Impact of the universal health insurance benefits on cervical cancer mortality in Colombia.

BACKGROUND: Cervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012. METHODS: We accessed 24,491 cervical cancer mortality records for 2006-2020 from the vital statistics of Colombia's National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013-2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods. RESULTS: The contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%; P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC - 0.29%; P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%; P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes. CONCLUSION: Improvement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.

Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes.

Background: Cervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women's lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism. Methods: Transcriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively. Results: A prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors. Conclusion: The aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients' prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy.

Clinical Outcomes and Prognostic Factors in Stage III C Cervical Cancer Patients Treated with Radical Radiotherapy or Radiochemotherapy.

Objective: Since the update of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria, there have been few reports on the prognosis of stage III C cervical cancer. Moreover, some studies have drawn controversial conclusions, necessitating further verification. This study aims to evaluate the clinical outcomes and determine the prognostic factors for stage III C cervical cancer patients treated with radical radiotherapy or radiochemotherapy. Methods: The data of 117 stage III C cervical cancer patients (98 III C1 and 19 III C2) who underwent radical radiotherapy or radiochemotherapy were retrospectively analyzed. We evaluated 3-year overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Prognostic factors were analyzed using the Log-rank test and Cox proportional hazard regression model. The risk of para-aortic lymph node metastasis (LNM) in all patients was assessed through Chi-squared test and logistic regression analysis. Results: For stage III C1 and III C2 patients, the 3-year OS rates were 77.6% and 63.2% (P = .042), and the 3-year DFS rates were 70.4% and 47.4% (P = .003), respectively. The pretreatment location of pelvic LNM, histological type, and FIGO stage was associated with OS (P = .033, .003, .042, respectively); the number of pelvic LNM and FIGO stage were associated with DFS (P = .015, .003, respectively). The histological type was an independent prognostic indicator for OS, and the numbers of pelvic LNM and FIGO stage were independent prognostic indicators for DFS. Furthermore, a pelvic LNM largest short-axis diameter ≥ 1.5 cm and the presence of common iliac LNM were identified as high-risk factors influencing para-aortic LNM in stage III C patients (P = .046, .006, respectively). Conclusions: The results of this study validated the 2018 FIGO staging criteria for stage III C cervical cancer patients undergoing concurrent chemoradiotherapy. These findings may enhance our understanding of the updated staging criteria and contribute to better management of patients in stage III C.

Total hysterectomy versus radical hysterectomy in neuroendocrine cervical cancer: a SEER-database analysis.

PURPOSE: We conducted this study to evaluate the efficacy of total hysterectomy versus radical hysterectomy in the treatment of neuroendocrine cervical cancer (NECC). METHODS: Eligible NECC patients were identified from the Surveillance, Epidemiology and End Results (SEER) database. Demographic characteristics, clinical treatment and survival of the patients were collected. The overall survival (OS) and cancer-specific survival (CSS) were estimated by Kaplan-Meier analysis with log-rank test. RESULTS: A total of 286 patients were included, with 104 patients undergoing total hysterectomy and 182 patients undergoing radical hysterectomy. The 5-year OS were 50.8% in the total hysterectomy group and 47.5% in the radical hysterectomy group (p = 0.450); and the corresponding 5-year CSS were 51.6% and 49.1% (p = 0.494), respectively. Along with surgery, radiotherapy was given to 49.0% of patients in the total hysterectomy group and 50.5% in the radical hysterectomy group; and chemotherapy was administered to 77.9% of patients in the total hysterectomy group and 85.7% in the radical hysterectomy group. Unexpectedly, in patients who received adjuvant radiotherapy with or without chemotherapy, the OS was superior in the total hysterectomy group compared with the radical hysterectomy group (p = 0.034). While in patients who received chemotherapy alone and those who received neither radiotherapy nor chemotherapy, the OS still remained comparable between the total hysterectomy and radical hysterectomy group. CONCLUSION: Compared with radical hysterectomy, total hysterectomy was not associated with compromised survival prognosis in patients with NECC. Total hysterectomy has the potential to be a surgical alternative in the multimodal management of NECC.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer.

BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

Assessment of secular trends of three major gynecologic cancers burden and attributable risk factors from 1990 to 2019: an age period cohort analysis.

BACKGROUND: This study aims to assess the long-term trends in the burden of three major gynecologic cancers(GCs) stratified by social-demographic status across the world from 1990 to 2019. To assess the trends of risk factor attributed mortality, and to examine the specific effects of age, period, cohort behind them in different regions. METHODS: We extracted data on the mortality, disability-adjusted life years(DALYs), and age-standardized rates(ASRs) of cervical cancer(CC), uterine cancer(UC), and ovarian cancer(OC) related to risks from 1990 to 2019, as GCs burden measures. Age-period-cohort analysis was used to analyze trends in attributable mortality rates. RESULTS: The number of deaths and DALYs for CC, UC and OC increased since 1990 worldwide, while the ASDRs decreased. Regionally, the ASDR of CC was the highest in low SDI region at 15.05(11.92, 18.46) per 100,000 in 2019, while the ASDRs of UC and OC were highest in high SDI region at 2.52(2.32,2.64), and 5.67(5.16,6.09). The risk of CC death caused by unsafe sex increased with age and then gradually stabilized, with regional differences. The period effect of CC death attributed to smoking showed a downward trend. The cohort effect of UC death attributed to high BMI decreased in each region, especially in the early period in middle, low-middle and low SDI areas. CONCLUSIONS: Global secular trends of attributed mortality for the three GCs and their age, period, and cohort effects may reflect the diagnosis and treatment progress, rapid socioeconomic transitions, concomitant changes in lifestyle and behavioral patterns in different developing regions. Prevention and controllable measures should be carried out according to the epidemic status in different countries, raising awareness of risk factors to reduce future burden.

Neoadjuvant chemotherapy followed by surgery versus concurrent chemoradiotherapy in patients with stage IIB cervical squamous cell carcinoma: a retrospective cohort study.

PURPOSE: This study aims to compare treatment outcomes between neoadjuvant chemotherapy (NACT) followed by surgery and concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: We conducted a retrospective cohort study involving patients with stage IIB CSCC treated at Guangxi Medical University Cancer Hospital between June 2012 and June 2019. We compared overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) between the NACT + surgery and CCRT groups. RESULTS: A total of 257 patients were enrolled: 165 underwent NACT + surgery and 92 received CCRT. Before propensity score matching, the NACT + surgery group exhibited lower 5-year OS (68.2% vs. 85.6%; hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.26-4.96; P = 0.009), LRFS (85.2% vs. 96.9%; HR = 5.88, 95% CI: 1.33-25.94; P = 0.019), and DMFS (81.9% vs. 97.4%; HR = 6.65, 95% CI: 1.51-29.23; P = 0.012) compared to the CCRT group. After propensity score matching, OS, LRFS, and DMFS remained worse in the NACT + surgery group compared to the CCRT group. CONCLUSION: NACT followed by surgery is associated with decreased OS, LRFS, and DMFS compared to CCRT among patients with stage IIB CSCC.

A novel prognostic biomarker in progression free survival for patients with cervical cancer, glucose to c-reactive protein ratio (GCR).

BACKGROUND: Cervical cancer is a tumor with high morbidity and mortality. The importance of inflammatory and metabolic parameters affecting progression-free survival (PFS) and overall survival (OS) has been investigated more intensively recently. We aimed to investigate the effect of glucose/c-reactive protein (CRP) ratio [GCR], which shows these two parameters together, on PFS in cervical cancer. METHODS: We retrospectively included 90 patients with adenocarcinoma and squamous cell carcinoma of the cervix. The effects of clinical variables, inflammatory and glycemic parameters on PFS and OS were analyzed by Kaplan-Meier method. The data were compared with the healthy control group of 90 individuals using the independent t test. The effect of parameters on mortality was analyzed using ROC curves and cut off values were determined. RESULTS: Glucose, CRP, CRP/lymphocyte ratio (CLR) and GCR were statistically significant in predicting mortality (p < 0.05). Disease stage, glucose, CRP, CLR and GCR were associated with overall survival. CRP, CLR and GCR were associated with progression-free survival (p < 0.05). In multivariate analysis, GCR was prognostic for PFS (p = 0.025). GCR was statistically significant while compared with the patient and healthy control group (p < 0.001). CONCLUSION: In cervical cancer, GCR rate was found to be prognostic independent of stage. Higher GCR rate was associated with longer PFS duration.

TPP1 is associated with risk of advanced precursors and cervical cancer survival.

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P<0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.

Outcomes of minimal access retroperitoneal para-aortic lymphadenectomy in patients with locally advanced cervical cancer.

BACKGROUND: To evaluate outcomes of laparoscopic retroperitoneal para-aortic lymphadenectomy for stage 1b3-3b cervical cancer. METHODS: Pathology databases searched for all para-aortic lymphadenectomy cases 2005-2016. Descriptive statistics were used to analyse baseline characteristics, cox models for treatment affect after accounting for variables, and Kaplan Meier curves for survival (STATA v15). RESULTS: 191 patients had 1b3-3b cervical cancer of which 110 patients had Para-aortic lymphadenectomy. 8 (7.3%) patients stage 1b3, 82 (74.6%) stage 2b, and 20 (18.1%) stage 3b cervical cancer. Mean lymph node count 11.7 (SD7.6). The intra-operative and post-operative 30 day complication rates were 8.8% (CI: 4.3%, 15.7%) and 5.3% (CI: 1.9%, 11.2%) respectively.Para-aortic nodes were apparently positive on CT/MRI in 5/110 (5%) cases. Cancer was found in 10 (8.9%, CI: 4.3%, 15.7%) cases on histology, all received extended field radiotherapy. Only 2 were identified on pre-operative CT/MRI imaging. 3 of 10 suspected node-positive cases on CT/MRI had negative histology. Para-aortic lymphadenectomy led to alteration in staging and radiotherapy management in 8 (8%, CI: 3.7%, 14.6%) patients. Mean overall survival 42.81 months (SD = 31.79 months). Survival was significantly higher for women undergoing PAN (50.57 (SD 30.7) months) compared to those who didn't (31.27 (SD 32.5) months). CONCLUSION: Laparoscopic retroperitoneal para-aortic lymphadenectomy is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.

We evaluated outcomes for patients with stage 1b3-3b cervical cancer that had lymph nodes removed prior to planning their chemoradiotherapy. There were 3 groups ­ patients that had their lymph nodes removed, those that did not and those that had their procedure abandoned so didn't have their lymph nodes removed. We looked at the lymph nodes down the microscope to see if they contained cancer and compared this to their pre-operative imaging. 8 patients had a change to their staging and treatment because they were found to have cancer in the lymph nodes. We found that the keyhole procedure to remove lymph nodes is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.

[Establishment of a prognostic nomogram and discussion on optimal treatment for cervical adenocarcinoma:a retrospective study based on SEER database and Chinese single-center data].

Objective: To establish and validate a predicting nomogram for cervical adenocarcinoma based on surveillance, epidemiology and end results (SEER) database and Chinese single-center data, and to explore the optimal treatment for cervical adenocarcinoma. Methods: This study selected 2 478 cervical adenocarcinoma patients from the SEER database as the training cohort, and 195 cervical adenocarcinoma patients from Cancer Hospital of Dalian University of Technology, Liaouing Cancer Hospital and Institute as an external validation cohort. Clinicopathological information and follow-up data of the two cohorts were collected. The radiotherapy group was defined as receiving comprehensive treatment based on concurrent chemoradiotherapy after initial diagnosis, while the surgery group was defined as receiving comprehensive treatment based on radical surgery. Log-rank test and cox regression were used to evaluate factors affecting the prognosis of cervical adenocarcinoma patients. A nomogram was drawn to predict the 3-year and 5-year overall survival rates of cervical adenocarcinoma patients, and then internal validation of the training cohort from SEER database and external validation of the hospital cohort were conducted. Results: (1) In the SEER database training cohort, there were 385 patients (15.54%, 385/2 478) in the radiotherapy group and 2 093 patients (84.46%, 2 093/2 478) in the surgery group. Overall survival time of the radiotherapy group was (55.8±51.3) months, while that of the surgery roup was (94.4±61.7) months, the difference between the two groups was statistically significant (χ2=256.44, P<0.001). Log-rank test showed that age, marital status, maximum of tumor diameters, pathological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and treatments were all significant factors affecting the overall survival time of cervical adenocarcinoma patients (all P<0.001). Multivariate Cox regression analysis showed that elder (>50 years old), single status, huge tumors (>4 cm), high pathological grades (G2, G3), and advanced FIGO stages (≥Ⅱa2 stage) were independent risk factors for the overall survival time of cervical adenocarcinoma patients (all P<0.05); compared with radiotherapy, surgery was a protective factor for the prognosis of cervical adenocarcinoma patients (HR=0.619, 95%CI: 0.494-0.777; P<0.001). Further analysis of locally advanced stage and Ⅲc stage of patients showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm (HR=0.414, 95%CI: 0.182-0.942; P=0.036) in locally advanced stage and Ⅲc T1 to T2 stage (HR=0.473, 95%CI: 0.307-0.728; P=0.001). (2) The external validation cohort consisted of 39 patients (20.00%, 39/195) in the radiotherapy group and 156 patients (80.00%, 156/195) in the surgery group. The overall survival time of patients in the radiotherapy group was (51.7±34.3) months, while that of the surgery group was (63.1±26.6) months (χ2=28.41, P<0.001). Further analysis was conducted on locally advanced stage and Ⅲc stage patients, and multivariate Cox regression analysis was performed after propensity score matching, which showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm in locally advanced stage (HR=0.141, 95%CI: 0.023-0.843; P=0.032) and Ⅲc T1 to T2 stage (HR=0.184, 95%CI: 0.036-0.947; P=0.043). (3) Establishment and internal and external validation of nomogram: based on the six factors screened out by the multivariate Cox regression model, the nomogram was developed to predict the prognosis of cervical adenocarcinoma patients. The consistency index of the internal and external validation were 0.801 and 0.766, respectively, and the calibration curves matched well with the ideal fitting line. Conclusions: The key to the treatment of cervical adenocarcinoma is to prioritize radical surgery for patients with conditions for radical tumor resection. Compared with concurrent chemoradiotherapy, patients with locally advanced stages (Ⅰb3, Ⅱa2), and Ⅲc (T1, T2) stages cervical adenocarcinoma could benefit from comprehensive treatment based on radical surgery. The nomogram of this study has been validated internally and externally, and show good survival prediction efficacy for cervical adenocarcinoma patients.

Comparison of Clinicopathological and Prognostic Characteristics Between Minimal Deviation Adenocarcinoma and Gastric-type Endocervical Adenocarcinoma.

BACKGROUND/AIM: Minimal deviation adenocarcinoma (MDA) is an extremely well-differentiated variant of gastric-type endocervical adenocarcinoma (GEA). This study compared the clinicopathological and prognostic characteristics of MDA to those of GEA. PATIENTS AND METHODS: Nine MDAs and 22 GEAs were included in this study. We reviewed electronic medical records and pathology slides to collect clinicopathological and prognostic information. RESULTS: GEA showed significantly higher stage at presentation, more frequent parametrial extension and lymphovascular space invasion, and recurrence than MDA. Patients with GEA had significantly lower survival rates than those with MDA. None of the cases with MDA exhibited singly dispersed or clustered tumor cells, diffuse stromal desmoplasia, severe nuclear pleomorphism, loss of nuclear polarity, or coarse chromatin, all of which were frequently observed in GEA. CONCLUSION: Significant differences were observed in the clinicopathological characteristics and patient outcomes between MDA and GEA. Further investigations using a larger cohort are warranted to determine the clinical behavior and aggressiveness of MDA.

A novel prognostic signature based on cancer stemness and metabolism-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma.

BACKGROUND: CESC is the second most commonly diagnosed gynecological malignancy. Given the pivotal involvement of metabolism-related genes (MRGs) in the etiology of multiple tumors, our investigation aims to devise a prognostic risk signature rooted in cancer stemness and metabolism. METHODS: The stemness index based on mRNA expression (mRNAsi) of samples from the TCGA dataset was computed using the One-class logistic regression (OCLR) algorithm. Furthermore, potential metabolism-related genes related to mRNAsi were identified through weighted gene co-expression network analysis (WGCNA). We construct a stemness-related metabolic gene signature through shrinkage estimation and univariate analysis, thereby calculating the corresponding risk scores. Moreover, we selected corresponding DEGs between groups with high- and low-risk score and conducted routine bioinformatic analyses. Furthermore, we validated the expression of four hub genes at the protein level through immunohistochemistry (IHC) in samples obtained from our patient cohort. RESULTS: According to the findings, it was found that six genes-AKR1B10, GNA15, ALDH1B1, PLOD2, LPCAT1, and GPX8- were differentially expressed in both TCGA-CSEC and GEO datasets among 23 differentially expressed metabolism-related genes (DEMRGs). mRNAsi exhibited a notable association with the extent of key oncogene mutation. The results showed that the AUC values for forecasting survival at 1, 3, and 5 years are 0.715, 0.689, and 0.748, individually. We observed a notable association between the risk score and different immune cell populations, along with enrichment in crucial signaling pathways in CESC. Four genes differentially expressed between different risk score groups were validated by IHC to be highly expressed in the CESC samples at the protein level. CONCLUSION: The current investigation indicated that a 3-gene signature based on stemness-related metabolic and 4 hub genes with differential expression between high and low-risk score subgroups may serve as valuable prognostic markers and potential therapeutic targets in CESC.

Comparison of outcomes between early-stage cervical cancer patients without high-risk factors undergoing adjuvant concurrent chemoradiotherapy and radiotherapy alone after radical surgery.

PURPOSE: For patients with early-stage cervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. PATIENTS AND METHODS: The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. RESULTS: A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rates were 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. CONCLUSION: There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.

Construction and efficacy test of a survival prediction model for locally advanced cervical cancer based on anti-angiogenesis.

OBJECTIVE: This study aimed to develop and evaluate an anti-angiogenesis-based model for predicting the survival and the potential benefits of targeted therapy for patients with localized advanced cervical cancer. METHODS: We collected clinical data from 163 patients with cervical cancer who received paclitaxel and cisplatin (TP) or TP plus bevacizumab during or after radiotherapy from June 2017 to February 2023. We analyzed the clinical measures of recent efficacy and overall survival (OS) using univariate and logistic multivariate and Cox regression methods, respectively. We constructed a nomogram model and evaluated its efficacy using the c-index, the area under the curve (AUC), a calibration curve, and the clinical decision curve (DCA). RESULTS: We found that targeted agents and hemoglobin were independent determinants of near-term efficacy (P < 0.05), while targeted agents and stage were independent factors of OS (P < 0.05). We developed a predictive model for an OS prognostic nomogram and performed internal validation 1000 times using the Bootstrap re-sampling method. The c-index was 0.81, and the AUC was 0.84 (P < 0.01).The calibration curves showed a good agreement between the projected and actual values. The DCA curve indicated that the model had a high positive predictive accuracy. CONCLUSION: We developed a novel anti-angiogenesis-based survival prediction model for patients with locally advanced cervical cancer. This model could estimate the benefit of targeted therapy before treatment, and it had good validation.

Meta-analysis of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer.

BACKGROUND: Neither improvements in surgical techniques and methods nor advances in radiotherapy equipment and techniques have significantly improved cervical cancer survival rates for quite some time. AIM: By comparing the effectiveness of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer, this study aimed to explore effective treatment methods for locally advanced cervical cancer, and provide a theoretical basis to guide clinical practice. METHODS: A search of PubMed, Embase, Scopus, Web of Science and Cochrane databases was undertaken to identify randomized controlled trials on the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer, where the intervention in the experimental group was neoadjuvant chemotherapy. Based on the inclusion and exclusion criteria, the studies were evaluated for quality according to the Cochrane Quality Rating Scale. Baseline information, intervention information and outcome indicators of the included studies were extracted. Meta-analysis was performed using RevMan 5.4. RESULTS: Significant differences in overall survival [relative risk (RR) 1.63, 95 % confidence interval (CI) 0.69-2.57; p = 0.0007] and complete remission rate (RR 0.37, 95 % CI -0.49 to 1.23; p = 0.041) were found between the two groups. Heterogeneity of the objective response rate showed p < 0.0001 and I2 = 99 % (I2 = 99 > 50 % and p > 0.1 for the Q-test suggested strong heterogeneity). The fixed effects model was chosen for the integration statistic [standardized mean difference (SMD) 0.81, 95 % CI -0.21 to 1.83; p = 0.12]; the difference was not significant (p > 0.05). Heterogeneity of the adverse effects of neoadjuvant chemotherapy showed p < 0.0001 and I2 = 98 % (I2 = 98 %>50 % and p > 0.1 for the Q-test suggested strong heterogeneity). The fixed effects model was chosen for the integration statistic (SMD -0.023, 95 % CI -0.95 to 0.49; p = 0.53); the difference was not significant (p > 0.05). CONCLUSIONS: The use of neoadjuvant chemotherapy for the treatment of locally advanced cervical cancer improved the objective response rate and the complete remission rate of patients, but failed to improve overall survival and adverse effects.

RECIST 1.1 versus clinico-radiological response assessment for locally advanced cervical cancer: implications on interpreting survival outcomes of future trials.

OBJECTIVE: To investigate differences in standard clinico-radiological evaluation versus Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for reporting survival outcomes in patients with locally advanced cervical cancer treated with chemoradiation and brachytherapy. METHODS: Between November 2017 and March 2020, patients recruited in cervical cancer trials were identified. MRI at diagnosis and at least one follow-up imaging was mandatory. Disease-free survival and progression-free survival were determined using standard evaluation (clinical examination and symptom-directed imaging) and RECIST 1.1. Agreement between criteria was estimated using κ value. Sensitivity analysis was done to test the sensitivity, specificity, and accuracy of RECIST 1.1 in detecting response to treatment. RESULTS: Sixty-nine eligible patients had at least one target lesion. Thirty-three patients (47.8%) had pathological lymph nodes. Of these 33 patients, RECIST 1.1 classified only 18% (6/33) as 'target nodal lesions' and the remaining nodes as 'non-target'. There were 6 (8.7%) and 8 (11.6%) patients with disease events using RECIST 1.1 and standard evaluation, respectively. The disease-free survival at 12, 18, and 24 months using RECIST 1.1 was 94.2%, 91.2%, 91.2%, and with standard evaluation was 94.2%, 89.7%, and 88.2%, respectively (p=0.58). Whereas, progression-free survival at 12, 18, and 24 months using RECIST 1.1 and standard evaluation were same (94.2%, 91.2%, and 91.2%, respectively). The κ value was 0.84, showing strong agreement in assessing disease-free survival, although an absolute difference of 3% between endpoint assessment methodologies. RECIST 1.1 had a sensitivity of 75% (95% CI 34.91% to 96.81%), specificity of 100% (95% CI 94.13% to 100%), and accuracy of 97.1% (95% CI 89.92% to 99.65%). CONCLUSIONS: The study showed 1.5% and 3% difference in disease-free survival at 18 and 24 months and no difference in progression-free survival between RECIST 1.1 and standard evaluation in a patient cohort with low event rate.

[18F]FDG-PET/CT-based risk stratification in women with locally advanced uterine cervical cancer.

BACKGROUND: [18F]FDG-PET/CT is used for staging and treatment planning in patients with locally advanced cervical cancer (LACC). We studied if a PET-based prediction model could provide additional risk stratification beyond International Federation of Gynaecology and Obstetrics (FIGO) staging in our population with LACC to aid treatment decision making. METHODS: In total, 183 patients with LACC treated with chemoradiation between 2013 and 2018 were included. Patients were treated according to FIGO 2009 and retrospectively reclassified according to FIGO 2018 staging system. After validation of an existing PET-based prediction model, the predicted recurrent free survival (RFS), disease specific survival (DSS) and overall survival (OS) at 1, 3, and 5 years, based on metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and highest level of [18F]FDG-positive node was calculated. Then the observed survival was compared to the predicted survival. An area under the curve (AUC) close to or higher than 0.7 was considered adequate for accurate prediction. The Youden (J) index defined survival chance cutoff values for low and high risk groups. RESULTS: All AUC values for the comparison between predicted and observed outcomes were > 0.7 except for 5-year RFS and for 5-year OS which were close to 0.7 (0.684 and 0.650 respectively). Cutoff values for low and high risk survival chance were 0.44 for the 3-year RFS and 0.47 for the 5-year OS. The FIGO 2009 system could not differentiate between the risk profiles. After reclassification according to FIGO 2018, all patients with stage IIIC2 and IVB fell in the high risk and almost all patients with stages IB2-IIIB and IVA in the low risk group. In patients with stage IIIC1 disease the FIGO stage cannot discriminate between the risk profiles. CONCLUSIONS: Low and high risk patients with LACC can be identified with the PET-based prediction model. In particular patients with stage IIIC1 need additional risk stratification besides the FIGO 2018 staging. The Kidd model could be a useful tool to aid treatment decision making in these patients. Our results also support the choice of [18F]FDG-PET/CT imaging in patients with LACC.

MRI-based volumetric tumor parameters before and during chemoradiation predict tumor recurrence and patient survival in locally advanced cervical cancer: a subgroup analysis of a phase II prospective trial.

BACKGROUND: This subgroup analysis of a prospective phase II trial aimed to identify valuable and accessible prognostic factors for overall survival (OS) and progression-free survival (PFS) of patients with locally advanced cervical cancer (LACC). METHODS: Patients with FIGO II to IVA cervical cancer were assessed in this study. All patients underwent concurrent chemoradiotherapy (CCRT) followed by brachytherapy. Tumor parameters based on MRI scans before and during CCRT were evaluated for Overall survival (OS) and Progression-free survival (PFS). RESULTS: A total of 86 patients were included in this analysis with a median follow-up period of 31.7 months. Three-year OS and PFS rates for all patients were 87.1% and 76.5%, respectively. Univariate Cox regression analysis showed that restaging tumor size (rTS) over 2.55 cm (p < 0.001), initial tumor volume (iTV) over 55.99 cc (p < 0.001), downstaging (p = 0.042), and restaging tumor volume (rTV) over 6.25 cc (p = 0.006) were significantly associated with OS. rTS (p < 0.001), iTV (p < 0.001), downstaging (p = 0.027), and rTV (p < 0.001) were identified as significant prognostic factors for PFS. In the stepwise multivariable analysis, only rTS > 2.55 cm showed statistically significant with OS (HR: 5.47, 95% CI 1.80-9.58, p = 0.035) and PFS (HR: 3.83, 95% CI 1.50-11.45; p = 0.025). CONCLUSIONS: Initial tumor size and restaging tumor volume that are easily accessible during radiotherapy provide valuable prognostic information for cervical cancer. MRI-based measurable volumetric scoring system can be readily applied in real-world practice of cervical cancer. CLINICAL TRIAL INFORMATION: This study is a subgroup analysis of prospective trial registered at ClinicalTrials.gov Identifier: NCT02993653.

Characteristics, treatment patterns, and outcomes in patients with high-risk locally advanced cervical cancer.

OBJECTIVE: To characterize the real-world treatment patterns and outcomes of patients with high-risk locally advanced cervical cancer (HR-LACC). METHODS: This retrospective study identified and randomly selected adults diagnosed between 2010 and 2018 from the ConcertAI Oncology Dataset. For patients initially treated with concurrent chemoradiotherapy (CCRT), we estimated real-world progression-free survival (rwPFS) among those with persistent disease, real-world time on CCRT, and recurrence-free survival (rwRFS) using Kaplan-Meier methods. RESULTS: The cohort included 300 patients. Median age at diagnosis was 51 years. 53.7 % were White and 30.0 % were Black; 52.0 % were premenopausal; 89.3 % had squamous cell histology; 75.3 % had stage III disease, and 92.7 % had no evidence of performance status impairment. Initial treatment included CCRT (N = 229), surgery (N = 28), antineoplastics only (N = 11), and radiation only (N = 5). Twenty-seven patients were untreated. Baseline characteristics for the CCRT-first patients were similar to the overall cohort; their median real-world time on treatment was 1.6 months; 78.2 % received cisplatin for a median of 1.2 months; 28.4 % received antineoplastics after CCRT, and 11.8 % initiated a second antineoplastic therapy. Of the CCRT-first patients, 27/143 with a complete response had subsequent recurrent disease (median rwRFS not reached). 179 patients had persistent disease, among whom median (95 % confidence interval [CI]) rwPFS was 29.7 (16.9-59.3) months. CONCLUSION: In this study of United States-based clinical practices, most HR-LACC patients received CCRT as initial treatment. Many patients developed persistent disease after CCRT indicating a need for improved first treatment and maintenance options.