The latest medical research on Ovarian Cancer
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Request AccessA phase II study of induction PD-1 blockade (nivolumab) in patients with surgically completely resectable mismatch repair deficient endometrial cancer (NIVEC).
Ovarian CancerClinicalTrials.gov Identifier: NCT05795244.
This is a multicenter, single-arm phase II trial. A total of 30 surgically resectable MMRd endometrial cancer patients will be enrolled. Inclusion criteria include clinical stage I-IIIC2, tumor specimen that demonstrates MMRd by immunohistochemistry or microsatellite instability. Exclusion criteria include multiple primary cancers, residual adverse effects of prior therapy or effects of surgery. Patients are treated with nivolumab 480 mg intravenously every 4 weeks up to 6 months followed by standard surgery and/or adjuvant treatment. The primary endpoint of the study is clinical CR rate or pathological CR rate after treatment of nivolumab. Secondary endpoints include objective response rate, progression-free survival, overall survival, and adverse events. Correlative studies include genomic characterization of tumors, assessment of immune infiltration of tumor microenvironment, and serial circulating cell-free DNA and immune biomarkers.
Prognostic impact of peritoneal cytology on treating endometrial cancer using data from the Japan Society of Obstetrics and Gynecology cancer registry.
Ovarian CancerThe prognostic value and clinical usage of peritoneal cytology in endometrial cancer are uncertain. This study aimed to determine whether positive cytology is associated with the prognosis for endometrial cancer.
A Japanese nationwide retrospective registry study was conducted between 2012 and 2019. Clinicopathological data were analyzed for patients who were registered in the Japan Society of Obstetrics and Gynecology (JSOG) gynecological tumor registry and underwent initial treatment for endometrial cancer.
In total, 83,027 patients who met the inclusion criteria were identified. Data on peritoneal cytology status and overall survival (OS) were available for 74,984 and 36,995 patients, respectively. Positive peritoneal cytology was found in 11,536 (15.4%) patients. A higher proportion of patients who had positive peritoneal cytology were related to advanced stages, high-grade histology, deep myometrial invasion, lymph node (LN) metastasis, and poor risk of recurrence. After controlling for age, stage, myometrial invasion, LN metastasis, distant metastasis, and risk of recurrence, positive peritoneal cytology was associated with poor prognosis (p<0.001). Multivariate Cox regression analysis revealed that clinicopathological factors (i.e., age, International Federation of Gynecology and Obstetrics stage, histological type, myometrial invasion, LN metastasis, distant metastasis, and peritoneal cytology), including positive peritoneal cytology, were also significant prognostic factors for OS.
Positive peritoneal cytology was a prognostic factor for endometrial cancer for the JSOG gynecological tumor registry.
Different surgical methods for FIGO stage IVB cervical cancer patients receiving chemotherapy: a population-based study.
Ovarian CancerTo assess survival differences between non-extensive surgery (NES) and extensive surgery (ES) in International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer patients receiving chemotherapy from a population-based database, the Surveillance, Epidemiology and End Results.
Propensity matching was conducted to minimize heterogeneity. Survival analysis was performed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards model.
A total of 154 patients met screening criteria, among whom 84 patients (84/154) underwent NES while 70 patients (70/154) underwent ES. After matching, no survival advantage was observed in ES group compared with NES group (p=0.066; hazard ratio [HR]=1.54; 95% confidence interval [CI]=0.97-2.42). Stratified analyses suggested ES prolonged overall survival in patients with histology other than squamous cell carcinoma and adenocarcinoma (p=0.028; HR=0.36; 95% CI=0.15-0.89) and American Joint Committee on Cancer (AJCC) T stage T1 (p=0.009; HR=0.18; 95% CI=0.05-0.66). Despite no survival benefit after regional lymph node surgery (p=0.629; HR=0.88; 95% CI=0.53-1.47), subgroup analyses demonstrated that patients younger than 50 (p=0.006; HR=0.21; 95% CI=0.07-0.64), with AJCC T stage T1 (p=0.002; HR=0.09; 95% CI=0.02-0.42), T3 (p=0.001; HR=0.02; 95% CI=0.00-0.21), hematogenous metastasis (p=0.036; HR=0.27; 95% CI=0.08-0.92) and without surgery of other sites (p=0.040; HR=0.01; 95% CI=0.00-0.79) might achieve longer survival after regional lymph node surgery.
In conclusion, ES or regional lymph node surgery may provide survival advantage for certain subgroup of FIGO IVB cervical cancer patients receiving chemotherapy. However, it deserves large scale prospective clinical trials to confirm.
Toripalimab combined with bevacizumab plus chemotherapy as first-line treatment for refractory recurrent or metastatic cervical cancer: a single-arm, open-label, phase II study (JS001-ISS-CO214).
Ovarian CancerTo evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC).
Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3-28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6-95.3) and the DCR was 95.8% (95% CI=78.9-99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4-34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed.
Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative first-line treatment option for patients with R/M CC.
ClinicalTrials.gov Identifier: NCT04973904.
Gut microbiome associated with PARP inhibitor efficacy in patients with ovarian cancer.
Ovarian CancerTo investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer.
This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing.
Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11-0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016).
High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.
Current peritonectomy practice during debulking surgery in patients with newly diagnosed advanced ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 4004).
Ovarian CancerBecause of the possible therapeutic benefit of removing occult tumor cells, a source of recurrence and chemoresistance, total parietal peritonectomy (TPP) is an alternative treatment for advanced epithelial ovarian/fallopian tube/primary peritoneal cancer. Interventional studies comparing TPP with selective parietal peritonectomy (SPP) are in progress. Since surgeons skilled in TPP are essential for such trials to be conducted, this nationwide survey aimed to examine current peritonectomy practice among gynecologic oncologists in Korea.
A 17-item questionnaire, developed by a surgery committee and reviewed by the scientific review board of the Korean Gynecology Oncology Group (KGOG), was distributed to 144 KGOG members. The questionnaire was divided into 3 categories: respondent demographics, peritonectomy practice during primary debulking surgery (PDS), and peritonectomy practice during interval debulking surgery (IDS).
We received 88 (61.1%) valid responses. Of the valid respondents, 98.9% and 93.8% performed SPP during PDS and IDS, respectively. Only 4.9% of the respondents performed TPP during IDS. Most respondents performed peritonectomy in cases where optimal postoperative outcomes were expected. Approximately 50.6% of the respondents had performed peritonectomy independently, while the others did so in cooperation with non-gynecologic surgeons. The primary reasons for not performing TPP were concerns about morbidity and uncertainty about the clinical benefits of the procedure.
SPP is the predominant technique used in both PDS and IDS in Korea. A small percentage (4.9%) of gynecologic oncologists have performed TPP during IDS. Accordingly, a study regarding the feasibility of TPP should be conducted before proceeding with a prospective clinical trial.
Humanized patient-derived xenograft mouse model bearing ovarian clear cell carcinoma.
Ovarian CancerThe study aimed to establish humanized patient-derived xenograft (PDX) mouse models of ovarian clear cell carcinoma (OCCC) and evaluate their therapeutic responses.
PDX models and their humanized counterparts (CD34+ humanized PDX models) derived from the same tumor source were developed, and the therapeutic responses were compared between the models.
Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor significantly reduced tumor size in traditional OCCC PDX models (p=0.021). Although differences in tumor growth between traditional PDX models and humanized PDX models were observed, they were not statistically significant (p=0.438). However, treatment effects of PI3K inhibitor differed significantly between conventional and humanized mice (p=0.006). In the Humanized PDX cohort, both programmed cell death protein-1 antibody monotherapy and PI3K inhibitor treatment slowed tumor growth relative to controls, with a synergistic effect noted during the latter part of the study, though these effects were not statistically significant.
This pioneering study successfully develop a humanized PDX model for OCCC, highlighting differential responses to treatments compared to conventional PDX models.
Clinical trial comparing the use of Orcellex® Brush versus Cervex-Brush® on vaginal vault smear cytology adequacy rate in patients treated with radiotherapy for cervical cancer.
Ovarian CancerThis study aims to evaluate and compare the Cervex-Brush® and Orcellex® Brush as sampling devices for vaginal vault smear cytology in cervical cancer patients treated primarily with radiotherapy.
A randomized crossover trial was conducted at a gynecological oncology center in Hong Kong to compare the Cervex-Brush® and Orcellex® Brush in terms of their vault smear adequacy rate in cervical cancer patients who underwent radiotherapy.
One hundred sixty cervical cancer patients treated with primary radiotherapy and undergoing follow-up surveillance by vaginal vault cytology were recruited. The smear adequacy rate was 90.6% for Cervex-Brush® and 91.9% for Orcellex® Brush. The rates of low cellularity for both brushes were similar (76.8% for Cervex-Brush® vs. 76.1% for Orcellex® Brush). The detection rates of abnormal smears were also not significantly different (2.8% for Cervex-Brush® vs. 4.2% for Orcellex® Brush). The 2 brushes were also not significantly different in terms of pain score and degree of bleeding. It was further observed that the second smear collection was more painful and patients who were on hormonal replacement therapy demonstrated less bleeding.
There was no difference between the Orcellex® brush and the Cervex-Brush® in terms of smear adequacy rate, rate of high cellularity and the detection of abnormal smears. There was also no significant difference between the 2 brushes in terms of pain and the degree of bleeding. Therefore, the Orcellex® Brush can be considered a suitable alternative sampling device for vault smear collection in patients who have undergone radiotherapy for cervical cancer.
ClinicalTrials.gov Identifier: NCT04461574.
Cost-effectiveness analysis of simple hysterectomy compared to radical hysterectomy for early cervical cancer: analysis from the GCIG/CCTG CX.5/SHAPE trial.
Ovarian CancerSHAPE (Simple Hysterectomy And PElvic node assessment) was an international phase III trial demonstrating that simple hysterectomy was non-inferior to radical hysterectomy for pelvic recurrence risk, but superior for quality of life and sexual health. The objective was to conduct a cost-effectiveness analysis comparing simple vs. radical hysterectomy for low-risk early-stage cervical cancer.
Markov model compared the costs and benefits of simple vs. radical hysterectomy for early cervical cancer over a 5-year time horizon. Quality-adjusted life years (QALYs) were estimated from health utilities derived from EQ-5D-3L surveys. Sensitivity analyses accounted for uncertainty around key parameters. Monte Carlo simulation estimated complication numbers according to surgical procedure.
Simple hysterectomy was more effective and less costly than radical hysterectomy. Average overall costs were $11,022 and $12,533, and average gains were 3.56 and 3.54 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. By year 3, these scores improved for simple hysterectomy (0.82) but not for radical hysterectomy (0.82). Assuming 800 early cervical cancer patients annually in Canada, the model estimated 3 vs. 82 patients with urinary retention, and 49 vs. 86 patients with urinary incontinence persisting 4 weeks after simple vs. radical hysterectomy, respectively. Results were most sensitive to variability in health utilities after surgery, but stable through wide ranges of costs and recurrence estimates.
Simple hysterectomy is less costly and more effective in terms of quality-adjusted life expectancy compared to radical hysterectomy for early cervical cancer.
ClinicalTrials.gov Identifier: NCT01658930.
Erratum: Recent breakthroughs in the management of locally advanced and recurrent/metastatic cervical cancer.
Ovarian CancerThis corrects the article on p. e30 in vol. 35, PMID: 38072400.
Bevacizumab combined with chemotherapy could be superior to chemotherapy alone in relapsed ovarian cancer after PARPi: evidence from a multi-center propensity score-matched analysis.
Ovarian CancerA retrospective, multi-center propensity score-matched (PMS) analysis was conducted to investigate the efficacy and safety of the treatment strategy that combines bevacizumab and chemotherapy for patients with relapsed epithelial ovarian cancer (EOC) who previously received poly ADP-ribose polymerase inhibitors (PARPis).
A total of 250 ovarian cancer (OC) patients relapsed after PARPi received chemotherapy with or without bevacizumab at 4 medical centers were enrolled in the study. For both treatments, Kaplan-Meier analysis and Cox regression were used to compare PFS.
In the multivariable analysis of 250 patients, the incorporation of bevacizumab into chemotherapy demonstrated a significant enhancement in PFS (hazard ratio [HR]=0.49; 95% confidence interval [CI]=0.34-0.72; p<0.001). Fifty-five patients were enrolled in Group A (bevacizumab combined with chemotherapy) and 55 were enrolled in Group B (chemotherapy alone regime) after PSM analysis. A statistically significant difference in PFS was observed between the 2 regimens (HR=0.62; 95% CI=0.40-0.97; p=0.036), suggesting that the bevacizumab combined with chemotherapy regimen confers superior clinical benefits. The median PFS was 11 months in Group A and 9 months in Group B. A significant variation was noted in PFS between patients without RCRS (HR=0.50; 95% CI=0.30-0.82) and the platinum-resistant subgroup (HR=0.31; 95% CI=0.14-0.68). Adverse effects of Grade 3-4 were more prevalent in Group A than in Group B. Additionally, instances of severe hypertension and bowel perforation were reported solely within Group A.
In patients diagnosed with EOC relapsed after PARPi, the regime of chemotherapy combined with bevacizumab is associated with better PFS.
Role of HPV E7/miR-143-3p/SH2D3A pathway in regulating the occurrence and development of cervical cancer.
Ovarian CancerThis study aims to explore the role of SH2D3A in cervical cancer, as well as its potential interaction with human papillomavirus (HPV) E7 and microRNA (miRNA).
Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to compare the expressions of SH2D3A in tissues. To assess the effects of SH2D3A on cervical cancer cell phenotypes, SH2D3A was knocked down in SiHa and HeLa cells, followed by cell proliferation (Cell Counting Kit-8 assay), apoptosis (flow cytometry), and invasion (Transwell assay) analyses. A transplantation tumor model was established to compare the tumorigenic ability of cervical cancer cells before and after SH2D3A silencing. Bioinformatics analysis predicted and dual-luciferase reporter assays verified the sponge adsorption effect of SH2D3A on miRNA. Western blot and qRT-PCR analyses were conducted to examine the impact on target genes following the downregulation of HPV E7 and SH2D3A.
SH2D3A expression was significantly elevated in cervical cancer tissues. SH2D3A silencing inhibited cell proliferation and invasion, induced apoptosis, and reduced tumorigenesis in nude mice. Bioinformatics tools identified a binding relationship between SH2D3A and miR-143-3p, confirmed by the luciferase reporter assays. Western blot analysis revealed that SH2D3A knockdown led to decreased levels of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) proteins. Additionally, qRT-PCR showed that SH2D3A mRNA levels decreased after HPV E7 silencing, whereas miR-143-3p levels significantly increased.
HPV E7 influences SH2D3A expression through miR-143-3p, thereby regulating the JAK1/STAT3 pathway. This mechanism promotes the occurrence and development of cervical cancer.