tbuckley/cabot-search huggingface dataset:
Demographics, pathologic characteristics, and pattern of recurrence of vulvar cancer at an academic hospital in South Africa: A 10-year retrospective review.
Authors: Adekunle Emmanuel Sajo, Edwin Mnisi, Cathy Visser, Sheynaz Bassa, Greta Dreyer
Journal: Journal of Clinical Oncology (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 1 st January 2012 and 31 st 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/mm 3 , 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 &gt;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 &amp; 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.
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: Tianxiang Yu, Bo Ding, Jingyun Xu, Sicong Liu, Yang Shen
Journal: Journal of Clinical Oncology (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 &lt;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 .
In-hospital outcomes of patients with ovarian cancer and venous thromboembolism: A Nationwide Inpatient Sample analysis.
Authors: Mrunanjali Gaddam, Rabia Iqbal, Jayalekshmi Jayakumar, Manasa Ginjupalli, Ankushi Sanghvi, Dhairya Nanavaty, Sujana Sanka, Rohit Sekandlapuram, Priya Thanneeru, Priya Hotwani, Vikash Kumar, Michelle Koifman, Samridhi Sinha, Ana Colon Ramos, Jincy Clement
Journal: Journal of Clinical Oncology (2024)

e17576 Background: Ovarian Cancer is one of the most common gynecological cancers. It has 5-year relative survival of 50.8 %. Around 12700 people die from this cancer each year, and it ranks fifth in cancer death among women. Studies have shown a strong association of ovarian cancer with venous thromboembolism (VTE) which includes deep venous thrombosis (DVT) and Pulmonary Embolism (PE). However, data surrounding outcomes associated with VTE in this population is limited. We aim to estimate the effect of VTE on mortality and healthcare utilization in this population. Methods: We queried the National Inpatient Sample (NIS) 2018-2020 to collect data for all adult hospitalizations &gt;18 years with a diagnosis of ovarian cancer using appropriate ICD 10 codes. These hospitalizations were further classified into hospitalizations with and without DVT and PE. Multivariate regression analysis was performed to study the impact of DVT/PE taking mortality as the primary outcome and total cost and length of hospital stay (LOS) as secondary outcomes in the subpopulation of ovarian cancer hospitalizations. Results: There were a total of 298085 adult hospitalizations with a diagnosis of ovarian cancer with a mean age of 63 years. Among hospitalizations with ovarian cancer, acute DVT was found in 2.75% and acute PE was present in 4.5 %. In these hospitalizations, in-patient mortality was 9.3% in those with either DVT or PE. Multivariate regression analysis revealed that among adults, hospitalizations with ovarian cancer had higher odds of Acute DVT [OR 3.5, P&lt;0.01] and Acute PE [OR 3.76, P&lt;0.01] than those without. The odds of all-cause mortality from VTE [OR 2.18, P&lt;0.01] were significantly higher in patients with ovarian cancer than those without. The total cost of hospital stay was 26211 $ ($22183 - $30238, p&lt;0.01) higher and LOS was 1.67 times higher (1.2 - 2.32; P&lt;0.01) when patients with ovarian cancer developed VTE (Table). Conclusions: Our study concludes that ovarian cancer patients who develop VTE tend to have worse outcomes in terms of mortality. Length of hospital stay and total hospital charge are also increased in patients developing VTE, thereby increasing healthcare utilization. This highlights the importance of having larger-scale studies in the future to assess outcomes in ovarian cancer patients with VTE and the need to formulate risk assessment models for the role of primary thromboprophylaxis. Adjusted analysis showing odds ratio of mortality, total hospital charge and LOS in ovarian cancer hospitalizations. [Table: see text]
Identification of potential biomarkers with alternative splicing landscape of HIPEC-treated ovarian cancer: An RNAseq sub-analysis of a HIPEC clinical trial.
Authors: Thanh Hue Dellinger, Nathaniel P. Hansen, Nora H. Ruel, Paul Henry Frankel, Susan Elaine Yost, Marta Invernizzi, Melissa Eng, Ernest Soyoung Han, Mustafa Raoof, Xiwei Wu, Hyejin Cho, Stephen Lee, Mehdi Kebria, Amy Hakim, Edward Wenge Wang, Isaac Benjamin Paz, Lorna Rodriguez-Rodriguez, Patrick Pirrotte
Journal: Journal of Clinical Oncology (2024)

e17577 Background: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy improves survival in ovarian cancer patients. Currently, no biomarkers exist to select for patients who best benefit from HIPEC. We compared the slicing landscape of ovarian cancer tumors of good and poor HIPEC responders in a Phase I clinical trial, to identify potential predictive biomarkers. Methods: A total of 35 ovarian cancer patients enrolled in a Phase I HIPEC trial (NCT01970722), in which nine patients had paired pre-and post treatment tissue samples collected. Pre-HIPEC tumor samples had RNA isolated, and whole-transcriptome library construction performed. FASTQ files from tumor samples were aligned to GRCH38 and ran through SplAdder (PMID:26873928) to identify alternative splicing events. Outlier splice events were ranked by mean log-likelihood score and converted to amino acid sequences using Bisbee (PMID:34031440). The top 15 outlier events were run through NetMHCpan (PMID:32406916) and DeepHLApan (PMID:31736974) to predict putative neoantigens. Results: Among nine HIPEC-treated ovarian cancer patients with available RNAseq data, five were considered good responders (≥12months PFS), and four as poor responders (&lt;12 months PFS). Alternative splicing analysis identified 519splice events as outliers between good and poor responders, with 250reported to be novel. Of the 250 novel splicing events, we identified a novel protein coding 3’ end splice event in CPNE1 which was alternatively spliced in at a Percent-Spliced-In (PSI) of 99% in three out four poor responders. The same splice event was alternatively spliced at a PSI of 30.3% in four out of five good responders. CPNE1 plays a role in calcium mediated intracellular processes, and is involved in the TNF-alpha receptor signaling pathway, thus playing an important role in cell proliferation, differentiation, apoptosis, and modulation of immune responses and induction of inflammation. The encoded novel peptide from the CPNE1 splice event produced six predicted strong binding sites based on a binding score&gt;0.80 and an immunogenic score&gt;0.80. Conclusions: CPNE1 was identified as a differentially spliced event in poor HIPEC responders with ovarian cancer. Poor HIPEC responders had higher immunogenic score. Alternative splicing analysis may be a promising method to determine potential biomarkers for HIPEC treatment in ovarian cancer patients. Clinical trial information: NCT01970722 .
Chemoresistance in high grade serous ovarian cancer molecular subtypes and the role of NRF2.
Authors: Helen Toma, Omar S. Al-Odat, Layla Hamad, Hansa Joshi, Rebeca Kelly, Chelsea Katz, Hadi Shojaei, Yahui Li, Ramkrishna Mitra, Nasrine Bendjilali, Francis R. Spitz, Christina Chu, Lauren Krill, Manoj Pandey, Yemin Wang, David Philip Warshal, Samera Hamad
Journal: Journal of Clinical Oncology (2024)

e17574 Background: Epithelial ovarian cancer accounts for 90% of ovarian cancer diagnoses, 70% of which are high grade serous subtype (HGSOC). The HGSOC is the most aggressive type of Ovarian Cancer with limited therapeutic options. Studies have shown that several molecular subtypes of HGSOC exist such as immunoreactive, differentiated, proliferative, and mesenchymal, which further complicate the effort of finding therapies for this deadly cancer. Nuclear erythroid-related factor-2 (NRF2) is a transcription factor that is found to be frequently activated in ovarian cancer. NRF2 normally protects cells from oxidative damage by regulating more than 500 genes in human body. Hyperactivation of NRF2 in cancer is found to protect cancer cells from oxidative damage, and thus, promotes tumor growth and metastases. NRF2 is also known as an anti-inflammatory pathway and a master regulator of immune cells differentiation, distribution, and infiltration. Patients with high-NRF2 tumors tend to have significantly lower survival than patients with Low-NRF2 tumors. In this study, we investigate the role of NRF2 in HGSOC subtype evolution and responses to chemotherapies. Methods: Two human HGSOC cell lines, OVCAR8 and PEO1 were used to identify and quantify the NRF2 protein level with its down-stream targets. We also quantified differentiation markers such as Vimentin, P63, PD-L1, that are associated with HGSOC subtypes, using western blotting. These human cell lines were also tested for Carboplatin and Paclitaxel half maximal inhibitory concentration (IC50) using MTT assay. RNA-seq data of human HGSOC from The Cancer Genome Atlas (TCGA) was analyzed to compare our in vitro studies with human tumors. Results: The human OVCAR8 cell line had a 50-fold higher expression of NRF2 and 12-fold higher expression of vimentin when compared to the PEO1 cell line. When treated with Carboplatin, the IC50 for OVCAR8 was 112 ± 3.6 µM vs 67.5 ± 5µM for PEO1. For Paclitaxel, the IC50s for the two cell lines were 5 ± 0.4nM and 4 ± 0.15nM, respectively. Finally, RNA sequencing data from the TCGA showed that the NRF2 activation score in mesenchymal subtype was significantly increased compared to the immunoreactive subtype (p=0.004). Conclusions: Our data show that expression of NRF2 is significantly higher in the mesenchymal (the most chemo-resistant and aggressive) subtype, while the subtypes with lower NRF2 tend to be more responsive to chemotherapies. These findings imply that targeting NRF2 in these subtypes could improve responses to chemotherapies and enhance tumor prognosis in patients with HGSOC.
Towards Ultrasound Wearable Technology for Cardiovascular Monitoring: From Device Development to Clinical Validation
Authors: AnaBelen Amado-Rey, AnaCarolina GonçalvesSeabra, Thomas Stieglitz
Journal: IEEE Reviews in Biomedical Engineering (2024)

The advent of flexible, compact, energy-efficient, robust, and user-friendly wearables has significantly impacted the market growth, with an estimated value of 61.30 billion USD in 2022. Wearable sensors have revolutionized in-home health monitoring by warranting continuous measurements of vital parameters. Ultrasound is used to non-invasively, safely, and continuously record vital parameters. The next generation of smart ultrasonic devices for healthcare integrates microelectronics with flexible, stretchable patches and body-conformable devices. They offer not only wearability, and user comfort, but also higher tracking accuracy of immediate changes of cardiovascular parameters. Moreover, due to the fixed adhesion to the skin, errors derived from probe placement or patient movement are mitigated, even though placement at the correct anatomical location is still critical and requires a user's skill and knowledge. In this review, the steps required to bring wearable ultrasonic systems into the medical market (technologies, device development, signal-processing, in-lab validation, and, finally, clinical validation) are discussed. The next generation of vascular ultrasound and its future research directions offer many possibilities for modernizing vascular health assessment and the quality of personalized care for home and clinical monitoring.
Clinical significance of the risk model based on exosome-derived miRNA and miR-486-5p for endometrial cancer.
Authors: Jianfeng Zheng, Xuefen Lin, Ruina Jiang, Yang Sun
Journal: Journal of Clinical Oncology (2024)

e17588 Background: Exosome-derived miRNAs are detectable in various body fluids and play a crucial role in the diagnosis and prognosis of endometrial cancer (EC). The objective of our study is to investigate the clinical significance of an exosome-derived miRNA-based risk model, specifically focusing on miR-486-5p for EC. Methods: The expression profile of plasma-derived exosomal miRNAs was obtained through high-throughput sequencing. The expression profile of mature miRNAs for patients with EC was also obtained from TCGA. The prognostic value of differentially expressed miRNAs was assessed using R packages. The accuracy and stability of exosomal miRNAs in diagnosing EC were assessed using machine learning algorithms. The risk model based on exosome-derived miRNA was established using LASSO Cox regression analysis. The clinical significance of the risk model, including prognosis and anti-tumor therapy, was identified and validated using R packages. The most significant exosomal miRNA, miR-486-5p, was selected for wet experiments, including quantitative real-time PCR, Western Blot, CCK8, colony formation, transwell migration, wound healing, flow cytometry, and dual-luciferase reporter assays. Six databases and comprehensive bioinformatics approaches were integrated to predict targets of miR-486-5p. Data of single cell RNA was used to screen out the recipient cell of exosomal miR-486-5p. Results: A total of 49 exosomal miRNAs exhibited differential expression between plasma samples obtained from women with EC and controls. A total of 33 exosomal miRNAs exhibiting prognostic significance were identified. The area under the receiver operating characteristic curve (AUC) of the diagnostic model calculated by machine learning algorithms exceeded 0.9 in all sets. The risk model based on exosome-derived miRNA could be used to stratify EC patients with different prognosis. The AUC value of the time-dependent ROC curve for the risk model exceeded 0.7. Additionally, our study revealed that patients with EC, stratified based on the risk model, exhibited varying responses to anti-tumor therapy such as Tamoxifen. The single-cell transcriptome sequencing data revealed a significantly elevated expression abundance of FOXO1, the miR-486-5p target gene, in macrophages within the immune microenvironment. The experimental results demonstrated that miR-486-5p exerted a promotive effect on cellular proliferation, migration, invasion, and metabolic dysfunction through the inhibition of FOXO1. Furthermore, we observed that the exclusion of miR-148a-3p via exosomes promoted macrophage M2 polarization by FOXO1-mediated metabolic dysfunction. Conclusions: Our data has provided insights into the clinical significance of the risk model based on exosome-derived miRNA, as well as revealing the mechanism involving miR-486-5p in metabolic dysfunction through FOXO1 for endometrial cancer.
A randomised phase II study of extended pleurectomy/decortication (e-PD) preceded or followed by chemotherapy in patients (pts) with early-stage pleural mesothelioma (PM): EORTC 1205
Authors: Jo Raskin, Veerle Surmont, Alexander P.W.M. Maat, Maha Yahia, Sjaak A. Burgers, Yassin Pretzenbacher, Frederic De Ryck, Robin Cornelissen, Houke M. Klomp, Ana Oliveira, Joachim Aerts, Paul Baas, Sandrine Marreaud, Jan P. Van Meerbeeck, Paul E.Y. Van Schil
Journal: European Respiratory Journal (2024)

The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown.
Development and validation of a prediction model for lymph node metastasis based on molecular classification in endometrial carcinoma.
Authors: Qiuyue Han, Quanhong Jiang, Jiaqi Xu, Yuan Zhang, Li Li, Beihua Kong, Kun Song, Hualei Bu, Ruifen Dong
Journal: Journal of Clinical Oncology (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.