6 Circulating miRNAs can be used as Non-invasive Biomarkers for the Detection of Cervical Lesions.

Background: Cervical cancer is the most common malignant tumor in the female reproductive system, while the efficacy of routine screening strategy is unsatisfied. New molecular tests need to be developed. miRNAs participate in many pathologic processes, and circulating miRNAs are promising non-invasive biomarkers in tumors. Objectives: This study aimed to identify the circulating miRNAs associated with both cervical cancer and cervical intraepithelial neoplasia (CIN), and establish a non-invasive classifier for cervical lesions using circulating miRNAs. Methods: This study consisted of 5 steps: miRNAs screening, miRNAs validation, classifier establishment, independent validation and in silico analyses. Three cohorts were included in our study: In screening stage, 24 samples including 14 cases and 10 controls were retrieved; In validation stage, 380 samples including 200 cases and 180 controls were recruited; In independent validation stage, 47 samples comprising 26 cases and 21 controls were included. miRNAs were quantified by RT-qPCR. A classifier was built with random forest algorithm using validation samples and selected miRNAs, which were then validated in an independent cohort. To explore the function of selected miRNAs, in silico analyses were performed. Target genes of selected miRNAs were predicted by the overlap of three online tools. Enrichment analyses were executed with predicted target genes. Differential analysis of target genes was carried out with open access expression assay datasets of cervical tissues. Results: 6 miRNAs (hsa-miR-26b-5p, hsa-miR-146b-5p, hsa-miR-191-5p, hsa-miR-484, hsa-miR-574-3p, hsa-miR-625-3p) were screened out from 754 miRNAs. They were associated with cervical lesions and were selected to establish a classifier. The accuracy of the classifier were 0.7218 (0.7117, 0.7319) in validation samples, which was 0.7021 in the independent cohort. 958 target genes were predicted and enriched in 23 pathways (MAPK, human papillomavirus infection and Wnt signaling pathway, etc.). 55 genes were identified as the most likely target genes by differential analysis. Conclusion: The 6 circulating miRNAs were related to cervical lesions and could serve as non-invasive biomarkers.

A case of SLE with COVID-19 and multiple infections.

The coronavirus disease 2019 (COVID-19) has become a global pandemic, which is induced by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with systemic lupus erythematosus (SLE) are susceptible to infections due to the chronic use of immunosuppressive drugs and the autoimmune disorders. Now we report a case of SLE infected with SARS-CoV-2, influenza A virus and Mycoplasma pneumoniae concurrently. The patient used hydroxychloroquine and prednisone chronically to control the SLE. After infection of SARS-CoV-2, she was given higher dose of prednisone than before and the same dosage of hydroxychloroquine. Besides, some empirical treatments such as antiviral, antibiotic and immunity regulating therapies were also given. The patient finally recovered from COVID-19. This case indicated that hydroxychloroquine may not be able to fully protect SLE patient form SARS-CoV-2. Intravenous immunoglobulin therapies and increased dose of corticosteroids might be adoptable for patient with both COVID-19 and SLE. Physicians should consider SARS-CoV-2 virus test when SLE patient presented with suspected infection or SLE flare under the epidemic of COVID-19.

Comparison of clinical and microbiological diagnoses for older adults with COVID-19 in Wuhan: a retrospective study.

BACKGROUND: The potential differences between a clinical diagnosis of coronavirus disease 2019 (COVID-19) (i.e., symptoms without positive virus test) and a microbiological diagnosis (i.e., positive virus test results) of COVID-19 are not known. AIMS: This study explored the differences between the two types of COVID-19 diagnosis among older patients in terms of clinical characteristics and outcomes. METHODS: A total of 244 inpatients aged ≥ 60 years with COVID-19 were included in this study, of whom 52 were clinically diagnosed and 192 were microbiologically diagnosed. Clinical and laboratory data on hospital admission and outcomes (discharged or died in hospital) of all patients were retrieved from medical records retrospectively. Patients who met the criteria for clinical diagnosis with negative virus test results were assigned to the clinical diagnosis group, whereas those with positive virus test results were assigned to the microbiological diagnosis group. After univariate analyses, two propensity score analyses [i.e., covariate adjustment using propensity score (CAPS) and propensity score matching (PSM)] were conducted to control bias. RESULTS: The clinical and microbiological diagnosis groups demonstrated significant differences in outcomes and in the majority of laboratory findings. After propensity score analyses, many differences between the two groups disappeared and the rate of mortality had no statistically significant difference (P = 0.318 and 0.828 for CAPS and PSM, respectively). CONCLUSIONS: Patients with similar signs, symptoms, and laboratory and imaging findings as confirmed COVID-19 cases may have a similar mortality risk, regardless of the virus test results, and require timely intervention to reduce their mortality.

Risk Factors for Mortality in 244 Older Adults With COVID-19 in Wuhan, China: A Retrospective Study.

BACKGROUND/OBJECTIVES: Previous studies have reported that older patients may experience worse outcome(s) after infection with severe acute respiratory syndrome coronavirus-2 than younger individuals. This study aimed to identify potential risk factors for mortality in older patients with coronavirus disease 2019 (COVID-19) on admission, which may help identify those with poor prognosis at an early stage. DESIGN: Retrospective case-control. SETTING: Fever ward of Sino-French New City Branch of Tongji Hospital, Wuhan, China. PARTICIPANTS: Patients aged 60 years or older with COVID-19 (n = 244) were included, of whom 123 were discharged and 121 died in hospital. MEASUREMENTS: Data retrieved from electronic medical records regarding symptoms, signs, and laboratory findings on admission, and final outcomes of all older patients with COVID-19, were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to explore risk factors for death. RESULTS: Univariate analysis revealed that several clinical characteristics and laboratory variables were significantly different (ie, P < .05) between discharged and deceased patients. Multivariable logistic regression analysis revealed that lymphocyte (LYM) count (odds ratio [OR] = 0.009; 95% confidence interval [CI] = 0.001-0.138; P = .001) and older age (OR = 1.122; 95% CI = 1.007-1.249; P = .037) were independently associated with hospital mortality. White blood cell count was also an important risk factor (P = .052). The area under the receiver operating characteristic curve in the logistic regression model was 0.913. Risk factors for in-hospital death were similar between older men and women. CONCLUSION: Older age and lower LYM count on admission were associated with death in hospitalized COVID-19 patients. Stringent monitoring and early intervention are needed to reduce mortality in these patients. J Am Geriatr Soc 68:E19-E23, 2020.

Adjuvant chemotherapy after surgery can improve clinical outcomes for patients with IB2-IIB cervical cancer with neoadjuvant chemotherapy followed by radical surgery.

The aim of the study is to evaluate the efficacy of postoperative treatments based on pathological response for cervical cancer patients who received neoadjuvant chemotherapy (NACT) followed by radical surgery. Firstly, a total of 756 cervical squamous cell cancer (SCC) patients with FIGO IB2-IIB were included in this retrospective study. Then data from a prospective cohort of 393 patients was employed for further validation. Overall survival (OS) and disease-free survival (DFS) were assessed. In the retrospective study, SCC patients who accepted adjuvant chemotherapy after radical surgery had a relatively better OS than those who received no therapy (P = 0.08, HR = 0.57). The result was more noticeable in the prospective cohort study (P = 0.006, HR = 0.28). In the combined analysis, adjuvant chemotherapy improved clinical outcomes compared with no therapy (P = 0.002 and 0.04 for OS and DFS). Particularly for patients with extra-cervical residual disease, adjuvant chemotherapy improved OS (log-rank P = 0.008, 0.004 and 0.001 in the retrospective, prospective and combined studies). Optimal response patients had good outcomes even without therapy. Our study indicates that adjuvant chemotherapy can benefit clinical outcomes for SCC patients with NACT followed by radical surgery, especially those with extra-cervical residual disease. For optimal response patients, there may be no need for further treatment. This finding needs to be validated in more future studies.

Whole-exome sequencing reveals genetic variants in ERC1 and KCNG4 associated with complete hydatidiform mole in Chinese Han women.

Complete hydatidiform mole (CHM) is a rare pregnancy-related disease with invasive potential. The genetics underlying the sporadic form of CHM have not been addressed previously, but maternal genetic variants may be involved in biparental CHM. We performed whole-exome sequencing of 51 patients with CHM and 47 healthy women to identify genetic variants associated with CHM. In addition, candidate variants were analyzed using single base extension and Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry in 199 CHM patients and 400 healthy controls. We validated candidate variants using Sanger sequencing in 250 cases and 652 controls, including 205 new controls. Two single nucleotide polymorphisms, c.G48C(p.Q16H) inERC1 and c.G1114A(p.G372S) in KCNG4, were associated with an increased risk of CHM (p<0.05). These variants may contribute to the pathogenesis of CHM and could be used to screen pregnant women for this genetic abnormality.

Genome-wide association study identifies four SNPs associated with response to platinum-based neoadjuvant chemotherapy for cervical cancer.

To identify genomic markers associated with the response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. A total of 596 patients with stage IA2-IIIB cervical cancer were enrolled in this study. One single nucleotide polymorphism (SNP) (rs6812281, per allele OR = 2.37, P = 9.0 × 10-9) located at 4q34.3 reached GWAS significance (P < 5.0 × 10-8). Another three SNPs, rs4590782 (10q26.2, P = 1.59 × 10-5, per allele OR = 0.48), rs1742101 (14q32.11, P = 7.11 × 10-6, per allele OR = 0.52), and rs1364121 (16q23.3, P = 3.15 × 10-6, per allele OR = 1.98), exhibited strong evidence of associations with response to neoadjuvant chemotherapy. Patients with a C allele (CT + CC) of rs4590782 had better 5-year overall survival rates (82.9% vs. 75.8%, P = 0.083) and 5-year disease-free survival rate (80.8% vs. 72.7%, P = 0.021) than those without a C allele. Our findings help to characterize the genetic etiology of the response to neoadjuvant chemotherapy in patients with cervical cancer.

Prognostic risk model development and prospective validation among patients with cervical cancer stage IB2 to IIB submitted to neoadjuvant chemotherapy.

This study was designed to develop a risk model for disease recurrence among cervical cancer patients who underwent neoadjuvant chemotherapy and radical surgery. Data for 853 patients were obtained from a retrospective study and used to train the model, and then data for 447 patients from a prospective cohort study were employed to validate the model. The Cox regression model was used for calculating the coefficients of the risk factors. According to risk scores, patients were classified into high-, intermediate-, and low-risk groups. There were 49 (49/144, 34%) recurrences observed in the high-risk group (with a risk score ≥ 2.65), compared with 3 (3/142, 2%) recurrences in the low-risk group (with a risk score < 0.90). Disease-free survival (DFS) was significantly different (log-rank p < 0.001) among the three risk groups; the risk model also revealed a significant increase in the accuracy of predicting 5-year DFS with the area under the ROC curve (AUC = 0.754 for risk model vs 0.679 for FIGO stage system); the risk model was also validated with data from the prospective study (log-rank p < 0.001, AUC = 0.766). Both high-risk and intermediate-risk patients can be more effectively identified by this risk model.

Association between vascular endothelial growth factor expression and lymph node metastasis in cervical cancer: A meta-analysis.

AIM: The expression of vascular endothelial growth factor (VEGF) by cancer cells has been identified as a factor that is associated with lymph node metastasis (LNM) in some cancers, but an accurate description of the relation between VEGF and LNM in cervical cancer is lacking. We conducted a concurrent meta-analysis to investigate this issue. METHODS: We searched PubMed and EMBASE for articles addressing the association between VEGF and cervical cancer. We used stata 12.0 and calculated the crude odds ratios (OR) and corresponding 95% confidence intervals (CI). Heterogeneity between the studies included was assessed by Cochran's Q-test. RESULTS: Overall, 16 relevant studies with 426 cases and 751 controls were included in our study. The results demonstrated that cervical cancer patients with VEGF-positive expression had a 2.87-fold higher risk of LNM than patients without VEGF-positive expression (95%CI = 1.85-4.44, P < 0.001). Furthermore, subgroup analysis by ethnicity revealed that VEGF-positive expression could increase the risk of LNM in cervical cancer among Asian populations (OR = 2.55, 95%CI = 1.61-4.03, P < 0.001) and Caucasian populations (OR = 8.81, 95%CI = 2.78-27.88, P < 0.001). Moreover, subgroup analysis by country revealed that VEGF-positive expression could increase the risk of LNM in cervical cancer among Chinese populations (OR = 3.38, 95%CI = 2.18-5.25, P < 0.001) but not among Korean populations (P = 0.84) or Japanese populations (P = 0.06). Subgroup analysis based on sample size proved that VEGF-positive expression was statistically associated with LNM in a large sample group. CONCLUSION: Our study revealed that VEGF-positive expression is related with higher risk of LNM in cervical cancer.

Optimal pathological response indicated better long-term outcome among patients with stage IB2 to IIB cervical cancer submitted to neoadjuvant chemotherapy.

The role of pathological response in long-term outcome is still unclear in cervical cancer patients treated with neoadjuvant chemotherapy (NACT) in China. This study aimed to investigate the effect of optimal pathologic response (OPR) on survival in the patients treated with NACT and radical hysterectomy. First, 853 patients with stage IB2-IIB cervical cancer were included in a retrospective analysis; a Cox proportional hazards model was used to investigate the relationship between pathological response and disease-free survival (DFS). In the retrospective database, 64 (7.5%) patients were found to have achieved an OPR (residual disease <3 mm stromal invasion); in the multivariate Cox model, the risk of death was much greater in the non-OPR group than in the OPR group (HR, 2.61; 95%CI, 1.06 to 6.45; P = 0.037). Next, the role of OPR was also evaluated in a prospective cohort of 603 patients with cervical cancer. In the prospective cohort, 56 (9.3%) patients were found to have achieved an OPR; the log-rank tests showed that the risk of recurrence was higher in the non-OPR patients than in the OPR group (P = 0.05). After combined analysis, OPR in cervical cancer was found to be an independent prognostic factor for DFS.

Risk model in stage IB1-IIB cervical cancer with positive node after radical hysterectomy.

The purpose of this study was to identify risk factors in patients with surgically treated node-positive IB1-IIB cervical cancer and to establish a risk model for disease-free survival (DFS) and overall survival (OS). A total of 170 patients who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment for node-positive International Federation of Gynaecology and Obstetrics (FIGO) stage IB1-IIB cervical cancer from January 2002 to December 2008 were retrospectively analyzed. Five published risk models were evaluated in this population. The variables, including common iliac lymph node metastasis and parametrial invasion, were independent predictors of outcome in a multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk) were defined using these variables. Five-year DFS rates for the low-, intermediate-, and high-risk groups were 73.7%, 60.0%, and 25.0%, respectively (P<0.001), and 5-year OS rates were 81.9%, 42.8%, and 25.0%, respectively (P<0.001). The risk model derived in this study provides a novel means for assessing prognosis of patients with node-positive stage IB1-IIB cervical cancer. Future study will focus on external validation of the model and refinement of the risk scoring systems by adding new biologic markers.

Development and validation of a surgical-pathologic staging and scoring system for cervical cancer.

BACKGROUND: Most cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs). METHODS: Records from 4,220 eligible cervical cancer cases (Cohort 1) were screened for surgical-pathologic risk factors. We constructed a surgical-pathologic staging and SPSs, which was subsequently validated in a prospective study of 1,104 cervical cancer patients (Cohort 2). RESULTS: In Cohort 1, seven independent risk factors were associated with patient outcome: lymph node metastasis (LNM), parametrial involvement, histological type, grade, tumor size, stromal invasion, and lymph-vascular space invasion (LVSI). The FIGO staging system was revised and expanded into a surgical-pathologic staging system by including additional criteria of LNM, stromal invasion, and LVSI. LNM was subdivided into three categories based on number and location of metastases. Inclusion of all seven prognostic risk factors improves practical applicability. Patients were stratified into three SPSs risk categories: zero-, low-, and high-score with scores of 0, 1 to 3, and ≥4 (P=1.08E-45; P=6.15E-55). In Cohort 2, 5-year overall survival (OS) and disease-free survival (DFS) outcomes decreased with increased SPSs scores (P=9.04E-15; P=3.23E-16), validating the approach. Surgical-pathologic staging and SPSs show greater homogeneity and discriminatory utility than FIGO staging. CONCLUSIONS: Surgical-pathologic staging and SPSs improve characterization of tumor severity and disease invasion, which may more accurately predict outcome and guide postoperative therapy.

Young Cervical Cancer Patients May Be More Responsive than Older Patients to Neoadjuvant Chemotherapy Followed by Radical Surgery.

OBJECTIVE: To evaluate the effects of age and the clinical response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer who received neoadjuvant chemotherapy followed by radical surgery. METHODS: A total of 1,014 patients with advanced cervical cancer who received NACT followed by radical surgery were retrospectively selected. Patients were divided into young (aged ≤35 years, n = 177) and older (aged >35 years, n = 837) groups. We compared the short-term responses and survival rates between the groups. The five-year disease-free survival (DFS) and overall survival (OS) rates were stratified by age, NACT response, and FIGO stage. RESULTS: The overall response rate was 86.8% in the young group and 80.9% in the older group. The young patients had an earlier FIGO stage (P<0.001), a higher rate of adenocarcinoma (P = 0.022), and more lymph node metastasis (P = 0.033) than the older patients. The presence of adenocarcinoma as the histological type (P = 0.024) and positive lymph node metastasis (P<0.001) were identified as independent risk factors for survival. When stratified by age and clinical response, young patients with no response to NACT had a worse clinicopathological condition compared with the other subgroups. Compared with non-responders, responders to NACT had a higher five-year DFS rate (80.1% versus 71.8%; P = 0.019) and OS rate (82.6% versus 71.8%; P = 0.003) among the young patients but not among the older patients. CONCLUSIONS: Responders to NACT aged 35 years or younger benefitted the most from NACT, while the young non-responders benefitted the least. Age might represent an important factor to consider when performing NACT in patients with cervical cancer.

Prospective cohort study to evaluate the efficacy of taxane plus platinum and CPT-11plus platinum regimes and to identify prognostic risk factors in cervical cancer patients.

OBJECTIVE: This study was designed to evaluate the response, toxicity and survival of taxanes plus platinum (TP) and CPT-11plus platinum (CP) as neoadjuvant chemotherapies with previously untreated cervical cancer, and to identify prognostic risk factors in these patients. METHODS: A cohort study was performed to evaluate the result of TP and CP regimes in the treatment of cervical cancer patients. RESULTS: The study included 567 patients with locally advanced cervical cancer (LACC) staged as FIGO IB-IIB in our clinical departments. Clinical response was found in 76.1% and 78% of patients in the TP and CP arms, respectively, and no treatment-related deaths were reported. During the follow-up period, disease-free survival (DFS) and overall survival (OS) for the TP and CP arms were not different (P = 0.384 for DFS, P = 0.800 for OS). The CP regime showed higher survival rate for endophytic growth style (P = 0.013 for DFS, P = 0.027 for OS). The CP regime also showed higher DFS and OS for G2 tumor (P = 0.027 for DFS, P = 0.032 for OS). In multivariate cox's proportional hazards regression model, the average death rates were much greater in the non-responder group (HR, 2.68), in the older (> 44 years) group (HR, 2.51), and in the FIGO stage II b patients (HR, 2.84). CONCLUSIONS: The CP regime showed higher survival rate for endophytic growth style or G2 tumor. Clinical response, age and FIGO stage were independent prognostic risk factors in this study for both DFS and OS.

Establishing a Nomogram for Stage IA-IIB Cervical Cancer Patients after Complete Resection.

BACKGROUND: This study aimed to establish a nomogram by combining clinicopathologic factors with overall survival of stage IA-IIB cervical cancer patients after complete resection with pelvic lymphadenectomy. MATERIALS AND METHODS: This nomogram was based on a retrospective study on 1,563 stage IA-IIB cervical cancer patients who underwent complete resection and lymphadenectomy from 2002 to 2008. The nomogram was constructed based on multivariate analysis using Cox proportional hazard regression. The accuracy and discriminative ability of the nomogram were measured by concordance index (C-index) and calibration curve. RESULTS: Multivariate analysis identified lymph node metastasis (LNM), lymph-vascular space invasion (LVSI), stromal invasion, parametrial invasion, tumor diameter and histology as independent prognostic factors associated with cervical cancer survival. These factors were selected for construction of the nomogram. The C-index of the nomogram was 0.71 (95% CI, 0.65 to 0.77), and calibration of the nomogram showed good agreement between the 5-year predicted survival and the actual observation. CONCLUSIONS: We developed a nomogram predicting 5-year overall survival of surgically treated stage IA-IIB cervical cancer patients. More comprehensive information that is provided by this nomogram could provide further insight into personalized therapy selection.

Association of 42 SNPs with genetic risk for cervical cancer: an extensive meta-analysis.

BACKGROUND: A large number of single nucleotide polymorphisms (SNPs) associated with cervical cancer have been identified through candidate gene association studies and genome-wide association studies (GWAs). However, some studies have yielded different results for the same SNP. To obtain a more comprehensive understanding, we performed a meta-analysis on previously published case-control studies involving the SNPs associated with cervical cancer. METHODS: Electronic searches of PubMed and Embase were conducted for all publications about the association between gene polymorphisms and cervical cancer. One-hundred and sixty-seven association studies were included in our research. For each SNP, three models (the allele, dominant and recessive effect models) were adopted in the meta-analysis. For each model, the effect summary odds ratio (OR) and 95% CI were calculated. Heterogeneity between studies was evaluated by Cochran's Q test. If the p value of Q test was less than 0.01, a random effect model was used; otherwise, a fixed effect model was used. RESULTS: The results of our meta-analysis showed that: (1) There were 8, 2 and 8 SNPs that were significantly associated with cervical cancer (P < 0.01) in the allele, dominant and recessive effect models, respectively. (2) rs1048943 (CYP1A1 A4889G) showed the strongest association with cervical cancer in the allele effect model (1.83[1.57, 2.13]); in addition, rs1048943 (CYP1A1 A4889G) had a very strong association in the dominant and recessive effect model. (3) 15, 11 and 10 SNPs had high heterogeneity (P < 0.01) in the three models, respectively. (4) There was no published bias for most of the SNPs according to Egger's test (P < 0.01) and Funnel plot analysis. For some SNPs, their association with cervical cancer was only tested in a few studies and, therefore, might have been subjected to published bias. More studies on these loci are required. CONCLUSION: Our meta-analysis provides a comprehensive evaluation of cervical cancer association studies.

Outcome of international Federation of gynecology and obstetrics stage IIb cervical cancer from 2003 to 2012: an evaluation of treatments and prognosis: a retrospective study.

OBJECTIVE: To compare the clinical outcomes of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical carcinoma receiving neoadjuvant chemotherapy followed by radical hysterectomy (RH) with those of patients receiving chemoradiation therapy (CRT) alone. METHODS: We retrospectively reviewed the medical records of patients with FIGO stage IIB cervical carcinoma. A total of 621 patients were eligible for the study according to the surgery-based or radiotherapy-based treatment; 285 patients received cisplatin-based neoadjuvant chemotherapy (NACT) followed by RH, and 336 patients underwent sequential or concurrent chemoradiation. The disease-free survival, overall survival, recurrence rates, and late complications were compared. Cox regression analysis was used to identify potential prognostic factors. RESULTS: Complete or partial response was seen in 77.6% (221/285) of the NACT-treated patients. Disease-free survival and overall survival rates of the patients who had NACT-sensitive responses were significantly higher than those who did not response (P = 0.021 and P = 0.008). Overall survival rates in the NACT + RH group were comparable with the concurrent chemoradiotherapy or chemoradiation groups (P > 0.05). Neoadjuvant chemotherapy followed by RH significantly decreased the recurrence rate (22.6% vs 35.5%), resulted in fewer treatment-related complications, and ultimately improved survival when compared with concurrent CRT. A survival benefit was observed for 63.9% of the patients in the NACT + RH group without adjuvant radiotherapy or CRT. CONCLUSIONS: Compared with concurrent chemoradiotherapy, NACT followed by RH achieved comparable survival outcomes for patients with FIGO stage IIB cervical cancer. This treatment method was significantly effective at reducing radiotherapy rates and complications, and it is worthy of recommending for younger patients.

The predictive value of serum squamous cell carcinoma antigen in patients with cervical cancer who receive neoadjuvant chemotherapy followed by radical surgery: a single-institute study.

OBJECTIVE: Neoadjuvant chemotherapy (NACT) could affect the levels of squamous cell carcinoma antigen (SCC-Ag). This study evaluates the predictive value of pre- and posttreatment SCC-Ag levels in patients with cervical cancer who were treated with NACT followed by radical surgery. METHODS: A total of 286 patients with Stage IB1-IIIB squamous cell carcinoma of the uterine cervix who were treated with NACT followed by radical hysterectomy were analyzed retrospectively. The relationship between SCC-Ag levels, the clinicopathologic parameters, the response to NACT and the three-year survival rate was investigated. RESULTS: The levels of SCC-Ag were elevated (>3.5 ng/mL) in 43.8% of patients before NACT, and 13.0% of patients after NACT. Pre- and posttreatment levels of SCC-Ag correlated with the response to NACT (P = 0.010, and P<0.001), deep stromal infiltration (P = 0.041, and P = 0.006), and lymph node status (P<0.001, and P<0.001). In the multivariate analysis, the elevated pretreatment level of SCC-Ag was demonstrated to be an independent risk factor for Lymph node metastases (P<0.001). Patients with both pre- and posttreatment SCC-Ag levels ≤3.5 ng/mL showed the best 3-year disease-free survival (DFS) and 3-year overall survival (OS) compared with patients with either pre- or posttreatment levels >3.5 ng/mL (P<0.001, and P<0.001, respectively). A multivariate analysis showed that posttreatment SCC-Ag levels were a strong independent predictor of OS (P = 0.001) and DFS (P = 0.012). CONCLUSION: Elevated pretreatment levels of SCC-Ag (>3.5 ng/mL) indicated a poor response to NACT and a higher risk of lymph node metastases. Elevated posttreatment levels of SCC-Ag were correlated with poor DFS and OS.

Could the extent of lymphadenectomy be modified by neoadjuvant chemotherapy in cervical cancer? A large-scale retrospective study.

BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) on topographical distribution patterns of lymph node metastasis in cervical cancer was unknown. METHODS: Patients with FIGO stage IB1-IIB who underwent radical surgery with or without NACT were enrolled (3527 patients). A matched-case comparison design was used to compare the effects of NACT on lymph node metastasis. RESULTS: We analyzed groups of 167 and 140 patients who were diagnosed with lymph node metastasis in the matched primary surgery group and NACT group, respectively, and no significant difference was observed (p = 0.081). The incidence of lymph node metastasis was significantly decreased in the NACT-responsive group compared to the non-responsive group (18.4% vs. 38.6%, P<0.001). The metastatic rates for every lymph node group also declined in the NACT-responsive group except for the deep inguinal and the para-aortic lymph node groups. Clinical response, deep stromal, parametrial and lymph vascular invasions were independent risk factors for lymph node metastasis in the NACT group. Furthermore, deep stromal invasion and lymph vascular invasion, but not the response to NACT, were independently associated with upper LNM. The number of lymph nodes involved, response to NACT, tumor histology and a positive vaginal margin were independent prognostic factors affecting DFS or OS rates in node-positive patients treated with NACT plus radical surgery. CONCLUSION: The frequency and topographic distribution of LNM are not modified by NACT, and clinical non-responders showed more involved LNs. A systemic and extensive lymphadenectomy should be performed in patients treated with NACT plus surgery regardless of the response to NACT.