appeared to be feasible and tolerable in previous studies. The aim of this Phase I/II study NCT06059014 is to assess the safety and clinical activity of this new Radiolabelled Therapy for mccRCC. Methods: PRadR is a multicentric, single-arm, open-label Phase I/II study evaluating PSMA targeted radionuclide therapy in adult patients with mccRCC. Patients must have received at least 2 prior regimens, including immunotherapy and antiangiogenic agents as per international guidelines, ECOG 0 to 1, with adequate hematologic, hepatic and renal function with a creatinine clearance according to CKD-EPI ≥ 40 mL/min/1.73m2. Only patients with tumor tracer uptake greater than background will be treated with 4 cycles of 7.4 GBq of 177Lu-PSMA-1 every 6 weeks. The primary endpoints are the incidence of severe toxicity (Safety run in) and the disease control rate at 24 weeks (DCR-24W) as per RECIST V1.1 (Phase II) in patients with a PSMA-positive mccRCC selected through 68Ga-PSMA PET. Secondary endpoints include overall response rate, duration of response, progression free survival, overall survival and safety according to NCI-CTCAE V5.0. During the safety run in, if more than one patient experiences severe toxicity during the first cycle over the first 6 treated patients, then a lower activity of 177Lu-PSMA-1 will be evaluated in an additional cohort of 6 patients (5.9 GBq). Using a Fleming-A’Hern single stage design with a target DCR24w of 30% and an inefficacy bound of 10% (α=5% one sided and 90% power) a total of 33 evaluable patients are required. If at least 7 successes (CR, PR or SD) at 24 weeks of treatment are observed, 177Lu-PSMA-1 will deserve further investigation in this setting. Translational studies will consist in comparing efficacy and toxicity to dosimetry of 177Lu-PSMA-1 in normal tissues and tumor lesions, and biomarkers obtained from blood samples or tumor tissues. First patient was enrolled in November 2023. Clinical trial information: NCT06059014 .
Adjuvant or rescue disitamab vedotin (RC48-ADC) for high-risk non-muscle invasive bladder cancer with HER2 overexpression: A phase II multi-center study.
Authors: Chen Junru , Liu Haoyang , Zhu Qiyu , Xu Chenhao , Wei Qiang , Liu Jiyan , Liu Zhenhua , Shen Pengfei , Bao Yige , Zhang Peng , Liao Banghua , Yao Jin , Chen Ni , Wu Kaijie , Liu Xiaodong , Zeng Hao 
Published: June 2024

TPS4625 Background: Non-muscle invasive bladder cancer (NMIBC) comprises approximately three-quarters of newly diagnosed cases of bladder cancer. Based on the risk of disease progression, NMIBC is categorized into low, intermediate, and high risk, with high-risk NMIBC patients facing a 5-year disease progression rate of up to 40%. The current standard treatment for high-risk NMIBC involves transurethral resection of the bladder tumor (TURBT) combined with intravesical Bacillus Calmette-Guérin (BCG) instillation as adjuvant therapy. In cases of BCG instillation treatment failure, the standard approach is radical cystectomy. Multiple studies have reported HER2 positivity in 20-44% of NMIBC cases, and HER2 overexpression (immunohistochemistry ≥2+) is closely linked to the progression and adverse prognosis of bladder cancer. Consequently, HER2 may serve as a novel therapeutic target for bladder cancer. Disitamab Vedotin (DV; RC48-ADC) is an antibody-drug conjugate (ADC) comprising a fully humanized HER2-directed monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a protease-cleavable mc-vc linker. Results from a Phase II clinical trial (NCT03507166) suggest that Disitamab Vedotin exhibits favorable efficacy and safety in HER2-positive metastatic urothelial carcinoma patients who have previously failed chemotherapy. This clinical trial aims to investigate the efficacy and safety of RC48-ADC as adjuvant or rescue therapy for high-risk NMIBC with HER2 overexpression and to explore molecular biomarkers predicting the efficacy of RC48-ADC. Methods: This multicenter, Phase II clinical trial will enroll two cohorts: Cohort A, consisting of 52 patients undergoing first-line adjuvant therapy, and Cohort B, with 25 patients receiving rescue therapy after BCG instillation failure, both exhibiting HER2 overexpression in high-risk NMIBC. Following the Simon two-stage optimal design, the first stage will involve enrolling 19 patients in Cohort A and 12 patients in Cohort B. After safety and baseline assessments, both cohorts will undergo six cycles of treatment with RC48-ADC (120 mg intravenous infusion every two weeks), totaling 12 weeks of treatment. Primary endpoints include safety, 12-month recurrence-free rate (Cohort A), and 3-month clinical complete response rate (Cohort B). Secondary endpoints encompass the 6-month recurrence-free rate (Cohort A), duration of response (Cohort B), recurrence-free survival, progression-free survival, overall survival, and quality of life (assessed through eEuroQoL EQ-5D and FACT-BI). Additionally, exploratory endpoints will investigate the relationship between biomarkers in tumor tissues, blood, and urine, and treatment efficacy. Clinical trial information: NCT05996952 .
A phase 1/2 study of EG-70 (detalimogene voraplasmid) intravesical monotherapy for patients with BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ.
Authors: Bryce Richard , Tosone Christine , Sullivan James C. , Linback Tammy , Steinberg Gary D. 
Published: June 2024

TPS4626 Background: High-risk non-muscle-invasive bladder cancer (NMIBC) is treated with adjuvant intravesical Bacille Calmette-Guérin (BCG). However, approximately 50% of patients experience recurrence and/or progression after BCG treatment and are considered unresponsive. EG-70 (detalimogene voraplasmid) is an investigational drug product that was specifically engineered for intravesical administration to elicit local stimulation of anti-tumor immune responses in the bladder and drive durable efficacy in patients with BCG-unresponsive NMIBC, while mitigating the risk of systemic toxicities from immune stimulation. The phase 1 (dose-escalation) part of the first-in-human LEGEND (NCT04752722) phase 1/2, open-label, multicenter study of EG-70 in patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) is complete: intravesical instillation of EG-70 was well tolerated with an overall complete response (CR) rate of 73%; and the recommended phase 2 dose (RP2D) was identified. Here we describe the ongoing phase 2 part of the study, which opened to enrollment in May 2023. Methods: Patient eligibility criteria: age ≥18 years; ECOG PS 0−2; BCG-unresponsive NMIBC with CIS, with or without resected coexisting papillary tumors, ineligible for, or have elected not to undergo, cystectomy; satisfactory bladder function with ability to retain study drug for ≥60 minutes. Prior checkpoint inhibitor treatment is allowed if completed within 30 days before study entry. Patients are treated with EG-70 at the RP2D (800 µg in 50 mL) by intravesical administration on weeks 1, 2, 5, and 6 of a 12-week cycle, for 4 cycles in one of two cohorts: BCG-unresponsive (Cohort 1); BCG-naïve or BCG-incompletely treated (Cohort 2). Patients in either cohort who exhibit stable disease (SD) or CR at week 12 will continue treatment until week 24; patients with progressive disease (PD) will discontinue treatment. Patients who experience or maintain CR at week 24 will receive additional cycles every 12 weeks until week 48; patients with SD or PD at week 24 will discontinue treatment. Patients with PD at any time after week 24 will discontinue treatment. Phase 2 primary objective: evaluate efficacy (CR rate at week 48) and safety of EG-70. Secondary objectives: evaluate progression-free survival, CR rate at 12, 24, 36 and 48 weeks, and duration of response. The study is being conducted in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines and with the principles of the Declaration of Helsinki. All patients provide written informed consent. The ongoing, registration-enabling phase 2 portion of the LEGEND study is anticipated to recruit approximately 100 patients from sites in North America, Europe, and the Asia-Pacific region. Clinical trial information: NCT04752722 .
Nanoliposomal Irinotecan With Fluorouracil and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Cholangiocarcinoma: A Phase II Study of the AIO Hepatobiliary-YMO Cancer Groups (NIFE-AIO-YMO HEP-0315)
Authors: Ettrich Thomas J. , Modest Dominik P. , Sinn Marianne , Striefler Jana K. , Opitz Bernhard , Goetze Thorsten , Gallmeier Eike , Angermeier Stefan , Fischer von Weikersthal Ludwig , Jacobasch Lutz , Waldschmidt Dirk , Niedermeier Michael , Sohm Michael , Berger Andreas W. , Manzini Giulia , Fehrenbach Uli , Auer Timo Alexander , Hosse Clarissa , Vogele Daniel , Sookthai Disorn , Schaaf Marina , Muche Rainer , Hinke Axel , Seufferlein Thomas , Perkhofer Lukas 
Published: June 2024

PURPOSE First-line therapy options in advanced cholangiocarcinoma (CCA) are based on the ABC-02 trial regimen (gemcitabine/cisplatin [G/C]). The NIFE trial examined nanoliposomal irinotecan/fluorouracil/leucovorin (nal-IRI/FU/LV) as alternative first-line therapy in advanced CCA. METHODS NIFE is a prospective, open-label, randomized, multicenter phase II study that aimed at detecting efficacy comparable with the standard treatment. Patients with advanced CCA were randomly assigned (1:1) to receive nal-IRI/FU/LV (arm A) or G/C (arm B). Stratification parameters were intrahepatic versus extrahepatic CCA, sex, and Eastern Cooperative Oncology Group (ECOG; 0/1). Arm A was designed as a Simon's optimal two-stage design and arm B served as a randomized control group. The primary goal was to exclude an inferior progression-free survival (PFS) at 4 months of only 40%, while assuming a rate of 60% on G/C population. RESULTS Between 2018 and 2020, overall 91 patients were randomly assigned to receive nal-IRI/FU/LV (n = 49) or G/C (n = 42). The NIFE trial formally met its primary end point with a 4-month PFS rate of 51% in patients receiving nal-IRI/FU/LV. The median PFS was 6 months (2.4-9.6) in arm A and 6.9 months (2.5-7.9) in arm B. Median overall survival (OS) was 15.9 months (10.6-20.3) in arm A and 13.6 months (6.5-17.7) in arm B. The exploratory comparison of study arms suggested a numerical but statistically not significant advantage for nal-IRI/FU/LV (hazard ratio for PFS, 0.85 [95% CI, 0.53 to 1.38] and for OS, 0.94 [95% CI, 0.58 to 1.50]). Analysis for stratification parameters revealed no differences for sex and ECOG, but for tumor localization. The objective response rate was 24.5% with nal-IRI/FU/LV and 11.9% with G/C. No unexpected toxicities occurred. AEs related to nal-IRI/FU/LV were mainly GI and to G/C hematologic. CONCLUSION Treatment of advanced CCA with nal-IRI/FU/LV demonstrated efficacy in first-line therapy without new safety findings and merits further validation.
Classicist Drama in Digital Times
Authors: Yeh Michelle 
Published: June 2024

Abstract
This article begins with an overview of the rise of internet drama, or web drama, in China in the past fifteen years. The new platform boasts several advantages, which accounts for its rapid development. Web drama has become so popular that it is replacing television drama series as the mainstream. The article then examines a major genre of web drama: stories set in traditional China. While costume drama or period drama, whether based on history or fiction, has always been popular, classicist web drama series in recent years stand out for their authenticity and creativity. Based on two case studies, the article explores two distinct themes. The first is Royal Nirvana (2019), a pseudo-historical drama that integrates Song-dynasty culture into the plot. In doing so, it beautifully demonstrates the appeal of “Chinese style” or “Asian aesthetics” in popular imagination. The second case study is The Untamed (2019), a fantasy martial arts tale that features two male protagonists who start out as diametrically opposed but end up as soul mates and loyal allies. The drama series skillfully transforms danmei or BL (boys’ love) in the original story into a subtly titillating relationship between two men. The article concludes with a discussion of the new business model that web drama has successfully introduced into the entertainment industry in contemporary China.