Meta-analysis Of Clinicopathological Characteristics And Prognostic Factors Of Cervical Small Cell Carcinoma And Neoadjuvant Chemotherapy

Part 1: The Clinicopathologic Characteristics and Prognosis of Cervical Small Cell CarcinomaObjective: To investigate the clinical characteristics,pathological features,treatment pattern,survival status and prognosis factors of small cell carcinoma of the cervix(SCCC).Methods: Clinical characteristics and follow-up data on 26 patients diagnosed with SCCC at Nanjing Medical University Affiliated Cancer Hospital of China from February 2014 to June 2018 were retrospectively analysed in this study.All patients were diagnosed by histopathology and immunohistochemistry and tested for human papillomavirus infection(HPV)status.Chromogranin(Cg A),Synaptophysin(SYN),and Neuronal cell adhension molecules 56(CD56)were performed to all patients.Kaplan-Meier method was used to calculate the survival rate,and Log-rank and Cox regression were used to analyze the prognostic factors of univariate and multivariate analysis respectively.Results: With a median follow-up time of 37 months,the 3-year Overall survival(OS)rate of all patients were 38.5%.There were 9 cases were FIGO stage Ia~IIa,17 cases were stage IIb~IV with median age of 45 years,and 15 cases were HPV positive(13 cases were HPV18 positive and 2 cases were HPV16 positive).The survival outcomes of patients(n=10)who underwent surgery combined with chemoradiotherapy was significantly higher than that of 16 patients who received only one or two therapy.The OS rate of HPV-positive patients trended to be lower than that of HPV-negative,but there was no significant difference(33.3% vs 45.5%,p = 0.171).In pathological immunohistochemistry,three diagnostic markers,SYN,Cg A and CD56,were analysed.The survival outcomes of patients with three postive markers or with two postive markers showed no statistically different(p=0.765).In addition,Ki-67(>30%),SYN expression,FIGO stage,lymph node metastasis,and vascular cancer thrombus were significantly associated with survival.Multivariate analysis shows that FIGO stage and lymph node metastasis are independent prognostic factors affecting the OS of SCCC patients.Conclusion: The overall survival outcomes of SCCC patients is poor.Initial staging,lymph node metastasis and vascular tumor thrombus are correlated with poor prognosis.Comprehensive treatment effectively improved patients' survival outcome,and it is recommended for all SCCC patients.PART2: A Meta-analysis of neoadjuvant chemotherapy for cervical small cell carcinomaObjective: To investigate the effect of preoperative neoadjuvant chemotherapy(NACT)on survival and prognosis of patients with small cell carcinoma of the cervix.Methods: We conducted a meta-analysis to estimate the effect of preoperative NACT for SCCC patients.Pub Med,EMBASE,Cochrane,WFSD,CNKI and Web of Science were used to search for studies conducted until June 1,2019.The pooled hazard ratio(HR)and its 95% confidence interval(CI)were calculated to evaluate the prognostic value of preoperative NACT on the overall survival of SCCC.Data were analysed using “meta” and “metagen” package in R v 5.6.2.The primary endpoint of interest was OS.Heterogeneity analysis was assessed by Q-test and I2.We used the Newcastle–Ottawa Scale to appraise the quality of cohort study.Results: We found eight cohort studies including 270 SCCC patients with low to moderate risk of bias in their methodological quality.The main end points of the eight cohort studies were OS and four of them described PFS.The results showed that for SCCC patients NACT may have a negative effect on OS compared with surgery alone or surgery plus adjuvant therapy(HR 1.84,95% CI 1.24-2.74).Similar results were achieved when it came to the subgroup analysis of subjects containing only early stage SCCC patients.The results of heterogeneity analysis showed that I2 =0 with P value of Q test equal to 0.75.Conclusion: Adding neoadjuvant chemotherapy before surgery may not improve the overall survival of SCCC,especially early stage SCCC patients have an adverse trend of survival.This study offers novel ideas to optimize the comprehensive treatment model for SCCC,and a direction for our future clinical research.NACT should be used with caution in early stage patients.