European Journal of Gynaecological Oncology,2025,46(8):1-10 DOI:10.22514/ejgo.2025.104
Systematic Review
Efficacy and safety of bevacizumab in the treatment of advanced or recurrent cervical cancer: a systematic review and a meta-analysis
Simin Xiao1,†, Yang Xu2,†, Siyuan Zeng3,4,†, Shunjie You5,*,, Chenming Hu6,*,, Yangbin Kou1,*,

1Radiology Department, The First Affiliated Hospital of Traditional Chinese Medicine of Chengdu Medical College/XinDu Hospital of Traditional Chinese Medicine, 610500 Chengdu, Sichuan, China

2Dalian Municipal Central Hospital, China Medical University, 116000 Dalian, Liaoning, China

3Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, 610041 Chengdu, Sichuan, China

4Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second Hospital, Sichuan University, 610041 Chengdu, Sichuan, China

5Department of Burn and Plastic Surgery, Ziyang Central Hospital, 641300 Ziyang, Sichuan, China

6The Center for Biomedical Research and Translational Surgery, Medical University of Vienna, 1090 Vienna, Austria

*Corresponding Author(s):kouyangbin@foxmail.com (Yangbin Kou); n12447146@students.meduniwien.ac.at (Chenming Hu);desysj@163.com (Shunjie You);

† These authors contributed equally.

History Submitted: 02 August 2024 | Accepted: 24 September 2024 | Published: 15 August 2025
Copyright:  ©2025  The Author(s). Published by MRE Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

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Abstract

Background: This meta-analysis aims to evaluate the safety and effectiveness of the combination of chemotherapy and bevacizumab versus chemotherapy alone in treating advanced or refractory cervical cancer (a/r CC), providing guidance for clinical practice. Methods: A computer search of studies on the combination of bevacizumab and chemotherapy was conducted up to 20 March 2024. Literature was screened and assessed based on inclusion and exclusion criteria and relevant data were extracted for analysis. Results: Ten studies were included. The meta-analysis showed that the overall survival (OS) of the platinum-paclitaxel plus bevacizumab group was significantly better than that of the traditional chemotherapy group (hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.68–0.85, p < 0.001; I2 = 17.2%). Progression-free survival (PFS) was also significantly improved in the combined group (HR = 0.59, 95% CI: 0.49–0.71, p < 0.001; I2 = 0.0%). The combined therapy group had higher rates of complete response (CR) (relative risk (RR) = 1.22, 95% CI: 1.00–1.47, p = 0.046) and partial response (PR) (RR = 1.38, 95% CI: 1.15–1.66, p = 0.001), while the incidence of progression disease (PD) was lower (RR = 0.43, 95% CI: 0.31–0.61, p < 0.001). No significant difference was found in stabilization disease (SD) between the groups (p = 0.998). However, the bevacizumab group exhibited a significantly higher incidence in terms of adverse events, including hypertension (p = 0.029), thrombosis (p < 0.01), and neutropenia (p = 0.011), while other side effects between the two groups, such as pain, gastrointestinal and genitourinary fistulas, and bleeding, showed no significant differences. Conclusion: The combination of bevacizumab and chemotherapy improves the survival and efficacy of patients with a/r CC compared to chemotherapy alone, though it is associated with a higher incidence of certain adverse events. The PROSPERO Registration: CRD42023451617.

Keywords:Angiogenesis inhibitors;Bevacizumab;Meta-analysis;Advanced or refractory cervical cancer;Targeted drug
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Cite this article

Simin Xiao, Yang Xu, Siyuan Zeng, Shunjie You, Chenming Hu, Yangbin Kou. Efficacy and safety of bevacizumab in the treatment of advanced or recurrent cervical cancer: a systematic review and a meta-analysis.European Journal of Gynaecological Oncology,2025,46(8):1-10 DOI:10.22514/ejgo.2025.104

1. Introduction

Cervical cancer (CC) is the most common malignant tumor in the gynecological reproductive system. Globally, the incidence rate of CC ranks fourth among female malignant tumors [1]. Research has shown that the onset age of CC tends to be younger, with a peak age of 45–49 years old [2], and the rate of late-stage detection is increasing, thus posing a serious threat to women’s health and quality of life. In recent years, the human papillomavirus (HPV) vaccine and thin-layer cytology test (TCT) have gradually become popular, but there are still 569,000 new cases of CC and 275,000 CC deaths worldwide every year. The preferred treatment option for patients with advanced or refractory cervical cancer (a/r CC) is synchronous radiotherapy and chemotherapy. The complete response (CR) rate after treatment can reach 70%–85%, but 29%–38% of patients experience recurrence and metastasis [1]. The 5-year survival rate after recurrence is only 3.8%–13.0%. Therefore, it is necessary to further explore the combination of multiple pathways for the treatment of a/r CC.

Some studies suggested that the lesion occurrence of CC is related to tumor blood vessels that provide blood supply for tumor growth, input nutrients, and output metabolites and conditions for tumor metastasis and spread [3]. Approximately 85% of CC patients have expression of epidermal growth factor receptor (EGFR) and it is closely related to their prognosis [4]. Targeted therapy based on EGFR brings new ideas for the treatment of CC. Among them, bevacizumab, a monoclonal antibody class anti angiogenic product, is recommended as a first-line anti-tumor drug. This drug can bind to vascular endothelial growth factor (VEGF), inhibit endothelial cell proliferation and neovascularization by blocking the interaction between VEGF and VEGF receptors on the surface of endothelial cells (EC) and thus inhibit tumor growth [5, 6].

The GOG240 Phase III clinical trial [7] is a randomized controlled phase III clinical trial, including 452 patients with recurrent, refractory, or a/r CC from 81 research centers in the United States, Canada and Spain. The results indicated that the combination of chemotherapy and bevacizumab group significantly extended the overall survival (OS) time compared with the chemotherapy alone, with the former being 16.8 months, the latter being 13.3 months. For patients with a/r CC, the combination of chemotherapy drugs and bevacizumab shows a sustained prolongation of OS compared with chemotherapy drugs alone [8]. Based on the results of this study, on 14 August 2014, the Food and Drug Administration (FDA) approved the combination of bevacizumab, paclitaxel, cisplatin, or topotecan for the treatment of recurrent refractory primary C.

The 2020 version of the National Comprehensive Cancer Network (NCCN) guidelines in the United States has added bevacizumab to the first-line chemotherapy regimen for a/r CC [9]. There are differences between the results of various studies. After the patients accepted radiotherapy and chemotherapy, the recurrence rate is high, while the survival rate is low. As a routine chemotherapy regimen for a/r CC, the combination of paclitaxel and platinum still needs to be improved. Bevacizumab, a molecular targeted drug, can inhibit vascular growth and has been applied in a/r CC patients [10, 11]. Through systematic review and meta-analysis, this study integrated data on the efficacy and safety of bevacizumab combined with chemotherapy in a/r CC, which filled the existing gap in the literature regarding adverse events related to the combined treatment strategy. Most importantly, this will provide valuable insights into optimizing individualized treatment in a/r CC in the future.

2. Methods

According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [12], the PRISMA checklist can be found as Supplementary material 1. We conducted a systematic review and meta-analysis on the efficacy and safety of bevacizumab combined with chemotherapy versus chemotherapy alone for treating a/r CC. Studies were retrieved from PubMed, Embase, and Cochrane Library up to 20 March 2024.

2.1 Retrieval strategy and selection criteria

Literature was retrieved from PubMed, Embase, and Cochrane databases from their establishment until 20 March 2024. The English search terms are: “Cervical cancer, advanced stage, recurrence, targeted therapy, bevacizumab, vascular endothelial growth factor”. The selection criteria are as follows: (1) Patients with a/r CC; (2) The study is a prospective and retrospective clinical study, including randomized controlled trials and cohort studies. In clinical controlled trials, only the study group receiving the combination of bevacizumab monotherapy and chemotherapy was included; (3) The primary outcome measure reports treatment response and/or patient survival data. Exclusion criteria: (1) Case reports, review literature; (2) The main outcome indicators are difficult to obtain; (3) During the study period, patients received other concurrent treatments besides bevacizumab and paclitaxel, such as other chemotherapy drugs or surgery therapy; (4) Repeated publication or inclusion of literature; (5) Non-English studies.

2.2 Data extraction and quality assessment

To ensure the accuracy and completeness of the extracted data, two researchers independently collected and organized the data based on the inclusion and exclusion criteria. In case of inconsistency in data collection, a consensus was reached through careful verification and discussion or provided third-party opinions. The information extracted from relevant studies includes author, study type, publication year, study area, number of cases, HR of OS and progression free survival (PFS), CR, partial response (PR), stabilization disease (SD), progression disease (PD) and Adverse Events. Meta-analysis was performed using Stata version 15.0. Heterogeneity among studies included through Cochran Q-test and I2 statistical evaluation. To make a judgment through inspection, the specific steps are as follows: If the p value of Q test is greater than 0.05 and I2 < 50%, it is considered that the studies are homogeneous and a fixed effects model is used. Conversely, if the studies are heterogeneous, a random effects model is used. The outcome indicators of this study, namely PFS and OS, were time related binary variables, and HR was used as the combined effect value; CR, PR, SD, PD used relative risk (RR) as the combined effect value. Funnel plots, Begg tests and Egger tests were used to check for potential publication bias in the data. According to the Newcastle-Ottawa Scale (NOS) scale, the quality of the included literature was evaluated. The scale consists of 7 items, with a total score of 14 points. Two researchers made judgments on individual literature, and a third researcher was added to make judgments when there was disagreement. The included randomized controlled trial (RCT) study referred to the Cochrane Collaboration Network’s setting of bias risk assessment items and independently evaluated the bias risk of each study.

3. Results

3.1 Qualified literature

Initially, a total of 1176 articles were retrieved, but after eliminating duplicates, 764 articles were still retained. According to the inclusion and exclusion criteria, 749 articles were excluded from the title and abstract review, and 5 articles with no available data were excluded based on article data records. Finally, through a full text review, a total of 10 studies and 1922 a/r CC patients were included. The basic information of eligible studies is shown in Table 1. All participants in the 10 studies were diagnosed with a/r CC. Please refer to the detailed flowchart below (Fig. 1). According to the NOS scale, the quality score of the included research literature is 7–8 points, all of which are of medium or high quality (Supplementary material 2).

Table 1.Characteristics of studies included in this meta-analysis.
Study, yearStudy designCountryDurationSample size (C/T)Age (C/T)Median follow-up (mon)Interventions of controlDoes of bevacizumabPrimary endpointsSecondary endpointsSurvival Analysis
Tewari 2017RCTUSA, Canada and Spain2009–2012225/22746.50 ± 12.10/48.90 ± 11.70NRcisplatin (50 mg/m2 on day 1 or 2) + paclitaxel (135 mg/m2 or 175 mg/m2 on day 1) or topotecan (0.75 mg/m2 on days 1–3) + paclitaxel (175 mg/m2 on day 1)15 mg/kg on day 1OSCR, PR, SD, PDUnivariate
He 2020CohortChina2014–2018134/13067.43 ± 7.53/67.22 ± 5.3338 (36–40)cisplatin (50 mg/m2 on day 1) + paclitaxel (175 mg/m2 on day 1)15 mg/kgOS, PFSNRUnivariate
Tao 2020CohortChina2016–2017161/12755.41 ± 15.17/52.31 ± 11.153.5 yrcisplatin (6 mg/mL/min) + paclitaxel (175 mg/m2)15 mg/m2OSCR, PR, SD, PDUnivariate
Youn 2020CohortKorea2015–201730/1153 (31–82)/51 (36–66)19 (3–108)cisplatin (50 mg/m2) + paclitaxel (175 mg/m2) + radiotherapy15 mg/kgOS, PFSCR, PR, SD, PDUnivariate
Cerina 2021CohortCroatia2016–201962/6756 (46–61)/51 (45–60)C: 10.9/T: 14.5cisplatin (50 mg/m2) + paclitaxel (175 mg/m2)15 mg/kgOS, PFSCR, PR, SD, PDMultivariate
Chu 2021CohortChina2015–2019122/12462.20 ± 6.84/62.10 ± 7.5924 (2–32)cisplatin (50 mg/m2 on day 1) + paclitaxel (175 mg/m2 on day 1)15 mg/kgOS, PFSNRUnivariate
Liu 2021CohortChina2014–201943/2160.58 ± 11.88/56.86 ± 12.54C: 43.93/T: 31.15cisplatin (50 mg/m2) + paclitaxel (175 mg/m2)15 mg/kgOS, PFSCR, PR, SD, PDUnivariate
Yang 2021CohortChina2016–201965/64NRNRChemotherapy + Radiation therapy7.5 mg/kg tri-weeklyOSNRMultivariate
Hwang 2022CohortKorea2007–202075/144NR33.7 (1.2–185.6)Chemotherapy + Radiation therapyNROSNRUnivariate
Yasunaga 2022CohortJapan2005–201959/3160 (28–80)/54 (34–84)0–121paclitaxel (175–180 mg/m2) and carboplatin (dosed to an area under curve of 5–6)15 mg/kgOSCR, PR, SD, PDMultivariate
OS: overall survival; CR: complete response; PR: partial response; SD: stabilization disease; PD: progression disease; PFS: Progression-free survival; C/T: Control/Treatment group; RCT: Randomized Controlled Trial; NR: Not Reported.
Flow chart of the meta-analysis.

Fig. 1.Flow chart of the meta-analysis.

3.2 Efficacy evaluation

The data on OS was obtained from 10 studies [13, 14, 15, 16, 17, 18, 19, 20, 21, 22], and there was low heterogeneity in OS among the studies (I2 < 50%, p = 0.285), using a fixed effects model. Using HR as the effect indicator, the meta-analysis results showed that the OS of the platinum + paclitaxel combined with bevacizumab group was better than that of the traditional chemotherapy group, and the difference was statistically significant (HR = 0.76, 95% CI: 0.68–0.85, p < 0.001; Heterogeneity (H): I2 = 17.2%, p = 0.285) (Fig. 2A). The data on PFS were obtained from five studies [14, 15, 19, 21, 22], and the heterogeneity of PFS among the studies was low (I2 < 50%, p = 0.713), so a fixed effects model was used. Using HR as the effect indicator, the meta-analysis results illustrated that the PFS of patients in the platinum + paclitaxel combined with bevacizumab group was significantly better than that in the traditional chemotherapy group, which indicated that the experimental group had a lower risk of worsening a/r CC compared with the control group (HR = 0.59, 95% CI: 0.49–0.71, p < 0.001; H: I2 = 0.0%, p = 0.713) (Fig. 2B). The overall efficacy was evaluated by CR, PR, SD and PD, with data from six studies [15, 16, 17, 18, 20, 21] included. Using RR as the effect indicator, the meta-analysis results demonstrated that the incidence of CR in the chemotherapy combined with bevacizumab group was higher than that in the chemotherapy alone group, and the difference was statistically significant (RR = 1.22, 95% CI: 1.00–1.47, p = 0.046; H: I2 = 46.9%, p = 0.094) (Fig. 3A). The incidence of PR in the chemotherapy combined with bevacizumab group was higher than that in the chemotherapy alone group (RR = 1.38, 95% CI: 1.15–1.66, p = 0.001; H: I2 = 0.0%, p = 0.574) (Fig. 3B). The incidence of PD in the chemotherapy combined with bevacizumab group was lower than that in the chemotherapy alone group (RR = 0.43, 95% CI: 0.31–0.61, p < 0.001; H: I2 = 14.3%, p = 0.322) (Fig. 3C). There was no statistically significant difference in the SD incidence between the combined group and the chemotherapy alone group (RR = 1.00, 95% CI: 0.64–1.57, p = 0.998; H: I2 = 61.9%, p = 0.033) (Fig. 3D). In terms of safety, the incidence of hypertension (p = 0.029, Fig. 4A), thrombosis (p < 0.01, Fig. 4B), and neutropenia (p = 0.011, Fig. 4C) was significantly higher in the combination therapy group compared to the chemotherapy-only group. Additionally, the incidence of pain (p = 0.455, Fig. 4D), gastrointestinal and genitourinary fistulas (p = 0.109, Fig. 4E), and bleeding (p = 0.147, Fig. 4F) showed no statistically significant differences between the two groups. Although these side effects were more frequent in the combination therapy group, they did not reach statistical significance.

Forest plots of OS and PFS. (A) OS; (B) PFS. HR: hazard ratio; CI: confidence interval.

Fig. 2.Forest plots of OS and PFS. (A) OS; (B) PFS. HR: hazard ratio; CI: confidence interval.

Forest plots of treatment response. (A) CR; (B) PR; (C) PD; (D) SD. RR: relative risk; CI: confidence interval.

Fig. 3.Forest plots of treatment response. (A) CR; (B) PR; (C) PD; (D) SD. RR: relative risk; CI: confidence interval.

Forest plots of Adverse Events. (A) hypertension, (B) thrombosis, (C) neutropenia, (D) pain, (E) gastrointestinal/genitourinary fistulas, (F) bleeding. RR: relative risk; CI: confidence interval.

Fig. 4.Forest plots of Adverse Events. (A) hypertension, (B) thrombosis, (C) neutropenia, (D) pain, (E) gastrointestinal/genitourinary fistulas, (F) bleeding. RR: relative risk; CI: confidence interval.

3.3 Publication bias and sensitivity analysis

The funnel plot and Egger tests were used to analyze the publication bias of the merged results. As shown in the funnel plot, there are basic symmetry on both sides and no significant publication bias (Fig. 5). Deleting a set of research data in sequence did not have significant impacts on the final results, and the meta-analysis results did not show any substantial changes, which indicated a good balance between the research results and overall stability (Fig. 6). The Egger test p-values for PFS and OS were 0.222 and 0.062, respectively, which suggested stable and reliable research conclusions (Fig. 7).

Funnel plot of main outcome indexes of bevacizumab combined with chemotherapy compared with chemotherapy alone. (A) OS; (B) PFS. HR: hazard ratio.

Fig. 5.Funnel plot of main outcome indexes of bevacizumab combined with chemotherapy compared with chemotherapy alone. (A) OS; (B) PFS. HR: hazard ratio.

Sensitivity analysis for the meta-analysis. (A) OS; (B) PFS.

Fig. 6.Sensitivity analysis for the meta-analysis. (A) OS; (B) PFS.

Egger’s publication bias funnel plots. (A) PFS; (B) OS.

Fig. 7.Egger’s publication bias funnel plots. (A) PFS; (B) OS.

4. Discussion

This meta-analysis, including 10 studies (1922 a/r CC patients), indicates that the combination of bevacizumab and traditional chemotherapy significantly improved OS (HR = 0.76, 95% CI: 0.68–0.85, p < 0.001) and PFS (HR = 0.59, 95% CI: 0.49–0.71, p < 0.001) compared to chemotherapy alone. Additionally, the combination therapy also led to higher CR (RR = 1.22, p = 0.046) and PR rates (RR = 1.38, p = 0.001), and a lower incidence of PD (RR = 0.43, p < 0.001). In terms of safety, the bevacizumab group had significantly higher rates of hypertension (p = 0.029), thrombosis (p < 0.01) and neutropenia (p = 0.011), but there was no significant difference in pain (p = 0.455), gastrointestinal and genitourinary fistulas (p = 0.109), or bleeding (p = 0.147). These findings suggest that while bevacizumab improves survival, it also increases the risk of certain adverse events.

Under normal circumstances, angiogenesis occurs in various physiological processes, such as embryo formation and wound healing. Abnormal blood vessels are the main mediator of tumor development [23]. Signal pathways, such as VEGF—VEGF receptor (VEGFR), platelet derived growth factor (PDGF)—PDGF receptor (PDGFR), and fibroblast growth factor (FGF)—FGF receptor (FGFR) can participate in the regulation of angiogenesis. The VEGF family composed of VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PLGF) and it plays a crucial role [24]. VEGFR-2 is the main functional receptor of VEGF, and its binding can regulate the proliferation and migration of EC, thereby promoting tumor angiogenesis [25]. Anti-angiogenesis prevents abnormal angiogenesis by blocking active signalling pathways in the tumor microenvironment (TME), thus leading to a lack of nutrition and oxygen in the tumor. At present, anti-angiogenic drugs mainly include monoclonal antibodies targeting VEGF, and tyrosine kinase inhibitors developed for multiple targets such as VEGFR, PDGFR and FGFR. Bevacizumab is the world’s first approved anti-tumor angiogenesis targeted drug, as well as the first recombinant humanized anti VEGF monoclonal antibody. It specifically binds to VEGF or VEGFR, thus blocking their binding to corresponding receptors/ligands, reducing tumor angiogenesis, and inhibiting tumor progression. Multiple clinical studies have confirmed that first-line treatment with bevacizumab can benefit patients with advanced epithelial ovarian cancer, thus making it one of the standard treatment options for patients with advanced epithelial ovarian cancer [25].

It has been recognized by the NCCN in the United States Multiple guidelines. For example, the International Federation of Gynecology and Obstetrics (FIGO) and the Chinese Society of Clinical Oncology (CSCO) are recommended, which can be used in combination with paclitaxel and cisplatin or paclitaxel and topotecan for the treatment of patients with persistent, a/r CC. For a/r CC patients, without bevacizumab, chemotherapy can achieve a treatment outcome of approximately 6–9 months of survival, generally not exceeding 10 months [26]. After the combination of bevacizumab, there will be a significant improvement in PFS and OS, which is consistent with the results of this meta-analysis study [27]. However, if bevacizumab and immunotherapy are combined, the survival period of patients with a/r CC can reach about 20 months [7]. In this regard, significant progress has been made in the comprehensive treatment of a/r CC, especially in targeted therapy and immunotherapy for recurrence.

In the future, further research can be conducted to determine whether different pathological types or gene subtypes have different responses to targeted therapy, aiming to provide personalized treatment options for a/r CC patients [11]. Currently, multiple clinical trials, including immunosuppressive agents combined with targeted therapy, chemotherapy, and radiotherapy, are being conducted, and the efficacy of these drugs in combination still requires more clinical data support. Based on the KEYNOTE-826 study, the 2022 NCCN CC guidelines recommend first-line treatment with pembrolizumab plus chemotherapy ± bevacizumab for programmed death-ligand 1 (PD-L1) positive patients, which marked a new layout for first-line treatment of a/r CC. In the KEYNOTE-826 study, the median OS of the experimental group and the control group were 26.4 months and 16.8 months, and the 2-year OS rates were 52.1% and 38.7%, respectively. The experimental group had significantly better OS. The median PFS of the two groups was 10.4 months and 8.2 months, and the 1-year PFS rates were 44.7% and 33.1%, respectively. The experimental group also had significantly better PFS [28]. At present, phase III clinical studies of multiple anti angiogenic drugs combined with immunotherapy and platinum containing chemotherapy are underway [29, 30]. Antibody–drug conjugate (ADC) drug monotherapy (Tisotumab Vedotin) has been approved in the second line of a/r CC, and the first line is actively explored, which may further change the treatment pattern of a/r CC. In the InnovaTV 204 trial, 102 patients who had previously received treatment for a/r CC were followed up (median follow-up time of 10.0 months), and the objective response rate of Tisotumab Vedotin was 24%. Among them, 7% of patients had CR and 17% had PR, which indicated a disease control rate of 72%. The median duration of relief of this drug was 8.3 months, and the observed median response time was 1.4 months [29]. We look forward to the release of more data and provide new treatment options for patients with persistent, recurrent and a/r CC.

For the advantages, firstly, it is currently the latest meta-analysis study that incorporates well-established RCTs and cohort studies. Secondly, this study comprehensively merged existing evidence through meta-analysis and obtained results with a higher level of evidence. However, this study also has some limitations. On the one hand, the number of patients included in RCTs is limited. On the other hand, different patients have different types of paclitaxel drugs, including paclitaxel, albumin paclitaxel, docetaxel and cabataxel, which leads to a moderate degree of heterogeneity in this study.

5. Conclusion

This meta-analysis proves that the combination of bevacizumab and chemotherapy significantly improves OS and PFS in a/r CC. The combination therapy also increases CR and PR rates while reducing the incidence of PD, but it is associated with higher risks of hypertension, thrombosis and neutropenia. Although bevacizumab offers clear survival and response benefits, close monitoring of side effects is essential to optimize patient safety.

Abbreviations

a/r CC, advanced or refractory cervical cancer; CR, complete response; PR, partial response; SD, stabilization disease; PD, progression disease; HPV, human papillomavirus; TCT, thin-layer cytology test; EGFR, epidermal growth factor receptor; VEGF, vascular endothelial growth factor; OS, overall survival; FDA, Food and Drug Administration; NCCN, National Comprehensive Cancer Network; PFS, progression free survival; HR, hazard ratio; RR, relative risk; NOS, Newcastle-Ottawa Scale; VEGFR, VEGF receptor; PDGF, platelet derived growth factor; PDGFR, PDGF receptor; FGF, fibroblast growth factor; FGFR, FGF receptor; PLGF, placental growth factor; TME, tumor microenvironment; FIGO, Federation of Gynecology and Obstetrics; CSCO, Chinese Society of Clinical Oncology; EC, endothelial cells; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; CI, Confidence Interval; RCT, Randomized Controlled Trial; ADC, Antibody-drug conjugate; PD-L1, programmed death-ligand 1; H, Heterogeneity.

Availability of data and materials

Some or all data, models, or code generated or used during the study are available from the corresponding author by request.

Author contributions

SMX—prepared the original draft of the manuscript; conducted a literature search. YX and SYZ—performed the statistical analysis. SMX YBK, CMH and SJY—reviewed and revised the article.

Ethics approval and consent to participate

Not applicable.

Acknowledgment

We would like to express our sincere gratitude for the financial support provided by the following projects, which has been essential for the successful execution of this research: “The Preoperative MR Transverse Relaxation Technique Can Be Used to Predict the Risk of Bone Cement Leakage During Vertebroplasty” (Project No: 2022607), “Efficacy and Safety Evaluation of Coix Seed Oil Combined with Transcatheter Arterial Chemoembolization in the Treatment of Hepatocellular Carcinoma at BCLC Stage B/C” (Project No: 2022LHZYYB-04), and “Improving the Rate of Standardized VTE Prevention in Orthopedic Major Surgery Patients During the Perioperative Period Through Enhanced Recovery After Surgery (ERAS) and the PDSA Cycle” (Project No: 2024311). Their funding has provided the necessary resources and support for our research endeavors.

Funding

This research was supported by the following projects: “The Preoperative MR Transverse Relaxation Technique Can Be Used to Predict the Risk of Bone Cement Leakage During Vertebroplasty” (Project No: 2022607), “Efficacy and Safety Evaluation of Coix Seed Oil Combined with Transcatheter Arterial Chemoembolization in the Treatment of Hepatocellular Carcinoma at BCLC Stage B/C” (Project No: 2022LHZYYB-04), and “Improving the Rate of Standardized VTE Prevention in Orthopedic Major Surgery Patients During the Perioperative Period Through Enhanced Recovery After Surgery (ERAS) and the PDSA Cycle” (Project No: 2024311). This funding has provided the essential resources and support for our research efforts.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

Supplementary material associated with this article can be found, in the online version, at https://oss.ejgo.net/files/article/1956167840636518400/attachment/Supplementary%20material.zip.

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