Explore the vast range of titles available.

Objective Neuroendocrine cervical carcinoma (NECC) is a rare but highly aggressive tumor. The clinical management of NECC follows neuroendocrine neoplasms and cervical cancer in general. However, the diagnosis and prognosis of NECC remain dismal. The aim of this study was to identify a specific protein signature for the diagnosis of NECC. Methods Protein and gene expression data for NECC and other cervical cancers were retrieved or downloaded from self-collected samples or public resources. Eleven machine-learning algorithms were packaged into 66 combinations, of which we selected the optimal algorithm, including randomForest, SVM-RFE, and LASSO, to select key NECC specific dysregulated proteins (kNsDEPs). The diagnostic effect of kNsDEPs was validated by a set of predictive models and immunohistochemical staining method. The dysregulation patterns of kNsDEPs were further investigated in other neuroendocrine carcinomas. Results Our results showed that NECC displays distinctive biological characteristics, such as HPV18 infection, and exhibits unique molecular features, particularly an enrichment in cytoskeleton-related functions. Furthermore, secretagogin (SCGN), adenylyl cyclase-associated protein 2 (CAP2), and calcyclin-binding protein (CACYBP) were identified as kNsDEPs. These kNsDEPs play a central role in cytoskeleton protein binding and showcase robust diagnostic ability and specificity for NECC. Moreover, the concurrent upregulation of SCGN and CACYBP, along with the downregulation of CAP2, represents a unique feature of NECC, distinguishing it from other neuroendocrine carcinomas. Conclusions This study uncovers the significance of kNsDEPs and elucidates their regulated networks in the context of NECC. It highlights the pivotal role of kNsDEPs in NECC diagnosis, thus offering promising prospects for the development of diagnostic biomarkers for NECC.

To explore and analyze the correlation between LncRNA TDRG1 expression degree and the prognosis of cervical carcinoma tissues. The cervical cancer tissues and para-carcinoma tissues of 106 patients with cervical carcinoma surgically removed in our hospital were chosen as specimens. LncRNA TDRG1 expression in cervical carcinoma tissues and para-carcinoma tissues was inspected by real-time fluorescence quantitative PCR, and the correlation between LncRNA TDRG1 and the clinicopathological parameters and disease prognosis was analyzed. The relative expression of LncRNA TDRG1 in cervical carcinoma tissues was critically gone up ( P  < 0.05) compared to para-carcinoma tissues. The relative expression of LncRNA TDRG1 in cervical carcinoma was correlated with FIGO staging, lymph node metastasis, infiltrating depth of cervical basal, and the differentiation of cancer cells ( P  < 0.05). According to the results of the Kaplan–Meier curve and Log-rank test, the overall survival conditions of subjects with low-lncRNA TDRG1 were superior to that of those with high-lncRNA TDRG1 expression ( P  < 0.05). The expression of LncRNA TDRG1 in cervical carcinoma tissues and the clinicopathological features in predicting the overall survival (OS) in sufferers with cervical carcinoma were investigated by the Cox regression model. LncRNA TDRG1 expression in cervical carcinoma tissues is tightly associated with the progression and prognosis of cervical carcinoma, which may be a latent biological indicator for clinical diagnosis and prognosis of cervical carcinoma.

At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2–IIB with node-positive disease or stage III–IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2–IIB node positive vs III–IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab–chemoradiotherapy group and 531 patients in the placebo–chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3–34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4–86·1) in the pembrolizumab–chemoradiotherapy group and 74·8% (70·1–78·8) in the placebo–chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50–0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab–chemoradiotherapy group and 371 (70%) of 530 in the placebo–chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab–chemoradiotherapy group and 90 (17%) of 530 patients in the placebo–chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. Merck Sharp & Dohme, a subsidiary of Merck & Co.

Background Cervical cancer is the tenth diagnosed cancer in the world. Early-stage and locally recurrent disease may be cured with radical surgery or chemo-radiotherapy. However, if disease persists or recurs, options are limited and the prognosis is poor. In addition to chemotherapy, bevacizumab, an antiangiogenic agent, has recently demonstrated its efficacy in this setting. Cabozantinib is an oral small molecule tyrosine kinase inhibitor that exhibits potent inhibitory activity against several receptor tyrosine kinases that are known to influence tumor growth, metastasis, and angiogenesis. The main targets of Cabozantinib are VEGFR2, MET and AXL. It is currently approved for the treatment of metastatic renal cell carcinoma, hepatocellular carcinoma and medullary thyroid carcinoma. Given its angiogenic properties associated with growth factor receptors inhibition, Cabozantinib represents a potential active treatment in cervical carcinoma. In this context, we propose to assess the efficacy and safety of cabozantinib monotherapy in advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment. Methods This study is a single-arm two-stage multicenter phase II aiming to simultaneously assess efficacy and safety of Cabozantinib among advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment. The main criterion will be based on both safety and clinical efficacy by conducting a Bryant-and-Day design. Safety endpoint is the proportion of patients with clinical gastro-intestinal (GI) perforation/fistula, GI-vaginal fistula and genito-urinary (GU) fistula events grade ≥ 2 (NCI CTCAE V.5.0) occurring up to one month after the end of treatment. Efficacy endpoint is the proportion of patients with disease control rate 3 months after Cabozantinib initiation. A patients’ self-reported quality of life evaluation is also planned, as well as the investigation of nutritional outcomes. Cabozantinib will be administered at the daily dose of 60 mg given orally, without interruption until disease progression or discontinuation for any cause. Discussion Cabozantinib is a promising drug for patients with advanced/metastatic cervical cancer where few therapeutics options are available after failure to platinum-based regimen metastatic CC. It appears challenging to assess the interest of Cabozantinib in this indication, taking into account the potential toxicity of the drug. Trial registration NCT04205799 , registered “2019 12 19”. Protocol version Version 3.1 dated from 2020 08 31.

Neuroendocrine cervical carcinoma (NECC) is a rare and highly aggressive gynecological tumor, with poor prognosis and limited standardized treatment options. Inflammation plays a significant role in tumor progression, and systemic inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have shown prognostic value in other malignancies. However, their role in NECC remains unclear. This single-center retrospective study included 25 NECC patients treated at our hospital between 2014 and 2024. Patients were divided into three groups based on treatment regimens: paclitaxel plus cisplatin combined with radiotherapy, etoposide plus cisplatin combined with radiotherapy, and radiotherapy alone. Baseline characteristics, inflammatory markers, and clinical outcomes were analyzed. Kaplan-Meier survival analysis and Log-rank tests were used to compare survival differences. The median survival time was significantly longer in the etoposide plus cisplatin plus radiotherapy group (1,000 days) compared to the paclitaxel plus cisplatin plus radiotherapy group (776 days) and the radiotherapy-alone group (347 days, P = 0.037). The radiotherapy-alone group had significantly higher neutrophil counts (median = 5.46 × 10 /L, P = 0.006), platelet counts (median = 282.5 × 10 /L, P = 0.017), NLR (median = 4.68, P < 0.05), and PLR (median = 231.93, P < 0.05), while LMR (median = 1.89, P < 0.05) was lower. For postoperative patients, the median survival time was 1,453 days for the surgery plus etoposide plus cisplatin plus radiotherapy group, compared to 987 days for the surgery plus paclitaxel plus cisplatin plus radiotherapy group (P = 0.048). Combined chemotherapy with etoposide plus cisplatin and radiotherapy significantly improves survival outcomes in NECC patients compared to radiotherapy alone. This regimen may be particularly beneficial for postoperative patients and those with high-risk factors such as lymphovascular space invasion. Further studies are needed to validate these findings and establish standardized treatment protocols for NECC.

Objective Small cell carcinoma of the cervix (SCCC) is rare but extremely aggressive and resistant to current therapies. We herein evaluate the efficacy of bevacizumab, apatinib, and anlotinib in recurrent/metastatic SCCC patients in a real-world setting. Methods Recurrent/metastatic SCCC patients were recruited between January 2013 and July 2020. Baseline characteristics were extracted from medical records, and patients were divided into an anti-angiogenic group and non-anti-angiogenic group. The efficacy of treatments was determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Kaplan–Meier analysis was performed for survival analysis. Results Sixteen patients received anti-angiogenic drugs after tumor recurrence/metastasis; of them, 10 cases received them as first-line treatment, 5 cases as second-line treatment, and 1 case as fourth-line treatment. Another 23 patients received traditional therapies, including surgery, chemotherapy, and radiotherapy. The use of anti-angiogenic drugs in first-line treatment significantly prolonged progression-free survival (PFS) compared to the controls, with a median PFS of 8 months (2-20 months) and 3 months (1-10 months), respectively (P = .025). This trend was also notable in patients who started anti-angiogenic treatment after the second-line recurrence/metastasis. However, there was no benefits for overall survival (OS) in either the 10 first-line cases or all 16 cases (P = .499 and .31, respectively). Both bevacizumab and small molecule drugs (apatinib and anlotinib) presented similar efficacy in SCCC patients. Conclusions At present, this is the largest cohort study that provides real-world data, showing that anti-angiogenic regimens could significantly prolong PFS in recurrent/metastatic SCCC. Aside from bevacizumab, the novel oral small molecule drugs provide more choices with similar efficacy. These findings warrant further validation in well-designed future studies.

Squamous cervical carcinoma (SCC) requires particular attention in diagnostic and clinical management. New diagnostic tools, such as (positron emission tomography–magnetic resonance imaging) PET–MRI, consent to ameliorate clinical staging accuracy. The availability of new technologies in radiation therapy permits to deliver higher dose lowering toxicities. In this clinical scenario, new surgical concepts could aid in general management. Lastly, new targeted therapies and immunotherapy will have more room in this setting. The aim of this narrative review is to focus both on clinical management and new therapies in the precision radiotherapy era.

Purpose Neuroendocrine cervical carcinoma (NECC) is an uncommon malignancy of the female reproductive system. This study aimed to evaluate cancer-specific mortality and to construct prognostic nomograms for predicting the survival of patients with NECC. Methods we assembled the patients with NECC diagnosed between 2004 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, we identified other patients with NECC from the Wenling Maternal and Child Health Care Hospital between 2002 to 2017. Fine and Gray’s test and Kaplan–Meier methods were used to evaluate cancer-specific mortality and overall survival (OS) rates, respectively. Nomograms were constructed for predicting cancer-specific survival (CSS) and OS for patients with NECC. The developed nomograms were validated both internally and externally. Results a total of 894 patients with NECC were extracted from the SEER database, then classified into the training cohort ( n  = 628) and the internal validation cohort ( n  = 266). Besides, 106 patients from the Wenling Maternal and Child Health Care Hospital served as an external validation cohort. Nomograms for predicting CSS and OS were constructed on clinical predictors. The validation of nomograms was calculated by calibration curves and concordance indexes (C-indexes). Furthermore, the developed nomograms presented higher areas under the receiver operating characteristic (ROC) curves when compared to the FIGO staging system. Conclusions we established the first competing risk nomograms to predict the survival of patients with NECC. Such a model with high predictive accuracy could be a practical tool for clinicians.

Background Neuroendocrine cervical carcinoma (NECC) is a rare but aggressive malignancy with younger patients compared to other common histology types. This study aimed to evaluate the impacts of ovarian preservation (OP) on the prognosis of NECC through machine learning. Methods Between 2013 and 2021, 116 NECC patients with a median age of 46 years received OP or bilateral salpingo-oophorectomy (BSO) and were enrolled in a retrospective analysis with a median follow-up of 41 months. The prognosis was estimated using Kaplan–Meier analysis. Random forest, LASSO, stepwise, and optimum subset prognostic models were constructed in training cohort (randomly selected 70 patients) and tested in 46 patients through receiver operator curves. Risk factors for ovarian metastasis were identified through univariate and multivariate regression analyses. All data processing was carried out in R 4.2.0 software. Results Among 116 patients, 30 (25.9%) received OP and showed no significantly different OS compared with BSO group ( p  = 0.072) and got better DFS ( p  = 0.038). After construction of machine learning models, the safety of OP was validated in lower prognostic risk group ( p  > 0.05). In patients ≤ 46 years, no impacts of OP were shown for DFS ( p  = 0.58) or OS ( p  = 0.67), and OP had no impact on DFS in different relapse risk population ( p  > 0.05). In BSO group, regression analyses showed that later stage, para-aortic LNM, and parametrial involvement were associated with ovarian metastasis ( p  < 0.05). Conclusions Preserving ovaries had no significant impact on prognosis in patients with NECC. OP should be considered cautiously in patients with ovarian metastasis risk factors.

Cervical high-grade squamous intraepithelial lesion (HSIL) is a well-recognized precursor to cervical squamous cell carcinoma (CSCC). This study aims to explore molecular mechanisms underlying this transition. The datasets of HSIL and CSCC were downloaded from gene expression omnibus database (GEO). HSIL and CSCC coexpression modules were analyzed by Weighted gene coexpression network analysis (WGCNA). Enrichment analysis were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). The immune microenvironment (TIME) was analyzed by CIBERSORT. Receiver operating characteristic (ROC) curve, and survival analysis were performed. The binding of FEN1 and its upstream regulator PCNA was determined by protein interaction, correlation analysis and rigid docking. Immune infiltration, immune checkpoint and docking with small molecule inhibitors was also analyzed. In vitro experiments were conducted to investigate the function and underlying mechanisms of FEN1 in HSIL and CSCC. A total of 30 sequentially expressed shared genes were identified as potential drug targets. Immune infiltration revealed an imbalance of M1/M2 macrophages, T γδ cells and T cells CD4 memory resting were negatively associated with tumor progression, forming a pro-cancer effect at the HSIL stage and progressing toward CSCC. The key gene FEN1 was over-expressed in HSIL and CSCC, and correlated with the prognosis of CSCC ( P  < 0.05). FEN1 interacts with PCNA to regulate macrophage-mediated immune infiltration, increase the risk of immune escape, and decrease the sensitivity to immune checkpoints. Small molecule inhibitor binds to FEN1 docking and inhibits its regulation. FEN1 expression is upregulated in both HSIL and CSCC, with a more pronounced increase in CSCC. Knockdown of FEN1 significantly inhibits the proliferation of cervical cancer cells. This study identifies FEN1 as a biomarker and therapeutic target to truncate or reverse CSCC progression at the HSIL stage.