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Purpose: Systemic immunity is essential for driving therapeutically induced antitumor immune responses, and the spleen may reflect alterations in systemic immunity. This study aimed to evaluate the predictive value of contrast-enhanced CT-based spleen radiomics for progression-free survival (PFS) in patients with locally advanced cervical cancer (LACC) who underwent definitive chemoradiotherapy (dCRT). Additionally, we investigated the role of spleen radiomics features and changes in spleen volume in assessing systemic immunity., Methods: This retrospective study included 257 patients with LACC who underwent dCRT. The patients were randomly divided into training and validation groups in a 7:3 ratio. Radiomic features were extracted from CT images obtained before and after dCRT. Radiomic scores (Radscore) were calculated using features selected through least absolute shrinkage and selection operator (LASSO) Cox regression. The percentage change in spleen volume was determined from measurements taken before and after treatment. Independent prognostic factors for PFS were identified through multivariate Cox regression analyses. Model performance was evaluated with the receiver operating characteristic (ROC) curve and the C-index. The Radscore cut-off value, determined from the ROC curve, was used to stratify patients into high- and low-risk survival groups. The Wilcoxon test was used to analyze differences in hematological parameters between different survival risk groups and between different spleen volume change groups. Spearman correlation analysis was used to explore the relationship between spleen volume change and hematological parameters., Results: Independent prognostic factors included FIGO stage, pre-treatment neutrophil-to-lymphocyte ratio (pre-NLR), spleen volume change, and Radscore. The radiomics-combined model demonstrated the best predictive performance for PFS in both the training group (AUC: 0.923, C-index: 0.884) and the validation group (AUC: 0.895, C-index: 0.834). Compared to the low-risk group, the high-risk group had higher pre-NLR (p = 0.0054) and post-NLR (p = 0.038). Additionally, compared to the decreased spleen volume group, the increased spleen volume group had lower post-NLR (p = 0.0059) and post-treatment platelet-to-lymphocyte ratio (p < 0.001)., Conclusion: Spleen radiomics combined with clinical features can effectively predict PFS in patients with LACC after dCRT. Furthermore, spleen radiomics features and changes in spleen volume can reflect alterations in systemic immunity., Competing Interests: Declarations Ethics approval and consent to participate Our retrospective study abided by the rules of medical ethics, and the Institutional Review Board (IRB) of Shandong Cancer Hospital approved this study. The number for the ethical statement was SDTHEC2024006159. All patients were informed before treatment, agreed to receive concurrent dCRT and signed informed consent forms. We protected patient privacy and excluded patient identification information from our analysis. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Magnetic resonance image-guided brachytherapy is essential in the management of locally advanced cervical cancer. This study compares disease and toxicity outcomes in cervical cancer patients treated with 24 Gy/3 fractions (Fr) versus the conventional 28 Gy/4 Fr., Methods and Materials: This retrospective study included 241 consecutive patients with International Federation of Gynecology and Obstetrics 2018 stage IB to IVA cervical cancer treated with definitive chemoradiation between April 2014 and March 2021. Disease-free survival (DFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Cumulative incidence of local failure (LF), distant failure (DF), and G2+ gastrointestinal (GI), urinary and vaginal toxicity were estimated using the cumulative incidence function with death as a competing risk and compared using Gray's test., Results: Of the 241 patients, 42% received 24 Gy/3 Fr and 58% received 28 Gy/4 Fr. With a median follow-up of 3.2 (range, 0.2-9.2) years, there were 14 local, 41 regional nodal, and 51 distant failures in 63 (26%) patients. No significant differences were found between the 24 Gy/3 Fr and 28 Gy/4 Fr groups in 3-year DFS (77% vs 68%, P = .21), the 3-year cumulative incidence of LF (5% vs 7%, P = .57), DF (22% vs 25%, P = .86), G2+ GI toxicity (11% vs 20%, P = .13), or G2+ vaginal toxicity (14% vs 17%, P = .48), respectively. The 3-year cumulative G2+ urinary toxicity rate was lower in the 24 Gy/3 Fr group (9% vs 23%, P = .03)., Conclusions: Patients with cervical cancer treated with 24 Gy/3 Fr had similar DFS, LF, DF, GI, and vaginal toxicity rates and a trend toward a lower G2+ urinary toxicity rate compared with those treated with 28 Gy/4 Fr. A less resource-intensive brachytherapy fractionation schedule of 24 Gy/3 Fr is a safe alternative to 28 Gy/4 Fr for definitive treatment of cervical cancer., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Locally advanced cervical carcinoma (LACC) remains a significant global health challenge owing to its high recurrence rates and poor outcomes, despite current treatments. This study aimed to develop a comprehensive risk stratification model for LACC by integrating Cox regression and competing risk analyses. This was done to improve clinical decision making. We analyzed data from 3428 patients with LACC registered in the Surveillance, Epidemiology, and End Results program and diagnosed them between 2010 and 2015. Cox regression and competing risk analyses were used to identify the prognostic factors. We constructed and validated nomograms for overall survival (OS) and disease-specific survival (DSS). Multivariate Cox regression identified key prognostic factors for OS, including advanced International Federation of Gynecology and Obstetrics stage, age, marital status, ethnicity, and tumor size. Notably, International Federation of Gynecology and Obstetrics stages IIIA, IIIB, and IVA had hazard ratios of 2.227, 2.451, and 4.852, respectively, significantly increasing the mortality risk compared to stage IB2. Ethnic disparities were evident, with African Americans facing a 39.8% higher risk than Caucasians did. Competing risk analyses confirmed the significance of these factors in DSS, particularly tumor size. Our nomogram demonstrated high predictive accuracy, with area under the curve values ranging from 0.706 to 0.784 for DSS and 0.717 to 0.781 for OS. Calibration plots and decision curve analyses further validated the clinical utility of this nomogram. We present effective nomograms for LACC risk stratification that incorporate multiple prognostic factors. These models provide a refined approach for individualized patient management and have the potential to significantly enhance therapeutic strategies for LACC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To investigate the efficacy and safety of robot-assisted radical hysterectomy (RARH) as a minimally invasive procedure in patients with cervical cancer that is curable by surgery., Materials and Methods: This study was a multicenter, open-label, single-arm clinical trial. The short-term outcome of open radical hysterectomy was used as the historical control. The primary endpoint was successful surgery with minimal blood loss (300 mL or less) and negative surgical margins. Secondary endpoints included surgical outcomes, recurrence-free survival (RFS), and overall survival (OS) rates., Results: Overall, 101 cases were enrolled in this study at 10 participating medical institutions and 100 underwent RARH. Among these cases, 89 met the primary endpoint, exceeding the threshold of 0.75 set by the lower limit. At 2 years postoperatively, 17 cases had recurrences, 4 were classified as International federation of Obstetrics and Gynecology Stage IB1 or lower, while 13 as IB2 or higher. There were three deaths, including one in Stage IB1 and two in Stage IIB in the second postoperative year, all of which had lymph node metastasis. The oncological outcomes for all cases showed RFS and OS rates of 82.7% and 96.9%, respectively, over a median observation period of 37 months. For cases with Stage IB1, RFS and OS were 94.1% and 98.5%, respectively., Conclusion: RARH demonstrated a significant reduction in blood loss while ensuring radicality, indicating the safety and efficacy of this procedure compared to conventional RH. Although it is conceivable that the results of this oncological analysis could change, as the data collection has not been fully completed, we plan to further evaluate the oncologic outcomes of RARH in future studies., Trial Registration: UMIN-CTR: UMIN000022278, registered on 11th May 2016., (© 2024. The Author(s).)

Patients with advanced and recurrent cervical cancer often lack satisfactory treatment outcomes. Thus, it is necessary to seek reliable biomarkers that provide the ability to identify the disease at an early stage and predict the patient prognosis, providing new strategies for the treatment of cervical cancer. The sequencing data of ITGA3 were retrieved from public datasets. Immune infiltration and sensitivity of potential immunotherapy and chemotherapy have been analyzed between two subgroups. Functional analysis was applied to excavate the related pathways of ITGA3 in cervical cancer. Furthermore, the impact of ITGA3 in tumor progression has been verified in vitro. The results revealed that the level of ITGA3 was upregulated in cervical cancer, and was positively correlated with worse prognosis. The tumor microenvironment of patients in the high-risk group was immunosuppressed. Patients in high-risk group may not benefit from immunotherapy, but be may be sensitive to several chemotherapy drugs. Notably, the angiogenesis, epithelial mesenchymal transition, and PI3K pathway were increased in high-risk group. Collectively, ITGA3 is a marker of poor prognosis and promotes tumor progression by regulating PI3K/AKT pathway in cervical cancer. Our results provide new insights for potential molecular targeted therapy and prognostic prediction of cervical cancer., (© 2024. The Author(s).)

Objective: To determine the relationship between the Silva pattern-based classification system and endocervical adenocarcinoma., Methods: The PubMed, Embase, Central Cochrane Library, and Web of Science databases were systematically searched for studies that investigated the correlation between the Silva classification system and the oncology prognosis or pathological features of endocervical adenocarcinoma, published in the period from January 2013 to March 2024., Results: A total of 19 eligible studies including 3122 cases were included in this systematic review and meta-analysis. The combined death rate in the Silva A, Silva B, and Silva C patterns was 0% (95% CI 0.0% to 0.4%), 2.6% (95% CI 0.4% to 5.9%), and 14.0% (95% CI 9.4% to 19.2%), respectively; the combined recurrence rate in the Silva A, Silva B, and Silva C patterns was 0.1% (95% CI 0.0% to 1.2%), 5.1% (95% CI 1.6% to 10.0%), and 19.4% (95% CI 14.7% to 24.4%), respectively; the combined lymphovascular invasion rate in the Silva A, Silva B, and Silva C patterns was 0% (95% CI 0.0% to 0.5%), 21.0% (95% CI 16.9% to 25.4%), and 58.8% (95% CI 50.1% to 67.3%), respectively; and the combined International Federation of Gynecology and Obstetrics (FIGO) I rate in the Silva A, Silva B, and Silva C patterns was 99.3% (95% CI 97.6% to 100%), 93.7% (95% CI 86.4% to 98.7%), and 82.4% (95% CI 74.9% to 88.9%), respectively., Conclusion: Our study found that Silva A was negatively correlated with death rate, while Silva C was positively correlated. There was no correlation regarding the death rate for Silva B. Based on these findings, it is suggested that the Silva pattern-based classification system can predict the prognosis of human papillomavirus (HPV)-related endocervical adenocarcinoma and assist in guiding patient treatment., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Radiation-induced lymphopenia (RIL) is closely related to the prognosis of cervical cancer patients and may affect the efficacy of immune checkpoint inhibitors (ICIs). However, the factors influencing RIL are not very clear. In addition to bone marrow (BM) dose-volume, animal studies indicate radiation-induced bowel injury may be a more crucial factor. Further clarification of the correlation between RIL and bowel dose-volume is important for cervical cancer treatment., Methods: Cervical cancer patients treated with postoperative radiotherapy or radical radiotherapy were eligible for this retrospective study. Clinical characteristics, dose parameters of bowel and BM, planning target volume (PTV) size, overall survival (OS) and progression-free survival (PFS) were recorded. The absolute lymphocyte count<0.5×10 9 /L at radiotherapy end was defined as severe RIL (sRIL). Hazard ratio (HR) and 95% confidence interval (Cl)were estimated using Cox regression models. Survival curve was plotted using the Kaplan-Meier method. On this basis, the receiver operating characteristics (ROC) curve was used to calculate the area under the curve (AUC) for radiation parameters with sRIL as the state variable., Result: A total of 118 cervical cancer patients were included in this study, with a median follow-up time of 57.6 months. In multivariable Cox regression analysis, international Federation of Gynecology and obstetrics (FIGO) stage (HR, 11.806; 95% CI, 3.256-42.809; p<0.001), concurrent chemotherapy (HR, 0.200; 95% CI, 0.054-0.748; p=0.017), sRIL after radiotherapy (HR, 6.009; 95% CI, 1.361-26.539; p=0.018), and pathological type (HR, 2.261; 95% CI, 1.043-4.901; p=0.039) were significantly correlated with OS. Patients with sRIL had significantly decreased OS (79.1% vs 94.1%; HR, 3.81; 95%CI, 1.46-9.92; p=0.023). In binary logistic regression analysis, sRIL was significantly correlated with bowel V45 (Odds radio (OR), 1.025; 95%CI, 1.007-1.044; p=0.007), BM V10 (OR, 0.987; 95%CI, 0.978-0.997; p=0.011), BM V20 (OR, 1.017; 95%CI, 1.002-1.031, p=0.027), and PTV size (OR, 0.998; 95%CI, 0.996-1.000; p=0.026). The ROC curve showed, bowel V45 (AUC=0.787, p<0.001) was the best indicator for predicting sRIL., Conclusion: SRIL after radiotherapy could significantly predict decreased OS. In addition, sRIL is associated with higher bowel, BM dose-volume, PTV size, indicating that the bowel may be an important organ leading to an increased risk of sRIL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LZ declared a shared affiliation with the author YX to the handling editor at time of review., (Copyright © 2024 Li, Chen, Liu, Xu and Ji.)

Background: Highly heterogeneity and inconsistency in terms of prognosis are widely identified for early-stage cervical cancer (esCC). Herein, we aim to investigate for an intuitional risk stratification model for better prognostication and decision-making in combination with clinical and pathological variables., Methods: We enrolled 2071 CC patients with preoperative biopsy-confirmed and clinically diagnosed with FIGO stage IA-IIA who received radical hysterectomy from 2013 to 2018. Patients were randomly assigned to the training set (n = 1450) and internal validation set (n = 621), in a ratio of 7:3. We used recursive partitioning analysis (RPA) to develop a risk stratification model and assessed the ability of discrimination and calibration of the RPA-derived model. The performances of the model were compared with the conventional FIGO 2018 and 9th edition T or N stage classifications., Results: RPA divided patients into four risk groups with distinct survival: 5-year OS for RPA I to IV were 98%, 95%, 85.5%, and 64.2%, respectively, in training cohort; and 99.5%, 93.2%, 85%, and 68.3% in internal validation cohort (log-rank p < 0.001). Calibration curves confirmed that the RPA-predicted survivals were in good agreement with the actual survivals. The RPA model outperformed the existing staging systems, with highest AUC for OS (training: 0.778 vs. 0.6-0.717; internal validation: 0.772 vs. 0.595-0.704; all p < 0.05), and C-index for OS (training: 0.768 vs. 0.598-0.707; internal validation: 0.741 vs. 0.583-0.676; all p < 0.05). Importantly, there were associations between RPA groups and the efficacy of treatment regimens. No obvious discrepancy was observed among different treatment modalities in RPA I (p = 0.922), whereas significant survival improvements were identified in patients who received adjuvant chemoradiotherapy in RPA II-IV (p value were 0.028, 0.036, and 0.024, respectively)., Conclusion: We presented a validated novel clinicopathological risk stratification signature for robust prognostication of esCC, which may be used for streamlining treatment strategies., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: This study aimed to investigate the prognostic value of miRNAs and ferroptosis-related genes in cervical squamous cell carcinoma., Methods: We mined data from public databases for differentially expressed miRNAs, ferroptosis-related genes, and clinical parameters and constructed a prognostic risk model. The predictive performance of the model was evaluated using survival and receiver operating characteristic curve analyses. We combined the clinicopathological features to construct a nomogram and evaluated its efficacy using calibration and clinical decision curves. The correlation between miRNA characteristics, risk score, and the tumor microenvironment was also studied. Next, consensus and key genes were screened, and their biological functions were analyzed using KEGG, GO, GSEA, and drug sensitivity analysis. Finally, the expression of miRNAs and key genes was detected using qRT-PCR and western blotting to verify the prediction results., Results: Seven miRNA signatures (miR-100-3p, miR-301a-5p, miR-331-3p, miR-425-5p, miR-502-3p, miR-505-5p, and miR-629-3p) were generated, and prognostic risk and nomogram models were successfully constructed. These models exhibited good accuracy. miRNA signatures correlated with the tumor microenvironment. Twelve consensus genes and three key genes (SLC2A1, ANO6, and TXNIP) were screened and their biofunctional diversity was identified using various analytical methods. qRT-PCR and western blotting were used to verify the expression of miR-301a-5p, miR-505-5p, SLC2A1, and TXNIP in cervical squamous carcinoma. The results were consistent with those of bioinformatics analyses., Conclusions: Seven miRNAs may serve as prognostic biomarkers of cervical squamous cell carcinoma. SLC2A1, ANO6, and TXNIP are associated with cervical squamous cell carcinoma and may serve as ferroptosis-related markers of the disease., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To ascertain the prognostic role of the expression levels of estrogen receptor (ER) and progesterone receptor (PR) within the stroma microenvironment of cervical cancer and explore their correlation with clinical parameters., Materials and Methods: This retrospective cohort study involved patients with cervical cancer diagnosed and treated at Hualien Tzu Chi Hospital between 2000 and 2010. ERα, PRB, and PR (A + B) expression levels in 169 cervical carcinoma samples, including both the tumor and stromal components, were independently scored by two pathologists, and survival and clinicopathological parameters were analyzed., Results: ERα or PRs were predominantly expressed in the stromal compartment rather than within cervical cancer cells. Their expression was observed comprehensively within the intra- and peritumor stroma cells. A stromal PRB expression significantly correlated with a lower 5-year mortality because of cervical cancer (p = 0.011). Particularly, levels of both stromal ERα and PRB expressions correlated with lower hematogenous distant metastase rates (p = 0.013 and p = 0.011, respectively). In the multivariable logistic regression analyses, stromal PRB independently conferred a lower risk of 5-year mortality (p = 0.022), regardless of age, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation, lymphovascular space invasion, and lymphatic and hematogenous metastases. Moreover, the incorporation of stromal PR (A + B) and PRB expression in the FIGO stage significantly enhanced the accuracy of survival prediction., Conclusion: Stromal PRB expression emerges as an independent and favorable prognostic marker for cervical squamous cell carcinoma and correlated with a low risk of hematogenous metastases. The findings imply that incorporating this marker into the FIGO stage better predicts the survival for cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background/aim: We hypothesized that adding bevacizumab to platinum-based neoadjuvant chemotherapy - whose efficacy for patients with recurrent or metastatic cervical cancer has already been proven - could optimize the therapy regimen, leading to improved response rates and survival outcomes., Patients and Methods: Forty patients with histologically confirmed cervical cancer with FIGO stage IB3-IVA who received platinum-based neoadjuvant treatment between March 2008 and January 2019 in the Department of Obstetrics and Gynecology of University Hospital Cologne were analyzed. Twenty patients were treated with additional bevacizumab. The comparative cohort consisted of 18 patients treated with neoadjuvant chemotherapy alone. The response rates and clinical outcomes, including progression-free survival and overall survival, were evaluated., Results: Neoadjuvant chemotherapy combined with bevacizumab significantly improved the response rate (p=0.046). The survival analysis showed that patients treated without bevacizumab had better progression-free survival up to FIGO stage IVA than patients treated with bevacizumab. However, overall survival was similar for both cohorts. For patients with advanced tumor stage, including FIGO IVB, progression-free survival and overall survival improved with the addition of bevacizumab. Pathological complete remission was a statistically significant prognostic factor for progression-free survival (p=0.039) but did not significantly affect overall survival (p=0.098)., Conclusion: While bevacizumab did not demonstrate a significant improvement in overall survival rates, it was associated with a notable reduction in tumor size and showed a trend towards improved clinical response rates. These findings suggest that bevacizumab may have potential in optimizing the neoadjuvant treatment approach., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Invasive stratified mucin-producing carcinoma (ISMC) is a rare but aggressive variant of endocervical adenocarcinoma (EAC). The aim of this study was to investigate the differences in clinicopathological features, patient outcomes, and programmed death-ligand 1 (PD-L1) expression among ISMC, usual-type EAC (UEA), and gastric-type EAC (GEA)., Patients and Methods: PD-L1 22C3 immunostaining was performed using 20 ISMCs, 20 UEAs, and 20 GEAs. Combined positive score (CPS) method was used to assess PD-L1 immunoreactivity., Results: ISMC was diagnosed at a younger age and showed a more advanced stage and shorter survival than UEA. The disease-free survival (DFS) and overall survival (OS) rates of ISMC patients were lower than those of UEA but comparable to those of GEA. ISMC type was an independent prognostic factor for predicting short DFS [hazard ratio (HR)=2.790, 95% confidence interval (CI)=1.153-6.756] and OS (HR=6.071, 95%CI=1.257-29.327). All ISMCs showed PD-L1 over-expression with a mean CPS of 44.5 (range=10-100), which was higher than those of UEA (mean CPS=8.2) and GEA (mean CPS=6.5). PD-L1 positivity (CPS≥1) was also an independent prognostic factor for worse OS (HR=2.472, 95%CI=1.097-5.570). Despite PD-L1 over-expression, ISMC patients treated with pembrolizumab showed no clinical response., Conclusion: All examined ISMCs over-expressed PD-L1. ISMC showed higher PD-L1 expression than UEA and GEA and worse survival than UEA. PD-L1 over-expression was found to be a significant predictor for worse DFS and OS in patients with ISMC. Our data suggest that PD-L1 over-expression is associated with poor ISMC prognosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Simlukafusp alfa (FAP-IL2v) is an immune cytokine engineered to selectively promote immune responses in the tumour microenvironment. We evaluated the antitumour activity and safety of FAP-IL2v plus atezolizumab in recurrent and/or metastatic cervical squamous cell carcinoma (SCC) in a phase 2 basket study (NCT03386721)., Methods: Patients with confirmed metastatic, persistent or recurrent cervical SCC who had progressed on ≥1 anti-cancer therapy and had measurable disease were enrolled. FAP-IL2v 10 mg was administered once every 3 weeks (Q3W) or once weekly (QW) for 4 weeks then once every 2 weeks (Q2W) with the corresponding Q3W or Q2W atezolizumab regimens. The primary endpoint was objective response rate by investigator assessment., Findings: Forty-eight patients were enrolled (Q3W: n = 47; QW/Q2W: n = 1). Among 45 response evaluable patients, objective responses occurred in 12 patients (27%; CI 16.0-41.0), including 3 complete and 9 partial responses. Responses occurred in 6/19 PD-L1 positive patients (32%; 95% CI 15.4-54.0) and 5/24 PD-L1 negative patients (21%; 95% CI 9.2-35.6). Median duration of response was 13.3 months (95% CI 7.6-NE). Median progression-free survival was 3.7 months (95% CI 3.3-9.0). Adverse events (AEs) were consistent with the known safety profile of each drug. AEs leading to withdrawal of either agent occurred in 6 patients (13%). Pronounced expansion and activation of natural killer and CD8 T cells in peripheral blood and increased tumour infiltration and inflammation were observed., Interpretation: FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC., Funding: F. Hoffmann-La Roche Ltd., Competing Interests: Declaration of interests L. Verlingue reports grants from Bristol-Myers Squibb; royalties or licenses from RESOLVED; payment or honoraria from Bristol-Myers Squibb; leadership or fiduciary role as CEO of RESOLVED; stock or stock options from RESOLVED; as part of the Drug Development Department (DITEP) of Gustave Roussy and Early Phase Unit of Centre Léon Bérard, L. Verlingue reports being Principal/Sub-Investigator of clinical trials for AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, argenx, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, AVEO pharmaceuticals, Basilea Pharmaceutica, Bayer, BBB Technologies, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eli Lilly, Exelixis, Faron Pharmaceuticals, F. Hoffmann-La Roche, Forma Therapeutics, GamaMabs Pharma, Genentech, GlaxoSmithKline, H3 Biomedicine, ImCheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Pharmaceuticals, Kura Oncology, Kyowa Kirin, Loxo Oncology, Lytix Biopharma, Medimmune, Menarini Ricerche, Merck Sharpe & Dohme, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners, Nanobiotix, Nektar Therapeutics, Novartis, Octimet Oncology, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, PharmaMar, Pierre Fabre, Medicament, Sanofi, Seattle Genetics, SOTIO, Servier, Syros Pharmaceuticals, Taiho Pharma, Tesaro, and Xencor; research grants from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen Pharmaceuticals, Merck Sharpe & Dohme, Novartis, Onxeo, Pfizer, Roche, and Sanofi; non-financial support (drug supplied) from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Medimmune, Merck Sharpe & Dohme, NH TherAGuiX, Onxeo, and Pfizer. H. Prenen reports payment or honoraria for presentations from Amgen, AstraZeneca, Bayer, Roche, and Sanofi; support for attending meetings from AstraZeneca, Bayer, and Roche; personal fees for participation on a Data Safety Monitoring Board or Advisory Board for Biocartis and Cureteq. E. M. Guerra Alia reports personal consulting fees for AstraZeneca, Clovis Oncology, GlaxoSmithKline, Merck Sharpe & Dohme, PharmaMar, and Roche; payment or honoraria from AstraZeneca (personal), Clovis Oncology, GlaxoSmithKline, Merck Sharpe & Dohme, and PharmaMar; personal payment for expert testimony from AstraZeneca, Clovis Oncology, GlaxoSmithKline, Merck Sharpe & Dohme, PharmaMar, and Roche; personal support for attending meetings and/or travel from AstraZeneca and GlaxoSmithKline. R. Perets reports personal consulting fees for 1Etx, Galmed Therapeutics, and Gilboa Therapeutics; payment or honoraria from Merck Sharpe & Dohme; support for attending meetings and/or travel from Pfizer. I Lugowska reports grants or contracts from Agenus and Roche; personal payment or honoraria from Bristol-Myers Squibb, Novartis, and Merck Sharpe & Dohme; support for attending a meeting and/or travel from ESMO; other financial interests or non-financial interests from Clinnote. A. Taus reports payment or honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharpe & Dohme, Pfizer, Roche, Sanofi, and Takeda. A. Oaknin reports institutional funding from AbbVie, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics, Bristol-Myers Squibb, Clovis Oncology, Eisai, Immunogen, Merck Sharpe & Dohme, Millennium Pharmaceuticals, PharmaMar, Regeneron Pharmaceuticals, Roche, and Tesaro; personal fees for participation on an Advisory Board from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, Genmab, GlaxoSmithKline, ImmunoGen, Itheos, Merck Sharpe & Dohme, Mersana Therapeutics, Novocure, OneXerna Therapeutics, PharmaMar, Regeneron, Roche, Sattucklabs, Seagen, and Sutro Biopharm. S. Goksu reports institutional payment or honoraria from Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Pfizer; participation on a Data Safety Monitoring Board or Advisory Board from Novartis and Pfizer. S. Roselló-Keränen reports personal payment or honoraria for presentations from Amgen, Merck Sharpe & Dohme, and Servier; personal fees for participation on an Advisory Board from Pierre Fabre and Sirtex. R. Dziadziuszko reports personal consulting fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharpe & Dohme, Pfizer, Novartis, Roche, and Takeda; payment or honoraria from AstraZeneca, Amgen, Pfizer, Novartis, Roche, and Takeda; support for attending meetings and or travel from Pfizer; receipt of equipment, materials, drugs, medical writing, gifts, or other services from Novartis and Pfizer. C. Habigt is a Roche employee with stock options. D. Marbach is a Roche employee. C. Boetsch is a Roche employee with stock options. D. Dejardin is a Roche employee with patents/stocks. N. Sleiman is a Roche employee. S. Evers is a former Roche employee and current shareholder. M. Richard is a Roche employee with stock options. C. Ardeshir is a Roche employee and shareholder. J. Charo is a Roche employee with patents/stocks. A. Kraxner is a Roche employee with stocks and stock options. V. Teichgräber is a Roche employee with stock options. N. Keshelava is a Roche employee with stock options. A. Italiano, D. Tosi, V. Moiseyenko, M. Gumus, C. Arslan, C. Lindsay, S. Deva, S. Rottey, I. Cicin, and A. Smolin have no disclosures to report., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This analysis assessed the association between regional income, screening coverage for cervical and breast cancer, and temporal trends in mortality from these cancers in different Brazilian health regions., Study Design: Spatiotemporal ecological study across 450 health regions of Brazil., Methods: Data from 2010 Demographic Census were used to assess income. Variations in income distribution within health regions were measured using the Gini index. Data on screening coverage were obtained from the Ambulatory Information System (SIA/SUS). Mortality was assessed from the Global Burden of Disease Study 2019 data. The average annual percentage change (AAPC) in cervical and breast cancer mortality rates, 2010-2018, was calculated by health regions. Results were presented in regional maps. The associations between income, screening coverage and mortality changes were estimated by bivariate spatial correlation., Results: Health regions located in the South and Southeast regions of Brazil had the greatest percentages of screening coverage and highest per capita incomes with the lowest Gini index values. From 2010 to 2018, mortality rates for cervical cancer were highest in the North and Northeast health regions. Breast cancer mortality rates were highest in the South and Southeast health regions. The AAPC in breast and cervical cancer mortality had a negative association with per capita income and screening coverage, and a positive association with the Gini index., Conclusions: There are large regional variations in income, screening coverage, and mortality rates for women with breast and cervical cancer. These inequities could be mitigated by policies to address income disparities and improved access to screening., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objective: Systemic immune, inflammatory, and nutritional indices are prognostic across multiple tumor sites. Comprehensive analysis of these markers in patients with locally advanced cervical cancer (LACC) treated with definitive (chemo)radiotherapy [(C)RT] is limited and may assist with future prognostication., Methods: For this retrospective cohort study, patients with LACC treated with definitive (C)RT were identified from a comprehensive cancer center's clinicopathological database. Pre-treatment indices were derived including systemic immune-inflammation index (SII), platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), albumin to alkaline phosphatase ratio (AAPR) and prognostic nutritional index (PNI). Univariate analysis was performed for PFS and OS. ROC curves were analyzed to determine optimal cut points. PFS and OS were assessed by the Kaplan-Meier method and Log-Rank test. Multivariate analysis was performed using Cox regression., Results: 196 patients were identified: median follow-up 7 years (IQR 2-11). Higher SII (≤700 vs >700; p = 0.01), higher PLR (≤ 250 vs >250; p < 0.001) and higher NLR (≤ 5 vs >5; p = 0.003) were associated with worse PFS. Higher SII (≤700 vs >700: p = 0.02), higher PLR (≤ 250 vs >250: p < 0.001) and higher NLR (≤ 5 vs >5; p = 0.01) were associated with worse OS. On multivariate analysis, SII, NLR and PLR were independently associated with PFS. SII and PLR were independently associated with OS., Conclusions: SII and PLR were independently associated with PFS and OS in patients with LACC treated with definitive (C)RT. NLR was independently associated with PFS. High inflammatory state is associated with shorter survival suggesting this as a target for interventions if validated in future studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MK is a consultant for Helix Biopharma (outside the scope of this study). MK is an Editorial Board Member for Gynecologic Oncology and was not involved in the editorial review or the decision to publish this article. The other authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer., Methods: International, multicenter, retrospective study., Inclusion Criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy ('SLN' group) or pelvic lymphadenectomy alone ('non-SLN' group)., Results: 1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5-98.5 versus 92.0 %,95 %CI:90.0-94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8-99.9 versus 96.8 %,95 %CI:95.4-98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266-0.959, p = 0.037 and HR:2.703,95 %CI:1.389-5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039)., Conclusion: Adding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Abu-Rustum received research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess the influence of geographies and race on the survival outcomes in patients diagnosed with cervical squamous cell carcinoma (CSCC) across three continents., Methods: This multicontinental retrospective study was conducted in 8 hospitals across Asia, Europe, and North America (NA). Clinicopathologic data of 595 patients with presumed early stages of CSCC, treated surgically, with curative intent was collected. Descriptive analysis and Cox regression models were produced., Results: A total of 595 patients, consisting of 445 (74.8 %) white, 75 (12.6 %) Blacks, and 75 (12.6 %) Asian patients were included. Geographical distribution comprised 69 % of patients from NA, 22 % from Europe, and 9 % from Asia. The median age at diagnosis was 46 years. The median overall survival (OS) and relapse-free survival (RFS) were 22.09 years and 21.19 years, respectively. Patient characteristics varied significantly across geographical regions, except for consensus tumor grade. Patients in Europe from middle-income countries with limited CC screening had a substantially higher risk of death than those in NA (HR, 1.79; 95 % CI, 1.13 to 2.79; p = 0.015). Patients from single center in Japan had higher risk of relapse than those from the four heterogeneous NA centers (sub-distribution hazard ratio, 2.19; 95 % CI, 1.22 to 3.95; p = 0.009), although OS did not differ significantly. Race remained statistically insignificant for survival outcomes across the three continents but seemed to influence survival outcomes in NA centers., Conclusion: Our study highlights impact of geographies and races on CSCC survival outcomes, emphasizing the need of considering these factors when developing targeted interventions against CSCC., Competing Interests: Declaration of competing interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The survival outcomes of Stage IIIC1 in FIGO 2018 showed significant heterogeneity and it seems unreasonable to administer a uniform treatment regimen for Stage IIIC1 patients. This study aimed to assess the survival outcomes among patients with locally advanced cervical cancer based on various lymph node statuses, T-stage classifications, and treatment modalities., Methods: This is a population-based cohort study utilizing the Surveillance, Epidemiology, and End Results Program from 2004 to 2018. Propensity score-based inverse probability of treatment weighting was used to achieve covariate balance. Women with locally advanced cervical cancer on different lymph node statuses who underwent radical hysterectomy + pelvic lymphadenectomy + chemoradiotherapy, chemoradiotherapy, or radiotherapy alone were examined. Trends, patient characteristics, and survival outcomes were compared across different treatment regimens., Results: Among 8777 patients analyzed, patients with early T-stage and married were identified as independent protective factors for cancer-specific survival regardless of lymph node status. The survival outcomes ranked in descending order as follows: T1N0>T2N0>T1N1 = T2N1>T3N0>T3N1. Therefore, the FIGO Stage IIIC1 was re-stratified into IIC (T1N1+T2N1) and IIIC1(T3N1). Patients who underwent radical hysterectomy combined with adjuvant therapy exhibited superior 5-year cancer-specific survival rates compared to those treated with chemoradiotherapy among IB3, IIA2, and IIC. The therapeutic efficacy of chemoradiotherapy surpassed that of radiotherapy alone in IIIA, IIIB, IIIC1(T3N1), and IVA patients., Conclusion: Restratification of Stage IIIC1 based on T-stage effectively discerns patients with divergent prognoses. Radical surgery + chemoradiotherapy is significantly associated with improved survival in early T-stage, regardless of lymph node status in locally advanced cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the significance of response assessment with magnetic resonance imaging (MRI) during chemoradiotherapy (CRT) for outcomes of adenocarcinoma of the cervix., Methods: A retrospective analysis of 102 patients diagnosed with FIGO 1B3-IVa cervical adenocarcinoma was conducted. Patients underwent definitive CRT and brachytherapy. Mid-treatment MRI-assessments were used to evaluate tumor response during radiotherapy, focusing on tumor volume reduction rate (TVRR), which was defined as an optimal reduction rate from initial tumor volume for tumor progression. Locoregional recurrence (LRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS) rates according to the tumor response were analyzed., Results: Forty-five (44.1 %) of 102 patients experienced tumor downstaging during CRT, with 72 (70.5 %) demonstrating a complete response on post-treatment MRI three months after radiotherapy. With a median follow-up of 35.5 months, the 3-year PFS and overall OS rates for all patients were 60.0 % and 84.0 %, respectively. LRR and DM rates at 3 years were 25.2 % and 23.3 %, respectively. Patients with TVRR≥81.8 % had significantly longer 3-year PFS (75.4 % vs. 36.2 %, P < 0.001) and OS (93.2 % vs. 69.0 %, P = 0.002) rates than the other patients with TVRR<81.8 %. LRR (10.6 % vs. 45.6 %, P = 0.003) and DM (14.6 % vs. 33.5 %, P = 0.008) rates at 3 years were significantly lower in TVRR≥81.8 % group compared to TVRR<81.8 % group. In the multivariate analysis, positive initial lymph node (hazard ratio [HR], 2.11; confidence interval [CI], 1.25-3.87; P = 0.02] and TVRR (HR, 0.42; CI, 0.19-0.93; P = 0.03) were significantly associated with PFS., Conclusion: Mid-treatment MRI assessment is crucial and higher rates of tumor volume reduction during radiotherapy indicates better prognosis for tumor recurrence and patient survival in cervical adenocarcinoma., Competing Interests: Declaration of competing interest The authors declare no financial or other interest that is relevant to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

It has been discovered that aberrant expression of RNF113A plays a significant role in various diseases, including esophageal cancer, hepatocellular carcinoma, and X-linked trichothiodystrophy syndrome. Nevertheless, its functional implications in cervical cancer (CC) remain unclear. The objective of this study was to investigate the role of RNF113A in both the development and prognosis of CC. To achieve this objective, a total of sixty cases were included in the follow-up investigation. The findings revealed a significant up-regulation of RNF113A protein in CC tissues compared to paired paracancerous tissues, and a high expression level of RNF113A was strongly associated with malignant phenotypes such as lymph node metastasis, differentiation degree, depth of invasion, and FIGO stage. Meanwhile, RNF113A was found to be an independent prognostic risk factor, with its high expression significantly correlating with a reduced overall survival period in patients. To elucidate the underlying cause and mechanism of the unfavorable prognosis associated with RNF113A, comprehensive functional investigations were conducted both in vitro and in vivo.Interestingly, it was revealed that RNF113A promoted migration and invasion while inhibiting apoptosis of CC cells, thereby contributing to a poor prognosis. Mechanistically, RNF113A regulated the progression and prognosis of CC through the miR197/Prp19/p38Mark signaling pathway. Overall, our findings underscore the potential clinical significance of RNF113A as an unfavorable prognostic factor in CC., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

In this multicenter retrospective cohort study of 99 patients who underwent salvage hysterectomy for residual disease in the uterine cervix following the completion of definitive radiotherapy for cervical cancer across 25 Japan Clinical Oncology Group-affiliated centers from 2005-2014, (i) time duration from the completion of definitive radiotherapy to the diagnosis of residual disease in the uterine cervix, (ii) salvage hysterectomy surgical margin status, and (iii) extent of residual disease, were independently associated with progression-free survival (PFS). Specifically, (i) time duration to identify residual disease of >62 days was associated with decreased PFS compared to ≤62 days (4-year rates 21.8% vs. 55.0%, adjusted-hazard ratio [aHR]=2.69, 95% confidence interval [CI]=1.55-4.67); (ii) presence of tumor in the surgical margin of hysterectomy specimen was associated with 4 times increased risk of disease progression compared to tumor-free surgical margin (4-year PFS rates 0% vs. 45.3%, aHR=4.27, 95% CI=2.20-8.29); and (iii) hazards of disease progression was 4.5-fold increased when the residual disease extended beyond the uterine cervix compared to residual disease within the uterine cervix only (4-year PFS rates 11.1% vs. 50.6%, aHR=4.54, 95% CI=2.60-7.95). In the absence of these 3 prognostic factors, 4-year PFS rate reached nearly 80% (78.6%, SAL-HYS criteria). In sum, these data suggested that early detection of persistent, residual disease following definitive radiotherapy for cervical cancer may be the key to improve survival if salvage hysterectomy is considered as a tailored treatment option. Ideal surgical candidate would be uterine cervix-contained disease and assurance of adequate tumor-free surgical margin., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objectives: This study aimed to investigate the influence of baseline sarcopenia and changes in body composition on survival during cervical cancer treatment., Methods: Patients diagnosed with stage IB1-IVB cervical cancer who underwent primary concurrent chemoradiation therapy (CCRT) between 2002 and 2022 were included. The exclusion criteria were prior radical hysterectomy, lack of pretreatment computed tomography (CT) imaging, or significant comorbidities. An artificial intelligence-based automatic segmentation program assessed body composition by analyzing CT images, defining L3 sarcopenia (L3 skeletal muscle index [SMI] <39cm 2 /m 2 ) and volumetric sarcopenia (volumetric SMI <180.4 cm 3 /m 3 ). Comparative and multivariate analyses identified the prognostic factors. The impact of body component changes during CCRT was explored., Results: Among 347 patients, there were 125 recurrences and 59 deaths (median follow-up, 50.5 months). Seven patients were excluded from the volumetric sarcopenia analysis because of incomplete baseline CT data, and 175 patients were included in the analysis of body composition changes. Patients with L3 sarcopenia had a lower 5-year progression-free survival (PFS) rate (55.6% vs. 66.2%, p = 0.027), while those with volumetric sarcopenia showed a poorer 5-year overall survival rate (76.5% vs. 85.1%, p = 0.036). Patients with total fat loss during CCRT had a worse 5-year PFS rate than those with total fat gain (61.9% vs. 73.8%, p = 0.029). Multivariate analyses revealed that total fat loss (adjusted hazard ratio [aHR], 2.172; 95% confidence interval [CI], 1.066-4.424; p = 0.033) was a significant factor for recurrence, whereas L3 sarcopenia was not. Volumetric sarcopenia increased the risk of death by 1.75-fold (aHR, 1.750; 95% CI, 1.012-3.025; p = 0.045)., Conclusions: Among patients with cervical cancer undergoing CCRT, initial volumetric sarcopenia and fat loss during treatment are survival risk factors. These findings suggest the potential importance of personalized supportive care, including tailored nutrition and exercise interventions., Competing Interests: Declaration of competing interest Soon Ho Yoon has stocks and stock options of MEDICAL IP. Other authors have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To find out the differences in gene characteristics between cervical cancer patients with and without lymph node metastasis, and to provide reference for therapy., Methods: From January 2018 to June 2022, recurrent cervical cancer patients 39 cases with lymph node metastasis and 73 cases without lymph node metastasis underwent testing of 1,021 cancer-related genes by next-generation sequencing. Maftools software was used to analyze somatic single nucleotide/insertion-deletion variation mutation, co-occurring mutation, cosmic mutation characteristics, oncogenic signaling pathways., Results: EP300 and FBXW7 were significantly enriched in lymph node-positive patients. Lymph node-positive patients with EP300 or FBXW7 mutations had lower overall survival (OS) after recurrence. Both lymph node-positive and -negative patients had plenty of co-occurring mutations but few mutually exclusive mutations. Lymph node-positive co-occurring mutation number ≥6 had lower OS, while lymph node-negative co-occurring mutation number ≥3 had lower OS after recurrence. The etiology of SBS3 was defects in DNA double strand break repair by homologous recombination, which exclusively exist in lymph node-positive patients. There was no difference in median tumor mutation burden (TMB) between positive and negative lymph nodes, but TMB was significantly associated with PIK3CA mutation., Conclusion: The somatic SNV/Indels of EP300 and FBXW7, SBS3 homologous recombination-mediated DNA repair defect were enriched in lymph node-positive patients. For lymph node-positive patients, EP300 or FBXW7 mutations predicted poor prognosis. No matter lymph node-positive or negative, more co-occurring mutation number predicted poor prognosis. PIK3CA mutation may account for the higher TMB and help identify patients who benefit from immunotherapy., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Purpose: This study sought to determine the predictive and prognostic value of clinicopathological parameters and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin (Hgb) level in predicting recurrence patterns and locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) in cervical cancer patients receiving definitive chemoradiotherapy (ChRT)., Methods: This study included 261 cervical cancer patients treated with ChRT. The primary endpoints were the predictors of local recurrence (LR) and distant metastasis (DM), whereas the secondary endpoints were LRFS and DMFS. The association of survival with potential prognostic factors was analyzed using Cox regression analysis, and the predictors of LR and DM were identified using logistic regression analysis., Results: The median follow-up time was 10.9 years. Recurrences occurred in 132 patients (50.6%) within a median of 11.2 months after definitive ChRT. NLR and PLR values were significantly higher in patients with LR and DM than in those without, with no significant differences in Hgb levels in patients with or without LR and DM. In the multivariable logistic regression analysis, lymph node metastasis, elevated NLR, and low Hgb level were significantly correlated with LR and DM. In the multivariable analysis, large tumor size, presence of lymph node metastasis, and elevated NLR were the independent predictors for poor LRFS and DMFS, and Hgb level was an additional prognostic factor for DMFS., Conclusion: Hematological markers, particularly NLR and Hgb, may serve as cost-effective and readily accessible indicators for predicting recurrence and survival in cervical cancer patients, contributing to their practical use in routine assessments., (© 2024. The Author(s).)

Objective: To evaluate the prevalence and prognostic role of programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) in patients with non-immunotherapy-treated advanced cervical cancer., Methods: Clinical data were retrospectively collected from medical records between January 1, 2008, and December 31, 2016, at Asan Medical Center (Korea); archived tumor samples were assessed for PD-L1 expression (combined positive score [CPS] ≥1) and TMB (≥175 mutations/exome). Overall survival (OS) was defined as time from advanced diagnosis or initiation of first-line or second-line systemic therapy until death/last follow-up. The association of OS with PD-L1 expression and TMB were analyzed using the log-rank test and Cox proportional hazards model adjusted for covariates., Results: Of 267 patients, 76.0% had squamous cell carcinoma (SCC), 24.0% had adenocarcinoma (AC)/adenosquamous carcinoma (ASC), 64.4% had PD-L1 CPS ≥1, and 32.6% had TMB ≥175 mutations/exome. PD-L1 CPS ≥1 and TMB ≥175 mutations/exome were more prevalent in SCC than in AC/ASC (73.9% and 37.2% vs. 34.4% and 17.7%). There was no association between OS and PD-L1 expression (CPS ≥1 vs. <1: adjusted hazard ratio [HR]=1.14; 95% confidence interval [CI]=0.84-1.53 from advanced diagnosis); OS trended shorter for the subgroup with TMB ≥175 versus <175 mutations/exome (adjusted HR=1.29; 95% CI=0.95-1.75)., Conclusion: Retrospective analysis of non-immunotherapy-treated patients with advanced cervical cancer demonstrated a higher prevalence of PD-L1 CPS ≥1 and TMB ≥175 mutations/exome in SCC versus AC/ASC. PD-L1 CPS ≥1 was not associated with OS; TMB ≥175 mutations/exome showed a trend toward shorter OS. Additional studies are needed to confirm these findings., Competing Interests: J-YP and M-HB have nothing to disclose. LC, CS, and PJ are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and own stock in Merck & Co., Inc., Rahway, NJ, USA. CT and XYJ are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. RC is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, owns stock in Merck & Co., Inc., Rahway, NJ, USA, and has two pending patents (Angiogenesis and mMDSC gene expression-based biomarker of tumor response to PD-1 antagonists; patent WO 2020/167619). SI is an employee of MSD Korea (employment [JCAP asso RDMA]), registered pharmacist (Korea), and stockholder of Merck & Co., Inc., Rahway, NJ, USA., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: The comprehensive treatment mode of combining concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (AC) is a commonly used mainstream model in the clinical practice of locally advanced cervical cancer (LACC). However, the necessity for AC after CCRT lacks sufficient evidence-based medical support. This study constructs a predictive model for the survival time dependence of CCRT ± AC for LACC based on the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging with internal validation, the prognosis was assessed with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin, and provides guidance for future stratified treatment. Materials and Methods: The retrospective analysis included 482 patients with LACC who CCRT from January 2016 to January 2023. Patients who used the 2009 FIGO staging were all standardized for the 2018 FIGO staging. The 482 patients with LACC were divided into a training set ( n = 290) and a validation set ( n = 192) at a ratio of 6:4. COX multivariate regression model and LASSO regression were used to screen for independent prognostic factors affecting progression-free survival (PFS) and overall survival (OS), and a nomogram clinical prediction model was constructed based on these factors. Evaluate the effectiveness of the model through the receiver operating characteristic curve, calibration curve, decision curve, risk heat map, and survival curves for risk stratification. Results: The PFS and OS independent prognostic risk factors affecting the 2018 FIGO staging of LACC during CCRT were validated to be similar to the 2009 FIGO staging prediction model reported in previous literature. In the training cohort, area under the curve (AUC) values at 1, 3, and 5 years were 0.941, 0.882, and 0.885 for PFS, and 0.946, 0.946, and 0.969 for OS, respectively. When applied to a test cohort, the model also showed accurate prediction result (AUC at 1, 3, and 5 years were 0.869, 0.891, and 0.899 for PFS, and 0.891, 0.941 and 0.878 for OS, respectively). Subgroup analysis suggests that patients with LACC, adenocarcinoma, stage IVA, pelvic lymph node metastasis, pretreatment hemoglobin ≤100 g/l and residual tumor diameter >2 cm, who received CCRT in the 2018 FIGO stage, may benefit more from adjuvant chemtherapy. Conclusions: Based on the 2018 FIGO staging, a nomogram prediction model for PFS and OS in patients with LACC undergoing CCRT was developed. The model, established by combining weighted clinical and pathological factors, can provide more personalized treatment predictions in clinical practice. For patients with high-risk factors such as residual tumor diameter > 2 cm after CCRT for LACC, AC may bring benefits.

Background: Cervical cancer is the fourth most common cancer among women. Radiomics has emerged as a new approach providing valuable information for cancer management. The aim of this study was to construct a radiomics nomogram to accurately predict survival outcomes in patients with locally advanced cervical cancer., Methods: This retrospective study enrolled a total of 582 locally advanced cervical cancer patients from three center (training cohort: n = 228; internal validation cohort: n = 98; external validation cohort: n = 256). Radiomic features were extracted from pretreatment MRI images. Least absolute shrinkage and selection operator logistic regression were applied to select radiomic features and calculated the radiomic scores. Univariate and multivariate Cox proportional hazards regression analyses were used to identify the independent prognostic clinic-radiological factors for cervical cancer, which were incorporated into the nomogram., Results: A total of six radiomic features were found to be associated with overall survival (OS) of locally advanced cervical cancer patients. The AUC of radiomic scores in the training cohort was 0.634-0.708 for the training cohort, 0.725-0.762 for internal validation cohort and 0.788-0.881 for the external validation cohort. Age, parametrial invasion, and radiomic score were the independent prognostic indicators for cervical cancer patients (Age: HR=1.041, 95% CI=1.012-1.071, p = 0.006; Parametrial invasion: HR=4.755, 95% CI=1.493-15.144, p = 0.008; HR=2.324, 95% CI=1.050-5.143, p = 0.037). The nomogram model incorporating these factors showed favorable discrimination in predicting the overall survival rates of cervical cancer patients, with the AUC values of 0.809, 0.808, and 0.862 for 1-, 2-, and 3-year predictions. The decision curve analysis (DCA) indicated that the nomogram model achieved the highest clinical net benefit across the entire range of reasonable threshold probabilities., Conclusion: The nomogram, incorporating clinicopathological factors and radiomic features derived from MRI images, showed satisfactory discrimination in predicting the OS rates of locally advanced cervical cancer patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Cervical cancer is a global health threat and a manifestation of inequality, and screening is an effective intervention. However, little is known about how screening coverage and quality assurance, influence cervical cancer mortality. We aimed to investigate the association between screening coverage, screening quality assurance and cervical cancer mortality among women from countries at different developmental levels., Methods: We obtained data on age-standardised mortality from cervical cancer from the GLOBOCAN 2020 database; coverage of cervical cancer screening from World Health Organization (WHO) Global Health Observatory; and cervical screening programme settings and quality assurance from the Cancer Screening in Five Continents (CanScreen5) database. We assessed the dependency of cervical cancer age-standardised mortality on screening coverage and quality assurance by simple and multiple regression models. We also used linear regression models to identify factors that improved the screening coverage., Results: The study included data from 53 countries. Reduced mortality was associated with increased screening programme quality assurance in 22 high-development countries. In 31 low-development countries, screening coverage in women aged 30-49 years was inversely associated with cervical cancer mortality. Political commitment (documentation of the cervical cancer screening policy as law) and financial support (treatment services provided free of charge) positively associated with screening coverage., Conclusions: Screening programmes need strengthening commensurate with local resources and context. Priority should be given to improving screening coverage through stronger political commitment and financial support in low-development countries, and to ensuring good performance at all levels in high-development countries., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Objective: This study aims to develop and validate a predictive model that integrates clinical features, MRI radiomics, and nutritional-inflammatory biomarkers to forecast progression-free survival (PFS) in cervical cancer (CC) patients undergoing concurrent chemoradiotherapy (CCRT). The goal is to identify high-risk patients and guide personalized treatment., Methods: We performed a retrospective analysis of 188 patients from two centers, divided into training (132) and validation (56) sets. Clinical data, systemic inflammatory markers, and immune-nutritional indices were collected. Radiomic features from three MRI sequences were extracted and selected for predictive value. We developed and evaluated five models incorporating clinical features, nutritional-inflammatory indicators, and radiomics using C-index. The best-performing model was used to create a nomogram, which was validated through ROC curves, calibration plots, and decision curve analysis (DCA)., Results: Model 5, which integrates clinical features, Systemic Immune-Inflammation Index (SII), Prognostic Nutritional Index (PNI), and MRI radiomics, showed the highest performance. It achieved a C-index of 0.833 (95% CI: 0.792-0.874) in the training set and 0.789 (95% CI: 0.679-0.899) in the validation set. The nomogram derived from Model 5 effectively stratified patients into risk groups, with AUCs of 0.833, 0.941, and 0.973 for 1-year, 3-year, and 5-year PFS in the training set, and 0.812, 0.940, and 0.944 in the validation set., Conclusions: The integrated model combining clinical features, nutritional-inflammatory biomarkers, and radiomics offers a robust tool for predicting PFS in CC patients undergoing CCRT. The nomogram provides precise predictions, supporting its application in personalized patient management., (© 2024. The Author(s).)

Background: Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival., Methods: The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m 2 for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m 2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35., Findings: Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group., Interpretation: Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer., Funding: Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre., Competing Interests: Declaration of interests GE reports consulting fees from MSD and Eisai; payment or honoraria from Eisai and GSK; support for attending meeting from MSD; and participation on Data Safety Monitoring Board or Advisory Board for GSK, MSD, and Eisai, outside the submitted work. JAL reports grants from AstraZeneca and Merck/MSD; consulting fees from AstraZeneca, Clovis Oncology, GSK, Artios Pharma, Merck/MSD, VBL Therapeutics, Bristol Myers Squibb, Nuvation, Immagene, Incyte, Immunogen/AbbVie, and Novocure; payment or honoraria from AstraZeneca, MSD/Merck, Clovis Oncology, and GSK; participation on Data Safety Monitoring Board or Advisory Board for Mersana and SutroBio; and leadership role on the European Society for Medical Oncology's Clinical Practice Guidelines—Gynaecological Cancer—until December, 2023, past Vice President role for the European Society of Gynaecological Oncology, until 2021, and Chair for National Ovarian Cancer Audit Committee, outside the submitted work. MM reports payment or honoraria from MSD, Eisai, GSK, Roche, and Medscape; support for attending meetings or travel from Daiichi Sanko; and past role as a Chair of Cervical Cancer Research Network (until September 2021), outside the submitted work. AM reports participation on data safety monitoring board or advisory board for Cannariabio (on an ovarian cancer trial, since 2023) and executive committee member role with the Gynecologic Cancer Intergroup (since 2024), outside the submitted work. AH reports honoraria for educational activities from AbbVie, Almirall, Boehringer Ingelheim, Clovis Oncology, Ipsen, Takeda, AstraZeneca, Daiichi Sankyo, Merck Serono, MSD, UCB, Kyowa Kirin, Servier, Sobi, Pfizer, and Roche, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Cervical cancer, despite being preventable through primary and secondary prevention strategies, remains one of the leading causes of morbidity and mortality among women in Brazil. This study aimed to analyze the temporal, spatial, and space-time patterns of cervical cancer mortality in Brazil. An ecological study was conducted using temporal, spatial, and space-time analysis techniques, using death certificates with cervical cancer as the underlying cause or associated condition among females in Brazil from 2000 to 2021. Death certificate and population data were provided by the Department of Health Informatics of the Unified Health System (DATASUS) and the Brazilian Institute of Geography and Statistics (IBGE), respectively. A total of 123,306 deaths associated with cervical cancer among women were registered during the study period. A rising trend in mortality was detected since 2014 onwards, after 14 years of decline. Particularly, an increase in mortality was observed among the younger age groups, and in the North and Northeast regions regardless of age. Heterogeneity in the spatial distribution of cervical cancer mortality was observed, with high mortality clusters around the country, but mostly concentrated in the North and Northeast regions. These findings suggest a need and an opportunity to develop efficient and effective health policies targeting those regions and groups of women at higher risk which in turn will allow for fast and significant reductions in cervical cancer mortality in Brazil., (© 2024. The Author(s).)

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

Background: Dose escalation with brachytherapy after pelvic irradiation is standard for treating cervical cancer. Its application can be impossible for some patients. Dose escalation with SBRT is widely used with high local control and acceptable toxicity rates in different body parts. The study enrolled patients who underwent SBRT treatment for dose escalation in the cervix., Methods: Patients who were pathologically diagnosed and treated with cervical SBRT after definitive CRT were included in the study. A total of 30 Gy in 5 fractions for the high-risk volume was prescribed. The first response evaluation was performed three months after the completion of treatment. Treatment toxicity was documented according to the RTOG-EORTC scale. Oncological outcomes and toxicity were assessed., Results: Between 02.2019 and 05.2023, 40 patients were treated with an SBRT boost after pelvic irradiation. The median follow-up time was 16 months (7-44 months). The median HR CTV was 47 cc (8,3-168,2 cc). There were 39 patients who achieved a complete response and one who achieved a partial response in the third month after treatment. There were two local or two regional recurrences. The 1-year metastasis-free survival was 88%, and the 1-year progression-free survival was 88%. During the follow-up period, one grade 3 gastrointestinal side effect was observed., Conclusions: SBRT which has low toxicity and reasonable locoregional control rates in a short follow-up period, may be an option for dose escalation in brachytherapy-ineligible cervical cancer patients., (© 2024. The Author(s).)

Objective: Immune checkpoint inhibitor (ICI) therapy activates the immune system to recognize and eliminate cancer cells that have escaped surveillance. This study aimed to compare the treatment outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without ICI., Methods: Data from 69 advanced and recurrent cervical cancer patients treated with first-line ICI plus platinum and paclitaxel (N = 33) or first-line platinum and paclitaxel (N = 36) were reviewed between March 2020 and January 2023 in this retrospective study. Patients chose treatment based on the actual disease condition, patient willingness, and medical advice. Additionally, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were calculated, and adverse events were gained., Results: There was no difference in baseline data between patients receiving the two different treatments (all P > 0.05). Complete response rate (18.2% vs. 8.3%; P = 0.294), ORR (48.5% vs. 30.6%; P = 0.127), and DCR (81.8% vs. 72.2%; P = 0.345) tended to ascend in patients treated with ICI plus platinum and paclitaxel compared to those treated with platinum and paclitaxel, although there was no statistical significance. In patients treated with ICI plus platinum and paclitaxel, the median PFS was 10.3 months and the median OS was not reached. Meanwhile, the median PFS and OS were 7.7 and 16.9 months in patients treated with platinum and paclitaxel. PFS (P = 0.036) and OS (P = 0.033) were increased in patients treated with ICI plus platinum and paclitaxel versus those treated with platinum and paclitaxel, which was verified by multivariate Cox regression analyses (both P < 0.05). No difference was observed in the occurrence of adverse events between patients receiving the two different treatments (all P > 0.05)., Conclusion: First-line ICI plus platinum and paclitaxel yields better treatment responses, longer survival, and non-differential adverse events versus first-line platinum and paclitaxel in advanced and recurrent cervical cancer patients., (© 2024. The Author(s).)

The study aimed to develop and validate a preoperative scoring system to predict the risk of lymph node metastasis (LNM) in cervical cancer (CC). A total of 426 stage IB1-IIA1 CC patients were randomly divided into two sets. A logistic regression model was used to determine independent factors that contribute to LNM. A preoperative scoring system was developed based on beta (β) coefficients. An area under the receiver operating curve (AUC) was used to test for model discrimination. Five-year overall survival (OS) rate was 91.7%. Multivariable logistic regression analysis showed that FIGO stage, tumor size, depth of invasion on MRI, and squamous cell carcinoma antigen levels were independent risk factors in the development set (all P < 0.05). The AUCs of the scoring system for the development and validation sets were 0.833 (95% CI = 0.757-0.909) and 0.767 (95% CI = 0.634-0.891), respectively. Patients who scored 0-2, 3-5, and 6-8 were classified into low-risk, medium-risk, and high-risk groups. Predicted rates were in accord with observed rates in both sets. The 5-year OS rates of the new groups were also significantly different for the entire group, development set, and validation set (all P < 0.05). LNM affects the prognosis of CC patients. The scoring system can be used to assist in evaluating the risk of LNM in CC patients preoperatively. It is easy to obtain and can provide reference for clinical treatment decision-making., (© 2024. The Author(s).)

Background: The increasing problems of drug and radiotherapy resistance in cervical cancer underscores the need for novel methods for its management. Reports indicate that the expression of MPC1 may be associated with the tumor microenvironment and the occurrence of ferroptosis in cervical cancer. The objective of this study was to visually illustrate the prognostic significance and immunological characterization of MPC1 in cervical cancer., Methods: The expression profile and prognostic significance of MPC1 were analyzed using various databases, including UALCAN, TIMER2, GEPIA2, and Kaplan-Meier Plotter. TISIDB, TIMER2, and immunohistochemical analysis were used to investigate the correlation between MPC1 expression and immune infiltration. GO enrichment analysis, KEGG analysis, Reactome analysis, ConsensusPathDB, and GeneMANIA were used to visualize the functional enrichment of MPC1 and signaling pathways related to MPC1. The correlation analysis was carried out to examine the relationship between MPC1 and Ferroptosis gene in TIMER 2.0, ncFO, GEPIA Database and Kaplan-Meier Plotter., Results: We demonstrated that the expression levels of MPC1 in cervical cancer tissues were lower than those in normal cervical tissues. Kaplan-Meier survival curves showed shorter overall survival in cervical cancer patients with low levels of MPC1 expression. The expression of MPC1 was related to the infiltrating levels of tumor-infiltrating immune cells in cervical cancer. Moreover, MPC1 expression was associated with the iron-mediated cell death pathway, and several important ferroptosis genes were upregulated in cervical cancer cells. Furthermore, after knocking down MPC1 in HeLa cells, the expression of these genes decreased., Conclusion: These findings indicate that MPC1 functions as a prognostic indicator and plays a role in the regulation of the ferroptosis pathway in cervical cancer., (© 2024. The Author(s).)

Background: Cervical cancer (CC) is a serious public health concern, being the fourth most common cancer among women and a leading cause of cancer mortality. In Brazil, many women are diagnosed late, and in Mato Grosso, with its geographical diversity, there are specific challenges. This study analyzed hospital survival and its predictors using data from the Hospital Information System (SIH) of the Unified Health System (SUS) in Mato Grosso from 2011 to 2023., Methods: Cox regression and Kaplan-Meier models were applied to determine survival time and identify mortality predictors. The adjusted Hazard Ratio (AHR) with a 95% Confidence Interval (CI) was used to measure the association between the factors analyzed., Results: The hospital mortality rate was 9.88%. The median duration of hospitalization was 33 days (interquartile range [IQR]: 12-36), with a median survival of 43.7%. Patients were followed up for up to 70 days. In the multivariable Cox model, after adjusting for potential confounders, the risk of death during hospitalization was higher in patients aged 40-59 years (AHR = 1.39, p = 0.027) and 60-74 years (AHR = 1.54, p = 0.007), in the absence of surgical procedures (AHR = 4.48, p < 0.001), in patients with medium service complexity (AHR = 2.40, p = 0.037), and in the use of ICU (AHR = 4.97, p < 0.001). On the other hand, patients with hospital expenses above the median (152.971 USD) showed a reduced risk of death (AHR = 0.21, p < 0.001)., Conclusion: This study highlights that hospitalized CC patients have reduced survival, underscoring the need for interventions to improve care, including strategies for early diagnosis and expanded access to adequately resourced health services., (© 2024. The Author(s).)

Objectives: To examine the benefits of extended-field chemoradiation with simultaneous integrated boost to positive lymph nodes, followed by image-guided adaptive brachytherapy in patients with cervical cancer with para-aortic metastasis., Methods: This retrospective cohort study enrolled 143 patients diagnosed between January 2011 and July 2023 at a single center. Survival and recurrence were evaluated using the Kaplan-Meier method and log-rank test. Cox regression was employed to identify prognostic factors and adjust for confounding factors. Patients were then stratified according to neoadjuvant chemotherapy, and its impact on survival outcomes was evaluated., Results: A total of 129 patients completed the entire treatment course. The 5-year overall survival rate was 57.6%, and the para-aortic failure rate was 6.8% after a median follow-up of 61 months (95% CI 49 to 82 months). Multivariate analysis indicated that neoadjuvant chemotherapy, larger primary tumor or pelvic/para-aortic lymph nodes, and lower hemoglobin nadir (for widespread metastasis-free survival only) predicted poorer survival. After propensity score matching, the 5-year para-aortic recurrence-free, widespread metastasis-free, and overall survival rates were 92.2% vs 92.8% (p=0.85), 50.8% vs 72.1% (p=0.007), and 47.5% vs 65.5% (p=0.037), respectively, in groups receiving neoadjuvant chemotherapy or not. Sixteen patients (12.4%) experienced grade 3-4 late toxicities. Patients who received neoadjuvant chemotherapy had a significantly higher incidence of grade 3-4 anemia and neutropenia than those who did not (45.2% vs 26.7% and 38.1% vs 21.8%, respectively), if including another 14 patients who discontinued treatment due to acute vomiting., Conclusion: Chemoradiation with simultaneous integrated boost to positive lymph nodes demonstrates favorable outcomes and acceptable late toxicities in para-aortic metastatic cervical cancer. Neoadjuvant chemotherapy has been shown to adversely affect outcomes, and acute vomiting is a major cause of treatment abortion., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: 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., Methods: 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., Findings: 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., Interpretation: 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., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co., Competing Interests: Declaration of interests DL, YX, KH, GS, ML, PR-E, AA, JC, LR, AJPdSG, FCM, LH, HA, J-YL, VS, FZ, LG, JS, ET, KL, NC, C-LC, MB, HZ, AO, MC, EP, TU, SP, and LRD received funding to their institutions from Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD) to support the study. DL reports grants or contracts from AstraZeneca, Clovis Oncology, Pharma&, Genmab, GSK, Immunogen, MSD, Pharmamar, Novartis, Seagen, Alkermes, Incyte, Roche, and Corcept; consulting fees from AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Novocure, Seagen, and Sutro; speaker fees from AstraZeneca, Corcept, Genmab, GSK, Immunogen, MSD, and Seagen; travel grants from AstraZeneca, Menarini, GSK, and MSD; advisory board participation for AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Oncoinvest, Novocure, Seagen, and Sutro; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for GCIG, MITO, and ENGOT. YX reports study funding, paid to the Peking Union Medical College Hospital, and support for attending meetings or travel from MSD. KH reports research contracts from Daiichi Sankyo, Eisai, MSD, and Takeda; advisory board fees from Chugai, Eisai, Takeda, MSD, Roche, Genmab, Sanofi, GSK, and Zymeworks; honoraria from Daiichi Sankyo, AstraZeneca, Chugai, Eisai, Genmab, MSD, Takeda, Sanofi, Kyowa Kirin, Kaken, and GSK; and travel support from Regeneron and Seagen. GS reports consulting fees from AstraZeneca, MSD, Coviden AG (a Medtronic company), Johnson & Johnson, and TESARO Bio Italy; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Baxter Healthcare, Olympus Europa, Intuitive Surgical, GSK, and Clovis Oncology Italy. ML reports payment for expert testimony from MSD, support for attending meetings or travel from MSD and AstraZeneca; and other financial or non-financial interests from MSD, AstraZeneca, and Roche. PR-E reports honoraria for educational events from MSD, AstraZeneca, Novartis, Asofarma, Pfizer, and Roche; support for attending ESMO and ASCO meetings from AstraZeneca, Pfizer, and Asofarma; and honoraria for advisory boards from MSD, Roche, AstraZeneca, Asofarma, BMS and Novartis. LR reports medical writing support from Merck, institutional grants from Merck, Zentalis, Karyopharn, GOG Foundation, Regeneron, ImmunoGen, Acrivon, CanariaBio, Corcept Therapeutics, and Seagen; consulting fees from AstraZeneca, Merck, GSK, Genmab, Seagen, GOG Foundation, Zentalis, ImmunoGen, Semline, Eisai, Caris, Nykode, and Clovis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Seagen and Genmab; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, from GOG Foundation. AJPdSG reports consulting fees and payment for expert testimony from Bayer, Astellas, and Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for expert testimony from Astellas, AstraZeneca, Bayer, and Janssen; and participation on a data safety monitoring board or advisory board for Astellas, Bayer, and Janssen. FCM reports honoraria for presentations from MSD and BMS; support for attending meetings or travel from AstraZeneca and MSD; and advisory board participation from Janssen and MSD. J-YL reports support for the present manuscript from MSD; grants or contracts from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, Beigene, BergenBio, BMS, CanariaBio, Corcept, Cellid, CKD, Clovis Oncology, Eisai, Genmab, Genemedicine, GII, GSK, ImmunoGen, Janssen, Kelun, Merck, Mersana, MSD, Novartis, Onconic Therapeutics, ONO, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Janssen, MSD, Roche, Takeda, and ONO; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for AstraZeneca, CanariaBio, Genmab, GII, ImmunoGen, Seagen, Merck, Sutro, Regeneron, and MSD. FZ reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, consulting fees, support for attending meetings or travel, and data safety monitoring board and advisory board participation for AstraZeneca, Daiichi, Eli-Lilly, Merck, Novartis, MSD, Pfizer, Genesis-Pharma, and Roche. LG reports institutional grants from IMV, Pfizer, Sutro Bio, Pharma, Merck Sharpe Dohme, Corcept Therapeutics, ImmunoGen, Shattuck Labs, Roche, Tesaro, K-Group, Beta Inc., GOG Foundation, GSK, AstraZeneca, OncoQuest Pharmaceuticals, Novocure, Alkermes, Espersas, and Mersana; consulting fees from Merck and GSK; payment or honoraria for lectures and presentations from Merck and GSK; support for attending meetings or travel from GSK, Merck, EndomERA, and Zentalis; and participation on advisory board meetings for GSK, Merck, Eisai, Novocure, Kora Health, Corcept, ImmunoGen, Canariabio, and Repare Therapeutics. JS reports grants or contracts from Roche, MSD, GSK, Tesaro, AstraZeneca, Eisai, Merck, and Novocure; consulting fees from Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, MSD, Eisai, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, BMS, Eisai, and Novartis; support for attending meetings or travel from GSK, Astra Zeneca, Roche, Novocure, Immunogen, Incyte, MSD, and Eisei; participation on a data safety monitoring board or advisory board for Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, Bristol Myers Squibb, MSD, Merck, Bayer, and PharmaMar; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for ENGAGE, ESGO, ASCO, ESGO, GCIG, Deutsche Stiftung Eierstockkrebs, and AGO; and medical writing assistance from MSD. ET reports honoraria for presentations and meeting travel support from Elektra. KL reports study funding from MSD; grants or contracts from GSK; lecture honoraria from Eisai and AstraZeneca; participation on a data safety monitoring board for Karyopharm; participation on an advisory board for Eisai, MSD, Nykode, AstraZeneca, and GSK; and serving as deputy medical director for the Nordic Society of Gynecological Oncology Clinical Trial Unit. NC reports institutional grants from AstraZeneca and Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK and MSD; payment for participation on a data safety monitoring board or advisory board for AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Mersana, MSD, Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris, Roche, and Novocure; and non-remunerated leadership role as Chair of the Alleanza Contro il Tumore Ovarico Scientific Committee. MB reports honoraria for lectures and educational events from Roche, AstraZeneca, and GSK; and support for attending meetings from Roche, AstraZeneca, and Viatris. AO reports consulting fees from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daïichi Sankyo, Debiopharm International, Eisai, Exelisis, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Sutro Biopharma, TORL Therapuetics, Zentalis, and Zymeworks; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from NSGO, Peerview, Peervoice, Medscape, Asociación Colombiada de Ginecológos Oncólogos, ESO, AstraZeneca, and GSK; support for attending meetings or travel from AstraZeneca, PharmaMar, and Roche; participation on a data safety monitoring board or advisory board from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daïichi Sankyo, Debiopharm International, Eisai, Exelisis, F Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Sutro Biopharma, TORL Therapuetics, Zentalis, and Zymeworks; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for Gynecologic Cancer Intergroup and European Society for Medical Oncology; and other financial or non-financial interests in Gynecologic Cancer Intergroup, European Society for Medical Oncology, American Society of Clinical Oncology, Spanish Society of Medical Oncology, and GOG Foundation. EP reports provision of study material from MSD; honoraria for lectures, presentations, and educational events from MSD, Roche, GSK, and AstraZeneca; and receipt of investigational drug for study treatment from MSD. PL, KY, ST, and SMK are current or former full-time employees of MSD and hold stock or restricted stock units in the company. SP reports research funding from Roche, MSD, GSK, Pfizer, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, MSD, Roche, Pfizer, Novartis, and GSK; and participation on a Data Safety Monitoring Board or Advisory Board for GSK, MSD, Eisai, Biontech, and AstraZeneca. LRD reports institutional grants from Merck, Genentech, Roche, AbbVie, Acrivon, Advaxis, Aduro BioTech, Alkermes, Blueprint, Constellation, Eisai, GSK, Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, and Zentalis; royalties or licenses from UpToDate, Wiley, and ASCO; editing for ASCO Connection; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Advance Medical, CEA Group, and Clinical Care Options; participation on a data safety monitoring board for Innovia and Aegenus (payment to institution); and roles as Secretary Treasurer for SGO (unpaid) and on the Editorial Board of the British Journal of Obstetrics and Gynaecology., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma., Methods and Materials: Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m 2 , once weekly for 5 weeks), radiotherapy (45-50.4 Gy/25-28 Fx, 5 fractions weekly), followed by brachytherapy (24-30 Gy/3-5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS)., Results: All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient experienced grade V AEs. The objective response rate (ORR) was 100%. At the data cutoff (June 30, 2023), the median follow-up was 31.8 months (9.5 to 37.8 months). The 2-year PFS rate was 81.8%. The 2-year LC and local regional control rates were both 95.5%, and the 2-year OS rate was 90.9%., Conclusions: Toripalimab combined with CCRT achieved good tolerance and showed promising anti-tumor effects in patients with locally advanced cervical cancer., (© 2024. The Author(s).)

Objective: Immunotherapy has led to changes in cervical cancer guidelines. Therefore, additional biomarkers to identify the ideal patient who would experience the most benefit may be important., Methods: We retrospectively collected 208 patients with R/M CC and recorded clinicopathologic information, peripheral blood markers and treatments to analyze the prognostic factors of clinical outcomes. Response rate comparison, univariate, and multivariate analyses were performed to assess the efficacy of different factors., Results: A total of 43.27% patients achieved objective responses, including 18 with complete response and 72 with partial response. Patients receiving first-line immunotherapy had much higher objective response rate (ORR) than the remaining patients (53.8% vs. 34.8%, p = 0.006). CRP >3 ECOG ≥1 and recurrence in 6 months predicted shorter progression free survival (PFS). CRP >3, GLU >6.1 independently predicted unfavorable overall survival (OS). Compared with no antiangiogenic therapy, previous antiangiogenic therapy reduced the median OS by nearly 14 months. Immunotherapy rechallenge was still effective after first immunotherapy failure, and combined with dual-immunotherapy or bevacizumab combined with chemoradiotherapy resulted in a 60.00% or 62.50% ORR, respectively. Patients with squamous cell carcinoma, with stable disease or objective response in the first immunotherapy or without chemotherapy in second immunotherapy had favorable clinical outcome., Conclusion: The baseline CRP levels in serum was an independent factor for PFS and OS of R/M CC patients treated with immunotherapy, and previous antiangiogenic therapy was associated with poor OS. Patients still show response to immunotherapy rechallenge and combined treatment with bevacizumab or candonilimab showed higher response rate than anti-PD-1 after immunotherapy failure., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Cervical cancer remains one of the leading causes of death from malignant diseases in women worldwide. Primary and secondary prevention have led to better outcomes in developed countries, whereas in developing countries, cervical cancer continues to be responsible for an unjustifiably high number of fatalities. The discovery of new tumor biomarkers can lead to earlier diagnosis, better therapeutic decisions, and improved treatment methods. IMP3 is a protein responsible for invasiveness and other aggressive characteristics of tumor processes. Its highly specific expression has been proven in various malignant processes. The level of IMP3 expression in cervical cancer cells could be used as a prognostic factor for a worse disease course. In this study, IMP3 expression was examined in 80 patients who underwent surgery for squamous cell cervical cancer in the first FIGO stage of the disease, and its association with disease-free period and overall survival was investigated. Data analysis did not show a statistically significant association between IMP3 expression and the mentioned primary outcomes, despite its association with clinical-pathological indicators of advanced disease. In conclusion, the analysis of IMP3 protein expression in patients with early-stage cervical cancer is of limited utility., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The prediction of postoperative recurrence and survival in cervical cancer patients has been a major clinical challenge. The combination of clinical parameters, inflammatory markers, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and MRI-derived radiomics is expected to support the prediction of recurrence-free survival (RFS), disease-free survival (DFS), tumor-specific survival (CSS), and overall survival (OS) of cervical cancer patients after surgery., Methods: A retrospective analysis of 181 cervical cancer patients with continuous follow-up was completed. The parameters of IVIM-DWI and radiomics were measured, analyzed, and screened. The LASSO regularization was used to calculate the radiomics score (Rad-score). Multivariate Cox regression analysis was used to construct nomogram models for predicting postoperative RFS, DFS, CSS, and OS in cervical cancer patients, with internal and external validation., Results: Clinical stage, parametrial infiltration, internal irradiation, D-value, and Rad-score were independent prognostic factors for RFS; Squamous cell carcinoma antigen, internal irradiation, D-value, f-value and Rad-score were independent prognostic factors for DFS; Maximum tumor diameter, lymph node metastasis, platelets, D-value and Rad-score were independent prognostic factors for CSS; Lymph node metastasis, systemic inflammation response index, D-value and Rad-score were independent prognostic factors for OS. The AUCs of each model predicting RFS, DFS, CSS, and OS at 1, 3, and 5 years were 0.985, 0.929, 0.910 and 0.833, 0.818, 0.816 and 0.832, 0.863, 0.891 and 0.804, 0.812, 0.870, respectively., Conclusions: Nomograms based on clinical and imaging parameters showed high clinical value in predicting postoperative RFS, DFS, CSS, and OS of cervical cancer patients and can be used as prognostic markers., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: This study analyzed the long-term clinical outcomes of cervical cancer patients recommended surgery but who did not undergo it using the Surveillance, Epidemiology, and End Results (SEER) database. The aim was to identify the subgroups with comparable overall survival (OS) and cancer-specific survival (CSS) through stratified analysis., Methods: Cases of cervical cancer were retrieved from SEER database using SEER*Stat software. This included patients in the non-surgery group (recommended surgery but did not undergo it), and a reference surgery group. Propensity score matching balanced differences between the non-surgery and surgery groups. Stratified analysis and log-rank tests were used to identify subgroups within the non-surgery group with comparable OS and CSS to the surgery group., Results: A total of 30,807 cervical cancer patients were included in the OS and CSS analysis. In the matched cohort (n = 1278), patients in the non-surgery group had significantly lower 5-year CSS (63.2 % vs. 80.1 %, P < 0.001) and 5-year OS (59.0 % vs. 78.0 %, P < 0.001). However, within the matched cohort, there was no statistically significant difference in OS and CSS between the non-surgery and surgery groups in subgroups diagnosed during 2010-2014 (P = 0.064, P = 0.182), 2015-2020 (P = 0.122, P = 0.518), T2 stage (P = 0.139, P = 0.052), T3 stage (P = 0.502, P = 0.317), or with distant metastasis (M1) (P = 0.411, P = 0.520)., Conclusion: Patients in the non-surgery group generally exhibited lower long-term clinical outcomes compared to those in the surgery group. However, with advancements in non-surgical treatment techniques, particularly notable in patients with T2, T3, and M1 stages, these differences are gradually diminishing., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: To analyze the survival outcomes of female patients with cervical, uterine, and ovarian cancers in Southeast China (Fujian Province) from 2011 to 2020 and to provide a reference basis for prognostic evaluation and prevention of gynecological malignancies., Methods: The data of 5823 patients with cervical, uterine, and ovarian cancers registered in the Fujian Provincial Cancer Prevention and Control System from 2011 to 2020 were enrolled for survival analysis and further stratified by age at diagnosis and township. Survival time was calculated up to March 30, 2022, and relative survival (RS) and age-standardized RS were calculated according to the International Cancer Survival Standards (ICSS)., Results: During 2011-2015, the 5-year RS for cervical, uterine, and ovarian cancers were 64.3 %, 64.2 %, and 44.7 %, respectively, while the age-standardized 5-year RS were 56.8 %, 47.9 %, and 27.9 %, respectively. During 2016-2020, the 5-year RS for cervical, uterine, and ovarian cancers were 72.3 %, 78.9 %, and 50.8 %, respectively, while the age-standardized 5-year RS were 64.5 %, 54.6 %, and 34.2 %, respectively. The 5-year RS for cervical and ovarian cancer all declined with age, while the 5-year RS for uterine cancer was highest at 45-54 years and lowest at 75 years. In addition, survival rates were broadly higher in urban than rural areas., Conclusion: Survival rates for cervical, uterine, and ovarian cancers have generally increased in the population covered by the Fujian Cancer Registry. However, survival rates remain lower than in developed countries. Emphasis should be placed on gynecological cancer screening and the introduction of effective treatments to improve survival rates for gynecological cancers., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: To develop and validate a T2-weighted magnetic resonance imaging (MRI)-based radiomic signature associated with disease-free survival (DFS) in locally advanced cervical cancer., Materials and Methods: The study comprised a training dataset of 132 patients (93 Norwegian; 39 The Cancer Imaging Archive (TCIA) and an independent validation Canadian dataset of 199 patients with FIGO stage IB-IVA cervical cancer treated with chemoradiation. Radiomic features were extracted using PyRadiomics. A radiomic signature was developed based on a multivariable radiomic prognostic model for DFS built using the training dataset, with minimal redundancy maximum relevancy feature selection method. Univariate and multivariable Cox regression analyses were then conducted to examine the association of the derived radiomic signature with DFS., Results: A radiomic signature was prognostic for DFS in the training cohort (Norwegian hazard ratio [HR] 5.54, p = 0.002; TCIA HR 3.59, p = 0.04). The radiomic signature remained independently associated with DFS (HR 3.70, p = 0.004) when adjusted for stage and tumor volume. The radiomic signature was also prognostic for DFS in the validation cohort, both on univariate analysis (HR 2.22, p = 0.003), and multivariable analysis adjusted for stage and tumor volume (HR 1.84, p = 0.04). The 4-year DFS rates of patients with radiomic signature score > 0 vs ≤ 0 were 48.2 % vs 87.9 %, and 56.4 % vs 80.8 % for training and validation cohorts respectively., Conclusion: An MRI-based radiomic signature can be used as a prognostic biomarker for DFS in patients with locally advanced cervical cancer undergoing chemoradiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To assess whether there were statistically significant differences in terms of overall survival (OS) and progression-free survival (PFS) between pelvic lymphadenectomy (PL) and sentinel lymph node biopsy (SLNB) alone as a nodal assessment method in patients with early-stage cervical cancer (IA1 with ILV to IB2 or IIA1 of the FIGO 2018 classification). A retrospective study was conducted among patients with early-stage cervical cancer who underwent radical surgery with pelvic lymph node assessment at La Paz University Hospital between 2005 and 2022. For nodal staging, either PL, SLNB + PL, or exclusive SLNB were performed, depending on the time period. Kaplan-Meier survival curves were compared between the PL and SLNB groups. Predictors of bilateral sentinel lymph node (SLN) detection were identified with Cox proportional hazard models. Among the 128 patients included, PL ± SLNB was performed in 79 (61.7%) patients and exclusive SLNB in 49 (38.3%) patients. There was no difference between PL and SLNB in OS (log-rank 0.0730) or PFS (log-rank 0.0189). Lower limb lymphedema (LLL) was significantly lower in the SLNB group (p = 0.001). Pelvic nodal assessment with SLNB alone did not worsen survival rates compared with the standard PL in patients with early-stage cervical cancer, and it is associated with a lower rate of LLL., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objective: This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis., Methods: A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups' progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared., Results: The surgical staging group started radiotherapy 10.2 days (range 9-12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively)., Conclusion: Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs., (© 2024. The Author(s).)

Objectives: This study aimed to investigate the changes in the incidence and mortality trends of ovarian cancer (OC), cervical cancer (CC) and uterine cancer (UC) in the Fujian Province, southeastern China., Design: Provincial, population-based, retrospective observational study., Setting: Fujian province, southeastern China between 2011-2020., Participants: From 2011 to 2020, 6178 new cases and 2037 deaths caused by 3 gynaecological cancers were eligible for analysis., Primary and Secondary Outcome Measures: The primary outcome measures were the incidence and mortality rates, including the age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR), of three gynaecological cancers. The secondary outcome measure was the prevalence (average annual per cent changes (AAPC))., Results: The incidence of all three gynaecological cancers increased from 2011 to 2020. CC had the slowest upward trend, with an AAPC of 2.54% over the period. However, it had the highest ASIR among the 3 cancers in 2020 (10.41/100 000). UC showed a rapid increase, with an AAPC of 15.15% from 2016 to 2020. While the mortality rate of UC remained stable, both CC and OC also exhibited rising trends, with the CC having the highest ASMR (3.05/100 000) in 2020. The ASMR for CC increased rapidly, with the highest AAPC of 5.51%. Conversely, changes in the ASMR for UC were not statistically significant (p=0.601). Moreover, high incidence rates were more common among perimenopausal women and older participants in the respective cancer groups where the increased mortality was observed., Conclusions: Gynaecological cancer burden remains a public health issue in Fujian Province, with an increasing incidence. Improving the healthcare system and promoting a healthy lifestyle should be highlighted to reduce the cancer burden., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cervical cancer is a common malignant tumor of the female reproductive system and the leading cause of death among women worldwide. The survival prediction method can be used to effectively analyze the time to event, which is essential in any clinical study. This study aims to bridge the gap between traditional statistical methods and machine learning in survival analysis by revealing which techniques are most effective in predicting survival, with a particular emphasis on improving prediction accuracy and identifying key risk factors for cervical cancer. Women with cervical cancer diagnosed between 2013 and 2015 were included in our study using data from the Surveillance, Epidemiology, and End Results (SEER) database. Using this dataset, the study assesses the performance of Weibull, Cox proportional hazards models, and Random Survival Forests in terms of predictive accuracy and risk factor identification. The findings reveal that machine learning models, particularly Random Survival Forests (RSF), outperform traditional statistical methods in both predictive accuracy and the discernment of crucial prognostic factors, underscoring the advantages of machine learning in handling complex survival data. However, for a survival dataset with a small number of predictors, statistical models should be used first. The study finds that RSF models enhance survival analysis with more accurate predictions and insights into survival risk factors but highlights the need for larger datasets and further research on model interpretability and clinical applicability., (© 2024. The Author(s).)