Recurrent Ovarian Cancer Research Articles

Oncolytic adenovirus MEM-288 encoding membrane-stable CD40L and IFNβ induces an anti-tumor immune response in high grade serous ovarian cancer

Single agent immune checkpoint inhibitors have been ineffective for patients with advanced stage and recurrent high grade serous ovarian cancer (HGSOC). Using pre-clinical models of HGSOC, we evaluated the anti-tumor and immune stimulatory effects of an oncolytic adenovirus, MEM-288. This conditionally replicative virus encodes a modified membrane stable CD40L and IFNβ. We demonstrated this virus successfully infects HGSOC cell lines and primary human ascites samples in vitro. We evaluated the anti-tumor and immunostimulatory activity in vivo in immune competent mouse models. Intraperitoneal delivery of MEM-288 decreased ascites and solid tumor burden compared to controls, and treatment generated a systemic anti-tumor immune response. The tumor microenvironment had a higher proportion of anti-tumor macrophages and decreased markers of angiogenesis. MEM-288 is a promising immunotherapy agent in HGSOC, with further pre-clinical studies required to understand the mechanism of action in the peritoneal microenvironment and clinical activity in combination with other therapies.

Robotic Recto-Sigmoid Resection with Total Intracorporeal Colorectal Anastomosis (TICA) in Recurrent Ovarian Cancer

BackgroundAbout 70% of women affected by ovarian cancer experience relapse within 2 years of diagnosis. Traditionally, the standard treatment for recurrent ovarian cancer (ROC) has been represented by systemic chemotherapy.1 Recently, several retrospective studies have suggested that secondary cytoreductive surgery could provide better clinical outcomes than chemotherapy alone, in the case of complete tumor cytoreduction.2,3 About 50% of patients with ROC have a pelvic component of the disease and 22% of patients present isolated pelvic recurrence, often involving the rectum.4,5 Minimally invasive secondary cytoreductive surgery is a feasible option and is associated with favorable perioperative outcomes.6–8 It is crucial to fully explore the peritoneal cavity before starting cytoreductive procedures in order to confirm the absence of carcinomatosis.9 The robotic system facilitates the identification of anatomical structures and makes it easier to perform complex surgical steps in narrow spaces. It also allows the integrated use of surgical tools such as intraoperative ultrasound and indocyanine green application.MethodsIn this video, we present the case of a 64-year-old woman who experienced a rectal recurrence of ovarian cancer after a platinum-free interval of 12 months. We describe, in a step-by-step manner, the surgical procedure of a robotic rectosigmoid resection with totally intracorporeal colorectal anastomosis (TICA).10–12ResultsRobotic secondary cytoreduction with complete gross resection was achieved. The patient did not report any intraoperative or postoperative complications. Final histology confirmed ROC.ConclusionTotally robotic rectosigmoid resection is a feasible option in isolated bowel recurrences. Thanks to continuous technical evolution, robot-assisted surgery has the potential to have a central role in the fight against solid tumors. Integration of multiple pre- and intraoperative technologies allows personalized surgery to be performed for each different patient.13,14

Comparison of CA-125 and HE4 in ovarian cancer recurrence detection

Purpose: This study aims to comprehensively evaluate CA-125 and HE4 as predictors of ovarian cancer (OC) recurrence in the same patient population. Methods: We systematically searched the WOS, PubMed, and Scopus databases on May 8, 2024, for studies investigating both tumor markers CA-125 and HE4 in the same patient population of ovarian cancer recurrence. We calculated pooled values of AUC, sensitivity, specificity, and univariate or multivariate hazard ratios (HR) for both tumor markers in serum using a random effects model and StataMP 17.0 software. Results: Thirteen articles comprising 1026 patients satisfied the inclusion criteria. Liquid-biopsy-based HE4 and CA-125 measurements were both proven to have high predictive value for detecting OC recurrence with comparable AUC values (AUCHE4:0.78, 95% CI=0.73-0.83; AUCCA125:0.80, 95% CI=0.73-0.88). While sensitivity of HE4 tests was higher than their specificity (SensitivityHE4=80.7%; 95% CI=73-88.4; I²=77.05%; p

Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT): protocol for an open-label, multicenter, umbrella study

BackgroundPlatinum-resistant, recurrent ovarian cancer has an abysmal prognosis with limited treatment options. Poly-(ADP-ribose)-polymerase (PARP), angiogenesis, and immune checkpoint inhibitors might improve the outcomes of platinum-resistant, recurrent ovarian cancer, but accurate...

An Emulated Target Trial Case Study of Real-World Overall Survival With Second-Line Maintenance Niraparib Versus Active Surveillance in Patients With Recurrent Ovarian Cancer.

This retrospective real-world study compared overall survival (OS) between patients with BRCA wild-type (BRCAwt) recurrent epithelial ovarian cancer (OC) who received niraparib second-line maintenance (2LM) versus active surveillance (AS) using target trial emulation, cloning, inverse probability of censoring weighting (IPCW) methodology to minimize immortal time bias. Eligible patients from a United States-based, deidentified, electronic health record-derived database were diagnosed with epithelial OC (January 1, 2011-May 31, 2021), were BRCAwt, and completed second-line (2L) therapy (January 1, 2017-March 2, 2022). Patient data were cloned at index (2L last treatment date), assigned to niraparib 2LM and AS cohorts, and censored when treatment deviated from clone assignment. Follow-up was measured from index to earliest of study end (May 31, 2022), last activity, or death. Median OS (mOS) and hazard ratios were estimated from stabilized IPCW Kaplan-Meier curves and Cox regression models. Overall, 199 patients received niraparib 2LM, and 707 had their care managed with AS. Key characteristics were balanced across cohorts after cloning and stabilized IPCW. Median follow-up was 15.6- and 9.3-months pre-cloning. IPCW mOS was 24.1 months (95% CI: 20.9-29.5) and 18.4 months (95% CI: 15.1-22.8) in niraparib 2LM and AS cohorts, respectively (hazard ratio, 0.77; 95% CI: 0.66-0.89). This real-world study provides supportive evidence of an OS benefit for patients with BRCAwt recurrent OC who received 2LM niraparib monotherapy compared with those whose care was managed with AS. The analytic strategies implemented were useful in minimizing immortal time bias and measured confounding.

778P Efficacy and safety of pamiparib monotherapy in recurrent ovarian cancer (rOC) after prior PARPi exposure: A prospective, open label, single-arm, phase II study

778P Efficacy and safety of pamiparib monotherapy in recurrent ovarian cancer (rOC) after prior PARPi exposure: A prospective, open label, single-arm, phase II study

718MO Mirvetuximab soravtansine (MIRV) in recurrent platinum-sensitive ovarian cancer (PSOC) with high folate receptor-alpha (FRα) expression: Results from the PICCOLO trial

718MO Mirvetuximab soravtansine (MIRV) in recurrent platinum-sensitive ovarian cancer (PSOC) with high folate receptor-alpha (FRα) expression: Results from the PICCOLO trial

757P Sustained long-term responders to niraparib maintenance in recurrent platinum-sensitive high-grade ovarian cancer (PSROC): A subanalysis of the GEICO-88R study

757P Sustained long-term responders to niraparib maintenance in recurrent platinum-sensitive high-grade ovarian cancer (PSROC): A subanalysis of the GEICO-88R study

749P Luveltamab tazevibulin, an antifolate receptor alpha (FRα) antibody-drug conjugate (ADC), in combination with bevacizumab (bev) in patients with recurrent high-grade epithelial ovarian cancer (EOC): STRO-002-GM2 phase I study

749P Luveltamab tazevibulin, an antifolate receptor alpha (FRα) antibody-drug conjugate (ADC), in combination with bevacizumab (bev) in patients with recurrent high-grade epithelial ovarian cancer (EOC): STRO-002-GM2 phase I study

764P How long is long enough? An international survey exploring practice variations on the recommended duration of maintenance therapy with PARP inhibitors in platinum sensitive recurrent ovarian cancer and long-term outcomes

764P How long is long enough? An international survey exploring practice variations on the recommended duration of maintenance therapy with PARP inhibitors in platinum sensitive recurrent ovarian cancer and long-term outcomes

766P A phase II trial of fuzuloparib in combination with apatinib vs. fuzuloparib alone for recurrent ovarian cancer (OC)

766P A phase II trial of fuzuloparib in combination with apatinib vs. fuzuloparib alone for recurrent ovarian cancer (OC)

754P Initial results from a first-in-human study of AZD5335, a folate receptor α (FRα)-targeted antibody-drug conjugate, in patients (pts) with platinum-resistant recurrent ovarian cancer (PRROC)

754P Initial results from a first-in-human study of AZD5335, a folate receptor α (FRα)-targeted antibody-drug conjugate, in patients (pts) with platinum-resistant recurrent ovarian cancer (PRROC)

Mediastinal Metastasis Isolated in Ovarian Cancer: A Systematic Review.

Isolated mediastinal metastases from ovarian carcinoma are considered exceptional. Since such metastases are considered advanced stage disease, systemic therapy is the indicated therapeutic approach; however, some articles report that surgical excision is also feasible. We reviewed the English-language literature to detect cases of isolated mediastinal ovarian cancer metastases and present the management applied as well as their outcomes. From 1998 to 2022, 15 such cases have been reported, with 4 of those cases being primary ovarian cancer presentation and 11 being ovarian cancer recurrence. The histology of the tumor was serious in all of the cases. Regarding the management of cancer, various methods were applied. In total, 11 of the patients underwent a surgical resection of the mediastinal metastasis, 2 received systemic therapy, 1 received a combination of palliative chemotherapy and radiation and the last patient was treated with laser debulking and radiotherapy. The mean reported follow-up was 11 months. Solitary mediastinal metastasis from ovarian cancer is very rare; physicians should pay close attention when routinely evaluating thoracic scans from patients with ovarian malignancy as well as individualizing the management in such patients, since surgical resection can also be performed. However, definitive conclusions cannot be drawn from the small number of case reports available.

Assessment of the efficacy and safety of anlotinib for the treatment of recurrent epithelial ovarian cancer

ObjectiveThe current research aims to evaluate the efficacy and safety of anlotinib, an orally administered small-molecular tyrosine kinase inhibitor (TKI), in the treatment of recurrent epithelial ovarian cancer (EOC).MethodsPatients with recurrent EOC subjected to treatment with anlotinib in Fourth Hospital of Hebei Medical University from 2020 to 2022 were included. The evaluation involved a thorough review of medical records, focusing on parameters such as the objective response rate (ORR), disease control rate (DCR), survival outcomes, and safety profile.ResultsThis study recorded 51 patients, with 26 patients undergoing anlotinib monotherapy. The median progression-free survival (PFS) was 4.0 months, whereas the median overall survival (OS) was not reached. Seven cases underwent a combined treatment of anlotinib with chemotherapy. Among them, two patients achieved partial response (PR), two were categorized as stable disease (SD), and three were identified as having progressive disease (PD). The ORR and DCR were 28.5% (2/7) and 57.1% (4/7), respectively. Additionally, 18 cases received anlotinib maintenance therapy, and the median PFS and the median OS were 7.0 months and 25.5 months, respectively. The most prevalent adverse effects included fatigue (38.6%), hypertension (27.3%), nausea and vomiting (25.0%) and hand-foot syndrome (25.0%).ConclusionAnlotinib demonstrated mild efficacy in the treatment of recurrent EOC, whether employed as monotherapy, chemotherapy-combined therapy, or maintenance therapy. The safety profile was proven manageable and well-tolerated, suggesting that anlotinib may emerge as a viable and novel treatment option for recurrent EOC.

A lightweight recurrence prediction model for high grade serous ovarian cancer based on hierarchical transformer fusion metadata

High-grade serous ovarian cancer has a high degree of malignancy, and at detection, it is prone to infiltration of surrounding soft tissues, as well as metastasis to the peritoneum and lymph nodes, peritoneal seeding, and distant metastasis. Whether recurrence occurs becomes an important reference for surgical planning and treatment methods for this disease. Current recurrence prediction models do not consider the potential pathological relationships between internal tissues of the entire ovary. They use convolutional neural networks to extract local region features for judgment, but the accuracy is low, and the cost is high. To address this issue, this paper proposes a new lightweight deep learning algorithm model for predicting recurrence of high-grade serous ovarian cancer. The model first uses ghost convolution (Ghost Conv) and coordinate attention (CA) to establish ghost counter residual (SCblock) modules to extract local feature information from images. Then, it captures global information and integrates multi-level information through proposed layered fusion Transformer (STblock) modules to enhance interaction between different layers. The Transformer module unfolds the feature map to compute corresponding region blocks, then folds it back to reduce computational cost. Finally, each STblock module fuses deep and shallow layer depth information and incorporates patient's clinical metadata for recurrence prediction. Experimental results show that compared to the mainstream lightweight mobile visual Transformer (MobileViT) network, the proposed slicer visual Transformer (SlicerViT) network improves accuracy, precision, sensitivity, and F1 score, with only 1/6 of the computational cost and half the parameter count. This research confirms that the proposed algorithm model is more accurate and efficient in predicting recurrence of high-grade serous ovarian cancer. In the future, it can serve as an auxiliary diagnostic technique to improve patient survival rates and facilitate the application of the model in embedded devices.

TEDOVA: vaccine OSE2101 +/- pembrolizumab as maintenance in platinum-sensitive recurrent ovarian cancer.

Ovarian cancer is a leading cause of death from gynecological cancers worldwide. Platinum-based chemotherapy provides the cornerstone of the medical management. In first line and subsequent relapses, maintenance strategies are offered to prolong intervals between lines of chemotherapy. Current maintenance options involve bevacizumab and poly ADP-ribose polymerase inhibitors, but these lines of therapy can only be used once in the disease course. Patients in first or second platinum sensitive relapse after poly ADP-ribose polymerase inhibitors and bevacizumab represent an area of unmet medical need. This academic sponsored, international Phase II randomized trial is evaluating the combination of a therapeutic cancer vaccine (OSE2101) with anti-PD1 (pembrolizumab) as maintenance therapy, in patients with platinum-sensitive recurrence regardless of number of prior lines and no progression after platinum-based chemotherapy.Clinical Trial Registration: NCT04713514 (ClinicalTrials.gov).

Comparison of Weekly Paclitaxel Regimens in Recurrent Platinum-Resistant Ovarian Cancer: A Single Institution Retrospective Study.

Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better tolerability profile without compromising efficacy.

KELIM score predicts outcome in patients with platinum-resistant/refractory recurrent ovarian cancer.

KELIM score predicts outcome in patients with platinum-resistant/refractory recurrent ovarian cancer.

Synergistic antitumor effect of liposomal-based formulations of olaparib and topotecan in primary epithelial ovarian cancer cells

BackgroundOlaparib is a PARP inhibitor inducing synthetic lethality in tumors with deficient homologous recombination (HRD) caused by BRCA1/2 mutations. The FDA has approved monotherapy for first-line platinum-sensitive, recurrent high-grade epithelial ovarian cancer. Combination therapy alongside DNA-damaging therapeutics is a promising solution to overcome the limited efficacy in patients with HRD. The present study was designed to develop topotecan- and olaparib-loaded liposomes (TLL and OLL) and assess the effectiveness of their combination in patient-derived ovarian cancer samples.MethodsWe used HEOC, four clear-cell tumors (EOC 1–4), malignant ascites, and an OCI-E1p endometrioid primary ovarian cancer cell line and performed NGS analysis of BRCA1/2 mutation status. Antiproliferative activity was determined with the MTT assay. The Chou-Talalay algorithm was used to investigate the in vitro pharmacodynamic interactions of TLLs and OLLs.ResultsThe OLL showed significantly higher efficacy in all ovarian cancer types with wild-type BRCA1/2 than a conventional formulation, suggesting potential for increased in vivo efficacy. The TLL revealed substantially higher toxicity to EOC 1, EOC 3, ascites and lower toxicity to HEOC than the standard formulation, suggesting better therapeutic efficacy and safety profile. The combination of studied compounds showed a higher reduction in cell viability than drugs used individually, demonstrating a synergistic antitumor effect at most of the selected concentrations.ConclusionsThe concentration-dependent response of different ovarian cancer cell types to combination therapy confirms the need for in vitro optimization to maximize drug cytotoxicity. The OLL and TLL combination is a promising formulation for further animal studies, especially for eliminating epithelial ovarian cancer with wild-type BRCA1/2.

Integrated analysis of spatial transcriptomics and CT phenotypes for unveiling the novel molecular characteristics of recurrent and non-recurrent high-grade serous ovarian cancer

BackgroundHigh-grade serous ovarian cancer (HGSOC), which is known for its heterogeneity, high recurrence rate, and metastasis, is often diagnosed after being dispersed in several sites, with about 80% of patients experiencing recurrence. Despite a better understanding of its metastatic nature, the survival rates of patients with HGSOC remain poor.MethodsOur study utilized spatial transcriptomics (ST) to interpret the tumor microenvironment and computed tomography (CT) to examine spatial characteristics in eight patients with HGSOC divided into recurrent (R) and challenging-to-collect non-recurrent (NR) groups.ResultsBy integrating ST data with public single-cell RNA sequencing data, bulk RNA sequencing data, and CT data, we identified specific cell population enrichments and differentially expressed genes that correlate with CT phenotypes. Importantly, we elucidated that tumor necrosis factor-α signaling via NF-κB, oxidative phosphorylation, G2/M checkpoint, E2F targets, and MYC targets served as an indicator of recurrence (poor prognostic markers), and these pathways were significantly enriched in both the R group and certain CT phenotypes. In addition, we identified numerous prognostic markers indicative of nonrecurrence (good prognostic markers). Downregulated expression of PTGDS was linked to a higher number of seeding sites (≥ 3) in both internal HGSOC samples and public HGSOC TCIA and TCGA samples. Additionally, lower PTGDS expression in the tumor and stromal regions was observed in the R group than in the NR group based on our ST data. Chemotaxis-related markers (CXCL14 and NTN4) and markers associated with immune modulation (DAPL1 and RNASE1) were also found to be good prognostic markers in our ST and radiogenomics analyses.ConclusionsThis study demonstrates the potential of radiogenomics, combining CT and ST, for identifying diagnostic and therapeutic targets for HGSOC, marking a step towards personalized medicine.