Clinical Study Of Locally Advanced Cervical Cancer

The Incidence of cervical cancer is secondary only to breast cancer in the nationally wide,and is considered as one of the most common malignant tumor in women.For the limited sanitation condition and sources of the developing countries,it is unpractical to carry out cervical cancer screening effectively,and most of the patients with cervical cancer diagnosis have been at the late stages.The extensive total hysterectomy is considered as the preliminary therapeutic strategy for early stage cervical cancer.The prognosis of the cervical cancer at early stages is satisfactory.According to a latest annual report from the international union of gynecology and obstetrics,the stage IB2 and type IIA cervical cancer(that is,locally advanced cervical cancer)are more prone to local invasion and distant metastasis with poorer prognosis compared with the cervical cancer at early stages.Therefore,the locally advanced cervical cancer acts as a serious threaten to the majority of women's health and life.It would be challenging for the gynecologic oncologists to explore treatments to improve the survival and prognosis of patients with locally advanced cervical cancer.Several therapeutics have been carried out including the chemotherapy,radiotherapy,surgery,and a variety of combined treatments with a large number of related research.In order to find an effective way to get the best clinical therapeutic effect,it would be crucial to retain function as far as possible and minimize the incidences of complications.Meanwhile,preoperative chemotherapy has been applied in patients with locally advanced cervical cancer.The preoperative adjuvant chemotherapy can be effective to control and shrink the tumor.This treatment could reduce the risks of operation,provide operation opportunity,and minimize the risk of distant metastases.This new locally advanced cervical cancer treatment is prevailing in these economically backward countries,especially the developing countries which are lack of radiation therapy equipment and professional staff.Preoperative chemotherapy could facilitate surgical treatment and solve the problem.So far,the application of new adjuvant treatment is still controversial in these patients with locally advanced cervical cancer(FIGO staging IB2-type IIA).The FIGO guidelines propose that the preoperative neoadjuvant chemotherapy should be considered as one of the treatment for these patients.However,the guidelines from National Comprehensive Cancer Network(National Comprehensive Cancer Network,NCCN)are different from the FIGO guidelines for patients with locally advanced cervical Cancer.They do not recommend the use of neoadjuvant chemotherapy for patients with locally advanced cervical cancer.Several researches propose the use of neoadjuvant chemotherapy in patients with locally advanced cervical cancer.However,there is still no standard guidelines for which kind of neoadjuvant chemotherapy regimens is preferred.Although most research suggest that the combined treatment should be based on the platinum.However,which kind of chemotherapy drugs,such as the vincristine,gemcitabine,paclitaxel,should be choose for neoadjuvant chemotherapy and attain the best clinical effect remain to be discussed.Therefore,we carried out a retrospective study based on locally advanced cervical cancer patients who received multiple neoadjuvant therapy.We explored new adjuvant chemotherapy for the treatment of patients with locally advanced cervical cancer,in order to optimize the treatment and offer therapeutic data for the future cases.Meanwhile,our results could provide theoretical basis to study the treatment for locally advanced cervical cancer.Part I: Study on the research topic of systematic reviews/meta-analysis of cervical cancerObjective: Using the visualization methods to evaluate the research topic of systematic reviews/meta-analysis of cervical cancer.Methods: Computer search the major Chinese and English database,search deadline is April 4,2018.Two researchers independently screened the systematic reviews and meta-analysis of cervical cancer according to inclusion and exclusion criteria.The keywords,provinces,authors and their units were extracted and sorted by BICOMS 2 software and generate cooccurrence matrix and word matrix,Net Draw 2.089 and g CLUTO 1.0 were used to draw the network diagram and cluster analysis.Results:(1)The number of systematic reviews and meta-analysis of cervical cancer showed a trend of increasing to decreasing.The authors of 26 provinces,autonomous regions and municipalities involved in the publication of the studies,the main authors were divided into 10 major cooperative groups,and the research institutions had fewer teams and cooperation.There are four major research themes.(2)The foreign cervical cancer systematic reviews/Meta-analysis first appeared in 1975.The volume of the literature in 2014 was the most.The most frequently published journals were Gynecologic oncology and The Cochrane database of systematic reviews.There were very few authors of high yield,and the research topics were divided into 4.Conclusion: The number of cervical cancer systematic reviews/meta-analysis is relatively small.The overall trend is from increasing to declining.There are many groups involved in research,there are few research institutes,and the links between institutions are not close enough.Between groups and teams,the cooperation still needs to be further strengthened.There are not many research themes and it is still necessary to further develop new research directions.Part II: The application neoadjuvant therapy for patients with locally advanced cervical cancer and the evaluation of curative effectObjective: To evaluate the curative effect neoadjuvant therapy for patients with locally advanced cervical cancer and the clinically relevant factors influencing the curative effects.Methods: This retrospective analysis included these patients who received neoadjuvant chemotherapy in the affiliated hospitals of Lanzhou University Medical School and People's Hospital of Gansu Province between January 2011 and December 2017.The clinical pathological data of these cervical cancer patients were completely intact in the study.Totally five kinds of chemotherapy regimens were included in this study.A total of 600 patients with locally advanced cervical cancer patients were included in this retrospective study.The clinical parameters including the selection,age,clinical stage,tumor differentiation,organization type,tumor diameter before treatment,chemotherapy regimens,were used to analyze the recent efficacy of neoadjuvant chemotherapy.Moreover,their correlations with curative effect of chemotherapy were evaluated.The curative effect of different chemotherapies on the overall survival and disease-free survival rate were also analyzed.Results:(1)In all the 600 cases with locally advanced cervical cancer,445 cases of neoadjuvant chemotherapy(including CR32,PR413)were effective.The total effective rate was 74.2%.The complete response rate was 7.2%(32/445).(2)The new adjuvant chemotherapy curative effect closely correlated with the tissue types of locally advanced cervical cancer.The effective rate for squamous carcinoma was 77.79%(386/495).The effective rate of squamous cell carcinomas efficiency was significantly higher than that of adenocarcinoma(P=0.000).The curative effect of neoadjuvant chemotherapy was unrelated with age and tumor diameter before treatment(P > 0.05).(3)The complete follow-up data of all 600 patients with locally advanced cervical cancer were included in this study.Using the Log Rank method comparison to analyze the different response of neoadjuvant chemotherapy in patients with locally advanced cervical cancer,we found that these patients were survived until the end of follow-up if these were curative after receiving the neoadjuvant chemotherapy.(4)The survival rate of these patients who were insensitive to neoadjuvant chemotherapy was significant lower.Conclusion: The preoperative neoadjuvant chemotherapy can significantly reduce the size of tumor,especially for the squamous cell carcinoma.The clinical curative effect of neoadjuvant chemotherapy significantly correlated with pathological types of cervical cancer.The curative effect of neoadjuvant chemotherapy was best in the squamous cell carcinoma.The new adjuvant chemotherapy combined with cervical cancer radical surgery can improve the survival rate of these patients with locally advanced cervical cancer.Part III: Clinical efficacy and safety of paclitaxel plus carboplatin as neoadjuvant chemotherapy prior to radical hysterectomy and pelvic lymphadenectomy for Stage IB2-IIB cervical cancerObjective: To assess the efficacy and toxicity of the combination of paclitaxel plus carboplatin as neoadju-vant chemotherapy(NACT)for locally advanced cervical cancer(LACC)prior to radical hysterectomy and pelvic lymph-adenectomy.Methods: We reviewed patients with cervical cancer of the International Federation of Gynecology and Obstetrics(FIGO)stage IB2-IIB who underwent neoadjuvant chemotherapy(NACT)with paclitaxel plus carboplatin followed by radical hysterectomy(NACT group)or only received primary radical surgery(PRS group)in our hospital between Jan 2009 and Dec 2017.Toxicity,NACT response,surgery pathological factors and survival data were col-lected and analyzed.Results: In the NACT group,the overall response rate was 71.3%(82/115).Eighteen(15.7%)patients achieved complete remission.Well differentiated tumors showed a more favorable response to NACT(P=0.011).Myelosuppression was the most common adverse effect(51.7%)and serious adverse effects were rare(3.4%).The median follow-up period was 44 months(range,6-75).The NACT responders had significantly longer OS and PFS when compared to the non-NACT responders and patients in the PRS group.Conclusion: Patients with LACC can benefit from neoadjuvant chemotherapy with paclitaxel plus carboplatin when they have response to the chemotherapeutic agents.Part IV: The significance of tumoral ERCC1 Status in patients with locally advanced cervical cancer treated with chemoradiation therapyObjective: ERCC1(excision repair cross-complementation group 1)expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites,but has not been well studied in cervical cancer patients.The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy(CRT)and to correlate expression with clinical outcome parameters.Methods and Materials: A total of 260 patients with locally advanced cervical cancer,treated with curative-intent radical CRT.Pretreatment formalin-fixed,paraffin-embedded tumor specimens were retrieved,and Tumoral ERCC1(FL297 antibody)was measured.Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival(PFS)and overall survival(OS)at 5 years.Results: The majority of patients had International Federation of Gynecology and Obstetrics(FIGO)stage II disease(n=119,45%);median tumor size was 5 cm.OS was associated with tumor size,pretreatment hemoglobin status,and FIGO stage.In addition,tumoral ERCC1 status was associated with PFSand OS.ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS.Conclusions: In this large cohort of locally advanced cervical cancer patients treated with radical CRT,stage,tumor size,and pretreatment hemoglobin status were significantly associated with PFS and OS.ERCC1 status appears to have prognostic impact on univariate analysis in these patients,but was not independently associated with outcome on multivariate analysis.