Clinical outcome of FIGO 2018 stage IB3/IIA2 cervical cancer treated by neoadjuvant chemotherapy followed by radical surgery due to lack of radiotherapy equipment: A retrospective comparison with concurrent chemoradiotherapy.

This study aimed to assess neoadjuvant chemotherapy's clinical outcomes such as efficacy, toxicity, and survival outcomes followed by radical hysterectomy ((NACT-RS) among women with cervical cancer stage IB3 and IIA2, by comparing concurrent chemoradiotherapy (CCRT) and NACT-RS. The study retrospectively reviewed patients with (2018 FIGO) stage IB3 and IIA2 cervical cancer who received preoperative neoadjuvant chemotherapy followed by NACT-RS or concurrent chemoradiotherapy (CCRT). The outcome measures were the 5-year survival and complication rates between the two groups. The median follow-up was 75 months. In total, 218 patients had stage IIA2, 136 patients had stage IB3, 201 patients received CCRT, and 153 patients received preoperative NACT-RS. In the CCRT group, the incidence of early complications (myelosuppression, gastrointestinal and urinary) was higher compared with that in the NACT-RS group (76.1 vs. 26.1%; p < 0.001, respectively). There was no significant difference between the two study groups concerning late complications. Five-year PFS was 79.9% and 85.5% in the NACT-RS and CCRT groups, respectively (p = 0.093). Five-year OS was 86.9% and 85.5% in the NACT-RS and CCRT groups, respectively (p = 0.97). In the multivariate clinicopathologic characteristics analysis for OS, initial tumor size > 4.3 cm (HR 5.11; p < 0.001), AC/ASC (HR 1.89; p = 0.02), histologic grade 2-3 (HR 2.25; p = 0.04), and 2018 FIGO stage IIA2 (HR 8.67; p < 0.001) were independent risk factors. The survival of patients with stage IB3 and IIA2 cervical cancer treated with NACT-RS was similar to that of patients treated with CCRT without increasing side effects.

Distinct clinical and genetic mutation characteristics in sporadic and Lynch syndrome-associated endometrial cancer in a Chinese population.

BACKGROUND: The diagnosis of Lynch syndrome-associated endometrial cancer patients is significant for early warning of their relatives. The purpose of this study was to provide diagnostic indicators of Lynch syndrome-associated endometrial cancer by screening the differential clinical and genetic characteristics. METHODS: Clinical information and hysterectomy specimens were collected from 377 eligible patients with endometrial cancer. The MLH1 methylation level was detected by an EZ DNA Methylation-Gold Kit. According to the above experimental results, the patients were then divided into sporadic endometrial cancer and suspected Lynch syndrome-associated endometrial cancer groups. A total of 62 samples were randomly selected for whole-exome sequencing. IBM SPSS Statistics 21 was used to compare the clinical data between the sporadic and suspected Lynch syndrome-associated endometrial cancer groups, and the relationship between the specific high-frequency-mutation genes and the clinical data. RESULTS: According to the results of MMR immunohistochemistry and MLH1 methylation, the sporadic endometrial cancer group included 361 patients and the suspected Lynch syndrome-associated endometrial cancer group included 16 patients in this study. In the clinical analysis, the average age of the suspected Lynch syndrome-associated endometrial cancer patients was 45.50 ± 11.50 years, which was significantly younger than the 51.17 ± 10.03 years of the sporadic endometrial cancer patients (P = 0.028). The average BMI of the suspected Lynch syndrome-associated endometrial cancer patients was 23.43 kg/m2 (CI: 20, 30), which was lower than the 26.50 kg/m2 of the sporadic endometrial cancer patients (P = 0.028). Combined with the WES data, MASP2, NADK and RNF223 were identified as three specific mutation sites related to age, FIGO stage and histology. CONCLUSIONS: Compared with the suspected endometrial cancer patients, the Lynch syndrome-associated endometrial cancer patients were younger and less obese. Mutations in MASP2, NADK and RNF223 might be regarded as genetic endometrial cancer features related to clinical characteristics.

Efficacy of preoperative brachytherapy for controlling vaginal bleeding in early-stage cervical cancer: a retrospective study.

BACKGROUND: In our clinical study, 11% of the patients with early-stage cervical cancers had different degrees of vaginal bleeding, which required a preoperative intervention. We set to assess the efficacy and safety of preoperative high-dose rate vaginal ovoid brachytherapy (HDR-VOBT) for the treatment of vaginal bleeding in women with early cervical cancer. METHODS: We retrospectively identified and reviewed patients with vaginal bleeding and early-stage cervical carcinoma, treated between January 2011 and December 2014 (median follow-up of 69 months). Of the 116 patients, 59 received preoperative HDR-VOBT (a dose of 8 Gy at 0.5 cm from the tumor surface), and 57 received traditional vaginal packing with gauze alone, followed by radical hysterectomy and lymphadenectomy. Analysis of the clinical parameters was performed using the chi-square test. The outcome measures were the 3- and 5-year survival and the complication rate. RESULTS: From the 116 patients, 25 had stage IB1, 49 had stage IB2, and 42 had stage IIA1 cervical cancer. No differences were observed regarding the 5-year overall survival (OS) (91.5% vs. 91.2%) and disease-free survival (DFS) (76.3% vs. 86%) between the preoperative HDR-VOBT group and the vaginal packing with gauze group. The mean volume of blood loss due to vaginal bleeding after treatment was 83.4 (range: 30-150) mL: 56.8 (range: 30-80) mL in the preoperative HDR-VOBT group and 111.1 (range: 80-150) mL in the gauze packing group (P<0.001). The mean time to achieve hemostasis was 3.5 h in the preoperative HDR-VOBT group and 8.1 h in the vaginal packing with gauze group (P<0.001). There was no significant difference in postoperative risk factors, complications, and survival between the two groups. CONCLUSIONS: Preoperative HDR-VOBT with a dose of 8 Gy at 0.5 cm from the surface of the tumor has a better hemostatic effect than vaginal packing with gauze, with no additional complications and no need for adjuvant treatment after the operation.

Clinicopathological risk factors in the light of the revised 2018 International Federation of Gynecology and Obstetrics staging system for early cervical cancer with staging IB: A single center retrospective study.

To validate the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer on the survival of patients who underwent radical hysterectomy for 2009 FIGO stage IB carcinomas.We retrospectively identified and reviewed 251 patients treated with radical hysterectomy for 2009 FIGO stage IB cervical carcinomas from January 2011 to December 2016. The re-staged IB cohort consisted of 2018 FIGO stage IB1 (tumor size <2 cm), IB2 (2-3.9 cm), IB3 (≥4 cm), and IIIC1p (any pelvic nodal metastasis) cervical cancer. The univariate log-rank test and multivariate Cox regression models were performed for all potential clinic pathological risk factors based on cancer stage.On re-staging the 251 patients with 2009 FIGO stage IB using the 2018 FIGO staging system, 96 patients (38.2%) had stage IB1, 109 patients (43.4%) had stage IB2, 28 patients (11.2%) had stage IB3, and 18 patients (7.2%) had stage IIIC1p. The 5-year overall survival (OS) rates of patients with 2018 FIGO stage IB1, IB2, IB3, and IIIC1p were 97.9%, 92.7%, 78.6%, and 61.1%, respectively. The 5-year progression-free survival rates were 97.9%, 92.7%,63.7%, and 20.8%, respectively. Factors significantly affecting OS and disease-free survival were 2018 FIGO stage≥IB3, histologic grade 2-3, and lymph node involvement.The revised 2018 FIGO staging system seemed to accurately reflect the survival rate, with a distinct statistical tendency for poorer 5-year disease-free survival and OS rates with increasing stage. Women with positive lymph nodes in this classification were classified as having stage IIIC disease, which can achieve more realistic survival results than the previous staging system. The prognostic discrimination of histologic grade should be considered when revising the staging system in the future.

Performance of HPV Genotyping Combined with p16/Ki-67 in Detection of Cervical Precancer and Cancer Among HPV-Positive Chinese Women.

Women with positive high-risk human papillomavirus (hrHPV) need efficient triage testing to determine colposcopy referrals. Triage strategies of combining p16/Ki-67 with extended HPV genotyping were evaluated in this study. In total, 899 women attending cervical cancer screening program and 858 women referred to colposcopy from five hospitals were recruited. All the participants were tested by HPV assays and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal results. HPV genotypes were divided into four strata (HPV16/18, HPV31/33/58/52, HPV45/59/56/66, and HPV51/39/68/35) according to their risks for cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The positive rates of four genotype strata among CIN3+ women were 3.47% (HPV51/39/68/35), 7.73% (HPV45/59/56/66), 14.7% (HPV31/33/58/52), and 78.1% (HPV16/18), respectively (P trend < 0.001). The positive rates of p16/Ki-67 increased with the elevation of HPV risk hierarchical from 65.0% in HPV51/39/68/35-positive women to 88.0% in HPV16/18-positive women (P trend < 0.001). p16/Ki-67 was an effective method for risk stratification of CIN2+ among HPV31/33/58/52- and HPV45/59/56/66-positive women [HPV31/33/58/52: OR for dual stain+ (ORDS+) of 26.7 (16.8-42.4) and OR for dual stain- (ORDS-) of 3.87(1.89-7.91); HPV45/59/56/66: ORDS+ of 10.3(5.05-21.0) and ORDS- of 1.27(0.38-4.26)]. The combination of HPV16/18 genotyping and p16/Ki-67 triage of HPV31/33/58/52/45/59/56/66-positive women resulted in a lower referral rate (40.1% vs. 41.3%; P < 0.001) as compared with triage of 12 other HPV-positive women with p16/Ki-67, although sensitivity and specificity levels for these two strategies were identical. Combining HPV extended genotyping and p16/Ki-67 can be considered as a promising strategy for cervical cancer screening and triage.

A retrospective validation study of sentinel lymph node mapping for high-risk endometrial cancer.

OBJECTIVES: To determine the feasibility and performance of sentinel lymph-node (SLN) mapping among women with high-risk endometrial cancer (EC). MATERIALS AND METHODS: Ninety-eight patients at high-risk EC were enrolled in this retrospective surgical trial from August 2016 to August 2018. All patients underwent intraoperative SLN biopsy, with ICG injection for laparoscopic staging; this was followed by pelvic and paraaortic lymphadenectomy (LAD). Outcomes included SLN detection rate, false-negative SLN algorithm rate, and the negative predictive value (NPV) of the SLN algorithm. The Chi-square test was used to analyze the relationship between SLN mapping and the risk factors. Then, we performed Kappa consistency check (P < 0.05 with Meaning), to estimate the consistency of SLN and lymph-node metastasis. RESULTS: Successful biopsy occurred in 94 patients (170 sides) among 98 patients (196 sides). At least 1 SLN was identified in 86.7% (170/196). Overall, the false-negative rate (FNR) was 11.8% (2/17), NPV was 97.3% (72/74), and sensitivity was 88.2% (15/17). 22/98 patients (22.4%) with high-risk EC had at least one metastatic lymph node identified. When the SLN algorithm was retrospectively applied, the FNR was 9.1% (2/22) and sensitivity was 90.9% (20/22). Considering the surgeon's experience, 68 cases of EC (except for 30 patients), the detection rate was 89.7% (122/136), NPV was 98.1% (50/51), and the FNR was 5.6% (1/18). The factor significantly affecting the detection rate of SLNs was lymphovascular space invasion (LVSI) (P = 0.016). SLN metastasis of EC was associated with depth of myometrial invasion (P = 0.034). The analysis result of SLN and the consistency of pelvic lymph-node metastasis status. As detected by Kappa coefficient was 0.939 (P < 0.001), suggests highly consistency. CONCLUSIONS: Our SLN detection rate for high-risk EC was the same as previously reported. When SLN is not detected, better after 30 patients' experience, is a reasonable alternative to complete LAD in high-risk EC. In addition, SLN shows high co-occurrence with pelvic lymph nodes. Therefore, SLN biopsy can be used to diagnose high-risk EC.

Neoadjuvant brachytherapy and chemotherapy followed by radical surgery for stage IB2 and IIA cervical cancer: A retrospective comparison with chemoirradiation.

The aim of the present study was to assess the immediate and long-term results of preoperative brachytherapy and chemotherapy followed by radical surgery compared with those of standard chemoirradiation in patients with stage IB2-IIA cervical cancer. The medical records of 70 patients with stage IB2 and IIA cervical cancer who were treated between June 2006 and June 2010 were reviewed. The patients received either standard chemoirradiation (CRT) treatment (n=20) or neoadjuvant brachytherapy with one cycle of chemotherapy followed by radical hysterectomy [operation (OT) group; n=50]. Further adjuvant chemoirradiation was administered to patients with high-risk disease. Early and late complications as well as survival were compared between the two groups. No serious operative complications occurred in the OT group. In the CRT group, the incidence of symptomatic vaginal stenosis, as well as that of proctitis and cystitis, was higher compared with that in the OT group (35 vs. 4% and 20 vs. 2%, repectively). The median follow-up period was 52 months (range, 11-84 months). In the CRT group, the 3-year overall and disease-free survival rates were 95% [95% confidence interval (CI): 76.14-86.46] and 90% (95% CI: 59.94-73.66), respectively, whereas in the OT group, the respective rates were 90% (95% CI: 72.93-83.07) and 90% (95% CI: 71.84-82.96). In conclusion, the survival of patients with stage IB2-IIA cervical cancer treated with preoperative brachytherapy and chemotherapy followed by radical surgery was similar to that of patients treated with chemoirradiation, but with a more favorable side effect profile. Thus, this tri-modal treatment option requires further evaluation in prospective randomized studies.

Clinical evaluation of human papillomavirus 16/18 oncoprotein test for cervical cancer screening and HPV positive women triage.

HPV-16 and -18 account for about 80% of cervical cancers. We evaluated the performance of HPV-16/18 oncoprotein to predict precancer and cancer in corresponding tissue biopsy specimens. 1,008 women attending cervical cancer screening program and 638 women referred to colposcopy with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) from 4 hospitals were recruited (1,646 in total). All women were tested OncoE6 (AVC), Liquid-Based Cytology (Hologic) and cobas HPV test (Roche). Colposcopy was performed on women with any abnormal results. The final diagnoses were based on a consensus panel review of the histology. There were 919 normal, 69 CIN1, 53 CIN2, 91 CIN3,474 squamous cell carcinoma(SCC) and 40 adenocarcinoma (ADC) cases, the prevalence of OncoE6 was 1.7%, 10.1%, 13.2%, 44.0%, 80.4% and 65.0%, respectively. The percent positive for cobas was higher than that of OncoE6 in detection of HPV16/18 in entire population (p < 0.001). However, the disparity of positive rate between these two tests became tiny among cervical cancer patients (CIN2: 26.4% vs. 13.2%, CIN3: 73.6% vs. 44.0%, SCC: 84.0% vs. 80.4%, ADC: 67.5% vs. 65.0%). OncoE6 was less sensitive than cobas (73.9% vs. 93.6%, p < 0.001), but more specific (97.1% vs. 75.4%, p < 0.001) for CIN3+ in entire population; OncoE6 yielded a sensitivity of 77.7% and a specificity of 91.0% for CIN3+ among cobas positive women, which can reduce nearly half of the colposcopy referral numbers. OncoE6 can be considered as a useful tool for cervical cancer screening and a potential powerful biomarker for HPV positive triage.