The latest medical research on Ovarian Cancer
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Request AccessThe effectiveness of CA125 and HE4 as clinical prognostic markers in epithelial ovarian cancer patients with BRCA mutation.
Ovarian CancerTo investigate the efficacy of cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in predicting survival outcomes based on breast cancer gene (BRCA) mutational status in epithelial ovarian cancer.
Medical records of 448 patients diagnosed with epithelial ovarian cancer at a single tertiary institution in Korea were retrospectively analyzed. Area under the curve, sensitivity, specificity, and accuracy were assessed using the CA125 and HE4 values after surgery and 3 cycles of chemotherapy to predict 1-year survival based on the BRCA mutational status. Kaplan-Meier analysis was used to obtain progression-free and overall survival to evaluate CA125 and HE4 effectiveness in predicting survival outcomes.
A total of 423 patients were analyzed, including 180 (42.6%) who underwent interval debulking surgery (IDS) and 243 (57.4%) who underwent primary debulking surgery (PDS). BRCA mutations were observed in 37 (15.2%) and 44 (22.4%) patients in the PDS and IDS groups, respectively. CA125 and HE4 normalization demonstrated the highest specificity in patients with or without BRCA mutations, with specificities of 97.1% and 99.1% in the PDS group and 78.6% and 86.2% in the IDS group, respectively. Normalizing HE4 alone may be an effective prognostic marker, with an area under the curve of 0.774 and specificity of 75.0%, in patients with BRCA mutations.
Normalizing both biomarkers emerged as the most effective predictive marker for the 1-year recurrence rate, regardless of BRCA mutational status. A negative HE4 value can be a useful predictor for 1-year recurrence-free survival in patients with BRCA mutations.
Cost-effectiveness analysis of single-dose or 2-dose of bivalent, quadrivalent, or nonavalent HPV vaccine in a low/middle-income country setting.
Ovarian CancerTo compare the health impact and economic benefits among individuals who did not receive the human papillomavirus (HPV) vaccine to those who received a single dose, or 2 doses. The comparison was stratified by 4 types of vaccine in conjunction with primary HPV screening in a low/middle-income country setting.
A Markov model was employed to simulate HPV infection and cervical cancer in a cohort of 100,000 12-year-old girls free of HPV. The study scrutinized 9 strategies: 1 dose and 2 doses of 2vHPV (Cervarix®), 2vHPV (Cecolin®), 4vHPV (Gardasil®), 9vHPV vaccine (Gardasil9®), and no vaccination. The primary outcome measure was the quality-adjusted life year (QALY) of each strategy. Incremental cost-effectiveness ratios were estimated over a lifetime horizon, accompanied by sensitivity analyses conducted.
All vaccination programs yielded 41,298-71,057 QALYs gained accompanied by cost savings of 14,914,186-19,821,655 USD compared to no vaccination. Administering 2 doses of 9vHPV vaccine emerged as the most cost-effective strategy, boasting 406 USD/QALY, within a lower willingness to pay threshold. Sensitivity analysis demonstrated an 80% probability of the cost-effectiveness of the 2 doses of 9vHPV vaccine regimen. Furthermore, uncertainty around the costs of vaccination and vaccine efficacy exerted the most substantial influence on the cost-effectiveness findings.
Oping for 2 doses of 9vHPV vaccine in conjunction with a primary HPV screening represents the most cost-effective option for implementing a school-based HPV vaccination program targeting 12-year-old girls in Thailand. Such findings provide valuable insights for policymakers in the realm of cervical cancer prevention.
LncRNA STARD7-AS1 suppresses cervical cancer cell proliferation while promoting autophagy by regulating miR-31-5p/TXNIP axis to inactivate the mTOR signaling.
Ovarian CancerCervical cancer (CC) is a serious gynecologic health issue for women worldwide. Long non-coding RNA (lncRNA) has been well-documented in controlling malignant behavior of various cancer cells. The role of lncRNA STARD7-AS1 in regulating CC cell proliferation and autophagy and its possible mechanism were investigated in this work.
RNA expression and protein levels were quantified by reverse transcription quantitative polymerase chain reaction and western blotting. The location of STARD7-AS1 in CC cells was examined using subcellular fraction assays. Cell Counting Kit-8 assays and colony forming assays were performed to measure CC cell viability and proliferation. Autophagy in CC cells was evaluated using macrophage-derived chemokine (MDC) staining and transmission electron microscopy. The binding between microRNA (miR)-31-5p and STARD7-AS1 (or thioredoxin-interacting protein [TXNIP]) was determined by performing luciferase reporter, RNA pull-down or RNA immunoprecipitation assays.
STARD7-AS1 overexpression significantly suppressed CC cell viability and proliferation while notably inducing autophagy. STARD7-AS1 upregulated TXNIP expression via interaction with miR-31-5p. In addition, the effects of STARD7-AS1 on CC cell proliferation and autophagy were reversed by TXNIP silencing. The suppressive effect of STARD7-AS1 overexpression on phosphorylated levels of mTOR and S6K1 was countervailed by TXNIP deficiency.
In conclusion, lncRNA STARD7-AS1 inhibits CC cell proliferation and promotes cell autophagy by targeting the miR-31-5p/TXNIP axis to inactivate the mTOR signaling.
Efficacy and safety of combined anlotinib-oral etoposide treatment for patients with platinum-resistant ovarian cancer.
Ovarian CancerDespite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC.
Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed.
Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1-68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9-100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3-11.6). The incidence of adverse events (any grade) was 100%, and the incidence of grade 3-4 adverse events was 54.5%.
Anlotinib combined with etoposide emerged effective for the treatment of PROC.
Comprehensive characterization of genomic features and clinical outcomes following targeted therapy and secondary cytoreductive surgery in OCCC: a single center experience.
Ovarian CancerOvarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS).
We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available.
64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage. Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progression-free survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0-16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%.
Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.
QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.
Ovarian CancerQL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.
SLAMF7 predicts prognosis and correlates with immune infiltration in serous ovarian carcinoma.
Ovarian CancerSignaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC).
The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA).
SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cell-specific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001).
SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC. Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.
Cost-effectiveness of atezolizumab plus chemotherapy for advanced/recurrent endometrial cancer.
Ovarian CancerThis study assessed the cost-effectiveness of atezolizumab in combination with chemotherapy for patients with advanced or recurrent endometrial cancer (EC) from the U.S. payer's perspective.
A cost-effectiveness study was conducted using a Markov model based on ENGOT-en7/MaNGO/AtTEnd clinical trials. The population consisted of patients with EC, stratified by mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) subgroups. The model simulated patients receiving either atezolizumab plus chemotherapy or chemotherapy alone. Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated using a Willingness-to-Pay (WTP) threshold of $150,000/QALY. Sensitivity analyses were performed.
Adding atezolizumab to chemotherapy in dMMR EC resulted in an incremental gain of 3.31 QALYs but at an additional cost of $855,042, leading to an ICER of $258,391.07/QALY compared to chemotherapy alone. In pMMR EC, there was a gain of 0.50 QALYs with an additional cost of $140,502, resulting in an ICER of $279,239.72/QALY. The overall ICER for EC was $216,459.34/QALY. Scenario analysis indicated that administering atezolizumab for a maximum of 2 years improved cost-effectiveness in dMMR EC, with an ICER of $70,695.96/QALY falling within the predetermined WTP threshold.
For patients with advanced or recurrent EC, the combination of atezolizumab and chemotherapy may not prove cost-effective. However, administering atezolizumab for a limited period of maximum 2 years could improve cost-effectiveness in dMMR EC.
Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy.
Ovarian CancerTo investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy.
Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves.
The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890.
Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.
Cost-effectiveness of pembrolizumab plus chemotherapy for advanced endometrial cancer.
Ovarian CancerTo assess the cost-effectiveness of pembrolizumab in combination with chemotherapy compared to chemotherapy alone, based on the results of the NRG-GY018 trial, in patients with advanced or recurrent endometrial cancer (EC), stratified by mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) subgroups.
A Markov model was used to simulate patients receiving either pembrolizumab plus chemotherapy or chemotherapy alone. Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated using a willingness-to-pay (WTP) threshold of $150,000/QALY. Univariate and probabilistic sensitivity analyses were conducted to assess the robustness of our findings.
The addition of pembrolizumab to chemotherapy led to an incremental gain of 4.05 QALYs at an additional cost of $167,224, resulting in an ICER of $41,305.09/QALY compared to chemotherapy alone in dMMR EC. Additionally, there were 0.93 additional QALYs at an additional cost of $83,661, which resulted in an ICER of $90,284.80/QALY in pMMR EC. Sensitivity analyses indicated that the cost of pembrolizumab, utility of progressed disease, and utility of progression-free survival had the greatest impact on the results. Probabilistic sensitivity analysis showed that pembrolizumab was considered cost-effective at a 100% probability at a WTP threshold of $150,000 per QALY.
Pembrolizumab, when combined with chemotherapy, was found to be cost-effective compared to chemotherapy alone both for patients with advanced or recurrent dMMR and pMMR EC from the perspective of a payer in the United States.
Patient and clinician priorities for information on treatment outcomes for advanced ovarian cancer: a Delphi exercise.
Ovarian CancerPatients with advanced ovarian cancer face a range of treatment options, and there is unwarranted variation in treatment decision-making between UK providers. Decision support tools that produce data on treatment outcomes as a function of individual patient characteristics, would help both patients and clinicians to make informed, preference- and values-based choices. However, data on treatment outcomes to include in such tools are lacking.
Following a literature review, a questionnaire was designed for use in a Delphi process to establish which treatment outcomes are important to both patients and clinicians in decision-making for treatment for advanced ovarian cancer. Patient and clinician panels were established.
Following 2 Delphi rounds, consensus was achieved for 7/11 items in the patient panel and 8/11 items in the clinician panel. Consensus across both panels was achieved for inclusion of both overall survival and progression free survival as important items in the decision-making process, although there remained differences of opinion as to whether these should be presented as relative or absolute values.
Information needs for treatment decision-making in ovarian cancer differ between and within patient and clinician groups. Whilst overall survival and progression free survival are universally accepted as important data items, decision support tools will need to be nuanced to allow presentation of a range of outcomes and associated probabilities, and in a range of formats, that can be tailored to the preferences of clinician and patients.
Mirvetuximab soravtansine in platinum-resistant recurrent ovarian cancer with high folate receptor-alpha expression: a cost-effectiveness analysis.
Ovarian CancerMirvetuximab soravtansine (MIRV), a new antibody-drug conjugate, versus the investigator's choice of chemotherapy (IC) was the first treatment to demonstrate benefits for progression-free and overall survival in platinum-resistant recurrent ovarian cancer (PROC) with high folate receptor-alpha (high-FRα) expression. Efficacy, safety, and economic effectiveness make MIRV the new standard of care for these patients.
Based on patients and clinical parameters from MIRASOL (GOG 3045/ENGOT-ov55) phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost and efficacy of MIRV and IC for PROC with high-FRα expression, considering the bevacizumab-pretreated situation from the American healthcare system. Total cost, life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net health benefits were the main outcome indicators and compared with willingness-to-pay threshold of $100,000/QALY. Sensitivity and scenario analyses were conducted.
Compared with the IC, MIRV was associated with incremental costs of $538,251, $575,674, and $188,248 with the corresponding QALYs (LYs) increased by 0.90 (1.55), 1.09 (1.88), and 0.53 (0.79), leading to ICERs of $596,189/QALY ($347,995/LY), $530,061/QALY ($306,894/LY), and $1,011,310/QALY ($680,025/LY) in the overall, bevacizumab-naïve, and bevacizumab-pretreated patients, respectively. When MIRV is reduced by more than 75%, it may be a cost-effective treatment.
At the current price, MIRV for PROC with high-FRα expression is not the cost-effective strategy in the US. However, its treatment has higher health benefits in bevacizumab-naïve patients, which is likely to be an alternative.
