New insights into molecular mechanisms underlying malignant transformation of endometriosis: BANCR promotes miR-612/CPNE3 pathway activity.

RESEARCH QUESTION: Does LncRNA BANCR promote the malignant transformation of endometriosis by activating the miR-612/CPNE3 pathway? DESIGN: The expression patterns of BANCR, miR-612 and CPNE3 in normal endometrium, eutopic endometrium from endometriosis, eutopic endometrium or malignant tissues from endometriosis-associated ovarian cancer. On the basis of primary normal endometrial stromal cells (NESC) and eutopic endometrial stromal cells (EESC), the regulatory relationships between BANCR, miR-612 and CPNE3, and the potential mechanisms that promote the malignant transformation of endometriosis, were elucidated in vitro and in vivo. RESULTS: The expression levels of BANCR and CPNE3 were lowest in normal endometrium, significantly increased in eutopic endometrium (P < 0.05) and was significantly increased in eutopic endometrium (P < 0.05). During the malignant transformation of endometriosis, the expression levels of BANCR and CPNE3 were significantly upregulated (P < 0.05), whereas those of miR-612 were significantly downregulated (P < 0.05). miRNA-612 was found to target BANCR and CPNE3. The overexpression and knockdown of BANCR in NESC and EESC upregulated and downregulated the expression of CPNE3 and promoted or prevented cell proliferation and migration, respectively; these effects were reversed by miR-612 mimics and inhibitor. These changes were all statistically significant (P < 0.05). In-vivo experiments revealed that BANCR significantly increased the survival of subcutaneous endometrial cells by regulating miR-612/CPNE3 (P < 0.05). CONCLUSION: The expression of BANCR gradually increased with the progression of endometriosis during malignant transformation, and promoted the proliferation and migration of endometrial cells via the miR-612/CPNE3 pathway. BANCR may represent a novel target for monitoring the malignant transformation of endometriosis.

Research advances in signaling pathways related to the malignant progression of HSIL to invasive cervical cancer: A review.

The progression of high-grade squamous intraepithelial lesion (HSIL) to invasive cervical cancer (ICC) is a complex process involving persistent human papillomavirus (HPV) infection and changes in signal transduction regulation, energy and material metabolism, cell proliferation, autoimmune, and other biological process in vaginal microenvironment and immune microenviroment. Signaling pathways are a series of interacting molecules in cells that regulate various physiological functions of cells, such as growth, differentiation, metabolism, and death. In the progression of HSIL to ICC, abnormal activation or inhibition in signaling pathways plays an essensial role. This review presented some signaling pathways related to the malignant progression of HSIL to ICC, including p53, Rb, PI3K/AKT/mTOR, Wnt/ß-catenin, Notch, NF-κB, MAPK, TGF-ß, JAK-STAT, Hippo, and Hedgehog. The molecular mechanisms involved in the biological process of pathway regulation were also analyzed, in order to illustrate the molecular pathway of HSIL progression to ICC and provide references for the development of more effective prevention and treatment methods.

Age-specific performance of human papillomavirus E6/E7 mRNA assay versus cytology for primary cervical cancer screening and triage: community-based screening in China.

Background: In the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach. Methods: Between April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts. Results: Our investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%-8.0% range, and were highest in 45-54-year olds. When compared with 35-44-or 45-54-year olds, HPV prevalence was highest in 55-64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35-44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7-100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3-82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6‰ vs. 7.3‰), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45-54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2‰ vs. 6.6‰). In 55-64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7-100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0-80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771-0.920] vs. 0.812 [95% CI: 0.734-0.891], P = 0.236). Conclusions: Primary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35-44 and 55-64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35-44 year old females.

The association between ambient PM2.5's constituents exposure and cervical cancer survival.

Increasing evidence links exposure to ambient particulate matter with a diameter less than 2.5 µm (PM2.5) with reduced survival in cancer survivors, but little was known about the association between PM2.5 exposure and cervical cancer survival. We analyzed data from 5144 cervical cancer patients diagnosed between January 2014 and December 2020, who completed recommended treatments. Exposure levels were determined by the monthly average concentration of ambient PM2.5 and its five constituents, obtained from Tracking Air Pollution in China (TAP) based on individual residential addresses. Log-rank tests and multivariate Cox Proportional Hazardous regression were performed to examine the impacts of PM2.5 and its constituents on overall survival (OS) of cervical cancer patients. We observed that for every increase of 1 µg/m3 in average individual exposure, the hazard ratios (95%CI) for ambient PM2.5, sulfate (SO42-), ammonium (NH4+), and nitrates (NO3-) were 1.078(1.069-1.086), 6.755(5.707-7.996), 2.123(1.935-2.329), and 3.717(3.237-4.267), respectively. Subgroups with longer OS had larger HRs of PM2.5 and its constituents, which might attributed to more cumulative exposure. No evidence of a threshold for the hazardous effects of PM2.5 on the OS of cervical cancer patients was identified. Furthermore, long-term exposure to PM2.5 was negatively associated with pretreatment counts of monocytes, neutrophils, and lymphocytes in peripheral blood of cervical cancer patients. In conclusion, elevated levels of PM2.5 mass, SO42-, NH4+, and NO3- in ambient PM2.5 exposure were associated with reduced OS among cervical cancer patients. There may be no discernible threshold effect of PM2.5 on the risk for cervical cancer patients.

Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial.

Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].

Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

Effectiveness of a single low-dose computed tomography screening for lung cancer: A population-based perspective cohort study in China.

The purpose of this perspective cohort study was to evaluate the effectiveness of low-dose computed tomography (LDCT) screening for lung cancer in China. This study was conducted under the China Urban Cancer Screening Program (CanSPUC). The analysis was based on participants aged 40 to 74 years from 2012 to 2019. A total of 255 569 eligible participants were recruited in the study. Among the 58 136 participants at high risk of lung cancer, 20 346 (35.00%) had a single LDCT scan (defined as the screened group) and 37 790 (65.00%) not (defined as the non-screened group). Overall, 1162 participants were diagnosed with lung cancer at median follow-up time of 5.25 years. The screened group had the highest cumulative incidence of lung cancer and the non-screened group had the highest cumulative lung cancer mortality and all-cause cumulative mortality. We performed inverse probability weighting (IPW) to account for potential imbalances, and Cox proportional hazards model to estimate the weighted association between mortality and LDCT scans. After IPW adjusted with baseline characteristics, the lung cancer incidence density was significantly increased (37.0% increase) (HR1.37 [95%CI 1.12-1.69]), lung cancer mortality was decreased (31.0% decrease) (HR0.69 [95%CI 0.49-0.97]), and the all-cause mortality was significantly decreased (23.0% lower) (HR0.77 [95% CI 0.68-0.87]) in the screened group. In summary, a single LDCT for lung cancer screening will reduce the mortality of lung cancer and all-cause mortality in China.

CD48 suppresses proliferation and migration as an immune-related prognostic signature in the cervical cancer immune microenvironment.

Cervical cancer (CC) is one of the most common malignant tumors in gynecology. Immunotherapy and targeted therapy are two particularly effective treatments. In this study, weighted gene co-expression network analysis and CIBERSORT algorithm that quantifies the composition of immune cells were used to analyze CC expression data based on the GEO database and identify modules related to T cells. Five candidate hub genes were identified by tumor-infiltrating immune cells estimation and Kaplan-Meier survival analysis according to CC data from The Cancer Genome Atlas (TCGA). Chemotherapeutic response, methylation, and gene mutation analyses were implemented so that the five candidate hub genes identified may be the potential biomarkers and therapeutic targets which were related to T cell infiltration. Moreover, the results of RT-qPCR revealed that CD48 was a tumor suppressor gene, which was negatively correlated with CC stages, lymph node metastasis, and differentiation. Furthermore, the functional study verified that the interference of CD48 was able to boost the proliferation and migration ability in vitro and the growth of transplanted tumors in vivo. Overall, we identified molecular targets related to immune infiltration and prognosis, regarded CD48 as a key molecule involved in the progression of CC, thus providing new insights into the development of molecular therapy and immunotherapeutics against CC.

Correlation of clinicopathological and prognostic characteristics between endometriosis-associated and primary ovarian cancer.

BACKGROUND: The main aim of this study was to establish the clinicopathological and prognostic correlations between endometriosis-associated and non-endometriosis-associated primary ovarian cancer, with a view to providing a reference guide for revision of diagnostic criteria for malignant transformation of endometriosis. METHODS: Clinicopathological and follow-up data of 174 patients with clear cell and endometrial ovarian cancer were retrospectively extracted. Cases were divided into endometriosis-associated and non-endometriosis-associated primary ovarian cancer for comparative analysis of clinicopathological characteristics and prognosis. RESULTS: Average age and post-menopausal rate in the endometriosis-associated ovarian cancer group were lower relative to the primary ovarian cancer group (P < 0.05). Body mass index, age at menopause, operation history, dysmenorrhea, complications, tumor size, tumor side, ascites, CA125, HE4, CA19.9, stage, differentiation, expression of ER, PR, P53, P16, Ki67, MMR, HNF-1ß and Napsin A were not significantly different between the groups (P > 0.05). Furthermore, rates of resistance to platinum chemotherapy, relapse, progression-free survival and overall survival were comparable between the two groups (P > 0.05). CONCLUSION: Endometriosis-associated and primary ovarian cancers of the same pathological type are speculated to be homologous in terms of origin from malignant transformation of endometriosis. It may therefore be necessary to revise the diagnostic criteria for ovarian endometriosis malignancy.

Short-term outcomes of transvaginal specimen extraction versus transumbilical specimen extraction following totally laparoscopic gastrectomy in female patients with gastric cancer: a retrospective analysis.

Introduction: Natural orifice specimen extraction (NOSE) laparoscopic surgery is emerging as a new and promising technique, especially in gastric cancer (GC). Aim: To analyze the difference between transvaginal and transumbilical specimen extraction following totally laparoscopic gastrectomy (TLG). Material and methods: Between January 2016 and July 2021, 37 consecutive female patients with GC who underwent either natural orifice specimen extraction surgery (NOSES) or TLG at our center were included and analyzed. Results: In total, 12 patients underwent NOSES, and 25 patients underwent TLG. The NOSES group had a shorter operative time (239.3 ±21.5 vs. 256.1 ±21.2 min, p = 0.031) and shorter specimen extraction time (17.0 ±4.2 vs. 30.8 ±4.3 min, p < 0.01). No significant difference was observed in the comparison of the radical validity including estimated blood loss, the number of harvested LNs and the comparisons of distal and proximal margin. In the postoperative recovery comparisons, the NOSES group had a shorter time to first fluids (3.9 ±0.5 vs. 5.6 ±1.2 days, p < 0.01), and time to starting a soft diet (5.6 ±0.7 vs. 7.7 ±1.7 days, p < 0.01). Postoperative pain in the NOSES group was significantly less. Postoperative hospital stay days in the NOSES group were fewer (10.2 ±2.2 vs. 12.4 ±2.9 days, p = 0.030). Overall, the postoperative complications were similar between the two groups (p = 0.438). When more cases were included, the results were similar. NOSES reduced hospital costs for GC patients, and it also applied to the premenopausal patients. Conclusions: NOSES was a safer and more reliable method as compared to transumbilical specimen extraction.

A population-based cross-sectional study on the situation of cervical cancer screening in Liaoning, China.

BACKGROUND: Cervical cancer (CC) screening is currently recognized as an effective intervention for CC. Previous studies found that the proportion of screening was low in China, especially in Liaoning. Therefore, we performed a population-based cross-sectional survey to investigate the situation of cervical cancer screening and analyze their related factors for providing a decision-making basis for sustainable and effective development of cervical cancer screening. METHODS: This population-based cross-sectional study involved aged 30 to 69 years in nine counties/districts in Liaoning from 2018 to 2019. Data were collected using the quantitative data collection methods, and analyzed in SPSS version 22.0. RESULTS: Overall, only 22.37% of 5334 respondents reported having ever been screened for cervical cancer in past 3 years, and 38.41% of respondents reported having the willingness for cervical cancer screening in next 3 years. In the rate of CC screening, multilevel analysis indicated that age, marital status, education level, type of occupation, medical insurance, family income, place of residence and regional economic level had a significant impact on proportion of screening. In the rate of CC screening willingness, multilevel analysis indicated that age, family income, health status, place of residence, regional economic level and CC screening still had a significant impact, but marital status, education level and medical insurance type had no significant impact. There was no significant difference in marital status, education level and medical insurance type after the factors of CC screening were added in the model. CONCLUSION: Our study found both proportion of screening and willingness were at a low level, and age, economic and regional factors were the main factors for implementation of CC screening in China. In the future, targeted policies should be formulated according to the characteristics of different groups of people, and reduce the gap in the current health service capacity between different regions.

Comparison between laparoscopic and abdominal radical hysterectomy for cervical adenosquamous carcinoma at stage IA2 to IIA2: A multicenter retrospective study.

OBJECTIVE: We aimed to compare the 5-year oncological outcomes of laparoscopic/abdominal radical hysterectomy (LRH/ARH) in patients with cervical adenosquamous carcinoma at stage IA2 to IIA2 based on the 2009 or 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria. METHODS: Based on the clinical diagnosis and treatment of cervical cancer in China (Four C) database, Cox risk regression models were applied to analyze tumor prognosis treated with ARH/LRH in FIGO 2009 and 2018 IA2-IIA2 patients and stratified findings according to tumor diameter (≤4 and >4 cm subgroups). And to avoid bias, propensity score matching (PSM) was also used for the cohort study. RESULTS: Based on FIGO 2009 staging criteria (n = 474), there was no significant difference between the ARH and LRH groups in 5-year disease-free survival (DFS) or overall survival (OS). Lymph node metastasis was a risk factor for 5-year DFS in this stage. After PSM, lymphovascular space invasion (LVSI) was an independent risk factor for 5-year OS in the tumors ≤4 cm subgroup. Based on FIGO2018 staging criteria (n = 322), cervical interstitial infiltration depth was an independent risk factor for 5-year OS in the total population and the tumor diameter ≤4 cm subgroup. CONCLUSIONS: Laparoscopic surgery was not a risk factor affecting the oncologic prognosis of adenosquamous carcinoma of the cervix based on either FIGO 2009 or 2018 staging of stage IA2-IIA2. In addition, LRH may be considered for patients with early-stage cervical adenosquamous carcinoma.

A Bayesian network predicting survival of cervical cancer patients-Based on surveillance, epidemiology, and end results.

This study aimed to build a comprehensive model for predicting the overall survival (OS) of cervical cancer patients who received standard treatments and to build a series of new stages based on the International Federation of Gynecologists and Obstetricians (FIGO) stages for better such predictions. We collected the cervical cancer patients diagnosed since the year 2000 from the Surveillance, Epidemiology, and End Results (SEER) database. Cervical cancer patients who received radiotherapy or surgery were included. Log-rank tests and Cox regression were used to identify potential factors of OS. Bayesian networks (BNs) were built to predict 3- and 5-year survival. We also grouped the patients into new stages by clustering their 5-year survival probabilities based on FIGO stage, age, and tumor differentiation. Cox regression suggested black ethnicity, adenocarcinoma, and single status as risks for poorer prognosis, in addition to age and stage. A total of 43,749 and 39,333 cases were finally eligible for the 3- and 5-year BNs, respectively, with 11 variables included. Cluster analysis and Kaplan-Meier curves indicated that it was best to divide the patients into nine modified stages. The BNs had excellent performance, with area under the curve and maximum accuracy of 0.855 and 0.804 for 3-year survival, and 0.851 and 0.787 for 5-year survival, respectively. Thus, BNs are excellent candidates for predicting cervical cancer survival. It is necessary to consider age and tumor differentiation when estimating the prognosis of cervical cancer using FIGO stages.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

Efficacy and Safety of the Anti-PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study.

PURPOSE: This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti-programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer. PATIENTS AND METHODS: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. The primary endpoints of the dose-expansion phase were safety and the objective response rate (ORR) of the 5 mg/kg dose. Efficacy was assessed by the third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). RESULTS: 104 patients were successfully enrolled into the study. Twelve patients were included in the dose-escalation phase, with one complete response and two partial responses in the 5 mg/kg treatment group. Ninety-two patients (5 mg/kg) were enrolled in the dose-expansion phase. Fifty-four patients (59.3%) had baseline PD-L1-positive tumor expression (combined positive score ≥1). ORR was 15.4% [95% confidence interval (CI), 8.7%-24.5%]. Median PFS was 4.44 months (95% CI, 2.37-5.75 months), and the median OS was 14.72 months (95% CI, 9.59-NE months). ORR of PD-L1-positive patients was 16.7%, and the ORR of PD-L1-negative patients was 17.9%. No treatment-related deaths occurred. CONCLUSIONS: Our study demonstrates that socazolimab has durable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti-PD-1/PD-L1 mAbs.

PM2.5 exposure and cervical cancer survival in Liaoning Province, northeastern China.

Particulate matter with a diameter of 2.5 µm or less (PM2.5) has frequently been reported to be associated with an increased incidence of cancer, but few studies have explored the association between PM2.5 exposure and cancer survival. We retrospectively analyzed the association between PM2.5 exposure and the overall survival (OS) of cervical cancer patients residing in 14 urban areas of Liaoning Province, northeastern China, during January 2014-October 2021. Patients from urban areas who completed the recommended treatments with complete follow-up information were included. The PM2.5 monitoring data of each urban area of Liaoning Province were retrieved, and individual exposure to PM2.5 after diagnosis was calculated as the average daily concentration in the city of residence from the date of discharge to the date of death or the last follow-up. Log-rank tests and Cox regression were performed to examine the relationship between PM2.5 exposure and cervical cancer survival. A total of 1753 cervical cancer patients were finally included, among whom 804 (45.9%) were from Shenyang City, the capital of Liaoning Province. The median average daily concentration of PM2.5 to which the patients were exposed was 45.0 (interquartile range 38.2-50.0) µg/m3. Both log-rank tests (grouped by quartiles, p < 0.001) and Cox regression (continuous, HR = 1.06, 95% CI 1.04-1.08) indicated that PM2.5 was significantly associated with shorter OS. Sensitivity analysis also confirmed the robustness of our findings. From the subgroup analysis, only the OS of stage II and stage III patients was associated with PM exposure. Our findings provide the insight that PM2.5 exposure might be associated with shorter OS of cervical cancer patients.

Comparison of survival outcomes between squamous cell carcinoma and adenocarcinoma/adenosquamous carcinoma of the cervix after radical radiotherapy and chemotherapy.

BACKGROUND: This study aimed to compare the survival outcomes between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix after radical radiotherapy and chemotherapy. METHODS: Propensity score matching (1:4) was used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients with SCC and AC/ASC in China. RESULTS: Five thousand four hundred sixty-six patients were enrolled according to the criteria. The 5-year OS and DFS in the SCC group (n = 5251) were higher than those in the AC/ASC group (n = 215). After PSM (1:4), the 5-year OS and DFS in the SCC group were higher than those in the AC/ASC group (72.2% vs 56.9%, p < 0.001, HR = 1.895; 67.6% vs 47.8%, p < 0.001, HR = 2.056). In stage I-IIA2 patients, after PSM (1:4), there was no significant difference in 5-year OS between the SCC group (n = 143) and the AC/ASC group (n = 34) (68.5% vs 67.8%, P = 0.175). However, the 5-year DFS in the SCC group was higher than that in the AC/ASC group (71.0% vs 55.7%, P = 0.045; HR = 2.037, P = 0.033). In stage IIB-IV patients, after PSM (1:4), the 5-year OS and DFS in the SCC group (n = 690) were higher than those in the AC/ASC group (n = 173) (70.7% vs 54.3% P < 0.001 vs 1.940%, P < 0.001 vs 45.8%, p < 0.001). CONCLUSIONS: For stage I-IIA2, there was no significant difference in 5-year survival time, but patients with AC/ASC were more likely to relapse. In the more advanced IIB-IV stage, the oncological outcome of radical radiotherapy and chemotherapy of cervical AC/ASC was worse than that of SCC.

Efficacy evaluation of vaginal-assisted laparoscopic radical hysterectomy and laparoscopic radical hysterectomy for cervical cancer: a single-center retrospective case series study.

Background: To investigate the survival outcomes of abdominal radical hysterectomy (ARH), laparoscopic radical hysterectomy (LRH), and vaginal-assisted laparoscopic radical hysterectomy (VALRH) in the treatment of cervical cancer patients. Methods: This was a retrospective study. We collected the clinical data of 654 patients with cervical cancer (406 ARH, 172 LRH, and 76 VALRH), then compared the effects of different surgical methods on recurrence and survival. Results: Total overall survival (OS) were no significant differences in three groups (P>0.05). Total disease-free survival (DFS) was significantly higher in ARH group than in LRH group [hazard ratio (HR) =2.8, 95% confidence interval (CI): 1.199-3.607, P=0.004]; however, there were no significant differences between the VALRH (94.7%) and ARH (93.3%) groups. Subgroup stratification analysis showed that the overall recurrence rate in LRH group was significantly higher than that of the ARH groups for patients with a tumor size from ≥2 to <4 cm, negative postoperative lymph nodes, and no postoperative adjuvant therapy (all P<0.05). However, in the subgroup with tumor sizes of ≥2, <4, and ≥4 cm, no matter whether the lymph nodes were positive or not, and those with no postoperative supplementary adjuvant therapy, LRH was associated with a significantly higher local pelvic recurrence rate than ARH (all P<0.05). No significant differences between VALRH and ARH in any of the subgroup analyses (all P>0.05). A Cox analysis indicated that LRH increased the risk of overall and local pelvic recurrence after surgery compared with ARH (HR =2.338, 95% CI: 1.186-4.661, P=0.014; HR =10.313, 95% CI: 2.839-37.460, P<0.001); however, no significant difference between VALRH and ARH (all P>0.05). Sensitivity analysis of surgeons did not change the conclusions. Conclusions: Our analyses showed that the local pelvic recurrence rates and overall recurrence rates of LRH were significantly higher than ARH. VALRH could avoid tumor intraperitoneal exposure and achieve the same tumor prognosis as open surgery. By improving the standardization of minimally invasive surgery for early cervical cancer and paying close attention to the tumor-free concept, minimally invasive radical hysterectomy may achieve the same tumor outcome as open surgery.

Value of diffusion-weighted imaging in preoperative evaluation and prediction of postoperative supplementary therapy for patients with cervical cancer.

Background: With the continuous progress of medical imaging technology, evaluation of cervical cancer is increasingly dependent on imaging methods. Diffusion-weighted imaging (DWI) plays an important role, and apparent diffusion coefficient (ADC) value is a unique quantitative parameter in the research of cervical cancer. Methods: In this prospective study, a total of 273 patients diagnosed with stage IB1 to IIIC1 cervical cancer based on the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging guidelines who underwent pelvic 3.0T magnetic resonance imaging (MRI), including MRI and DWI, were enrolled, and the diagnostic value of preoperative staging of cervical cancer was compared between the MRI and DWI groups. The DWI group was used to explore the potential association of mean ADC (ADCmean) with different pathological characteristics and receiver operating characteristic (ROC) curves of ADCmean generated to predict the appropriate postoperative supplementary therapy. Results: The diagnostic coincidence rate of DWI was higher than that of MRI in preoperative staging of cervical cancer (χ2, P<0.05) and determined as stages IB1 + IB2 + IIA1 (90.91%), IB3 + IIA2 (93.48%), and IIIC1p (95.16%). The DWI staging results were consistent with postoperative pathological staging (Kappa value =0.865, P<0.001). We observed significant differences in ADCmean values in relation to pathological type, histological grade, depth of stromal infiltration, tumor diameter, lymphovascular invasion, and pelvic lymph node metastasis of cervical cancer (all P<0.05). The area under the ROC curve (AUC) was 0.815, with the best predictive value for postoperative supplementary therapy in cervical cancer (sensitivity 80.0%, specificity 74.0%) at ADCmean of 0.910×10-3 mm2/s. Conclusions: The DWI is a useful tool for preoperative evaluation of cervical cancer. In local cervical lesions, ADCmean varies in relation to different clinicopathological characteristics and a reference index of <0.910×10-3 mm2/s can be effectively applied to predict the need for postoperative supplementary therapy.