The latest medical research on Ovarian Cancer

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Clinical Trial Protocol for HyNOVA: Hyperthermic and Normothermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III epithelial OVArian, fallopian tube and primary peritoneal cancer (ANZGOG1901/2020).

Ovarian Cancer

ANZCTR Identifier: ACTRN12621000269831.

This initial stage of HyNOVA is a phase II study of 80 women with International Federation of Gynaecology and Obstetrics stage III epithelial ovarian cancer, with at least stable disease following 3-4 cycles of neoadjuvant chemotherapy, achieving interval-CRS to <2.5 mm residual disease. Participants are randomized 1:1 to receive IP cisplatin 100 mg/m² for 90 minutes either as HIPEC, heated to 42°C (41.5°C-42.5°C), or NIPEC, at 37°C (36.5°C-37.5°C). The primary outcome is the proportion of AEs ≥ grade 3 occurring within 90 days. Secondary outcomes are AE of interest, surgical morbidity, patient reported outcomes, resource allocation, feasibility, progression-free survival and overall survival. AEs are measured using both CTCAE v5.0 and Clavien-Dindo classification, particularly infection, pain, bowel dysfunction, and anemia. Tertiary outcomes are potential predictive biomarkers measured before and after HIPEC/NIPEC including circulating cell-free tumor DNA, tissue factors, and systemic inflammatory markers. There are 4 participating Australian sites with experience in CRS and HIPEC for peritoneal malignancy. HyNOVA is funded by an MRFF grant (APP1199155).

Circular RNA intraflagellar transport 80 facilitates endometrial cancer progression through modulating miR-545-3p/FAM98A signaling.

Ovarian Cancer

Endometrial cancer (ECa) is a common gynecological malignancy. Circular RNAs (circRNAs) have been identified as key regulators of human tumorigenesis and development. Herein, we explored the role and mechanism of circular RNA intraflagellar transport 80 (circ-IFT80, also called circ_0067835) in ECa.

Circ-IFT80, microRNA-545-3p (miR-545-3p), and family with sequence similarity 98 member A (FAM98A) were quantified by quantitative real-time polymerase chain reaction or Western blot. The biological characteristics of ECa cells were evaluated via Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, transwell, tube formation and flow cytometry assays. Dual-luciferase reporter assay or RNA pull-down assay was employed to verify the binding relationship between miR-545-3p and circ-IFT80 or FAM98A. Xenograft assays were conducted to analyze the effect of circ-IFT80 in vivo.

Circ-IFT80 and FAM98A were up-regulated, and miR-545-3p was down-regulated in ECa tissues and cells. Knockdown of circ-IFT80 blocked proliferation, migration, invasion and angiogenesis and promoted apoptosis in ECa cells. Moreover, circ-IFT80 harbored a binding site for miR-545-3p, and the effects of circ-IFT80 were mediated by miR-545-3p. FAM98A was a direct target of miR-545-3p, and miR-545-3p hindered ECa cell progression via targeting FAM98A. Circ-IFT80 induced FAM98A expression through miR-545-3p. Furthermore, silence of circ-IFT80 suppressed tumor growth in vivo.

Circ-IFT80 may promote the malignant progression of ECa cells at least in part by modulating miR-545-3p/FAM98A axis, providing a potential therapeutic target for ECa.

Association between hospital treatment volume and survival of women with gynecologic malignancy in Japan: a JSOG tumor registry-based data extraction study.

Ovarian Cancer

Associations between hospital treatment volume and survival outcomes for women with 3 types of gynecologic malignancies, and the trends and contributing factors for high-volume centers were examined.

The Japan Society of Obstetrics and Gynecology tumor registry databased retrospective study examined 206,845 women with 80,741, 73,647, and 52,457 of endometrial, cervical, and ovarian tumor, respectively, who underwent primary treatment in Japan between 2004 and 2015. Associations between the annual treatment volume and overall survival (OS) for each tumor type were examined using a multivariable Cox proportional hazards model with restricted cubic splines. Institutions were categorized into 3 groups (low-, moderate-, and high-volume centers) based on hazard risks.

Hazard ratio (HR) for OS each the 3 tumors decreased with hospital treatment volume. The cut-off points of treatment volume were defined for high- (≥50, ≥51, and ≥27), moderate- (20-49, 20-50, and 17-26), and low-volume centers (≤19, ≤19, and ≤16) by cases/year for endometrial, cervical, and ovarian tumors, respectively. Multivariate analysis revealed younger age, rare tumor histology, and initial surgical management as contributing factors for women at high-volume centers (all, p<0.001). The proportion of high-volume center treatments decreased, whereas low-volume center treatments increased (all p<0.001). Treatment at high-volume centers improved OS than that at other centers (adjusted HR [aHR]=0.83, 95% confidence interval [CI]=0.78-0.88; aHR=0.78, 95% CI=0.75-0.83; and aHR=0.90, 95% CI=0.86-0.95 for endometrial, cervical, and ovarian tumors).

Hospital treatment volume impacted survival outcomes. Treatments at high-volume centers conferred survival benefits for women with gynecologic malignancies. The proportion of treatments at high-volume centers have been decreasing recently.

Accuracy of human papillomavirus tests on self-collected urine versus clinician-collected samples for the detection of cervical precancer: a systematic review and meta-analysis.

Ovarian Cancer

The human papillomavirus (HPV) test is an effective screening tool to prevent cervical cancer. Urinary sampling for HPV detection improves the accessibility and participation of screening services and reduces the cost and burden on physicians. The clinical accuracy of urinary HPV test has yet to be determined via meta-analysis. This study assessed the clinical accuracy of these tests to detect cervical intraepithelial neoplasia (CIN) 2 or worse.

Relevant studies were identified using the PubMed, Embase, and Cochrane databases. Research eligibility was based on the clinical accuracy of HPV test on clinician-collected samples as a comparator test, and urine as an index test. The reference standard was the presence of CIN2 or worse. The pooled absolute, relative sensitivity, and specificity of the urinary HPV test versus clinician-collected samples were assessed using a bivariate model.

The pooled sensitivity of urinary HPV test was significantly lower than that of clinician-collected samples (ratio=0.84, 95% confidence interval [CI]=0.78-0.91). However, some polymerase chain reaction (PCR)-based HPV test such as GP5+/6+ (relative sensitivity=0.98, 95% CI=0.91-1.05), SPF10 (relative sensitivity=0.98, 85% CI=0.88-1.08) and non GP5+/6+ PCR (relative sensitivity=1.00, 95% CI=0.88-1.14) showed similar sensitivity in both the urine and clinician-collected samples.

Our findings indicate that HPV test with some PCR-based assay on urine versus clinician-collected samples demonstrate similar clinical accuracy to detect CIN2 or worse. It suggests that urinary HPV test may present itself as a decent alternative screening tool for the detection of cervical pre-cancer.

PROSPERO identifier: CRD42021227901.

Cause-specific mortality rate of ovarian cancer in the presence of competing risks of death: a nationwide population-based cohort study.

Ovarian Cancer

This nationwide cohort study aimed to evaluate the cause-specific mortality (probability of death by ovarian cancer, probability of death by other causes) under the competing risks of death in women with ovarian cancer.

The Korea Central Cancer Registry was searched to identify women with primary ovarian cancer diagnosed between 2006 and 2016. Epithelial ovarian cancer cases were identified using the International Classification of Diseases for Oncology 3rd edition. We estimated the cause-specific mortality according to age (<65 years, ≥65 years), stage (local, regional, and distant), and histology (serous, mucinous, endometrioid, clear cell, and others) under the competing risks framework; moreover, cumulative incidences were estimated.

We included 21,446 cases. Cause-specific mortality continuously increased throughout 10 year follow-up. Compared with women aged <65 years, ovarian cancer-specific mortality (5-year, 28.9% vs. 61.9%; 10-year, 39.0% vs. 68.6%, p<0.001) and other cause mortality (5-year, 1.7% vs. 4.8%; 10-year, 2.8% vs. 8.2%, p<0.001) increased in women aged ≥65 years. This trend was consistent across all the stages and histological types. There was a substantial increase in competing risks from 1.1% in women aged <65 years to 8.0% in women aged ≥65 years in patients with early-stage (p<0.001) non-serous ovarian cancer (p<0.001).

Older age at diagnosis is associated with increasing ovarian cancer-specific mortality and competing risks. Given the substantial effect of competing risks on elderly patients, there is a need for assessment tools to balance the beneficial and harmful effects to provide optimal treatment.

Transabdominal cardiophrenic lymph node dissection for cytoreductive surgery in advanced ovarian cancer.

Ovarian Cancer

Minimizing residual tumors is one of the most important prognostic factors in the management of advanced ovarian cancer [1]. In ovarian cancer patients with cardiophrenic lymph node (LN) metastases, transabdominal cardiophrenic lymph node dissection (CPLND) has been performed along with the surgery on the primary site [2]. However, CPLND for the complicated locations in the thoracic cavity is still technically challenging. This video aims to share our surgical technique for the transabdominal CPLND.

A 60-year-old woman who presented with suspicious bilateral ovarian cancer was hospitalized for cytoreductive surgery. Preoperative CT demonstrated peritoneal seeding and multiple LN metastases including right anterior, lateral, posterior, and left anterior cardiophrenic LNs. The gynecology and general surgery team underwent hysterectomy, bilateral salpingo-oophorectomy, supracolic omentectomy, lower anterior resection, right diaphragmatic and bladder peritonectomy, pelvic and paraaortic LN dissection, and appendectomy. The thoracic surgeon took over the operation because the pelvic cavity was regarded as R0. CPLND was performed by transabdominal, subxiphoid approach. The procedure is narrated in the video.

Complete clearance of CPLN leaving no gross residual disease was possible without complication. A long, transverse incision of the anterior diaphragm was closed with a 1-0 polypropylene in the way of double layered continuous running suture and 8 times ties for the final knot.

Transabdominal CPLND can be used safely and effectively without change of patient's position and with minimal diaphragmatic injury. However, this approach may be unfeasible for metastatic internal mammary LN dissection and still needs meticulous surgical skills to avoid complications.

A novel gene signature associated with poor response to chemoradiotherapy in patients with locally advanced cervical cancer.

Ovarian Cancer

We aimed to investigate the distinct transcriptional landscape in poor responders to concurrent chemoradiotherapy (CCRT) and to gain mechanistic insights into treatment resistance in cervical cancer.

RNA sequencing was performed in patients with locally advanced cervical cancer treated with platinum-based CCRT. Transcriptome data of no durable benefit (NDB; progression-free period <3 years) and durable clinical benefit (DCB; progression-free period >5 years) patients were compared. The NDB score was estimated for each patient using differentially expressed genes between NDB and DCB patients. The potential response to programmed death-1 blockade was estimated using the tumor immune dysfunction and exclusion (TIDE) score and T-cell-inflamed gene expression profile (GEP).

NDB patients exhibited a distinct transcriptional profile compared to DCB patients, such as higher signatures of extracellular matrix organization and epithelial-to-mesenchymal transition. The fraction of cancer-associated fibroblasts (CAFs) within the tumor was significantly higher in NDB patients than in DCB patients. High NDB scores were significantly associated with poor survival in the Cancer Genome Atlas cervical cancer cohort (n=274; p=0.015) but only in patients who received curative aim radiotherapy (p=0.002). Patients with high NDB scores displayed significantly higher TIDE prediction scores and lower T-cell-inflamed GEP scores than those with low NDB scores.

Patients with cervical cancer having poor CCRT or RT outcomes exhibited a distinct gene signature that could predict treatment outcomes. For poor responders, immune checkpoint inhibitors may be less effective whereas CAF-targeting treatments may be a promising approach.

Impact of COVID-19 on gynecologic cancer treatment in Japan: a nationwide survey by the Japan Society of Gynecologic Oncology (JSGO).

Ovarian Cancer

As coronavirus disease 2019 (COVID-19) rages on, it is a challenging task to balance resources for treatment of COVID-19 and malignancy-based treatment. For the development of optimal strategies, assessing the conditions and constrains in treatment during the COVID-19 pandemic is pertinent. This study reported about a nationwide survey conducted by the Japan Society of Gynecologic Oncology.

We interviewed 265 designated training facilities about the state of their clinical practice from the time period between March and December 2020. We asked the facility doctors in charge to fill a web-based questionnaire.

A total of 232 facilities (87.5%) responded. A decrease in the number of outpatient visits was reported, and the major reason attributed was reluctance of patients to visit hospitals rather than facility restrictions. The actual number of surgeries decreased by 3.9%, compared to 2019. There was a significant difference when the variable of "Prefectures operating under special safety precautions" or not was introduced. There was no increase in the rate of advanced stages in the three cancer types studied. However, 34.1% participants perceived COVID-19 affected management and prognosis.

Refraining from visiting hospitals based on the patient's judgment may be expected to be an issue in the future. No significant decrease in surgeries was observed, and it would seem that there were few forced changes in treatment plans, but "the State of Emergency" had an impact. There was no increase in the rate of advanced cancers, but this will need to be monitored.

Evaluation of partial genotyping with HPV16/18 for triage of HPV positive, cytology negative women in the COMPACT study.

Ovarian Cancer

While cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV+ women to avoid over-referral to colposcopy may be setting specific. We compared absolute and relative risk (RR) of >CIN2/3 within 12 months of a negative cytologic result in women HPV16/18+ compared to those with a 12-other high-risk HPV (hrHPV) genotype to identify women at greatest risk of high-grade disease and permit less aggressive management of women with other hrHPV infections.

Participants were 14,160 women aged 25-69 years with negative cytology participating in the COMparison of HPV genotyping And Cytology Triage (COMPACT) study. Women who were HPV16/18+ were referred to colposcopy. Those with a 12-other hrHPV type underwent repeat cytology after 6 months and those with >abnormal squamous cells of undetermined significance went to colposcopy.

Absolute risk of >CIN2 in HPV16/18+ women was 19.5% (95% CI=12.4%-29.4%). In women 25-29 years and HPV16+ it was 40.0% (95% CI=11.8%-76.9%). Absolute risk of >CIN3 in women HPV16/18+ was 11.0% (95% CI=5.9%-19.6%). For women 30-39 years and HPV16+ it was 23.1% (95% CI=5.0%-53.8%). Overall risk of >CIN2, >CIN3 in women with a 12-other hrHPV HPV type was 5.6% (95% CI=3.1%-10.0%) and 3.4% (95% CI=1.6%-7.2%) respectively. RR of >CIN2, >CIN3 in HPV16/18+ vs. 12-other hrHPV was 3.5 (95% CI=1.7-7.3) and 3.3 (95% CI=1.2-8.8), respectively.

Primary HPV screening with HPV16/18 partial genotyping is a promising strategy to identify women at current/future risk of >CIN2 in Japan without over-referral to colposcopy.

Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000013203.

Prehabilitation for medically frail patients undergoing surgery for epithelial ovarian cancer: a cost-effectiveness analysis.

Ovarian Cancer

To assess the potential cost-effectiveness of prehabilitation in medically frail patients undergoing surgery for epithelial ovarian cancer (EOC).

We created a cost-effectiveness model evaluating the impact of prehabilitation on a cohort of medically frail women undergoing primary surgical intervention for EOC. Cost was assessed from the healthcare system perspective via (1) inpatient charges from 2018-2019 institutional Diagnostic Related Grouping data for surgeries with and without major complications; (2) nursing facility costs from published market surveys. Major complication and non-home discharge rates were estimated from the literature. Based on published pilot studies, prehabilitation was determined to decrease these rates. Incremental cost-effectiveness ratio for cost per life year saved utilized a willingness-to-pay threshold of $100,000/life year. Modeling was performed with TreeAge software.

In a cohort of 4,415 women, prehabilitation would cost $371.1 Million (M) versus $404.9 M for usual care, a cost saving of $33.8 M/year. Cost of care per patient with prehabilitation was $84,053; usual care was $91,713. When analyzed for cost-effectiveness, usual care was dominated by prehabilitation, indicating prehabilitation was associated with both increased effectiveness and decreased cost compared with usual care. Sensitivity analysis showed prehabilitation was more cost effective up to a cost of intervention of $9,418/patient.

Prehabilitation appears to be a cost-saving method to decrease healthcare system costs via two improved outcomes: lower complication rates and decreased care facility requirements. It represents a novel strategy to optimize healthcare efficiency. Prospective studies should be performed to better characterize these interventions in medically frail patients with EOC.

Real-time intraoperative ureter visualization with a novel Near-Infrared Ray Catheter during laparoscopic hysterectomy for gynecological cancer.

Ovarian Cancer

Ureteral injuries are well-known complications of gynecologic surgery, with a higher prevalence in laparoscopic surgery than in laparotomy [1]. The...

Updated clinical guideline for human papillomavirus vaccine: the Korean Society of Gynecologic Oncology guidelines.

Ovarian Cancer

Since the human papillomavirus (HPV) vaccine guidelines were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2011, 2016, and 2019...