Extensive peritoneal metastasis and malignant ascites continue to pose substantial challenges in achieving favorable treatment outcomes for ovarian cancer. Berberine (BBR), an active component of numerous traditional Chinese herbs, has demonstrated potent anti - tumor effects across various malignancies, including ovarian cancer. In this study, we comprehensively evaluated the impact of BBR on the growth and metastasis of ovarian cancer both in vitro and in vivo. RNA - sequencing was employed to elucidate the underlying mechanisms. Specifically, we investigated lipid metabolism and mitochondrial function in ovarian cancer cells and mice, comparing BBR - treated and untreated groups. Additionally, CIBERSORT analysis and immunohistochemical (IHC) staining were utilized to confirm BBR's ability to enhance the infiltration of tumor-infiltrating immune cells into adipose tissue and improve the inflammatory tumor microenvironment. Our findings indicate that BBR significantly inhibits the growth and metastasis of ovarian cancer in vitro and in vivo. The effects can be attributed to two key processes. Firstly, BBR suppresses the lipid metabolism by downregulating lipid uptake related receptor CD36, lipid metabolic enzyme and mitochondrial function. Secondly, BBR alleviates the aging of adipose tissue and adipose derived stem cells (ADSCs), thereby decreasing the secretion of senescence-associated secretory phenotype (SASP). These ultimately lead to the increasing the improvement of tumor infiltrating immune cells, such as CD4⁺ helper T cells (CD3⁺CD4⁺) and cytotoxic T lymphocytes (CD3⁺CD8⁺), and inflammation in ovarian cancer tissue. Collectively, these findings suggested a potential therapeutic effect of BBR in the treatment of advanced ovarian cancer, particularly cases complicated by peritoneal metastasis and malignant ascites.

Adding the anti-PD-L1 antibody atezolizumab to frontline chemotherapy-bevacizumab regimen did not improve progression-free survival (PFS) in ovarian cancer (OC) patients in IMagyn050 trial. This post-hoc analysis assessed the efficacy of atezolizumab in a subgroup of patients with particularly poor prognosis, as defined by the GCIG meta-analysis-characterized by a poor chemosensitivity and a suboptimal surgical resection.

This analysis included 1199 evaluable participants with ≥3 available CA-125 concentrations, as required for KELIM score. The prognostic factors were identified through univariable and multivariable analyses. If both the KELIM score (unfavorable <1.0, vs favorable ≥1.0) and surgical outcome (suboptimal, vs optimal resection) demonstrated independent prognostic value, they were to be combined into prognostic subgroups. The PFS benefit of atezolizumab versus placebo was then evaluated within each of these defined subgroups.

Both the KELIM score and surgical outcome were independent prognostic factors. Combining these two parameters generated three distinct prognostic subgroups. In the poor prognosis subgroup (n = 269), defined by both an unfavorable KELIM score (<1.0) and suboptimal cytoreduction, the addition of atezolizumab was associated with a significantly longer median PFS compared to placebo (14.3 vs 11.3 months; HR 0.75, 95 % CI 0.59-0.95). This benefit was observed in both neoadjuvant and adjuvant settings. No significant PFS benefit was observed in the other prognostic subgroups.

The poor prognostic OC patient subgroup, may have an extension of PFS from treatment intensification with atezolizumab added to frontline chemotherapy-bevacizumab regimen. This hypothesis-generating outcome warrants further understanding on the added role of ICI in the frontline setting.

In patients with the rare adult-type granulosa cell tumor (aGCT), surgery is the primary treatment for both primary and recurrent disease. In cases of inoperable disease, systematic therapy is administered, but variable response rates and drug resistance complicate predicting the most effective therapy. Drug screen testing on patient-derived cell lines may offer a solution. In a national prospective study on aGCT, fresh tissue was cultured into 2D cell lines, testing 27 clinical and experimental drugs. Dose-response curves and synergy were calculated using GraphPad Prism and CompuSyn software. We established 34 patient-derived cell lines from tissue of 20 patients with aGCT. Of these, seven patients had a primary diagnosis of aGCT and 13 patients had recurrent disease. In eight patients, multiple tumor locations were cultured. On each cell line, 10 monotherapies and 17 combinations of drugs were tested. Carboplatin/gemcitabine showed efficacy and synergy in almost all patient-derived cell lines. Synergy could not be detected in the regular carboplatin/paclitaxel and carboplatin/etoposide combinations. Experimental combinations alpelisib/fulvestrant and alpelisib/gemcitabine showed efficacy of more than 75%. Drug screens on patient-derived tumor cell lines reflect the reality of the variable response of systemic therapy in patients with aGCT. In future research, this technique may be used to personalize the systemic treatment of patients with aGCT in a clinical study. The good response to carboplatin/gemcitabine in our patient-derived cell lines can then be confirmed in a clinical setting.

Along with BRCA mutation status, homologous recombination deficiency (HRD) testing is a prognostic and predictive biomarker for poly-ADP-ribose polymerase (PARP) inhibitor therapy indication in high-grade epithelial ovarian, fallopian tube, or peritoneal cancer. Approximately 50% of high-grade serous ovarian cancers exhibit HRD, even in the absence of germline or somatic BRCA1/2 loss-of-function mutations. In this scenario, access to a validated diagnostic HRD test can optimize treatment selection and increase the effectiveness of the intervention.

To technically validate an in-house next-generation sequencing (NGS)-based HRD test, QIAseq Custom Panel (QIAGEN), by comparing it with the reference assay, MyChoice CDx® Plus HRD (Myriad Genetics), which is used in routine care.

This is a prospective cohort study conducted at the Oncoclínicas Precision Medicine (OCPM) laboratory using samples from patients with advanced or relapsed platinum-sensitive ovarian cancer eligible for HRD testing in a diagnostic clinical setting at Oncoclínicas and Co. We assessed the performance of the in-house test (GS Focus HRD) using Cohen's kappa statistic to measure agreement with the gold standard assay (MyChoice® HRD Plus CDx) in HRD status classification, along with other accuracy metrics.

In total, 41 samples were analyzed (20 HRD-positive, 19 HRD-negative, and 2 inconclusive results with the MyChoice® HRD Plus CDx assay). The GS Focus HRD test demonstrated high concordance for HRD status with the reference test (kappa: 0.8 and 95% CI: 0.60-0.98). Overall accuracy, sensitivity, and specificity were 90%. Six samples had BRCA1/2 mutations identified by the MyChoice® HRD Plus CDx, all of which were detected by the GS Focus HRD test.

In summary, the results demonstrate substantial agreement and high accuracy of the NGS-based GS Focus HRD test compared to MyChoice® HRD Plus CDx. Our in-house assay is eligible for diagnostic test approval and market access as per Brazilian regulations.

This study aimed to develop a deep learning (DL) prognostic model to evaluate the significance of intra- and peritumoral radiomics in predicting outcomes for high-grade serous ovarian cancer (HGSOC) patients receiving platinum-based chemotherapy.

A DL model was trained and validated on retrospectively collected unenhanced computed tomography (CT) scans from 474 patients at two institutions, which were divided into a training set (N = 362), an internal test set (N = 86), and an external test set (N = 26). The model incorporated tumor segmentation and peritumoral region analysis, using various input configurations: original tumor regions of interest (ROIs), ROI subregions, and ROIs expanded by 1 and 3 pixels. Model performance was assessed via hazard ratios (HRs) and receiver operating characteristic (ROC) curves. Patients were stratified into high- and low-risk groups on the basis of the training set's optimal cutoff value.

Among the input configurations, the model using an ROI with a 1-pixel peritumoral expansion achieved the highest predictive accuracy. The DL model exhibited robust performance for predicting progression-free survival, with HRs of 3.41 (95% CI: 2.85, 4.08; P < 0.001) in training set, 1.14 (95% CI: 1.03, 1.26; P = 0.012) in internal test set, and 1.32 (95% CI: 1.07, 1.63; P = 0.011) in external test set. KM survival analysis revealed significant differences between the high-risk and low-risk groups (P < 0.05).

The DL model effectively predicts survival outcomes in HGSOC patients receiving platinum-based chemotherapy, offering valuable insights for prognostic assessment and personalized treatment planning.

In epithelial ovarian cancer (EOC), platinum resistance, potentially mediated by cancer stem cells (CSCs), often leads to relapse and treatment failure. Here, the role of spindle pole body component 25 (SPC25) as a key determinant promoting stemness and platinum resistance in EOC cells, with its expression being correlated with adverse clinical outcomes is delineated. Mechanistically, SPC25 acts as a scaffolding platform, orchestrating the assembly of an SPC25/RIOK1/MYH9 trimeric complex, triggering RIOK1-mediated phosphorylation of MYH9 at Ser1943. This prompts MYH9 to disengage from the cytoskeleton, augmenting its nuclear accumulation, thus potentiating CTNNB1 transcription and subsequent activation of Wnt/β-catenin signaling. CBP1, a competitive inhibitory peptide, can disrupt the formation of the aforementioned trimeric complex, diminishing the activity of the SPC25/RIOK1/MYH9 axis-mediated Wnt/β-catenin signaling, and thus attenuate CSC phenotypes, thereby enhancing platinum efficacy in vitro, in vivo, and in patient-derived organoids. Therefore, targeting the SPC25/RIOK1/MYH9 axis, which mediates the maintenance of stemness and platinum resistance in EOC cells, may enhance platinum sensitivity and increase survival in patients with EOC.

Despite documented evidence that ovarian cancer cells express immune-checkpoint molecules, such as PD-1 and PD-L1, and of a positive correlation between the presence of tumour-infiltrating lymphocytes and favourable overall survival outcomes in patients with this tumour type, the results of trials testing immune-checkpoint inhibitors (ICIs) in these patients thus far have been disappointing. The lack of response to ICIs can be attributed to tumour heterogeneity as well as inherent or acquired resistance associated with the tumour microenvironment (TME). Understanding tumour immunobiology, discovering biomarkers for patient selection and establishing optimal treatment combinations remains the hope but also a key challenge for the future application of immunotherapy in ovarian cancer. In this Review, we summarize results from trials testing ICIs in patients with ovarian cancer. We propose the implementation of a systematic CD8+ T cell-based immunophenotypic classification of this malignancy, followed by discussions of the preclinical data providing the basis to treat such immunophenotypes with combination immunotherapies. We posit that the integration of an accurate TME immunophenotype characterization with genetic data can enable the design of tailored therapeutic approaches and improve patient recruitment in clinical trials. Lastly, we propose a roadmap incorporating tissue-based profiling to guide future trials testing adoptive cell therapy approaches and assess novel immunotherapy combinations while promoting collaborative research.

Epithelial ovarian cancer (EOC) presents considerable difficulties in prognostication and treatment strategy development. Bevacizumab, an anti-angiogenic medication, has demonstrated potential in enhancing progression-free survival (PFS) in EOC patients. Nevertheless, the identification of individuals at elevated risk of disease progression following treatment remains a challenging task. This study was to develop and validate a deep learning (DL) model using retrospectively collected computed tomography (CT) plain scans of inoperable and recurrent EOC patients receiving bevacizumab treatment diagnosed between January 2013 and January 2024. A total of 525 patients from three different institutions were retrospectively included in the study and divided into training set (N = 400), internal test set (N = 97) and external test set (N = 28). The model's performance was evaluated using Harrell's C-index. Patients were categorized into high-risk and low-risk group based on a predetermined cutoff in the training set. Additionally, a multimodal model was evaluated, incorporating the risk score generated by the DL model and the pretreatment level of carbohydrate antigen 125 as input variables. The Net Reclassification Improvement (NRI) metric quantified the reclassification performance of our optimal model in comparison to the International Federation of Gynecology and Obstetrics (FIGO) staging model. The results indicated that DL model achieved a PFS predictive C-index of 0.73 in the internal test set and a C-index of 0.61 in the external test set, along with hazard ratios of 34.24 in the training set (95% CI: 21.7, 54.1; P < 0.001) and 8.16 in the internal test set (95% CI: 2.5, 26.8; P < 0.001). The multimodal model demonstrated a C-index of 0.76 in the internal test set and a C-index of 0.64 in the external test set. Comparative analysis against FIGO staging revealed an NRI of 0.06 (P < 0.001) for the multimodal model. The model presents opportunities for prognostic assessment, treatment strategizing, and ongoing patient monitoring.

The 'Best of ESGO 2024' article includes a selection of the most highly rated original research presented during the 25th Annual Congress of the European Society of Gynaecologic Oncology (ESGO), held in Barcelona, Spain, March 7-10, 2024. Of 1218 asbtracts submitted, 35 studies presented during the best oral sessions, mini oral sessions, best three minute presentations session, and young investigator session were selected by the ESGO abstract committee and the authors of the European Network of Young Gynae Oncologists (ENYGO). There was a strong focus on the surgical treatment of early stage cervical cancer and the management of advanced or recurrent gynecological cancers using induction therapy, immunotherapy, and maintenance therapy. With this work, ENYGO and ESGO aim to focus the attention of clinicians, scientists, patients, and all stakeholders interested in gynecologic oncology on research advances in the field.

Gynecological disorders have the characteristics of high incidence and recurrence rate, which sorely affects female's health. Since ancient times, traditional Chinese medicine (TCM), especially tonic medicine (TM), has been used to deal with gynecological disorders and has unique advantages in effectiveness and safety.

In this article, we aim to summarize the research progress of TMs in-vivo and in-vitro, including their formulas, single herbs, and compounds, for gynecological disorders treatment in recent years, and to offer a reference for further research on the treatment of gynecological disorders and their clinical application in the treatment of TMs.

Relevant information on the therapeutic potential of TMs against gynecological disorders was collected from several scientific databases including Web of Science, PubMed, CNKI, Google Scholar and other literature sources.

So far, there are 46 different formulas, 3 single herbs, and 24 compounds used in the treatment of various gynecological disorders such as premature ovarian failure, endometriosis breast cancer, and so on. Many experimental results have shown that TMs can regulate apoptosis, invasion, migration, oxidative stress, and the immune system. In addition, the effect of TMs in gynecological disorders treatment may be due to the regulation of VEGF, PI3K-AKT, MAPK, NF-κB, and other signaling pathways. Apparently, TMs play an active role in the treatment of gynecological disorders by regulating these signaling pathways.

TMs have a curative effect on the prevention and treatment of gynecological disorders. It could relieve and treat gynecological disorders through a variety of pathways. Therefore, the appropriate TM treatment program makes it more possible to treat gynecological disorders.

Endometrioid ovarian adenocarcinoma is a common subtype of epithelial ovarian cancer that can arise on a background of endometriosis. Maximal cytoreductive effort with an aim to remove all macroscopic disease (achieve R0) is the single independent prognostic factor for survival. Complex multidisciplinary surgeries may be required in order to achieve this.

Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration.

PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects.

The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.

Approximately 50% of tubo-ovarian high-grade serous carcinomas (HGSCs) have functional homologous recombination-mediated (HR) DNA repair, so-called HR-proficient tumors, which are often associated with primary platinum resistance (relapse within six months after completion of first-line therapy), minimal benefit from poly(ADP-ribose) polymerase (PARP) inhibitors, and shorter survival. HR-proficient tumors comprise multiple molecular subtypes including cases with CCNE1 amplification, AKT2 amplification or CDK12 alteration, and are often characterized as "cold" tumors with fewer infiltrating lymphocytes and decreased expression of PD-1/PD-L1. Several new treatment approaches aim to manipulate these negative prognostic features and render HR-proficient tumors more susceptible to treatment. Alterations in multiple different molecules and pathways in the DNA damage response are driving new drug development to target HR-proficient cancer cells, such as inhibitors of the CDK or P13K/AKT pathways, as well as ATR inhibitors. Treatment combinations with chemotherapy or PARP inhibitors and agents targeting DNA replication stress have shown promising preclinical and clinical results. New approaches in immunotherapy are also being explored, including vaccines or antibody drug conjugates. Many approaches are still in the early stages of development and further clinical trials will determine their clinical relevance. There is a need to include HR-proficient tumors in ovarian cancer trials and to analyze them in a more targeted manner to provide further evidence for their specific therapy, as this will be crucial in improving the overall prognosis of HGSC and ovarian cancer in general.

Ovarian surveillance in women with hereditary breast and ovarian cancer who do not undergo risk-reducing salpingo-oophorectomy has been controversial. Therefore, this study aimed to demonstrate the clinical features of ovarian surveillance at our institution using a technique that combines serum cancer antigen 125 measurements, transvaginal ultrasonography, and uterine endometrial cytology.

We retrospectively examined 65 women, who had not undergone risk-reducing salpingo-oophorectomy diagnosed with hereditary breast and ovarian cancer between 2000 and 2021 at our hospital. Clinical information was obtained and analyzed through a chart review. The details of the treatment course were reviewed for patients who had developed ovarian cancer.

Overall, 5 of the 65 women were diagnosed with ovarian cancer based on abnormal findings during periodic surveillance. All patients who developed ovarian cancer were asymptomatic, even if the cancer was at an advanced stage. Two of the 65 patients had endometrial cytology abnormalities, both of whom had ovarian cancer. All patients who developed ovarian cancer underwent primary debulking surgery, and complete gross resection was achieved. None of the patients experienced ovarian cancer recurrence.

The ovarian surveillance strategy at our institution for women with hereditary breast and ovarian cancer who do not undergo risk-reducing salpingo-oophorectomy can identify asymptomatic ovarian cancer and contribute to achieving complete gross resection during primary surgery. Ovarian surveillance may contribute to a reduction in ovarian cancer mortality.

We aimed to compare 7 newer immunotherapies and targeted therapies for platinum-resistant relapsed ovarian cancer.

We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library electronic databases for phase III trials involving platinum-resistant recurrent ovarian cancer (PRrOC) patients treated with immunotherapy or targeted therapy in combination with chemotherapy. The quality of the included trials was assessed using the GRADE method. The primary outcome of comparison was progression-free survival, and secondary outcomes included overall survival and safety.

This analysis included 7 randomized phase III controlled trials, encompassing 2485 PRrOC patients. Combining bevacizumab plus chemotherapy and lurbinectedin demonstrated statistically significant differences in progression-free survival compared to all other regimens of interest. However, no statistically significant differences were observed in the overall survival. Nivolumab and mirvetuximab exhibited fewer serious adverse events than the other regimens of interest.

Our findings indicate that bevacizumab combined with chemotherapy and lurbinectedin monotherapy has significant efficacy in patients with PRrOC. For patients with PRrOC who have exhausted treatment options, nivolumab and mirvetuximab may be considered as alternatives because of their better safety profiles.

Chemotherapy and targeted drugs-induced senescent ovarian cancer cells that accumulate in peritoneal adipose tissue contribute significantly to chronic inflammation, disrupt homeostasis, and may fuel various aspects of cancer progression. However, the pro-senescence effects of chemotherapy and targeted drugs on adipose derived stem cells (ADSCs) within peritoneal adipose tissue remain poorly understood. In this study, we show that the first-line chemotherapy and targeted drugs can induce the cellular senescence of ADSCs in vitro and increase the aging of peritoneal adipose tissue in vivo. These treatments significantly promoted the dysregulation of glucose and lipid metabolism, including insulin resistance and liver lipid accumulation. Our study shows that dasatinib and quercetin, as senolytics, effectively restore glucose homeostasis in mice with ovarian cancer and significantly reduce adipose tissue aging. Importantly, combining these drugs with Carboplatin or Olaparib results in a marked decrease in both peritoneal and adipose tissue metastasis of ovarian cancer cells. Mechanistically, we revealed that there is crosstalk between ovarian cancer cells and senescent ADSCs. The crosstalk increases inflammatory cytokines and chemokines production in ADSCs and notably upregulates chemokine receptors on cancer cells. Collectively, these data indicate that senescent ADSCs induced by chemotherapy and targeted therapy drugs impair adipose tissue function. However, the senolytic drugs dasatinib and quercetin, can significantly ameliorate organ aging and damage induced by these treatments. Notably, dasatinib and quercetin combined with Carboplatin or Olaparib reduced the peritoneal and adipose tissue metastasis of ovarian cancer, ultimately benefiting the mice undergoing chemotherapy and targeted therapy.

This multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between maintenance therapy with two poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and niraparib, in patients with BRCA-mutated, newly diagnosed advanced epithelial ovarian cancer (EOC) who responded to platinum-based chemotherapy.

We enrolled stage III-IV EOC patients with germline and/or somatic BRCA1/2 mutations that had received maintenance therapy with olaparib or niraparib. A 3:1 propensity score matching was conducted using two variables: residual disease size and the presence of germline variants. The primary outcome was progression-free survival (PFS), and the secondary outcomes were time to first subsequent therapy (TFST), overall survival (OS), and treatment-emergent adverse events (TEAEs).

In the propensity score-matched analysis, 80 patients who received olaparib and 31 patients who received niraparib were matched (3:1). In the propensity score-matched cohort, median PFS with olaparib vs. niraparib was not reached vs 31.5 months (HR, 1.08; 95% CI, 0.47-2.52; p = 0.854). The median TFST was not reached vs 31.8 months (HR, 1.20; 95% CI, 0.51-2.81; p = 0.682), and neither olaparib nor niraparib reached the median OS (HR, 0.42; 95% CI, 0.01-17.61; p = 0.649). In terms of the incidence rates of any-grade hematologic or non-hematologic TEAEs, higher rates of thrombocytopenia (p = 0.021) and neutropenia (p = 0.011) were observed in the niraparib group.

Advanced EOC patients with BRCA1/2 mutations exhibited no significant difference in OS between olaparib and niraparib, indicating the need to consider individualized strategies for selecting PARP inhibitors based on adverse event profiles.

Almost all patients with ovarian cancer will experience relapse and eventually develop platinum-resistant. The poor prognosis and limited treatment options have prompted the search for novel approaches in managing platinum-resistant ovarian cancer (PROC). Therefore, a meta-analysis was conducted to evaluate the efficacy and safety of combination therapy with vascular endothelial growth factor (VEGF) /VEGF receptor (VEGFR) inhibitors for PROC.

A comprehensive search of online databases was conducted to identify randomized clinical trials published until December 31, 2022. Pooled hazard ratios (HR) was calculated for overall survival (OS) and progression-free survival (PFS), while pooled odds ratio (OR) was calculated for objective response rate (ORR) and treatment-related adverse events (TRAEs). Subgroup analysis was further performed to investigate the source of heterogeneity.

In total, 1097 patients from eight randomized clinical trials were included in this meta-analysis. The pooled HRs of OS (HR = 0.72; 95% CI: 0.62-0.84, p < 0.0001) and PFS (HR = 0.52; 95% CI: 0.45-0.59, p < 0.0001) demonstrated a significant prolongation in the combination group compared to chemotherapy alone for PROC. In addition, combination therapy demonstrated a superior ORR compared to monotherapy (OR = 2.34; 95%CI: 1.27-4.32, p < 0.0001). Subgroup analysis indicated that the combination treatment of VEGF/VEGFR inhibitors and chemotherapy was significantly more effective than monochemotherapy in terms of OS (HR = 0.71; 95% CI: 0.61-0.84, p < 0.0001), PFS (HR = 0.49; 95% CI: 0.42-0.57, p < 0.0001), and ORR (OR = 2.97; 95% CI: 1.89-4.67, p < 0.0001). Although the combination therapy was associated with higher incidences of hypertension, mucositis, proteinuria, diarrhea, and hand-foot syndrome compared to monochemotherapy, these toxicities were manageable and well-tolerated.

The meta-analysis demonstrated that combination therapy with VEGF/VEGFR inhibitors yielded better clinical outcomes for patients with PROC compared to monochemotherapy, especially when combined with chemotherapy. This analysis provides more treatment options for patients with PROC.

[ https://www.crd.york.ac.uk/PROSPERO ], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42023402050.

This study investigated the effect of poly(ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy after first- and second-line chemotherapy on platinum sensitivity in patients with recurrent high-grade serous epithelial ovarian cancer (rHGSOC).

This study retrospectively analyzed 172 patients with rHGSOC treated at Zhejiang Cancer Hospital and Jiaxing Maternity and Child Health Care Hospital between January 2017 and December 2021. The 1st-PARPi group comprised patients who received a PARPi as maintenance therapy after first-line chemotherapy (n=23), and the 1st-control group comprised those who did not (n = 105). Similarly, the 2nd-PARPi group comprised patients not given a PARPi in their first-line treatment (n = 30), and the 2nd-control group comprised those who were given a PARPi (n = 89).

Among the 23 patients in the 1st-PARPi group and the 105 patients in the 1st-control group, nine and 99 were platinum-sensitive, and 14 and six were platinum-resistant, respectively (hazard ratio [HR]: 14.46, P < 0.0001). Among the 30 patients in the 2nd-PARPi group and 89 patients in the 2nd-control group, 10 and 71 were platinum-sensitive, and 20 and 18 were platinumresistant, respectively (HR: 4.37, P < 0.0001). Age, stage, residual tumor, the courses of platinumbased chemotherapy, and breast cancer susceptibility gene mutations were not associated with platinum sensitivity when using a PARPi as maintenance therapy after first- and second-line chemotherapy.

Patients with rHGSOC using a PARPi were more likely to be platinum-sensitive and develop platinum resistance independent of PARPi duration. Care should be taken when using a PARPi as maintenance therapy after first- and second-line chemotherapy.

Exposure to paclitaxel and carboplatin has the risk of developing hypersensitivity reactions (HSRs), which could necessitate using less effective treatments to avoid anaphylaxis. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen; therefore, this study investigated rates and benefits of successful desensitization in patients with gynecologic cancers (GC).

We collected data from 241 patients with GC who had at least one cycle of platinum or taxane chemotherapy. The rate of HSRs and successful desensitization were evaluated, and an outcome analysis was conducted.

The rate of HSRs to platinum and taxane was 6.39% and 13.07%, respectively. We observed a 100% success rate of desensitization in our cohort. Patients with HSR were significantly younger (57.1 vs. 64.9 years, p = 0.030) in the taxane cohort. Importantly, the overall survival (OS) of patients with platinum and taxane HSRs who underwent desensitization was comparable to that of patients with no HSRs (platinum vs. controls; median OS 60.36 vs. 60.39 months, p = 0.31; taxane vs. controls; OS 80.29 vs. 60.00 months, p = 0.59).

Thus, we show that desensitization for platinum and taxane HSRs is safe and effective, resulting in an outcome that is well comparable to patients without HSR. Based on these observations, desensitization procedures might be considered as standard of care before switching to less effective treatment for patients with GC.

Current treatment strategies for primary epithelial ovarian cancer (EOC) have significantly evolved, and the value of complete cytoreduction has not yet been reassessed. The study aimed to investigate the impact of residual disease after cytoreductive surgery for EOC on survival outcomes within the recent paradigm of frontline ovarian cancer treatment.

We searched relevant literature from the MEDLINE, Embase, and Cochrane Library databases to identify randomized controlled trials and prospective clinical trials of primary EOC published between 1 January 2000 and 22 September 2022. To evaluate the impact of postoperative residual tumors on progression-free survival (PFS) and OS, we constructed a linear regression model for log-transformed median PFS and OS. Patients who did or did not receive first-line maintenance therapy were examined.

A total of 97 trials with 43,260 patients were included:2476 received poly(ADP-ribose) polymerase (PARP) inhibitors and 6587 received bevacizumab. Multivariable analysis of the linear regression model of all studies revealed that the median OS increased by 12.97% for every 10% increase in complete cytoreduction rates, independent of the use of systemic maintenance. In the subgroup analysis of patients receiving maintenance therapies, the effect of complete tumor clearance was potentiated, with a median OS increase of 19.13% for every 10% increase in complete cytoreduction rates.

Total macroscopic tumor clearance at the initial presentation of EOC significantly prolongs OS. Our results establish the importance of complete surgical cytoreduction, even after the introduction of recent advances in frontline treatment for EOC.

Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor. Selective glucocorticoid receptor modulation with relacorilant may restore chemosensitivity and enhance chemotherapy efficacy.

This three-arm, randomized, controlled, open-label phase II study (ClinicalTrials.gov identifier: NCT03776812) enrolled women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma treated with ≤4 prior chemotherapeutic regimens. Patients were randomly assigned 1:1:1 to (1) nab-paclitaxel (80 mg/m2) + intermittent relacorilant (150 mg the day before, of, and after nab-paclitaxel); (2) nab-paclitaxel (80 mg/m2) + continuous relacorilant (100 mg once daily); or (3) nab-paclitaxel monotherapy (100 mg/m2). Nab-paclitaxel was administered on days 1, 8, and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) by investigator assessment; objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety were secondary end points.

A total of 178 women were randomly assigned. Intermittent relacorilant + nab-paclitaxel improved PFS (hazard ratio [HR], 0.66; log-rank test P = .038; median follow-up, 11.1 months) and DOR (HR, 0.36; P = .006) versus nab-paclitaxel monotherapy, while ORR was similar across arms. At the preplanned OS analysis (median follow-up, 22.5 months), the OS HR was 0.67 (P = .066) for the intermittent arm versus nab-paclitaxel monotherapy. Continuous relacorilant + nab-paclitaxel showed numerically improved median PFS but did not result in significant improvement over nab-paclitaxel monotherapy. Adverse events were comparable across study arms, with neutropenia, anemia, peripheral neuropathy, and fatigue/asthenia being the most common grade ≥3 adverse events.

Intermittent relacorilant + nab-paclitaxel improved PFS, DOR, and OS compared with nab-paclitaxel monotherapy. On the basis of protocol-prespecified Hochberg step-up multiplicity adjustment, the primary end point did not reach statistical significance (P < .025). A phase III evaluation of this regimen is underway (ClinicalTrials.gov identifier: NCT05257408).

Although numerous epidemiological studies investigated the association between dietary fat intakes or serum lipid levels and ovarian cancer risk, a consistent and explicit conclusion for specific dietary fats or serum lipids that increase the risk of ovarian cancer is not available. In this study, a systematic review and meta-analysis were conducted to assess the key dietary fats and serum lipids that increased the risk of ovarian cancer. Databases such as PubMed, Web of Science, and EMBASE were searched for observational studies. A total of 41 studies met the inclusion criteria, including 18 cohort and 23 case-control studies (109,507 patients with ovarian cancer and 2,558,182 control/non-ovarian cancer participants). Higher dietary intakes of total fat (RR = 1.19, 95% CI = 1.06-1.33, I2 = 60.3%), cholesterol (RR = 1.14, 95% CI = 1.03-1.26, I2 = 19.4%), saturated fat (RR = 1.13, 95% CI = 1.04-1.22, I2 = 13.4%), and animal fat (RR = 1.21, 95% CI = 1.01-1.43, I2 = 70.5%) were significantly associated with a higher risk of ovarian cancer. A higher level of serum triglycerides was accompanied by a higher risk of ovarian cancer (RR = 1.33, 95% CI = 1.02-1.72, I2 = 89.3%). This meta-analysis indicated that a higher daily intake of total fat, saturated fat, animal fat, and cholesterol and higher levels of serum triglycerides were significantly associated with an increased risk of ovarian cancer.

Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized cancer treatment in recent years. These drugs present a favorable safety profile, even though the potential risk of thromboembolic events (TEs) during their use has not been addressed yet. In addition, PARPi have been involved in an active scientific debate regarding non-oncologic indications, particularly during the Coronavirus Disease 2019 pandemic, including potential anti-thromboembolic effect.

To clarify whether patients treated with PARPi for metastatic solid tumors are either at increased or decreased risk of TEs, we conducted a systematic review of the literature and meta-analysis, including all phase 3 randomized controlled trials (RCTs) which investigated PARPi in this setting. Search was conducted through Medline, EMBASE, Pubmed, SCOPUS and Google Scholar in February 2023, including the proceedings of the principal oncology meetings of the last 10 years, with no time restriction. For each included study, frequencies of TEs in experimental and control arm were collected.

Our search identified 2,369 reports, of which 20 were lastly selected. A total of 4,946 patients were included, across 12 different RCTs. The meta-analysis did not demonstrate either an increased or a reduced risk in TEs in patients treated with PARPi for metastatic disease (OR 1.50, range: 1.00-2.24; 95% CI; P = 0.050), with low heterogeneity and low publication bias.

Although our research did not confirm either increased or decreased risk of TEs for PARPi use, no safety alerts emerged. Thromboembolic risk assessment models should always be integrated in daily clinical routine, to identify high-risk patients.

Drug resistance results in poor outcomes for most patients with metastatic cancer. Adaptive Therapy (AT) proposes to address this by exploiting presumed fitness costs incurred by drug-resistant cells when drug is absent, and prescribing dose reductions to allow fitter, sensitive cells to re-grow and re-sensitise the tumour. However, empirical evidence for treatment-induced fitness change is lacking. We show that fitness costs in chemotherapy-resistant ovarian cancer cause selective decline and apoptosis of resistant populations in low-resource conditions. Moreover, carboplatin AT caused fluctuations in sensitive/resistant tumour population size in vitro and significantly extended survival of tumour-bearing mice. In sequential blood-derived cell-free DNA and tumour samples obtained longitudinally from ovarian cancer patients during treatment, we inferred resistant cancer cell population size through therapy and observed it correlated strongly with disease burden. These data have enabled us to launch a multicentre, phase 2 randomised controlled trial (ACTOv) to evaluate AT in ovarian cancer.

This meta-analysis aims to systematically analyze the efficacy and toxicity of mirvetuximab soravtansine (MIRV) as second-line and above treatment for advanced or recurrent ovarian cancer.

Candidate studies were identified in PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases up to 1 May 2023. Objective response rate (ORR), progression-free survival (PFS), the incidence of adverse events (AEs), and incidence of grade ≥ 3 AEs were extracted and calculated by meta-analysis of merging ratios or mean to describe the efficacy and toxicity of MIRV.

Seven eligible prospective studies were included in this meta-analysis, including 605 patients with advanced ovarian cancer who received second-line or higher therapy. ORR of MIRV was 34.2% (95% confidence interval [CI] 25.0-43.5), and PFS was 5.82 months (95%CI 4.47-7.18). The overall incidence of AEs was 87.4% (95%CI 52.9-100.0) and the incidence of grade ≥ 3 AEs was 27.1% (95%CI 18.9-36.1). The most common AEs were vision blurring, nausea, and diarrhea, with incidence of 46.7% (39.6-53.8), 41.8% (34.0-49.9), and 41.3% (30.4-52.5), respectively.

MIRV has definite efficacy and good safety as a novel choice for second-line and above treatment of advanced or recurrent FRα positive ovarian cancer. This may have promising application in patients with platinum-resistant diseases.

CRD42023428599.

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and despite advancements in therapeutics, most women unfortunately still succumb to their disease. Immunotherapies, in particular immune checkpoint inhibitors (ICI), have been therapeutically transformative in many tumour types, including gynaecological malignancies such as cervical and endometrial cancer. Unfortunately, these therapeutic successes have not been mirrored in ovarian cancer clinical studies. This review provides an overview of the ovarian tumour microenvironment (TME), particularly factors associated with survival, and explores current research into immunotherapeutic strategies in EOC, with an exploratory focus on novel therapeutics in navigating drug resistance.

Accurate lymph node metastasis (LNM) prediction is crucial for patients with advanced epithelial ovarian cancer (AEOC) since it guides the decisions about lymphadenectomy. Previous studies have shown that occult lymph node metastasis (OLNM) is common in AEOC. The objective of our study is to quantitatively assess the probability of occult lymph node metastasis defined by 18F-Fluorodeoxyglucose PET/CT in AEOC and explore relationship between OLNM and PET metabolic parameters. The patients with pathologically confirmed AEOC who underwent PET/CT for preoperative staging at our institute were reviewed. Univariate and multivariate analysis were performed to evaluate the predictive value of PET/CT-related metabolic parameters for OLNM. The result of our study showed metastatic TLG index had a better diagnostic performance than other PET/CT-related metabolic parameters. Two variables were independently and significantly associated with OLNM in multivariate analysis: metastatic TLG index and primary tumor location. The logistic model combining metastatic TLG index, primary tumor location, and CA125 might be a promising tool to effectively predict the individualized possibility of OLNM for AEOC patients.

Metabolism-associated genes (MAGs) are important regulators of tumor progression and can affect a variety of physiological processes. In this study, we focused on the relationship between MAGs and Ovarian cancer (OC) prognosis.

Metabolism-related genes were extracted from the Cancer Genome Atlas (TCGA) database. Through univariate COX and lasso regression models, a dynamic risk model based on MAGs was established. Compared with other clinical factors, demonstrated the ability of the model to predict the prognosis of patients with OC. The clinical samples were used to verify the expression of these MAGs.

A metabolism-associated gene signature was constructed by LASSO Cox regression analysis in OC, which was composed of 3-MAGs (PTGIS, AOC3, and IDO1). The signature was used to classify the OC patients into high-risk and low-risk groups. The overall survival of the low-risk group was significantly better than that of the high-risk group. The analysis of the therapeutic effect of bevacizumab showed that bevacizumab was not conducive to improving the prognosis of the low-risk group.

We constructed a prognostic model of MAGs in OC, which can be used to predict the prognosis of OC patients and may have a good guiding significance in the individualized treatment of patients.

The actual 5-year survival rates for Gynecological Endometrioid Adenocarcinoma with Squamous Differentiation (GE-ASqD) are rarely reported. The purpose of this study was to evaluate how histological subtypes affected long-term survivors of GE-ASqD (> 5 years). We conducted a retrospective analysis of patients diagnosed GE-ASqD from the Surveillance, Epidemiology, and End Results database (2004-2015). In order to conduct the studies, we employed the chi-square test, univariate cox regression, and multivariate cox proportional hazards model. A total of 1131 patients with GE-ASqD were included in the survival study from 2004 to 2015 after applying the inclusion and exclusion criteria and the sample randomly split into a training set and a test set at a ratio of 7:3. Five machine learning algorithms were trained based on nine clinical variables to predict the 5-year overall survival. The AUC of the training group for the LR, Decision Tree, forest, Gbdt, and gbm algorithms were 0.809, 0.336, 0.841, 0.823, and 0.856 respectively. The AUC of the testing group was 0.779, 0.738, 0.753, 0.767 and 0.734, respectively. The calibration curves confirmed good performance of the five machine learning algorithms. Finally, five algorithms were combined to create a machine learning model that forecasts the 5-year overall survival rate of patients with GE-ASqD.

The chaperone-mediated autophagy (CMA) pathway is deregulated in different types of cancers; however, its role in cancer stem cells (CSCs) is unknown yet. Development of ovarian cancer, the most lethal gynecological type of cancer, involves the metastasis of CSCs to the abdominal cavity. This study aims to determine the role of CMA in ovarian CSCs. We found that the transcription factor EB (TFEB) and trehalose, a disaccharide that induces TFEB activation, enhance the expression of octamer-binding transcription factor 4 (OCT4) stem cell and lysosomal-associated membrane protein 2A (LAMP2A) CMA markers. However, trehalose did not increase the level of the LC3II macroautophagy marker in ovarian CSCs. In A2780 and SKOV3 ovarian CSCs, LAMP2A and heat shock protein 70 (HSC70) exhibited higher expression levels than in normal adherent cells. Our results showed that the silencing of the LAMP2A gene resulted in reduced sphere formation and enhanced GLUT5 expression in ovarian CSCs. Moreover, the treatment with fructose reduced sphere formation and enhanced the expression levels of LAMP2A, SOX2, and OCT4 in ovarian CSCs. The KEGG functional analysis revealed that differentially expressed genes were enriched in the ferroptosis pathway in A2780-spheroid (SP) cells after treatment with fructose. In A2780-SP and SKOV3-SP cells, the level of SLC7A11 decreased whereas FTH increased after treatment with fructose. Taken together, our results suggest that CMA is mediated in CSCs via fructose metabolism.

To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS).

We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors.

Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2-32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081-9.757, P = 0.036).

PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode.

Ovarian cancer (OC) is gynecological cancer, and diagnosis and treatment are continuously advancing. Next-generation sequencing (NGS)-based diagnoses have emerged as novel methods for identifying molecules and pathways in cancer research. The NGS-based applications have expanded in OC research for early detection and identification of aberrant genes and dysregulation pathways, demonstrating comprehensive views of the entire transcriptome, such as fusion genes, genetic mutations, and gene expression profiling. Coinciding with advances in NGS-based diagnosis, treatment strategies for OC, such as molecular targeted therapy and immunotherapy, have also advanced. Immunotherapy is effective against many other cancers, and its efficacy against OC has also been demonstrated at the clinical phase. In this review, we describe several NGS-based applications for therapeutic targets of OC, and introduce current immunotherapeutic strategies, including vaccines, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cell transplantation, for effective diagnosis and treatment of OC.

Ovarian cancer is the most deadly gynecologic malignancy, and its incidence is gradually increasing. Despite improvements after treatment, the results are unsatisfactory and survival rates are relatively low. Therefore, early diagnosis and effective treatment remain two major challenges. Peptides have received significant attention in the search for new diagnostic and therapeutic approaches. Radiolabeled peptides specifically bind to cancer cell surface receptors for diagnostic purposes, while differential peptides in bodily fluids can also be used as new diagnostic markers. In terms of treatment, peptides can exert cytotoxic effects directly or act as ligands for targeted drug delivery. Peptide-based vaccines are an effective approach for tumor immunotherapy and have achieved clinical benefit. In addition, several advantages of peptides, such as specific targeting, low immunogenicity, ease of synthesis and high biosafety, make peptides attractive alternative tools for the diagnosis and treatment of cancer, particularly ovarian cancer. In this review, we focus on the recent research progress regarding peptides in the diagnosis and treatment of ovarian cancer, and their potential applications in the clinical setting.

Patients with unresectable disease during cytoreductive surgery (CRS) for advanced-stage ovarian cancer are underreported. Knowledge of treatment and survival after surgery is limited. The aim of this study is to address the knowledge gap about postoperative treatment and survival of patients whose surgery was abandoned due to unresectability after abdominal exploration.

Women with FIGO stage IIIB-IV epithelial ovarian cancer whose disease was considered to be unresectable during surgery were included in this prospective study, a post hoc analysis of the PlaComOv study. The unresectable disease was defined as the inability to achieve at least suboptimal CRS without attempted CRS after careful inspection of the entire abdomen. Preoperative clinical data, perioperative findings, postoperative treatment and survival data were analyzed.

From 2018 to 2020, 27 patients were included in this analysis. Treatment ranged from the cessation of treatment to one or several lines of chemotherapy with or without maintenance therapy. The median overall survival was 16 (IQR 5-21) months (95%CI 14-18). At 24 months of follow-up, four patients (15%) were alive.

This study indicated a two-year survival of 15%. Optimal treatment strategies in terms of survival benefits are still ill-defined. Further study of this specific group of patients is warranted. We advocate an (inter)national registry of patients with unresectable cancer and comprehensive follow-up.

Low-grade serous ovarian cancer (LGSOC) is a rare form of epithelial ovarian cancer that generally exhibits a protracted course and is less sensitive to chemotherapy than high-grade serous ovarian cancer. Over the past decade, it has become clear that patients with LGSOC have a clinically distinct course and are molecularly and histologically unique from patients with high-grade serous ovarian cancer.

Endocrine therapy is frequently used for the treatment of patients with recurrent LGSOC and is now also part of the standard upfront treatment of this disease, with an ongoing phase III clinical trial seeking to determine if chemotherapy can be eliminated altogether from the initial treatment of LGSOC. Tumors are frequently found to exhibit alterations affecting the mitogen-activated protein kinase (MAPK) pathway, recently leading to developments in the use of targeted treatments for those patients with recurrent disease. LGSOC is a clinically, histologically, and molecularly unique form of epithelial ovarian cancer. Recent advances in the understanding of endocrine and molecular drivers of this disease have led to changes in both the treatment of newly diagnosed and recurrent disease, with ongoing studies focused on refining upfront therapy and seeking novel targeted combinations for those patients with recurrent disease.

To characterize the somatic mutational landscape, investigate associations between genetic alterations and clinical outcomes, and determine the prevalence of pathogenic germline mutations in low-grade serous ovarian carcinomas (LGSC).

Patients with LGSC tumors who underwent panel-based sequencing of up to 505 genes were identified. Data on somatic and germline mutations; copy-number alterations; and clinicopathologic features, including age at diagnosis, platinum sensitivity, and overall survival (OS), were collected.

Following central pathology rereview, 119 patients with LGSC were identified for analysis. Of these, 110 (92%) had advanced-stage disease (stages III/IV). Somatic KRAS (33%), NRAS (11%), EIF1AX (10%), and BRAF (11%) alterations were the most common; MAPK pathway alterations were found in 60% (n = 71) of LGSCs. KRAS mutations were significantly associated with age at diagnosis more than 50 years (P = 0.02) and platinum-sensitive disease (P = 0.03). On multivariate analysis, MAPK pathway alterations (P = 0.02) and platinum sensitivity (P = 0.005) were significantly associated with improved OS. Seventy-nine patients (66%) underwent germline genetic testing; seven pathogenic germline mutations were identified: MUTYH (n = 2), BAP1 (n = 1), RB1 (n = 1), CHEK2 (n = 1), APC (n = 1), and FANCA (n = 1). There were no germline BRCA1/2 mutations. One germline MUTYH-associated LGSC harbored loss-of-heterozygosity at the MUTYH locus, and the patient with the germline BAP1 mutation also harbored a somatic BAP1 frameshift mutation.

This study showed that MAPK pathway alterations in LGSC, including KRAS mutations, are independently associated with platinum sensitivity and prolonged survival. Germline data, which were limited, identified few pathogenic germline mutations in patients with LGSC. See related commentary by Veneziani and Oza, p. 4357.