Clinical implication of naive and memory T cells in locally advanced cervical cancer:A proxy for tumor biology and short-term response prediction

Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.

Specific Immunotherapy in Advanced Cervical-Uterine Cancer Using Humanized Monoclonal Antibody Nimotuzumab and CIMAvax-EGF^®Therapeutic Vaccine

Cervical uterine cancer represents the fourth most common malignant neoplasm worldwide in the female sex in terms of incidence, principally from epithelial origen. The high expression of EGFR in this tumor leads to the search for therapeutic alternatives. An Expanded Access Clinical Program was carried out in parallel groups, randomized, multicenter and prospective study, to evaluate the survival of patients with advanced cervical carcinoma, without therapeutic alternative, who would be treated with the therapeutic vaccine CIMAvax-EGF®, the humanized mAb nimotuzumab or the combination of both products, which targeted EGF and EGFR respectively. The patients were included between 2008 and 2010 with a more than five years follow-up. The results show that the serious adverse events related to the experimental treatments were 0.9%;1.1% and 2.6% and a median ITT survival of 9.1, 23.5, and 16.3 months for CIMAvax-EGF®, nimotuzumab and the combination of both, respectively. Thus fulfilling the hypothesis of safety and efficacy proposed in the investigation was achieved. The three therapeutic regimens achieved overall survival rates greater than 35% at 60 months, encouraging results for advanced uterine cervical cancer. A phase III clinical trial is proposed to consolidate these results in a greater number of patients with nimotuzumab as study drug.

Association between Pretreatment Levels of Serum Vascular Endothelial Growth Factor (VEGF) and Survival Outcomes in Locally Advanced Cervical Cancer Patients

Objective: To evaluate the association between pretreatment levels of serum vascular endothelial growth factor (VEGF) and long-term treatment outcomes in patients with locally advanced cervical cancer (LACC). Methods: Thirty-nine patients diagnosed with LACC (stage IIB-IVA) and obtaining blood for serum VEGF were identified. All patients received complete treatment as radical radiotherapy with or without concurrent chemotherapy. Surveillance for all patients was every 3 months during the first 2 years, and every 6 months later. Results: Mean age of 39 patients was 52.3 ± 10.8 years old. Twenty-three patients (59.0%) had stage IIB, and 16 patients (41.0%) had stage IIIB. Histological cell type was mostly squamous cell carcinoma (89.7%). The median and 75th percentile level of serum VEGF were 610.2 pg/ml (0.0 - 4067.2 pg/ml) and 825.6 pg/ml, respectively. At median follow-up of 37.0 months (range, 26.8 - 46.3 months), the 3-year OS rate was 78.6%. Clinical stage (p = 0.04) and 75th percentile of VEGF level (p = 0.04) were impacted on OS in univariable analysis. The 3-year OS of patients in stage IIB with serum VEGF of ≤825.6 pg/ml and of > 825.6 pg/ml was slightly different, 94.4% and 80.0% respectively (p = 0.34), whereas there were many differences in stage IIIB, 71.4% and 25.0% in patients with serum VEGF of ≤825.6 pg/ml and of >825.6 pg/ml respectively (p = 0.05). Conclusion: High pretreatment serum VEGF level has an influence on OS for LACC. It is potentially used as a predictive factor, especially in patients stage IIIB, in order to provide efficient treatment and improve survival outcomes in the future.

Neoadjuvant intra-arterial infusion chemotherapy followed by surgery in patients with locally advanced cervical cancer

Objective： The aim of this study was to investigate the role of preoperative neoadjuvant intra-arterial infusion chemotherapy （NAIC） in treating locally advanced cervical caner. Methods： Nineteen locally advanced cervical cancer （LACC） patients from November 2003 to November 2005 were analyzed retrospectively. NAIC was administrated 2 courses every 2 weeks using a combination of 30 mg/m^2 bleomycin and 50 mg/m^2 cisplatin via bilateral femur artedes. The response to NAIC was assessed by pelvic examination and imaging diagnostics and histological analysis. Two weeks after NAIC radical hysterectomy with pelvic lymphadenectomy was performed. Results： Radical hysterectomy with pelvic lymphadenectomy were performed in 18 patients successfully. The mean tumor reduction rate was 73.04%. The overall clinical response rate of NAIC was 84.2% with 2 complete responses and 16 partial responses. Only 1 nonresponder. Six of 7 cases who had parametrial infiltration had a absence after chemotherapy, no significant change was observed in 1 case who followed by radiotherapy. Multivariate logistic regression analysis indicated that tumor volume prior to treatment was determining factor affecting the efficacy of NAIC in LACC. Conclusion： pre-operative NAIC inhibited the growth of LACC, minimized the size, eliminate effectively the pathologic dsk factors in the pelvic cavity, to improve the operability in cervical cancer patients with stage lib or above, considered inoperable.

Effect of cisplatin-based concurrent radiochemotherapy on malignant degree of advanced cervical cancer and expression of proto-oncogene and tumor suppressor genes

Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 patients with advanced cervical cancer who were treated in our hospital between July 2013 and December 2016 were collected and divided into control group and observation group according to random number table, with 41 cases in each group. The control group of patients received radiotherapy alone, while the observation group of patients received cisplatin-based concurrent radiochemotherapy. Tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were compared between two groups of patients before and after treatment.Results:Before treatment, differences in tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were not statistically significant between two groups of patients. After treatment, serum tumor markers SCC, CA50, CA724 and CEA levels of observation group were significantly lower than those of control group;proto-oncogene DEK, c-myc and PIK3CA mRNA expression in tumor tissue were significantly lower than those of control group;tumor suppressor genes p53, SOCS-1, FHIT and PTEN mRNA expression in tumor tissue were significantly higher than those of control group.Conclusions:Cisplatin-based concurrent radiochemotherapy can effectively reduce the tumor malignancy and balance the proto-oncogene / tumor suppressor gene expression in patients with advanced cervical cancer.

Effect of Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy on the cellular malignant biological processes in advanced cervical cancer lesion

Objective:To study the effect of Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy on the cellular malignant biological processes in advanced cervical cancer lesion.Methods: Patients who were diagnosed with advanced cervical cancer in the Second People Hospital of Banan District Chongqing between April 2015 and March 2017 were selected and divided into two groups, group A received Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy, and group B received cisplatin + intensity-modulated radiation therapy. Serum contents of tumor markers, tumor invasion molecules and tumor proliferation molecules of two groups of patients were detected before treatment as well as 2 weeks and 4 weeks after treatment.Results: Serum E-cad, STMN1, Fas and p53 levels of both groups of patients 2 weeks and 4 weeks after treatment were significantly higher than those before treatment while TSGF, TK1, SCC-Ag, CA125, OPN, MMP9, NGAL, CyclinE, CyclinD1 and PCNA levels were significantly lower than those before treatment, and serum E-cad, STMN1, Fas and p53 levels of group A 2 weeks and 4 weeks after treatment were significantly higher than those of group B while TSGF, TK1, SCC-Ag, CA125, OPN, MMP9, NGAL, CyclinE, CyclinD1 and PCNA levels were significantly lower than those of group B.Conclusion: Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy for advanced cervical cancer can induce cancer cell apoptosis and inhibit cancer cell proliferation and invasion.

Long-term survival outcomes and immune checkpoint inhibitor retreatment in patients with advanced cervical cancer treated with camrelizumab plus apatinib in the phase II CLAP study

Background:Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer(CLAP study;NCT03816553).We herein present the updated long-term results of the CLAP study and explore potential biomarkers for survival.The outcomes of patients who underwent immune checkpoint inhibitor(ICI)retreatment were also reported.Methods:In this phase II trial,eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4-week cycles for up to two years.Treatment was continued until disease progression,unacceptable toxicity,or withdrawal of consent.Results:Between January 21 and August 1,2019,a total of 45 patients were enrolled.Data were analyzed as of July 31,2023,representing>48 months since treatment initiation for all patients.Nine(20.0%)patients completed the 2-year study.The median duration of response(DOR)was 16.6 months,and 45.0%of patients achieved a DOR of≥24 months.The 12-month progression-free survival(PFS)rate was 40.7%(95%confidence interval[CI],25.2-55.6),with an 18-month PFS rate of 37.8%(95%CI,22.7-52.8).The median overall survival(OS)was 20.3 months(95%CI,9.3-36.9),and the 24-month OS rate was 47.8%(95%CI,31.7-62.3).Age>50 years,programmed death-ligand 1(PD-L1)combined positive score(CPS)≥1(versus[vs.]<1),CPS≥10(vs.<1),high tumor mutational burden,and PIK3CA mutations were associated with improved PFS(hazard ratio[HR]<1)and longer OS(HR<1).Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs.Among them,2(25.0%)achieved a partial response,while 5(62.5%)had stable disease.Notably,four patients who received retreatment with ICIs survived for more than 45months.No new safety signals were identified in the present study.Conclusion:Long-term survival follow-up data demonstrated that camrelizumab plus apatinib has robust,sustained,and durable efficacy in patients with advanced cervical cancer who progress after first-line platinum-based chemotherapy.No new safety signals were noted with long-term treatment.

Preliminary evaluation of pelvic vascular bed isolation chemotherapy in the treatment of advanced cervical carcinoma

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The impact of artificial intelligence-assisted intensity-modulated radiotherapy plan optimization on the radiation doses received by the rectum and bladder as well as radiation-induced injuries in patients with locally advanced cervical cancer

This study aimed to investigate the impact of artificial intelligence-assisted intensity-modulated radiotherapy(IMRT)plan optimization on the radiation doses received by the rectum and bladder as well as radiation-induced injuries in patients with locally advanced cervical cancer.A total of 100 patients with locally advanced cervical cancer were enrolled and divided into a conventional IMRT group and an artificial intelligence-assisted IMRT group.The results showed that in terms of the radiation doses to the rectum and bladder,all dosimetric parameters(such as mean dose,maximum dose,and volume-dose parameters,etc.)in the artificial intelligence-assisted group were significantly lower than those in the conventional group(p<0.05).Regarding radiation-induced injuries,the incidences and severities of both acute and late radiation-induced proctitis and cystitis in the artificial intelligence-assisted group were lower than those in the conventional group(p<0.05).These findings suggest that artificial intelligence-assisted IMRT plan optimization can effectively reduce the radiation doses to the rectum and bladder and decrease radiation-induced injuries in patients with locally advanced cervical cancer,which is expected to provide a more precise and safer treatment strategy for radiotherapy of locally advanced cervical cancer.However,this study has limitations such as a limited sample size and being a single-center study.Future research with multi-center,large-sample,and more in-depth investigations is needed.

Evaluation of the Factors Associated with Delay in Initiation of Treatment of Advanced Stage Cervical Cancer Patients in Bangladesh

Research Background: Cervical cancer is the second most common cancer in women and the third leading cause of female cancer death in Bangladesh. Delay in initiation of treatment in advanced stage cervical cancer patients is an important modifiable risk factor for cancer-related mortality. Identifying elements associated with delay of diagnosis will help reduce barriers to timely treatment of cervical cancer. Research Objectives: The objective of this study was to analyze the factors leading to delay in diagnosis and treatment of women with advanced stage cervical cancer. Methods: A cross-sectional observational study analyzed the factors associated with delay in initiation of treatment for 138 patients with advanced-stage cervical cancer from November 2019 to October 2020 at the National Institute of Cancer Research and Hospital (NICRH) in Dhaka, Bangladesh. Advanced-stage cervical cancer patients between the ages of 30 to 70 years were included in this study. Face-to-face interviews with the participants used a predesigned data collection sheet. In this study, three components of delay were identified: primary delay due to patient factors, healthcare provider delay, and healthcare-system infrastructure delay. Factors associated with delay were the independent variables and durations of delay were the outcome variables. Descriptive statistics were expressed as mean + standard deviation, median, percentage, and frequency. Results: One hundred and thirty-eight patients with advanced stage cervical cancer were included in the study. The mean age of the patients was 48.74 (±9.57) years. Thirty-four percent of patients were illiterate. More than half (57.25%) of the patients were from lower middle-class families. Delays were categorized as patient-related, healthcare provider delay, and healthcare-system infrastructure related. Patient-related factors included low monthly income, residence in a rural area, embarrassment, fear, lack of knowledge regarding cervical cancer, delay in contacting a spouse, family member or friend prior to the first medical encounter. These elements predicted a primary delay of more than 60 days (P value Conclusion: Three broad categories of delay in diagnosis and treatment of cervical cancer: patient-related factors, healthcare provider-related factors, and healthcare-system infrastructure factors were analyzed. Illiteracy, lack of awareness regarding cervical cancer, lack of health-seeking behavior, and poor income status were associated with patient-related primary delay. Nonperformance of speculum examination in the initial consultation, misdiagnosis, inappropriate management, and delay in referral to the cancer treatment center by primary healthcare providers were the contributing factors for healthcare provider delay. Lack of availability and accessibility of health services and limitation of radiotherapy resources led to healthcare-system infrastructure delays. All three categories of delay must be addressed through the education of communities, the gynecologic training of community healthcare providers, the improvement of medical infrastructure, and the increase of medical resources.

Concurrent chemoradiotherapy for cervical cancer： background including evidence-based data, pitfalls of the data, limitation of treatment in certain groups

Concurrent chemoradiotherapy （CCRT） is regarded as the standard treatment for locally advanced uterine cervical cancer （LACC）, including stage Ib2-IVa disease [International Federation of Gynecology and Obstetrics （FIGO） staging]. However, approximately a third of eligible patients in previous studies died of LACC despite receiving CCRT. The therapeutic significance of CCRT alone in stage Ⅲ-IVa disease has not yet been confirmed. Effective treatment of some LACC is beyond the scope of CCRT. The objective of the present review is to highlight some challenging work aimed at overcoming this seemingly intractable disease. CCRT with increased peak concentrations of cisplatin （CDDP）, surgery following CCRT, adjuvant chemotherapy （CT） following CCRT, and neoadjuvant CT followed by CCRT are strategies expected to enhance the therapeutic efficacy of CCRT. If patients with LACC were divided into those with low-risk or high-risk systemic disease or prognoses, novel strategies should be assessed in the group with high-risk disease.

Different strategies of treatment for uterine cervical carcinoma stage ⅠB2-ⅡB

Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival of 60%. During the last decades, the initial treatment for these women has been debated and largely varies through different countries. Thus, radical concurrent chemoradiation is the standard of care in United Sated and Canada, and neoadjuvant chemotherapy followed by radical surgery is the first line of treatment in some institutions of Europe, Asia and Latin America. Until today, there is no evidence of which strategy is better over the other. This article describe the evidence as well as the advantages and disadvantages of the main strategies of treatment for women affected by uterine cervical cancer stage ⅠB2-ⅡB.

动脉与静脉新辅助化疗联合手术治疗局部晚期宫颈癌疗效研究

目的探讨动脉与静脉2种给药途径的新辅助化疗(NACT)对局部晚期宫颈癌患者化疗效果的影响。方法回顾性收集2009年1月1日—2016年12月31日在首都医科大学附属北京妇产医院、北京大学人民医院、北京大学第一医院、北京大学第三医院、北京朝阳医院、北京安贞医院、北京世纪坛医院共7家北京地区三甲医院入院接受NACT联合宫颈癌根治术(RH)治疗的ⅠB2/ⅡA2期(FIGO2009)宫颈癌患者178例的临床病历资料并进行分析。按不同化疗方案分为动脉给药组104例和静脉给药组74例,比较2组患者术后病理高危因素及临床结局差异,以及化疗后骨髓抑制程度的差异。结果动脉给药组化疗后总有效率与静脉给药组比较差异无统计学意义(P>0.05),而淋巴结转移率低于静脉给药组(χ^(2)/P=6.311/0.010)。动脉给药组化疗后血红蛋白低于静脉给药组,骨髓抑制程度轻于静脉给药组(t/χ^(2)=2.864、2.299,P=0.005、0.022)。动脉给药组根治术后仍需补充放疗的比例低于静脉给药组(χ^(2)=8.029,P=0.003)。结论在局部晚期宫颈癌患者中,动脉化疗在减少术后病理高危因素及术后补充放疗率方面,具有潜在优势。

晚期宫颈癌患者行白蛋白结合型紫杉醇联合顺铂治疗前后的变化分析

目的 分析晚期宫颈癌患者行白蛋白结合型紫杉醇联合顺铂治疗前后的变化。方法 100例晚期宫颈癌患者,随机分为研究组和对照组,每组50例。两组患者均接受规定治疗方案同步放化疗,研究组使用注射用紫杉醇(白蛋白结合型)联合顺铂化疗治疗,对照组采用溶剂型紫杉醇联合顺铂化疗治疗。比较两组患者病情缓解程度、毒副反应发生情况(血红蛋白降低、血小板减少、白细胞减少、中性粒细胞减少、胃肠道反应、肝功能异常)、治疗前后肿瘤标志物指标[癌胚抗原(CEA)、鳞状细胞癌抗原(SCC-Ag)、细胞角蛋白19片段抗原(CYFRA21-1)、糖类抗原125(CA125)]水平、2年内病情恶化、生存情况。结果 研究组治疗后的病情总缓解率66.00%高于对照组的46.00%,差异有统计学意义(P<0.05)。研究组胃肠道反应发生率16.00%低于对照组的34.00%,差异有统计学意义(P<0.05)。治疗后,研究组患者CEA(8.05±1.19)U/ml、SCC-Ag(1.86±0.41)ng/ml、CYFRA21-1(8.11±1.52)ng/ml、CA125(26.32±2.86)U/ml均低于对照组的(8.86±1.38)U/ml、(2.13±0.49)ng/ml、(9.03±1.85)ng/ml、(27.64±3.13)U/ml,差异有统计学意义(P<0.05)。研究组治疗后2年内的病情恶化率46.00%低于对照组的66.00%,生存率82.00%高于对照组的64.00%,恶化时间(1.15±0.54)年、死亡时间(1.48±0.46)年均晚于对照组的(0.91±0.52)、(1.23±0.45)年,差异有统计学意义(P<0.05)。结论 给予晚期宫颈癌患者白蛋白结合型紫杉醇联合顺铂治疗可增加病灶缓解程度,减少胃肠道反应,降低治疗后短期内的病情恶化发生率,同时提高患者生存能力。

超声造影预测局部晚期宫颈癌同步放化疗早期疗效的临床价值

目的 探讨超声造影(CEUS)预测局部晚期宫颈癌(LACC)患者同步放化疗(CCRT)早期疗效的临床价值。方法 选取临沂市肿瘤医院收治的LACC患者65例,于治疗前1周内及体外放疗结束后分别进行CEUS检查,通过定量分析时间-强度曲线(TIC)获得达峰时间(TP)、梯度(Grad)、曲线下面积(Area)及峰值强度(PI);测量治疗前后瘤体最大径,计算肿瘤消退率。体外放疗结束后根据治疗效果分为敏感组53例和不敏感组12例,比较两组上述参数的差异。采用Spearman相关分析法分析CEUS参数与肿瘤消退率的相关性;二元Logistic回归分析筛选预测LACC患者CCRT早期疗效的影响因素;绘制受试者工作特征(ROC)曲线分析其预测效能。结果 65例LACC患者治疗前和体外放疗结束后瘤体最大径分别为(60.7±14.6)mm、(31.2±16.9)mm,肿瘤消退率为(49.2±23.2)%。敏感组治疗前Grad、PI均低于不敏感组,差异均有统计学意义(均P<0.05);敏感组体外放疗结束后Grad、Area及PI均低于不敏感组,TP高于不敏感组,差异均有统计学意义(均P<0.001)。敏感组体外放疗结束后Grad、Area及PI均较治疗前降低,TP较治疗前升高,差异均有统计学意义(均P<0.05)。相关性分析显示,治疗前Grad、PI与肿瘤消退率均呈负相关(r=-0.602、-0.499,均P<0.05);体外放疗结束后Grad、PI与肿瘤消退率均呈负相关(r=-0.859、-0.913,均P<0.05)。二元Logistic回归分析显示,治疗前Grad、PI均为预测LACC患者CCRT早期疗效的独立影响因素(均P<0.05)。ROC曲线分析显示,治疗前Grad、PI预测LACC患者CCRT早期疗效的曲线下面积分别为0.802、0.894。结论 CEUS在预测LACC患者CCRT早期疗效中有一定的临床价值。

局部晚期宫颈癌患者血清KRT17蛋白表达水平对动脉介入新辅助化疗效果的影响

目的:检测局部晚期宫颈癌(LACC)患者血清角蛋白17(KRT17)的表达水平,及其对动脉介入新辅助化疗(NACT)效果的影响。方法:选取2017年1月—2018年6月就诊的70例LACC患者,采用动脉介入新辅助化疗联合手术治疗,治疗前通过酶联免疫吸附试验(ELISA)检测患者血清KRT17蛋白的浓度,根据其中位数水平,分为低表达组及高表达组,比较两组患者的无进展生存期(PFS)、总生存期(OS)、盆腔无进展生存期(PPFS)、无远处转移生存期(DMFS)的差异,以评价KRT17蛋白在采用新辅助化疗的LACC患者中的表达水平及其临床意义。结果:LACC患者血清KRT17蛋白浓度中位数为0.65μg/L,所有患者的KRT17蛋白浓度范围为0.49~1.26μg/L。34例患者为低表达组,36例患者为高表达组。血清KRT17蛋白浓度用于预测LACC患者的NACT疗效的受试者工作特征(ROC)曲线下面积(AUC)为0.897[95%CI(0.816,0.978)],敏感性和特异性分别为90.6%、81.6%。血清KRT17低表达组和高表达组患者中位PFS分别为57.23和48.75个月;中位OS分别为58.1和55.5个月;中位PPFS分别为56.9和49.9个月;中位DMFS分别为57.1和50.1个月。Kaplan-Meier生存曲线显示血清KRT17表达水平升高与LACC患者PFS、OS、PPFS、DMFS缩短呈现正相关(P<0.01)。结论:KRT17蛋白在LACC患者血清中表达升高,且其升高水平可作为NACT治疗LACC患者预后不良的预测因素。

中晚期宫颈癌患者血清HE4、TK1、DCLK1水平变化及其与化疗效果的关系

目的 分析中晚期宫颈癌患者血清人附睾蛋白4(HE4)、胸苷激酶1(TK1)、双皮质素样激酶1(DCLK1)变化及其与化疗效果的关系。方法 收集2020年1月至2023年1月于郑州大学第一附属医院接受化疗的215例中晚期宫颈癌患者的病历资料,根据纳入患者的化疗效果将其分为良好组和不良组,其中良好组疗效评估结果为完全缓解(CR)与部分缓解(PR),共173例,不良组疗效评估结果为稳定(SD)与进展(PD),共42例。比较两组血清HE4、TK1、DCLK1水平等临床资料,分析中晚期宫颈癌患者血清HE4、TK1、DCLK1水平与化疗效果的关系。结果 良好组临床分期为Ⅱ期比例、高分化比例、无淋巴结转移比例均高于不良组,肿瘤最大直径以及血清HE4、TK1、DCLK1水平均低于不良组,差异均有统计学意义(P<0.05);经logistic多因素分析显示,肿瘤的临床分期达到Ⅳ期、分化程度为中低分化、淋巴结转移以及血清HE4、TK1、DCLK1水平升高均为影响中晚期宫颈癌患者化疗效果的独立因素(P<0.05);经Spearman相关性分析显示,中晚期宫颈癌患者临床分期、淋巴结转移以及血清HE4、TK1、DCLK1水平与其化疗效果成负相关,分化程度与其化疗效果成正相关(P<0.05)。结论 中晚期宫颈癌患者临床分期越晚、分化程度越差、临床转移以及HE4、TK1、DCLK1水平越高,越不利于患者的化疗,上述指标对其预后均具有一定预测价值。

中国地区局限性晚期宫颈癌动脉介入新辅助化疗有效性与安全性:基于随机对照试验的Meta分析与GRADE证据评分

目的评估新辅助动脉介入化疗(NAIC)和新辅助全身静脉化疗(NIVC)治疗局部晚期宫颈癌(LACC)的有效性与安全性。方法通过检索PubMed、Web of Science、Embase、中国知网、万方数据库获取符合主题的随机对照试验(RCT),经文献质量评估和数据提取后使用Stata 17.0进行统计学分析,使用GRADE质量评价系统对结局进行质量评估。结果共纳入14项RCT,合计1063例LACC患者。Meta分析结果表明,NAIC和NIVC在有效性指标方面:完全缓解(CR)[RR=1.23,95%CI(0.91,1.67),P=0.174]、部分缓解(PR)[RR=1.10,95%CI(0.86,1.20),P=0.874]、总缓解(TR)[RR=1.10,95%CI(0.95,1.25),P=0.212]、无变化(NC)[RR=0.62,95%CI(0.33,1.16),P=0.137]和进展(PD)[RR=1.43,95%CI(0.41,4.99),P=0.574]间的差异无统计学意义;在安全性指标方面:胃肠道反应[RR=0.96,95%CI(0.76,1.23),P=0.755]、肝肾功能损害[RR=0.71,95%CI(0.41,1.23),P=0.226]差异无统计学意义,而在骨髓抑制[RR=0.62,95%CI(0.45,0.86),P=0.04]的发生率方面,NAIC较NIVC更优。此外,GRADE评分结果显示CR、PR、TR、NC为高质量证据。结论对于LACC患者,NAIC在治疗后骨髓抑制的发生率较NIVC更低、更安全,在其他有效性与安全性指标上两者并未发现显著差异。临床医师根据患者的实际情况综合评估,选择适宜新辅助化疗方案。

DCE-MRI定量参数与局部进展期宫颈癌患者临床病理特征及疗效的关系

目的研究动态对比增强磁共振成像(dynamic contrast-enhanced magnetic resonance imaging,DCE-MRI)定量参数与局部进展期宫颈癌临床病理特征及同步放化疗疗效的关系。方法选取河南科技大学第一附属医院2017年1月~2022年12月收治的68例局部进展期宫颈癌患者,接受DCE-MRI扫描,分析宫颈癌患者DCE-MRI定量参数[容量转移常数(volume transfer constant,K^(trans))、速率常数(rate constant,K_(ep))、细胞外间隙容积分数(extracellular space volume fraction,V_(e))]与临床病理特征关系;宫颈癌患者均接受同步放化疗,根据放化疗情况,将68例局部进展期宫颈癌患者分为有效组(n=39)与无效组(n=29),对比两组治疗前DCE-MRI定量参数,采用多因素Logistic回归分析探究疗效影响因素,绘制受试者工作特征(receiver operating characteristic,ROC)曲线分析DEC-MRI定量参数对患者疗效预测价值。结果鳞癌患者K^(trans)值较腺癌高(P<0.05);低分化患者K^(trans)、K_(ep)值较中高分化患者高(P<0.05);临床分期≥Ⅲa期患者K^(trans)、K_(ep)、V_(e)值均较<Ⅲa期高(P<0.05);不同肿瘤直径、是否淋巴结转移、是否脉管浸润患者之间DCE-MRI定量参数K^(trans)、K_(ep)、V_(e)值比较无明显差异(P>0.05)。有效组治疗前DCE-MRI定量参数K^(trans)、K_(ep)、V_(e)值均高于无效组(P<0.05)。多因素Logistic回归分析显示,临床分期≥Ⅲa期、K^(trans)、K_(ep)、V_(e)值均是影响局部进展期宫颈癌疗效的危险因素(P<0.05)。K^(trans)、K_(ep)、V_(e)值及三者联合预测疗效的ROC曲线下面积分别为0.962、0.950、0.860、0.997。结论DCE-MRI定量参数与局部进展期宫颈癌患者临床病理特征有一定关系,可作为患者同步放化疗疗效预测指标。

Correlations between alterations of T-helper 17 cells and treatment efficacy after concurrent radiochemotherapy in locally advanced cervical cancer (stage IIB-IIIB): a 3-year prospective study

Background::Recently,T-helper 17(Th17)cells have been proved to play an important role in promoting cervical cancer.But,till now,few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments.This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer(LACC)patients before and after concurrent chemoradiotherapy(cCRT)and to analyze the correlations between the alterations in Th17 cells and treatment efficacy.Methods::A prospective study with 49 LACC(International federation of gynecology and obstetrics[FIGO]stage IIB-IIIB)patients and 23 controls was conducted.Patients received the same cCRT schedule and were followed up for 3 years.Circulating Th17 cells(CD3+CD8-interleukin[IL]-17+T cells)and related cytokines IL-17,transforming growth factor-β(TGF-β),IL-10,IL-23,IL-6,and IL-22 were detected before and after cCRT.Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed.Kaplan-Meier analysis was used for overall survival(OS)and progression-free survival(PFS).Results::We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study.The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls,and it significantly decreased after cCRT(P<0.05).After cCRT,patients were divided into two groups based on the average of the Th17 cells declined.The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times.Compared with the control patients,LACC patients had higher IL-6,IL-10,IL-22,TGF-βlevels and a lower IL-23 level(P<0.05).After cCRT,IL-6,IL-10,IL-17,IL-23 level significantly increased and TGF-βlevel significantly decreased compared with the levels before cCRT(P<0.05).Conclusion::Circulating Th17 cells in the LACC patients(FIGO stage IIB-IIIB)were higher than those in the controls,but they generally decreased after cCRT.A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.