bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunologic effects of B cell depletion on T cells in high-risk prostate cancer.
Authors: Kim Sangwoo Shawn , Murtadha Jamillah , Miyauchi Sayuri , Ryan Stephen T , Zhang Jing , Pittman Emily , Messer Karen , Karin Michael , Kane Christopher J. , Shabaik Ahmed , Howell Stephen B. , Jamieson Christina , Sharabi Andrew 
Published: June 2024

5096 Background: High-risk prostate cancer (HR-PCa) remains one of the leading causes of cancer-related death. Previous studies reported that a high density of immunosuppressive B cells in HR-PCa resection specimens was found to correlate with biochemical failure. In this context, a single arm prospective study assessing neoadjuvant rituximab, an anti-CD20 monoclonal antibody used to deplete B cells, was previously conducted on patients with HR-PCa eligible for radical prostatectomy (“PROTUX”). Here, we performed deep TCR sequencing to elucidate the impact of B cell depletion on T cells in prostate cancer patients. Methods: A single arm study enrolled patients with HR-PCa to receive neoadjuvant rituximab prior to radical prostatectomy (NCT: 01804712). Patients were treated with rituximab 375 mg/m2 once weekly for 4 treatments followed by prostatectomy within 14 days of the final treatment of rituximab. A matched cohort of patients with HR-PCa who underwent prostatectomy without any prior therapy were used as controls. Specimens from 14 patients were retrieved and genomic DNA was isolated using a QIAamp DNA FFPE Advanced UNG kit. TCR sequencing was performed with Adaptive Biotechnologies using the Ultradeep TCRB v4b assay. Data were then analyzed using the Adaptive immunoSEQ Analyzer. Groups were compared using a Mann-Whitney U test. Statistical analysis and graphing were done in Prism 10 and R. Results: We observed that patients treated with rituximab had higher TCRb productive clonality (0.080 vs 0.026, p = 0.03). Strikingly, the calculated number of T cells present in prostatectomy samples was significantly greater in patients receiving rituximab compared to controls (1.18 cells/ng DNA input vs 0.10 cells/ng, p = 0.002). Maximum productive frequency and the cumulative frequency of the top 10 clones were not significantly different between the two cohorts. However, we found that the T cells from patients who received rituximab had longer TCRb CDR3 regions (proportion CDR3 ≥16 amino acids of 0.232 vs 0.197, p = 0.007), suggesting a less antigen-experienced phenotype. Conclusions: Using specimens from a clinical trial assessing the use of neoadjuvant rituximab in HR-PCa, we found that B cell depletion can significantly affect T cell infiltration, clonality, and phenotype. Given the increasing appreciation for crosstalk between T cells and B cells in mediating anti-tumor immune responses, these findings suggest a context dependent role of B-cells in patients with HR-PCa. Clinical trial information: NCT01804712 .
Socio-economic disparities in prostate cancer hospitalizations and outcomes across the United States.
Authors: Imeh Michael , Gvajaia Ani , Amaeshi Lemchukwu , Raza Ali , Uwumiro Fidelis 
Published: June 2024

5103 Background: Socioeconomic class (SEC), measured by educational attainment, is recognized as a notable factor influencing outcomes in prostate cancer. This study evaluated the effects of income status on the prevalence, treatment, and hospitalization outcomes among men diagnosed with prostate cancer. Methods: The combined 2016–2020 nationwide inpatient sample database was queried for all hospitalizations for a primary diagnosis of prostate cancer using ICD-10-CM codes. Socioeconomic status was defined based on the Agency for Healthcare Research and Quality (AHRQ) median annual income index into the lowest SEC ($1–$49,999), the lower SEC ($50,000–$64,999), the high SEC ($65,000–$85,999), and the highest SEC ($≥86,000). Baseline characteristics were compared using Pearson’s χ2 tests and the Kruskal-Wallis test for nominal and continuous variables. Outcomes of interest were hospitalization rates, treatment, and outcomes (including mortality, complications, and resource utilization). The adjusted odds ratios of the outcomes were assessed using a stepwise multivariable logistic regression, adjusted for age, sex, race, insurance status, illness severity, risk of mortality, and comorbidity burden. This was done using the All Patient Refined Diagnosis Related Groups (APR-DRG) metrics and the Charlson comorbidity index. Results: The study analyzed 244,520 hospitalizations for prostate cancer. The median age of the cohort was 64 years (interquartile range: 59–69 years). Most were white Americans (69.9%) and blacks (16.3%). Approximately 53,550 (21.9%) were in the lowest SEC, 58,196 (23.8%) were in the lower SEC, 61,619 (25.2%) in the high SEC, and 66,803 (27.3%) in the highest SEC. Hospitalizations in the highest SEC were younger than those in the lowest SEC (63.7 vs. 66.5; P<0.001). Hospitalizations in the lowest SEC were correlated with greater mortality (655, 1.2%; AOR: 1.43; 95% CI: 1.22-1.56; P=0.011) compared with those in the highest SEC (475, 0.7%; AOR: 0.86; 95% CI: 0.65-0.97; P<0.001). The highest SEC correlated with higher rates of prostatectomy (2,995, 4.5%; AOR: 1.29; 95% CI: 1.08-1.10; P<0.001), whereas the lowest SEC had lower rates (1,810, 3.4%; AOR: 0.52-0.98; P=0.008). The lower and lowest SECs had higher frequencies of chemotherapy (8.1% and 7.4%, respectively; P for all <0.001). SEC did not correlate with the likelihood of immunotherapy (P = 0.738), radiotherapy (P = 0.073), length of hospital stays (P = 0.283), or mean hospital costs (P = 0.582). Hospitalizations in the higher SECs had lower odds of erectile dysfunction (highest SEC, AOR: 0.83; 95% CI: 0.74-0.93; P = 0.001; and high SEC, AOR: 1.13; 95% CI: 1.02-1.24). Conclusions: Prostate cancer affects the younger demographics of patients with higher SECs. However, hospitalizations in patients with lower SECs present with more advanced disease and result in poorer mortality outcomes than those in patients with higher SECs.
An open label, single arm phase II, multicenter trial of durvalumab and BVAC-C, in patients with HPV 16- or 18-positive cervical cancer and failure of first-line platinum-based chemotherapy (DURBAC).
Authors: Choi Chel Hun , Kim Byoung-Gie , Lee Jeong-Won , Kim Tae-Joong , Lee Yoo-Young , Cho Duck , Park Byoung-Kwan Hun , Song Sang Yong , Kim Dae-Yeon , Kim Kidong , Kim Hee Seung , Lee Jung-Yun , Lim Myong Cheol , Jeon Insu , Song By-yeong , Shin Kwang-Soo , Kim Wuhyun , Kang Chang-Yuil 
Published: June 2024

5513 Background: In the phase I/IIa study of HPV positive recurrent cervical carcinoma, BVAC-C, a pioneering B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant E6/E7 gene of HPV type 16/18, demonstrated favorable tolerability. The ongoing phase 2 clinical trial investigates the potential synergistic effects of combining BVAC-C with durvalumab (MEDI4736), an anti-PD-L1 therapy, to enhance anti-tumor immune responses. Methods: The trial comprises two parts. Part A, utilizing a 3+3 dose-escalation design, assesses BVAC-C combined with 1500 mg durvalumab to establish the maximum tolerated dose (MTD) and recommended dose for Part B. Part B, with an expansion phase involving up to 25 patients, focuses on safety and clinical efficacy, measured by the 6-month progression-free survival (PFS) rate. Part A enrollment commenced in September 2021 across six Korean centers, with 9 participants enrolled and MTD determined by November 2022. 25 patients were enrolled in Part B enrollment was completed with 25 patients by December 2023. Tumor response evaluation follows RECIST 1.1 criteria and iRECIST. The essential eligibility criteria comprise histologically confirmed cervical carcinoma with HPV 16/18 positivity, recurrence following or resistance to a solitary prior first-line platinum-based chemotherapy ± bevacizumab, lack of prior exposure to immune-oncology (IO) drugs, and the presence of measurable disease according to RECIST v1.1. Results: Among 29 patients available for this interim analysis, 6-month PFS-rate was 51% (95% CI 33 – 77). The objective response rate (ORR) was 29.2% (7/24), with 2 complete responses. The disease control rate (DCR) was 66.7% (16/24). With a median follow up of 7 months, the median duration of response (DOR) and PFS were not reached. All evaluated patients exhibited inflammatory cytokine responses (IFN-γ or TNF-α) and robust E6/E7-specific T cell responses following BVAC-C vaccinations. Notably, immune responses correlated with clinical outcomes. The most common treatment-emergent adverse events (TEAEs) were pyrexia and myalgia, mostly grade 1 and manageable. Conclusions: The combination of BVAC-C and durvalumab demonstrates promise as a second-line treatment option with a manageable safety profile for patients with recurrent HPV 16/18 positive cervical cancer. The survival data is scheduled to receive an update during the upcoming ASCO meeting. Further studies are warranted to identify potential biomarkers of treatment response. Clinical trial information: NCT04800978 .
Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): A final overall survival analysis of a multicenter, open-label, randomized, phase 3 trial.
Authors: Zang Rongyu , Zhu Jianqing , Liu Jihong , Jiang Rong , Cheng Xi , Chen Yulian , Jia Huixun , Shi Tingyan , Guo Yi , Feng Yanling , Tu Dongsheng , Zhang Yuqin , Huang Xiao , Jiang Shiyang , Gao Wen , Yang Huijuan , Zhang Ping 
Published: June 2024

5520 Background: Surgery for platinum-sensitive relapsed ovarian cancer is widely practiced but has contradictory outcomes of survival in previously published studies. Methods: This multicenter, open-label, randomized, phase 3 trial was performed in four primarily academic centers in China. Eligible patients were aged ≥18 years old with platinum-sensitive relapsed ovarian cancer and were predicted to have resectable disease according to the international model (iMODEL) combined with PET-CT, which was reported previously. Overall survival (OS) and progression-free survival were the co-primary end points in hierarchical testing and planned for the final analysis of OS with a two-sided alpha of 0.05, when 209 deaths happened. Results: Between July 19, 2012 and June 3, 2019, 357 patients were enrolled. Patients were randomly assigned to receive surgery (182 pts.) or control (175 pts.). Median follow-up was 82.5 m. The median OS was 58.1 m in the surgery group and 52.1 m in the control group (hazard ratio [HR] for death, 0.80; 95% confidence interval [CI], 0.61 to 1.05; P=0.109). Overall, 61/175 (35%) patients in the control group crossed to surgery in subsequent therapies. A sensitive analysis showed that adjusted HR for death for crossover to surgery was 0.76 (95% CI, 0.58 to 0.99) (Table). When excluding the center with the highest crossover rate, secondary cytoreduction provided a 21.0-m benefit of overall survival over a control therapy. The highest crossover surgery rate was 49% in patients with 4-19 sites of relapse. The hazard ratio for death in patients with 1-19 sites was 0.69 (95% CI, 0.46 to 1.03). Patients with a complete resection had the most favorable outcome, with a median OS of 73 m. Median time to second subsequent therapy was 34.8 m vs 28.1 m (HR 0.68; 0.55-0.87). 24 of 182 (13.2%) patients remained relapse free and alive over 60 m in the surgery group, as compared with 5 of 175 (0.6%) patients in the control group. Conclusions: Secondary cytoreduction did not increase overall survival in the intention-to-treat population but led to a longer duration of overall survival when the crossover effect was taken into consideration. These findings are arguably clinically meaningful and support the efficacy of secondary cytoreduction in specialized centers and selected patients. ClinicalTrial.gov: NCT01611766. Res Sponsor: Shanghai Gynecologic Oncology Group. Clinical trial information: NCT01611766 . [Table: see text]
Unveiling the unique identity of clear-cell endometrial cancer (CCEC): A comprehensive comparative analysis with ovarian counterpart and other endometrial subtypes.
Authors: Blanc-Durand Felix , Ngoi Natalie , Rouleau Etienne , Pautier Patricia , Michels Judith , Ouali Kaïssa , Genestie Catherine , Lim Yi Wan , Lim Diana , Wijaya Silvana Talisa , Leary Alexandra , Tan David Shao Peng 
Published: June 2024

5521 Background: Clear cell endometrial cancer (CCEC) is a rare and poorly understood entity, comprising less than 10% of endometrial cancer cases. In contrast, clear-cell ovarian cancer (CCOC) ranks as the second most prevalent subtype among epithelial ovarian cancers. CCOC is distinguished by specific phenotypic and molecular features, coupled with an overall aggressive behavior. CCEC and CCEC both share clinical and pathologic characteristics, suggesting common pathogenesis. This study aims to elucidate the molecular landscape of CCEC, in comparison with CCOC and other EC subtypes (nEC). Methods: We conducted a multicenter, retrospective analysis of CCOC, CCEC and nEC patients from Institut Gustave Roussy in France and National University Cancer Institute in Singapore. All patients underwent comprehensive molecular profiling using the tumor-based FoundationOneCDX panel. Results: This study analyzed 19 patients with CCEC, 81 patients with CCOC and 91 patients with nEC. CCEC exhibited distinct clinical and molecular features compared to CCOC or nEC. CCEC patients were significantly older (mean age 64.6 years) compared to CCOC (53.0 years, p<0.001) and nEC (59.9 years, p<0.001) cohorts. They also presented more frequently with FIGO IV disease (63.2%) versus 16.7% in CCOC patients (p<0.001) and 28.9% in nEC patients (p=0.007). Compared to CCOC, CCEC harbored significantly fewer ARID1A mutations (15.8% vs 54.3%, p=0.004), fewer KRAS mutations (0% vs 19.8%, p=0.035), significantly more TP53 mutations (42.1% vs 13.6%, p=0.008), and higher loss-of-heterozygosity (LOH) scores (10.5% vs 4.5%, p=0.004). Compared to nEC, CCEC exhibited significantly fewer CTNNB1 mutations (0% vs 18.7%, p=0.04), fewer PTEN mutations (5.3% vs 57.1%, p<0.001) and fewer KRAS mutations (0% vs 22.0%, p=0.021). Additionally, CCEC had higher LOH scores (10.5% vs 3.7%, p=0.019), and tended be less frequently associated with microsatellite instability (0% vs 19.3%, p=0.07) compared to nEC. Conclusions: CCEC significantly differs from CCOC and nEC in both clinical and molecular aspects. These findings support the consideration of CCEC as a distinct entity, advocating for a personalized approach that takes into account both the clear-cell aspect and the endometrial cancer molecular stratification.
Nimotuzumab in combination with radiotherapy for elderly patients with locally advanced cervical squamous cell carcinoma: Results from a prospective, multicenter, open-label, single-arm trial.
Authors: Qu Ang , Wang Jun jie , Zhuo Yanhong , Liu Zi , Zhu Hong , Wei Lichun , Sun Xiaoge , Gao Yuhua , Cheng Huijun , Zhao Fengju , Song Yipeng , Wen QingLian , Zhou Xiaohong , Wang Ping , Yang Jialin , Zou Lijuan , Yuan Xiangkun , Wu Dongyue , He Jianli , Zhang Yun Yan 
Published: June 2024

5527 Background: Locally advanced cervical squamous cell carcinoma (LACSCC) is associated with poor survival, and elderly patients generally have fewer treatment options due to chemotherapy intolerance. Nimotuzumab is a humanized monoclonal antibody that has demonstrated therapeutic activity in many tumors. We conducted a single-arm trial to investigate the efficacy and safety of combining nimotuzumab and radiotherapy for elderly patients with LACSCC. Methods: In this prospective, multicenter, open-label, and single-arm trial, patients with LACSCC were registered (NCT04976478) and enrolled from Nov 2021 to Jan 2023. All patients were ≥ 65 years old, had ECOG of 0-2, histological diagnosis of cervical squamous cell carcinoma, clinical stage IB3-IVA (FIGO 2018), intolerant to chemotherapy, or refused chemotherapy. The regimen was nimotuzumab (200 mg once in a week for 6 weeks) combined with radiotherapy. The radiotherapy scheme contained intensity-modulated radiotherapy (IMRT)/volumetric intensity-modulated arc therapy (VMAT) with pelvic/extended field irradiation (45-50.4Gy, 1.8-2.0Gy/f, 25-28f), and brachytherapy (HR-CTV D90, 80-85Gy), of which brachytherapy plus external beam radiotherapy was completed in 8 weeks. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Other assessed endpoints were objective response rate (ORR), disease control rate (DCR) and complete response rate (CRR). All adverse events were monitored and recorded. Results: As of Jan 2023, 119 elderly patients have been enrolled and all patients were included in the efficacy and safety analysis. The median follow-up was 16.16 months (95% CI: 13.14-17.45). Nimotuzumab combined with radiotherapy resulted in favorable OS (1 year-OS: 96.03%, 95% CI: 89.75-98.50; 2 year-OS: 90.21%, 95% CI: 78.98-95.60), and DFS (1 year-DFS: 85.71%, 95% CI: 76.98-91.31; 2 year-DFS: 78.31%, 95% CI: 66.67-86.29). The ORR was 89.92%, DCR was 93.28%, and CRR was 52.94%. A total of seven patients died, of which three were due to disease progression and two were of unknown causes. The most common Grade 3-5 adverse events (AEs) mainly included leukopenia (3.36%), anemia (2.52%), and neutropenia (1.68%). None of the patients developed severe AEs or deaths. So far, this trial is still ongoing. Conclusions: Among elderly LACSCC patients, adding nimotuzumab to radiotherapy indicated promising efficacy and appeared to have manageable toxicity. Nimotuzumab plus radiotherapy could represent a novel treatment strategy for this population. Clinical trial information: NCT04976478 .
Use of cell-free DNA from ascites to identify variants and tumour evolution in a cohort of patients with advanced ovarian cancer.
Authors: Werner Bonnita , Powell Elyse , Duggan Jennifer , Cortesi Marilisa , Lee Yeh Chen , Arora Vivek , Athavale Ramanand , Dean Michael , Warton Kristina , Ford Caroline 
Published: June 2024

5547 Background: Accurate and clinically relevant molecular profiling is critical in the evolving landscape of precision treatments for ovarian cancer. Malignant ascites, a common manifestation in advanced ovarian cancer, provides easy access to tumour material in the form of cell-free DNA (cfDNA). Ascites fluid is an ideal liquid biopsy to enable molecular profiling and application of precision medicine as an alternative to tissue biopsy. Objectives: We aimed to identify clinically relevant variants in ascites and to examine tumour evolution by comparing matched samples from different points in the disease trajectory. Methods: A unique cohort of sequential ascites-derived cfDNA samples (26 samples from 15 participants, interval range 13-559 days), from people with ovarian cancer (clear cell and high-grade serous, aged 36-82) was collected. These were sequenced with the Illumina TSO-500 assay, along with matched DNA from ascites-derived tumour cells (n=5) and archived FFPE-tissue from surgery (n=5). cfDNA from one patient was additionally analysed with PCR-free sequencing, using an Oxford Nanopore Technology R9.4.1 MinION. Results: cfDNA had similar tumour purity, variant detection and reference alignment as well as improved coverage when compared to FFPE and ascites cell DNA. Somatic ovarian cancer-associated driver mutations were detected in 100% of cfDNA samples at mutation fractions of up to 0.9 MAF. 3 confirmed cases with somatic BRCA1/BRCA2 mutations were identifiable in ascites cfDNA, of these, ascites preceded surgery by 100 days or more in 2 cases, enabling earlier access to tumour tissue and expediting PARP-inhibitor access. Combined analysis of large-scale genomic alterations, loss of heterozygosity and tumour mutation burden identified 6 cases of high genomic instability (including 4 with mutations in BRCA1 and BRCA2). Over sequential ascites samples, changes in copy number profiles were observed and prevalence of subclones shifted by >10% in 6 of 10 participants. Additionally, in one participant, selective deletion of Chr17p13.1 and a chromothripsis-affected Chr8q emerged between interval debulking surgery and disease recurrence, resulting in changes to clinically relevant TP53 and MYC variants over time. No artefactual single-base substitution signatures were observed in cfDNA, though results from 2 of 5 FFPE samples were >20% sequencing artefact. Conclusions: Our work demonstrated the reliability of using cfDNA from ascites for molecular profiling, allowing a liquid biopsy of ovarian cancer when tumour tissue access may be restricted. This approach improves accessibility of tumour material, allowing capture of clinically actionable mutations prior to surgery or upon recurrence, following tumour evolution.
Overall survival (OS) in patients with platinum-sensitive relapsed ovarian cancer (PSROC) treated with olaparib maintenance monotherapy: Update from the L-MOCA trial.
Authors: Gao Qing-lei , Zhu Jianqing , Zhao Weidong , Huang Yi , An Ruifang , Zheng Hong , Qu Pengpeng , Wang Li , Zhou Qi , Wang Danbo , Lou Ge , Wang Jing , Low John , Kong Beihua , Yin Rutie , Lv Weiguo , Liu Jihong , Sun Wei , Zang Rongyu , Ma Ding 
Published: June 2024

5559 Background: The open-label, single-arm, L-MOCA trial (NCT03534453) was the first study to demonstrate promising efficacy and tolerability of olaparib maintenance monotherapy in Asian patients with PSROC (median progression-free survival 16.1 months). Here we report the interim OS analysis. Methods: The study enrolled Asian patients with high-grade epithelial PSROC who had received ≥2 prior lines (L) of platinum-based chemotherapy and achieved complete or partial response. Patients were treated with oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. A prespecified descriptive analysis of OS, a secondary endpoint, was conducted after approximately 3 years of follow-up. OS was analyzed in the full analysis set (FAS; defined as patients who received olaparib) and in subgroups defined by biomarker status ( BRCAmutation /homologous recombination deficiency (HRD) status) and prior L of anticancer therapy. Results: By the date of data cutoff (16 Nov 2023), the median duration of follow-up was 40.0 months (range 0.5–64.2); 105 (46.9%) deaths occurred. In the FAS (N=224), the median OS was 54.4 months (95% CI 43.8–not evaluable [NE]). Median OS was not reached (NR; 51.9–NE) in the BRCA mutant ( BRCAm) subgroup and 44.3 months (34.8–59.1) in the BRCA wild-type ( BRCAwt) subgroup. In patients who had tumors with HRD, median OS was 59.1 (43.5–NE); among them, patients with HRD BRCAwt showed a median OS of 54.6 months (33.0–NE); in the homologous recombination proficiency (HRP) subgroup, median OS was 37.2 months (28.3–56.1). Adverse events of any grade occurred in 222 (99.1%) patients. The incidence of myelodysplastic syndrome and acute myeloid leukemia remained low (3 [1.3%]). No new safety signals were identified. Conclusions: Olaparib showed promising OS benefit in Asian patients with PSROC, regardless of the BRCA mutation or HRD status, with a well-tolerated safety profile. Clinical trial information: NCT03534453 . [Table: see text]