Search Results (132)

Background: It is crucial to predict the response to chemotherapy and identify prognostic markers for recurrence and survival in patients with epithelial ovarian cancer (EOC), in order to effectively manage patient care. The CA-125 elimination rate constant K (KELIM) has recently been developed as a means of assessing the chemotherapy response and has been tested mainly in patients enrolled in randomized controlled trials. The objective of this study was to investigate whether the KELIM score is a prognostic marker for progression-free survival (PFS) and overall survival (OS) in EOC, utilizing its role in predicting the chemotherapy response in real-life settings. Method: Demographic, surgical, and survival data of patients with EOC operated on in Antalya Training and Research Hospital between January 2015 and December 2021 were obtained from the electronic gynecological oncology clinic database system and analyzed retrospectively. Results: A total of 102 patients with EOC were included; 30 patients (29.4%) had a KELIM score ≥ 1 and 72 (70.6%) patients had a KELIM score < 1. In the group with a KELIM score < 1, recurrence and refractory disease occurred in 49 patients, while it was 11 patients in the group with a KELIM score ≥ 1 (p = 0.004). PFS was 12 months and 32 months in the groups with KELIM scores of <1 and ≥1, respectively (p = 0.012). There was no difference between groups regarding OS (p = 0.139). In the whole group, KELIM score (<1 vs. ≥1) and type of surgery (IDS vs. PDS) were found to be independent prognostic factors for PFS (RR = 0.44; 95%CI: 0.22–0.88; p = 0.021 and RR = 2.97; 95%CI: 1.76–5.01; p < 0.001, respectively). Conclusion: We found that a favorable KELIM score was associated with better PFS in all groups of patients undergoing surgery for EOC in a real-life setting. With the increasing number of studies, the KELIM score will play an important role in providing better guidance to clinicians at the initial presentation of patients and in subsequent treatment planning. Full article

Ovarian cancer is the most lethal gynecologic malignancy, which causes 313,959 new cases and 207,252 deaths worldwide annually. The lack of specific symptoms, together with no effective screening tools, results in 75% of patients receiving their diagnosis at an advanced stage. The combination of cytoreductive surgery with platinum-based chemotherapy plays a pivotal role in the treatment of advanced epithelial ovarian cancer, but patients still experience poor long-term survival because of frequent relapses and chemotherapy resistance. The treatment landscape has evolved because bevacizumab and Poly-ADP Ribose Polymerase inhibitors now serve as frontline and maintenance therapies for homologous recombination-deficient tumors. Treatment decisions for recurrent disease depend on platinum sensitivity assessment, which determines the appropriate therapeutic approach, while targeted agents deliver significant benefits to specific patient groups. The development of antibody-drug conjugates such as mirvetuximab soravtansine and immunotherapy, including checkpoint inhibitors and cancer vaccines, demonstrates promising investigative potential. The precision of therapy improves through the use of emerging biomarkers and molecular profiling techniques. The future management of this disease may change because of innovative approaches that include adoptive cell therapy, cytokine therapy, and oncolytic viruses. The progress made in ovarian cancer treatment still faces challenges when it comes to drug resistance, survival improvement, and life quality preservation. The development of translational research alongside clinical trials remains essential to bridge treatment gaps while creating personalized therapies based on molecular and clinical tumor characteristics. Full article

Background and Objectives: Epithelial ovarian cancer (EOC) is a complex disease characterized by heterogeneous clinical, pathological, and molecular features. Diagnosed frequently at advanced stages, it presents significant challenges in treatment due to the risks of resistance and recurrence. While bevacizumab, by inhibiting angiogenesis, offers a valuable therapeutic option for platinum-sensitive recurrent ovarian cancer (PSROC), its impact on overall survival (OS) remains incompletely understood. This retrospective study aims to compare treatment responses in high- and low-risk groups of patients with PSROC and to evaluate the effects of bevacizumab on survival within these risk strata. Materials and Methods: This retrospective study included patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV EOC who received chemotherapy or chemotherapy plus bevacizumab for platinum-sensitive recurrence. Patients were classified according to risk groups, and their clinicopathological characteristics were compared. Survival analyses and adverse events regarding risk groups and bevacizumab use were examined. In this study, the effect of bevacizumab on survival in patients with PSROC was evaluated for the first time according to risk stratification, and the relationship between treatment response and survival was investigated according to recurrence localization. Results: Of the 174 patients included in this study, 102 (58.6%) were classified as low risk and 72 (41.4%) were classified as high risk. Significant differences in survival were observed between the risk groups. In the low-risk group, progression-free survival and overall survival were markedly longer compared to the high-risk group. Median PFS was 13.7 months in the low-risk group and 10.8 months in the high-risk group (p = 0.007). Median OS was 36.5 and 23.5 months, respectively (p = 0.003). In low-risk patients, the addition of bevacizumab to chemotherapy significantly increased median PFS (13.5 months vs. 9.7 months, p = 0.029); however, this advantage did not translate into a significant overall survival benefit (39.4 months vs. 33.3 months, p = 0.669). Conversely, in the high-risk group, bevacizumab use provided significant benefits in both PFS and OS. Median PFS was 13.9 months in the bevacizumab group and 8.8 months in the control group (p < 0.001). Median OS was calculated as 36.5 and 23.2 months, respectively (p < 0.001). Conclusions: Our study is among the first to comprehensively compare the effectiveness of bevacizumab treatment in patients with platinum-sensitive recurrent ovarian cancer based on clinical risk groups and recurrence patterns using real-world data. The current literature lacks a comprehensive analysis that simultaneously evaluates these two critical parameters. In this respect, our study aims to contribute to developing more personalized treatment strategies for specific patient subgroups. Full article

Epithelial ovarian cancer (EOC) is diagnosed at an advanced stage in over half of the patients and its prognosis remains unfavorable. CA125, one of the most frequent positive tumor markers in patients with EOC, has certain limitations. Therefore, more accurate clinical biomarkers are needed. Liquid biopsy with cancer related molecules, such as circulating tumor DNA, is a new option for cancer diagnosis and prognosis. We explored the potential of plasma metabolomic and proteomic analyses as novel monitoring methods for the patients with EOC. Of seven patients, six experienced disease recurrence or progression. CA125 plasma measurements were conducted for disease monitoring. Plasma metabolome and proteome analyses were performed using liquid chromatography–tandem mass spectrometry. Ten and four metabolome indicators were significantly increased and decreased in association with chemotherapeutic resistance, respectively. In addition, thirty-seven and nine proteins displayed high and low levels associated with chemotherapeutic resistance, respectively. Several metabolome pathways and protein concentrations corresponded to the clinical course of each patient. This pilot study suggested the potential of the assessment of metabolome and proteome analysis as a useful tool for developing novel monitoring biomarkers for patients with recurrent EOC. Full article

Homologous recombination deficiency (HRD) is a key biomarker associated with increased sensitivity to PARP inhibitors (PARPi) in advanced epithelial ovarian cancer. Accurate identification of HRD status is essential for selecting patients most likely to benefit from these therapies. Current diagnostic approaches combine sequencing to detect mutations in homologous recombination repair genes—particularly BRCA1 and BRCA2—with genome-wide analysis of structural genomic alterations indicative of HRD. This review briefly outlines the biological basis of HRD and its clinical significance and then focuses on currently available assays for HRD assessment. We compare their molecular strategies, including the use of targeted gene panels and genomic instability metrics such as loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions. The review also highlights the strengths and limitations of each platform and discusses their role in guiding clinical decision-making. Challenges related to dynamic tumor evolution and the interpretation of HRD status in recurrent disease settings are also addressed. Full article

Background: Cisplatin resistance is a major cause of tumor recurrence and mortality in high-grade serous ovarian cancer (HGSOC). Extrachromosomal circular DNA (eccDNA) has emerged as a critical factor in tumor evolution and drug resistance. However, the specific contribution of eccDNA to cisplatin resistance in HGSOC remains unclear. Methods: We performed whole-genome sequencing, Circle-Seq, and RNA-Seq in four pairs of primary and cisplatin-resistant (cisR) HGSOC cell lines to characterize genome-wide eccDNA distribution and features. Functional enrichment analyses were subsequently conducted on differentially expressed eccDNA-related genes. Results: In the SKOV3 cisR cell line, we identified a large extrachromosomal circular DNA (ecDNA) carrying the HIF1A gene, which regulates DNA repair, drug efflux, and epithelial–mesenchymal transition, contributing to cisplatin resistance. Using Circle-Seq, we detected a total of 161,062 eccDNAs, most of which were less than 1000 bp and distributed across all chromosomes. Notably, the number of eccDNAs on chromosome 21 differed significantly between the primary and cisR cell lines. Additionally, eccDNAs were predominantly located in non-coding repetitive elements. Functional analysis of eccDNA-related differentially expressed genes revealed that, compared to primary cell lines, cisR cell lines were associated with mitotic spindle assembly, regulation of vascular permeability, and cell differentiation. eccDNA-related genes involved in these pathways include MISP, WIPF1, RHOD, KRT80, and PLVAP. Conclusions: Our findings suggest that eccDNAs, particularly ecDNA amplifications like HIF1A, contribute significantly to cisplatin resistance mechanisms in HGSOC. These insights highlight eccDNA as a potential target for overcoming therapeutic resistance and improving treatment outcomes in ovarian cancer. Full article

Background/Objectives: Due to the rarity and histological heterogeneity of non-epithelial ovarian cancers (NEOCs), monitoring their reproductive and oncological outcomes is challenging. Therefore, this study aimed to investigate the oncological and reproductive outcomes of patients with NEOCs treated with fertility-sparing surgery over the past 10 years at our tertiary referral university clinic. Methods: This retrospective study included all the NEOC patients diagnosed and treated with fertility-sparing surgery from 2010 to 2019. The patient demographic and clinical characteristics; data regarding the treatment andthe clinical, laboratory, and imaging findings during follow-up; and disease recurrences were recorded. In this study, the recurrence-free survival and the overall survival were the oncological outcomes. The reproductive outcomes were assessed as attempting and achieving pregnancy. Results: This study included 39 patients. The most frequent NEOCs were granulosa cell tumors (53.8%). The majority of the tumors were in the IA or IC1 stage. The initial therapy was generally a unilateral salpingo-oophorectomy (30.8%). Adjuvant chemotherapy was received by 48.7% of the patients. An NEOC recurrence was registered in 25.6% of the patients, mostly during the first two postoperative years. The recurrence-free survival was 76.92%. A regression analysis showed that amore advanced stage of NEOC was the most important predictor of disease recurrence. The overall survival rate was 87.2%, with a mean time to an adverse outcome of 23.01 +/−10.68 months. The regression analysis showed that better survival depended mostly on not having disease recurrence. After treatment, ten patients tried to conceive and seven succeeded. All the children were in good condition upon birth. Conclusions: Fertility-sparing treatment for NEOCs was proven as a safe and successful option in terms of both oncological and reproductive outcomes. Full article

Ovarian cancer (OC) is a global health problem that frequently presents at advanced stages, is predisposed to recurrence, readily develops resistance to platinum-based drugs, and has a low survival rate. Predictive, preventive, and personalized medicine (PPPM/3PM) offers an integrated solution with the use of genetic, proteomic, and metabolic biomarkers to identify high-risk individuals for early detection. Metabolic reprogramming is one of the key strategies employed by tumor cells to adapt to the microenvironment and support unlimited proliferation. Pyruvate kinases M1 and M2 (PKM1/2) are encoded by the PKM gene, a pivotal enzyme in the last step of the glycolytic pathway, which is at the crossroads of aerobic oxidation and the Warburg effect to serve as a potential regulator of glucose metabolism and influence cellular energy production and metabolic reprogramming. Commonly, the ratio of PKM1-to-PKM2 is changed in tumors compared to normal controls, and PKM2 is highly expressed in OC to induce a high glycolysis rate and participate in the malignant invasion and metastatic characteristics of cancer cells with epithelial/mesenchymal transition (EMT). PKM2 inhibitors suppress the migration and growth of OC cells by interfering with the Warburg effect. Proteoforms are the final structural and functional forms of a gene/protein, and the canonical protein PKM contains all proteoforms encoded by the same PKM gene. The complexity of PKM can be elucidated by proteoformics. The OC-specific PKM proteoform might represent a specific target for therapeutic interventions against OC. In the framework of PPPM/3PM, the OC-specific PKM proteoform might be the early warning and prognosis biomarker. It is important to clarify the molecular mechanisms of PKM proteoforms in cancer metabolism. This review analyzes the expression, function, and molecular mechanisms of PKM proteoforms in OC, which help identify specific biomarkers for OC. Full article

Background: Serous epithelial ovarian cancer is typically diagnosed at an advanced stage and often recurs following treatment. Isolated organ recurrence is rare in this disease, making treatment planning a critical decision. Therefore, we investigated the survival rates of patients who developed isolated liver recurrence. Methods: The entire cohort included patients who underwent cytoreductive surgery between January 1993 and December 2020. We evaluated patients who completed primary chemotherapy after cytoreductive surgery based on their status of isolated liver recurrence. We created two groups: patients with isolated parenchymal recurrence and patients with isolated capsular recurrence. Staging was based on the International Federation of Gynecology and Obstetrics (FIGO) 2014 staging criteria. For patients treated before 2014, cancer staging was adapted to the FIGO 2014 system based on a surgical and pathological assessment. Results: The mean ages of patients with liver capsule and parenchymal recurrence at the time of primary surgery were 47 ± 10.6 and 49 ± 8.9 years, respectively. The median recurrence of patients with capsular recurrence was 13 (2–70) months. In patients with parenchymal recurrence, the duration was 10 months (4–80) and was statistically insignificant. While survival was 41.5 (5–120) months in patients with capsular recurrence, it was 34 (12–120) months in patients with parenchymal recurrence, but there was no statistical difference. Conclusions: In our 27 years’ of experience with EOC management, we have studied patients with isolated liver recurrences. The finding that either capsular or parenchymal liver recurrence has no significant impact on overall survival suggests that both types of recurrence can be managed with similar treatment and follow-up approaches. This observation could simplify patient management and improve outcomes by allowing clinicians to focus on optimal surgical and systemic treatment strategies rather than the anatomic pattern of recurrence. Full article

Background/Objectives: Hyperthermic intraperitoneal chemotherapy (HIPEC) was revealed as a promising adjunct to cytoreductive surgery (CRS) in the treatment of advanced epithelial ovarian cancer (EOC). This review evaluated the impact HIPEC had on survival outcomes, recurrence patterns and safety in patients that underwent HIPEC in conjunction with interval and secondary CRS for advanced and recurrent ovarian cancer. Methods: A thorough search was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar to identify relevant studies published until 1 January 2025. The studies were assessed for survival outcomes, recurrence patterns, safety, and quality of life. The risk of bias was evaluated using the ROB 2 tool for randomized and ROBINS-I for non-randomized articles. The results are presented narratively, highlighting key findings, comparing results and assessing inconsistencies and limitations. Results: HIPEC demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in cases with optimal cytoreduction (CC-0/CC-1). The recurrence patterns showed a reduction in peritoneal dissemination with HIPEC, although extraperitoneal recurrences were reported in some cases. Most studies reported comparable morbidity rates between HIPEC and non-HIPEC groups, with acceptable safety profiles. The variability in the HIPEC protocols and the limited quality-of-life and cost-effectiveness data were noteworthy limitations. Conclusions: HIPEC, when performed during interval or secondary CRS, offers survival benefits and can modify recurrence patterns in advanced EOC, although challenges related to protocol standardization, patient selection, and long-term outcomes persist. Future research should focus on multicenter trials with uniform protocols, long follow-up periods and patient-centered outcomes to further validate the role of HIPEC in clinical practice. Full article

Ovarian cancer (OC) is characterized by high mortality rates due to late diagnosis, recurrence, and metastasis. Here, we show that extracellular signaling molecules secreted by adipose-derived mesenchymal stem cells (ASCs) and OC cells—either in the conditioned medium (CM) or within small extracellular vesicles (sEVs)—modulate cellular responses and drive OC progression. ASC-derived sEVs and CM secretome promoted OC cell colony formation, invasion, and migration while upregulating tumor-associated signaling pathways, including TGFβ/Smad, p38MAPK/ERK1/2, Wnt/β-catenin, and MMP-9. Additionally, OC-derived sEVs and CM induced a pro-tumorigenic phenotype in ASCs, enhancing their invasiveness and expression of tumor-associated factors. Notably, both ASCs and OC cells exhibited increased expression of E-cadherin and Snail/Slug proteins, key markers of epithelial/mesenchymal hybrid phenotype, enhancing cellular plasticity and metastatic potential. We also demonstrated that these cellular features are, at least in part, due to the presence of tumor-supportive molecules such as TNF-α, Tenascin-C, MMP-2, and SDF-1α in the CM secretome of ASCs and OC cells. In silico analyses linked these molecular changes to poor prognostic outcomes in OC patients. These findings highlight the critical role of sEVs and tumor/stem cell-derived secretome in OC progression through bidirectional interactions that impact cellular behavior and phenotypic transitions. We suggest that targeting EV-mediated communication could improve therapeutic strategies and patient outcomes. Full article

Background: The objective in epithelial ovarian cancer is to reach maximal cytoreduction with no visible residual tumor. Tumor detection during cytoreductive surgery depends on visual inspection, palpation, or blind biopsy, methods that lack reliability for identifying microscopic disease. Although the importance of microscopic disease in epithelial ovarian cancer is controversial, it may harbor chemoresistant cells and explain the high recurrence rates. Fluorescence-guided surgery (FGS) is an emerging approach. However, the potential in ovarian cancer remains underexplored; the majority of the existing evidence pertains to gastrointestinal tumors and a limited group of ovarian cancer patients. Their comparative effectiveness is still uncertain. Objective: To systematically review and evaluate the role of fluorescence-guided surgical techniques in detecting microscopic disease in ovarian cancer and compare their efficacy to total peritonectomy. Data Sources: A systematic search was made in three databases (PubMed, Web of Science, and Embase). The search was conducted from 1975 to 2024, including randomized controlled trials, observational studies, and conference abstracts in the last 25 years. Study Selection: Clinical studies published in English involving ovarian cancer patients undergoing FGS or total peritonectomy were included. Case reports, reviews, animal studies, and studies involving mixed cancer populations without ovarian cancer-specific data were excluded. Two independent reviewers screened 631 studies, yielding 12 eligible studies for final analysis. Data Extraction and Synthesis: Data were extracted and synthesized in accordance with PRISMA and MOOSE guidelines, using random-effects models for independent analysis. Sensitivity, specificity, positive predictive value (PPV), and odds ratios (ORs) were grouped, accompanied by subgroup analyses based on the fluorescence agent employed. For quality assessment, we utilized the NIH quality tool. Main Outcome(s) and Measure(s): The primary outcome was the rate of change in surgical management due to fluorescence guidance or total peritonectomy. Secondary outcomes comprised lesion-level sensitivity, specificity, and PPV. Safety outcomes included adverse events associated with fluorescence agents. Results: There were 12 studies involving 429 ovarian cancer patients. FGS improved the detection of microscopic disease compared to standard visualization methods, with a pooled sensitivity of 0.77. Folate receptor-targeted agents had high sensitivity (84%) but low specificity (26%). Aminolevulinic acid (5-ALA) showed superior diagnostic accuracy with a sensitivity of 84% and a specificity of 96%. Total peritonectomy showed no significant advantage over FGS for detecting microscopic disease. The adverse events were mild, with no serious events reported. We observed a high heterogeneity across studies and methodologies. Conclusions and Relevance: Fluorescence-guided surgery utilizing fluorescence tracers demonstrates potential in improving the detection of microscopic disease and may change surgical management in epithelial ovarian cancer, particularly with 5-ALA. Variability in performance and limited data on survival outcomes necessitates additional research. Total peritonectomy does not offer further advantage in the detection of microscopic disease. Future trials should focus on standardizing methodology and evaluating the effects of microscopic disease removal on survival outcomes. Registration: The study was registered to PROSPERO as CRD42024578274. Full article

Background and Objectives: Epithelial ovarian–tubal–peritoneal cancer (EOC) is the most common type of ovarian cancer. Optimal cytoreductive surgery is the most important prognostic factor in its management. When complete cytoreduction is anticipated to be challenging, neoadjuvant systemic chemotherapy (NACT) becomes an alternative. Imaging modalities are utilized in the decision-making process for primary treatment. The purpose of this study is to evaluate the diagnostic performance and accuracy of preoperative MRI, CT, and 18F-FDG PET/CT in detecting the extent of EOC. Materials and Methods: Between 2017 and 2018, 24 patients with primary (with or without neoadjuvant chemotherapy) or recurrent EOC diagnosed at the Department of Gynecologic Oncology, Istanbul University, Istanbul Faculty of Medicine, were enrolled in this study. These 24 women underwent preoperative imaging modalities within 7 days prior to surgery. The results were compared with histopathological findings, considered the gold standard. Results: We evaluated 24 anatomic regions most commonly involved in EOC. The sensitivity of MRI, CT, and PET/CT in detecting ≥ 0.5 cm implants was 95%, 84%, and 86%, respectively. However, when including implants < 0.5 cm, sensitivity decreased significantly to 40%, 38%, and 42%, respectively. The calculated area under the curve (AUC) for tumors, including those < 0.5 cm, was evaluated as weak for all three modalities (MRI: 0.689, CT: 0.678, PET/CT: 0.691), with PET/CT detecting the largest area. For detecting tumors ≥ 0.5 cm, the AUCs were 0.974, 0.921, and 0.923 for MRI, CT, and PET/CT, respectively. The largest AUC was calculated with MRI, and the AUCs for all three methods were evaluated as excellent. Accuracy was comparable among all three imaging modalities, and no statistically significant differences were found (p < 0.05). Conclusions: While imaging modalities are valuable tools for evaluating abdominal spread in epithelial ovarian cancer (EOC), they have demonstrated limited success in detecting miliary disease. The risk of false negatives for miliary tumors on PET/CT may be mitigated by combining it with other imaging modalities such as MRI or CT. Further investigations are necessary to identify more accurate imaging techniques for this challenging clinical scenario. Full article

Background/Objective: Platinum-resistant ovarian cancer (PROC) has limited therapeutic options, and the role of cytoreductive surgery (CRS) in improving survival outcomes remains uncertain. We performed a systematic review to evaluate the oncological benefit of CRS on PROC patients and the associated surgical morbidity and mortality. Methods: We followed a prospective protocol according to PRISMA guidelines. We searched PubMed, Medline, and Embase till October 2024. We used a “Population Intervention Comparator Outcomes (PICO)” framework. Our population included women with epithelial PROC who underwent CRS with/without chemotherapy. Our outcomes included overall survival (OS), progression-free-survival (PFS), post-operative morbidity and mortality and Quality of Life. Results: Our search yielded 6590 citations; six studies (N = 155 patients) were included. There is limited evidence available on the role of CRS in PROC, with notable variation in reported outcomes and outcomes’ measures; therefore, we were unable to perform quantitative synthesis. CRS demonstrated survival benefits in well-selected PROC patients, particularly those with limited, isolated recurrences, low tumour burden, and good performance status. Complete resection (R0) was associated with significantly longer OS/PFS compared to those who had suboptimal surgeries (R1/R2). Conclusions: CRS seems to extend survival in carefully selected PROC patients, especially those with limited disease spread and favourable surgical profiles. Nevertheless, CRS carries substantial surgical risks, and its benefits appear contingent upon achieving R0. Further prospective trials with standardised patient selection criteria are needed to define CRS’s role in PROC. At present, CRS in PROC should be considered within a multidisciplinary approach in specialised gynaecological oncology centres, with the careful assessment of patient-specific risk factors and potential for R0 resection. Full article

The enzyme topoisomerase II alpha (TOP2A) plays a critical role in DNA replication and cell proliferation, making it a promising target for cancer therapy. In epithelial ovarian cancer (EOC), TOP2A overexpression is associated with poor prognosis and resistance to conventional treatments. This review explores the biological functions of TOP2A in EOC and discusses its potential as a therapeutic target. We highlight studies on the mechanisms through which TOP2A contributes to tumor progression and recurrence. Additionally, we evaluate the clinical implications of targeting TOP2A, including the use of TOP2A inhibitors and their combination with novel drugs. We provide a comprehensive overview of the current understanding and future directions for targeting TOP2A in the management of EOC. Full article