Objective: To investigate the effect of hsa_circ_0000392 (circ_0000392) on the radiosensitivity of cervical cancer cells and explore its potential mechanism. Methods: Cervical cancer tissues and adjacent normal tissues of 42 patients with cervical cancer who were confirmed pathologically for the first time in Huaihe Hospital of Henan University from 2016 to 2019 were collected. According to the patients' response to radiotherapy, the cancer tissues were divided into radio-sensitive tissues and radio-resistant tissues. The expressions of circ_0000392, miR-145-5p, and CRKL in radiation-sensitive, radiation-resistant cervical cancer tissues and Hela, SiHa cells were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. SiRNA circ_0000392, miR-145-5p mimic, miR-145-5p inhibitor, pcDNA 3.1-CRKL and its negative control were transfected into HeLa and Siha cells, respectively. After radiation induction, the survival fraction of cells was detected by clone formation assay, apoptosis was detected by flow cytometry, and the expressions of apoptosis-related proteins Bax and Bcl-2 and ERK pathway protein p-ERK1/2 and ERK1/2 were detected by western blot. The targeting relationship between circ_0000392, miR-145-5p and CRKL was verified by dual luciferase reporter gene assay. The effect of circ_0000392 on radiotherapy sensitivity of cervical cancer in vivo was observed in the tumor formation experiment in nude mice. Results: circ_0000392 and CRKL were upregulated in radiation-resistant tissues and cancer cells of cervical cancer, while miR-145-5p was downregulated. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ 6 Gy group were (78.67±10.97) and (71.00±9.54), respectively, which were lower than those in si-Ctrl+ 6 Gy group [(176.00±22.27) and (158.33±17.56), respectively]. The apoptosis rates were (41.55±3.40)% and (31.41±3.29)%, respectively, which were higher than those in si-Ctrl+ 6 Gy group [(15.91±1.37)% and (13.70±1.89)%, P<0.05]. The protein expression of Bax was higher than that of si-Ctrl+ 6 Gy group, and the protein expressions of Bcl2 was lower than those of si-Ctrl+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ miR-145-5p inhibitor+ 6 Gy group were (171.33±25.01) and (137.00±21.66), higher than those in si-circ_0000392#1+ inhibitor NC+ 6 Gy group [(84.67±17.79) vs (71.00±11.00), P<0.05]. The apoptosis rates were (17.41±2.58) % and (15.96±1.25) %, lower than those of si-circ_0000392 #1+ inhibitor NC+ 6 Gy [(40.29±2.92)% and (30.82±2.34)%, respectively, P<0.05]. The expression of Bax protein was lower than that of si-circ_0000392#1+ inhibitor NC+ 6 Gy group, and the expressions of Bcl2 protein were higher than those of si-circ_0000392#1+ inhibitor NC+ 6 Gy group. Circ_0000392 can target miR-145-5p, and CRKL is the downstream target gene of miR-145-5p. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ 6 Gy group were (74.33±10.02) and (66.00±12.17), respectively, which were lower than those of mimic NC+ 6 Gy group [(197.67±17.21) vs (157.67±11.59), respectively, P<0.05]. The apoptosis rates were (45.58±2.16)% and (32.10±3.55)%, higher than those of mimic NC+ 6 Gy group [(15.85±2.45)% and (13.99±1.69)%, respectively, P<0.05]. The expression of Bax protein was higher than that of the mimic NC+ 6 Gy mimic group, and the expression of Bcl2 protein was lower than that of the mimic NC+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ pcDNA-CRKL+ 6 Gy group were (158.00±15.88) and (122.33±13.65), respectively, which were higher than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(71.33±8.02) vs (65.67±12.22), P<0.05]. The apoptosis rates were (19.50±3.45)% and (17.04±0.94)%, respectively, which were lower than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(44.33±2.36)% and (32.05±2.76)%, respectively, P<0.05]. The expression of Bax protein was lower than that of miR-145-5p mimic+ pcDNA group+ 6 Gy group, and the expression of Bcl2 protein was higher than that of miR-145-5p mimic+ pcDNA+ 6 Gy group. Sh-circ_0000392 group had smaller tumor volume and decreased tumor weight (P<0.05). The relative mRNA expression levels of circ_0000392, miR-145-5p and CRKL and the relative protein expression levels of CRKL, Bcl-2 and p-ERK1/2 were decreased, while the relative expression level of Bax protein was increased (P<0.05). Conclusion: Circ_0000392 could enhance the radiosensitivity of cervical cancer cells, and its mechanism may be related to the regulation of CRKL/ERK signaling pathway by targeting miR-145-5p, which provides a new reference for enhancing the radiosensitivity of cervical cancer cells.
Animals ; Mice ; Female ; Humans ; Uterine Cervical Neoplasms/radiotherapy* ; bcl-2-Associated X Protein/genetics* ; Mice, Nude ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Apoptosis ; MicroRNAs/genetics* ; Cell Proliferation ; Cell Line, Tumor

Objective: To investigate the effect of hsa_circ_0000392 (circ_0000392) on the radiosensitivity of cervical cancer cells and explore its potential mechanism. Methods: Cervical cancer tissues and adjacent normal tissues of 42 patients with cervical cancer who were confirmed pathologically for the first time in Huaihe Hospital of Henan University from 2016 to 2019 were collected. According to the patients' response to radiotherapy, the cancer tissues were divided into radio-sensitive tissues and radio-resistant tissues. The expressions of circ_0000392, miR-145-5p, and CRKL in radiation-sensitive, radiation-resistant cervical cancer tissues and Hela, SiHa cells were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. SiRNA circ_0000392, miR-145-5p mimic, miR-145-5p inhibitor, pcDNA 3.1-CRKL and its negative control were transfected into HeLa and Siha cells, respectively. After radiation induction, the survival fraction of cells was detected by clone formation assay, apoptosis was detected by flow cytometry, and the expressions of apoptosis-related proteins Bax and Bcl-2 and ERK pathway protein p-ERK1/2 and ERK1/2 were detected by western blot. The targeting relationship between circ_0000392, miR-145-5p and CRKL was verified by dual luciferase reporter gene assay. The effect of circ_0000392 on radiotherapy sensitivity of cervical cancer in vivo was observed in the tumor formation experiment in nude mice. Results: circ_0000392 and CRKL were upregulated in radiation-resistant tissues and cancer cells of cervical cancer, while miR-145-5p was downregulated. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ 6 Gy group were (78.67±10.97) and (71.00±9.54), respectively, which were lower than those in si-Ctrl+ 6 Gy group [(176.00±22.27) and (158.33±17.56), respectively]. The apoptosis rates were (41.55±3.40)% and (31.41±3.29)%, respectively, which were higher than those in si-Ctrl+ 6 Gy group [(15.91±1.37)% and (13.70±1.89)%, P<0.05]. The protein expression of Bax was higher than that of si-Ctrl+ 6 Gy group, and the protein expressions of Bcl2 was lower than those of si-Ctrl+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ miR-145-5p inhibitor+ 6 Gy group were (171.33±25.01) and (137.00±21.66), higher than those in si-circ_0000392#1+ inhibitor NC+ 6 Gy group [(84.67±17.79) vs (71.00±11.00), P<0.05]. The apoptosis rates were (17.41±2.58) % and (15.96±1.25) %, lower than those of si-circ_0000392 #1+ inhibitor NC+ 6 Gy [(40.29±2.92)% and (30.82±2.34)%, respectively, P<0.05]. The expression of Bax protein was lower than that of si-circ_0000392#1+ inhibitor NC+ 6 Gy group, and the expressions of Bcl2 protein were higher than those of si-circ_0000392#1+ inhibitor NC+ 6 Gy group. Circ_0000392 can target miR-145-5p, and CRKL is the downstream target gene of miR-145-5p. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ 6 Gy group were (74.33±10.02) and (66.00±12.17), respectively, which were lower than those of mimic NC+ 6 Gy group [(197.67±17.21) vs (157.67±11.59), respectively, P<0.05]. The apoptosis rates were (45.58±2.16)% and (32.10±3.55)%, higher than those of mimic NC+ 6 Gy group [(15.85±2.45)% and (13.99±1.69)%, respectively, P<0.05]. The expression of Bax protein was higher than that of the mimic NC+ 6 Gy mimic group, and the expression of Bcl2 protein was lower than that of the mimic NC+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ pcDNA-CRKL+ 6 Gy group were (158.00±15.88) and (122.33±13.65), respectively, which were higher than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(71.33±8.02) vs (65.67±12.22), P<0.05]. The apoptosis rates were (19.50±3.45)% and (17.04±0.94)%, respectively, which were lower than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(44.33±2.36)% and (32.05±2.76)%, respectively, P<0.05]. The expression of Bax protein was lower than that of miR-145-5p mimic+ pcDNA group+ 6 Gy group, and the expression of Bcl2 protein was higher than that of miR-145-5p mimic+ pcDNA+ 6 Gy group. Sh-circ_0000392 group had smaller tumor volume and decreased tumor weight (P<0.05). The relative mRNA expression levels of circ_0000392, miR-145-5p and CRKL and the relative protein expression levels of CRKL, Bcl-2 and p-ERK1/2 were decreased, while the relative expression level of Bax protein was increased (P<0.05). Conclusion: Circ_0000392 could enhance the radiosensitivity of cervical cancer cells, and its mechanism may be related to the regulation of CRKL/ERK signaling pathway by targeting miR-145-5p, which provides a new reference for enhancing the radiosensitivity of cervical cancer cells.
Animals ; Mice ; Female ; Humans ; Uterine Cervical Neoplasms/radiotherapy* ; bcl-2-Associated X Protein/genetics* ; Mice, Nude ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Apoptosis ; MicroRNAs/genetics* ; Cell Proliferation ; Cell Line, Tumor

OBJECTIVE: To identify the problems in clinical radiotherapy planning for cervical cancer through quantitative evaluation of the radiotherapy plans to improve the quality of the plans and the radiotherapy process. METHODS: We selected the clinically approved and administered radiotherapy plans for 227 cervical cancer patients undergoing external radiotherapy at Sun Yat-sen University Cancer Center from May, 2019 to January, 2022. These plans were transferred from the treatment planning system to the Plan IQ^TM workstation. The plan quality metrics were determined based on the guidelines of ICRU83 report, the GEC-ESTRO Working Group, and the clinical requirements of our center and were approved by a senior clinician. The problems in the radiotherapy plans were summarized and documented, and those with low scores were re-planned and the differences were analyzed. RESULTS: We identified several problems in the 277 plans by quantitative evaluation. Inappropriate target volume selection (with scores < 60) in terms of GTV, PGTV (CI) and PGTV (V_{66 Gy}) was found in 10.6%, 65.2%, and 1% of the plans, respectively; and the PGTV (CI), GTV, and PCTV (D_98%, HI) had a score of 0 in 0.4%, 10.1%, 0.4%, 0.4% of the plans, respectively. The problems in the organs at risk (OARs) involved mainly the intestines (the rectum, small intestine, and colon), found in 20.7% of the plans, and in occasional cases, the rectum, small intestine, colon, kidney, and the femoral head had a score of 0. Senior planners showed significantly better performance than junior planners in PGTV (V_{60 Gy}, D_98%), PCTV (CI), and CTV (D_98%) (P≤0.046) especially in terms of spinal cord and small intestine protection (P≤0.034). The bowel (the rectum, small intestine and colon) dose was significantly lower in the prone plans than supine plans (P < 0.05), and targets coverage all met clinical requirements. Twenty radiotherapy plans with low scores were selected for re-planning. The re-planned plans had significantly higher GTV (D_min) and PTV (V_{45 Gy}, D_98%) (P < 0.05) with significantly reduced doses of the small intestines (V_{40 Gy} vs V_{30 Gy}), the colon (V_{40 Gy} vs V_{30 Gy}), and the bladder (D_35%) (P < 0.05). CONCLUSION Quantitative evaluation of the radiotherapy plans can not only improve the quality of radiotherapy plan, but also facilitate risk management of the radiotherapy process.
Humans ; Female ; Uterine Cervical Neoplasms/radiotherapy* ; Rectum ; Colon ; Kidney ; Organs at Risk

OBJECTIVE: To investigate the influence of positioning accuracy of the multi-leaf collimators (MLC) on the passing rate of the plan dose verification for volumetric modulation arc therapy (VMAT) of cervical cancer using an Elekta linear accelerator. METHODS: The dose distributions were measured using Sun Nuclear's Mapcheck and Arccheck semiconductors matrix before and after MLC calibration in30 cervical cancer patients undergoing VMAT. Dosimetric comparisons were performed with 2D and 3D gamma passing rates of 3%, 3 mm and 2%, and 2 mm. The 3D gamma distribution was reconstructed with respect to the patient's anatomy using 3DVH software to evaluate the possible influence of MLC positioning accuracy. RESULTS: Before and after MLC calibration, the gamma passing rates of Mapcheck were (88.80±1.81)% and (99.25 ± 0.53)% under 3% and 3 mm standard, respectively, with an average increase of 10.45%. The corresponding gamma passing rates of Arccheck were (87.61±1.98)% and (98.13±0.99)%, respectively, with an average increase of 10.52%. The gamma passing rates of 3DVH were (89.87±2.28)% and (98.3±1.15)%, respectively, with an average increase of 8.43%. CONCLUSION The MLC positioning accuracy is one of the main factors influencing dosimetric accuracy of VMAT for cervical cancer. The application of Autocal software facilitates MLC calibration and improves the accuracy and safety of VMAT delivery for cervical cancer.
Female ; Humans ; Particle Accelerators ; Quality Control ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy, Intensity-Modulated/methods* ; Uterine Cervical Neoplasms/radiotherapy*

Objective: To determine the effect of tumor metastasis-associated gene 1 (MTA1) on the sensitivity of HeLa cells to radiotherapy, and to clarify its molecular mechanism. Methods: The transcriptome differences between MTA1 knocked down Hela cells and control cells were analyzed, and the differentially expressed genes (DEGs) was used to perform Gene-Set Enrichment Analysis (GSEA) and Gene Ontology (GO) cluster analysis. Flow cytometry was used to detect apoptosis in MTA1-overexpressed HeLa cells and control cells before and after 10 Gy X-ray irradiation. Cloning formation assay and real-time cellular analysis (RTCA) were used to monitor the cell proliferation before and after 2 Gy X-ray irradiation. To dissect the underlying molecular mechanisms of MTA1 affecting the sensitivity of radiotherapy, the proteins encoded by the DEGs were selected to construct a protein-protein interaction network, the expression of γ-H2AX was detected by immunofluorescence assay, and the expression levels of γ-H2AX, β-CHK2, PARP and cleaved caspase 3 were measured by western blot. Results: By transcriptome sequencing analysis, we obtained 649 DEGs, of which 402 genes were up-regulated in MTA1 knockdown HeLa cells and 247 genes were down-regulated. GSEA results showed that DEGs associated with MTA1 were significantly enriched in cellular responses to DNA damage repair processes. The results of flow cytometry showed that the apoptosis rate of MTA1 over-expression group (15.67±0.81)% after 10 Gy X-ray irradiation was significantly lower than that of the control group [(40.27±2.73)%, P<0.001]. After 2 Gy X-ray irradiation, the proliferation capacity of HeLa cells overexpressing MTA1 was higher than that of control cells (P=0.024). The numbers of colon in MTA1 over-expression group before and after 2 Gy X-ray irradiation were (176±7) and (137±7) respectively, higher than (134±4) and (75±4) in control HeLa cells (P<0.05). The results of immunofluorescence assay showed that there was no significant expression of γ-H2AX in MTA1 overexpressed and control HeLa cells without X-ray irradiation. Western blot results showed that the expression level of β-CHK2 in MTA1-overexpressing HeLa cells (1.04±0.06) was higher than that in control HeLa cells (0.58±0.25, P=0.036) after 10 Gy X-ray irradiation. The expression levels of γ-H2AX, PARP, and cleaved caspase 3 were 0.52±0.13, 0.52±0.22, and 0.63±0.18, respectively, in HeLa cells overexpressing MTA1, which were lower than 0.87±0.06, 0.78±0.12 and 0.90±0.12 in control cells (P>0.05). Conclusions: This study showed that MTA1 is significantly associated with radiosensitivity in cervical cancer HeLa cells. MTA1 over-expression obviously reduces the sensitivity of cervical cancer cells to X-ray irradiation. Mechanism studies initially indicate that MTA1 reduces the radiosensitivity of cervical cancer cells by inhibiting cleaved caspase 3 to suppress apoptosis and increasing β-CHK2 to promote DNA repair.
Apoptosis/genetics* ; Caspase 3/metabolism* ; Female ; HeLa Cells ; Humans ; Poly(ADP-ribose) Polymerase Inhibitors ; Radiation Tolerance/genetics* ; Repressor Proteins/metabolism* ; Trans-Activators/metabolism* ; Uterine Cervical Neoplasms/radiotherapy*

OBJECTIVES: The automatic delineation of organs at risk (OARs) can help doctors make radiotherapy plans efficiently and accurately, and effectively improve the accuracy of radiotherapy and the therapeutic effect. Therefore, this study aims to propose an automatic delineation method for OARs in cervical cancer scenarios of both after-loading and external irradiation. At the same time, the similarity of OARs structure between different scenes is used to improve the segmentation accuracy of OARs in difficult segmentations. METHODS: Our ensemble model adopted the strategy of ensemble learning. The model obtained from the pre-training based on the after-loading and external irradiation was introduced into the integrated model as a feature extraction module. The data in different scenes were trained alternately, and the personalized features of the OARs within the model and the common features of the OARs between scenes were introduced. Computer tomography (CT) images for 84 cases of after-loading and 46 cases of external irradiation were collected as the train data set. Five-fold cross-validation was adopted to split training sets and test sets. The five-fold average dice similarity coefficient (DSC) served as the figure-of-merit in evaluating the segmentation model. RESULTS: The DSCs of the OARs (the rectum and bladder in the after-loading images and the bladder in the external irradiation images) were higher than 0.7. Compared with using an independent residual U-net (convolutional networks for biomedical image segmentation) model [residual U-net (Res-Unet)] delineate OARs, the proposed model can effectively improve the segmentation performance of difficult OARs (the sigmoid in the after-loading CT images and the rectum in the external irradiation images), and the DSCs were increased by more than 3%. CONCLUSIONS Comparing to the dedicated models, our ensemble model achieves the comparable result in segmentation of OARs for different treatment options in cervical cancer radiotherapy, which may be shorten time for doctors to sketch OARs and improve doctor's work efficiency.
Female ; Humans ; Image Processing, Computer-Assisted/methods* ; Machine Learning ; Organs at Risk/radiation effects* ; Radiotherapy Planning, Computer-Assisted/methods* ; Uterine Cervical Neoplasms/radiotherapy*

OBJECTIVES: Patients with cervical cancer who have received radiotherapy often suffer from systemic muscle volume reduction and quality of life decline due to systemic effects of tumor and side effects of radiotherapy. The purpose of this study was to investigate the status of muscle fitness, quality of life, and psychological pain in patients with cervical cancer who received radiotherapy, and to explore the correlation between muscle fitness, quality of life, and psychological pain. METHODS: A total of 202 cervical cancer patients aged 19-71, who received radiotherapy in Hunan Cancer Hospital from July 2020 to February 2021, were selected by convenience sampling method. Functional Assessment of Cancer Therapy Cervix (FACT-CX) and Distress Thermometer (DT) were used for the survey. The patient's grip strength was assessed by a handgrip meter and compared with that of healthy Chinese women of the same age. The correlation between muscle fitness and quality of life and psychological pain was analyzed. RESULTS: The grip strength of cervical cancer patients receiving radiotherapy was significantly lower than that of healthy Chinese women at the same age ( CONCLUSIONS The grip strength of patients with cervical cancer undergoing radiotherapy is generally decreased, which is affected by many factors, and is closely related to the quality of life and psychological pain of patients. In the future, dynamic attention should be paid to the changes of grip strength and related functions in patients receiving radiotherapy for cervical cancer, the potential risks in the treatment should be identified early, and targeted intervention should be taken.
Anxiety ; Female ; Hand Strength ; Humans ; Psychological Distress ; Quality of Life ; Uterine Cervical Neoplasms/radiotherapy*

OBJECTIVE: The causal association of human papillomavirus (HPV) in uterine cervical cancer was well established and this oncogenic virus was reported to be a biomarker for overall recurrence and central pelvic recurrence. The objective of the present systematic review and meta-analysis was to assess the role of HPV DNA testing in early detection of recurrence among cervical cancer survivors after radiotherapy.METHODS: We performed a systematic review and meta-analysis by means of searching electronic databases for published articles between January 1984 and June 2018, on the basis of standard systematic review guidelines prescribed by major agencies namely Cochrane Collaboration (https://www.cochrane.org) and Campbell Collaboration (https://www.campbellcollaboration.org). The meta-analysis component was further modified appropriately for the synthesis of sensitivity and specificity results.RESULTS: A total of 1,055 cervical cancer cases who had received pelvic radiation with or without chemotherapy from ten cohort studies were evaluated. The overall pooled sensitivity and specificity of HPV DNA testing was 0.84 (95% confidence interval [CI]= 0.66–0.94) and 0.35 (95% CI=0.20–0.54) respectively. The positive likelihood ratio was 1.3 (95% CI=1.0–1.7) and the negative likelihood ratio was 0.45 (95% CI=0.18–1.10) with an estimated diagnostic odds ratio of 3 (95% CI=1–9).CONCLUSION: The screening for HPV DNA testing during follow-up facilitates early detection of recurrence after radiotherapy.
Cervix Uteri ; Cohort Studies ; Cooperative Behavior ; DNA ; Drug Therapy ; Female ; Follow-Up Studies ; Human Papillomavirus DNA Tests ; Humans ; Mass Screening ; Odds Ratio ; Oncogenic Viruses ; Radiotherapy ; Recurrence ; Sensitivity and Specificity ; Survivors ; Uterine Cervical Neoplasms

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.CONCLUSION: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.
Antigens, CD274 ; Biopsy ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Flow Cytometry ; Heavy Ion Radiotherapy ; Humans ; Radiotherapy ; Treatment Outcome ; Uterine Cervical Neoplasms

cervical cancer in patients who have already received more than two kinds of comprehensive treatment.METHODS: Forty-eight patients with recurrent or metastatic cervical cancer after radiotherapy or surgery who received apatinib between June 2016 and June 2017 were involved in this study. These patients experienced progression after first-line or second-line chemotherapy. There were 38 patients with cervical squamous cell carcinoma, 8 with adenocarcinoma, and 2 with adenosquamous carcinoma. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were reviewed and evaluated.RESULTS: All patients had complete follow-up records, and the median follow-up time was 14.5 months (5.5–20.5 months). Among the 48 patients, 14.58% achieved a partial response and 52.08% achieved stable disease. The overall response rate and disease control rate were 14.58% and 66.67%, respectively. The median time that the 48 patients received oral apatinib was 8.2 months. The median PFS was 4.6 months (95% confidence interval [CI]=3.31–5.26) and OS was 13.9 months (95% CI=8.37–17.96). The main apatinib-related adverse reactions were leukopenia (37.5%), neutropenia (41.67%), hemorrhage (37.5%), hypertension (33.33%), proteinuria (12.5%), fatigue (37.5%), and hand-foot syndrome (27.08%). Most of them were grade 1–2, and no drug-related death occurred.CONCLUSIONS: Apatinib can improve the disease control rate of recurrent and metastatic cervical cancer when chemotherapy has failed, and the treatment is well tolerated. This represents that apatinib may be a new treatment option for metastatic cervical cancer patients.]]>
Adenocarcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Fatigue ; Follow-Up Studies ; Hand-Foot Syndrome ; Hemorrhage ; Humans ; Hypertension ; Leukopenia ; Molecular Targeted Therapy ; Neutropenia ; Proteinuria ; Radiotherapy ; Retrospective Studies ; Uterine Cervical Neoplasms