Recurrent Ovarian Cancer Research Articles

Intraperitoneal immunotherapy with denileukin diftitox (ONTAK) in recurrent refractory ovarian cancer

BackgroundDenileukin diftitox (ONTAK) is a diphtheria/IL-2R fusion protein able to deplete regulatory T cells in peripheral blood. Regulatory T cells in the local immune microenvironment have been shown to be associated with poor prognosis in ovarian cancer. This study examined whether denileukin diftitox (ONTAK) could be safely administered intraperitoneal in patients with advanced refractory ovarian cancer and assessed its effects on regulatory T cells and tumor associated cytokines in ascites and peripheral blood. Patients and methodsA phase I dose escalation study of intraperitoneal denileukin diftitox (ONTAK) enrolled 10 patients with advanced, refractory ovarian carcinoma at 3 doses (5 μg/kg, 15 μg/kg, and 25 μg/kg). Serial CA-125 measurements assessed clinical response. Regulatory T cells were quantified using RT-PCR and cytokine levels measured by Luminex. ResultsThe maximum tolerated dose was 15 μg/kg with a dose limiting toxicity observed in 1 out of 6 patients in the expansion group. The majority of adverse events were transient grades 1–2. One patient treated at the 25 μg/kg dose experienced cytokine storm with prolonged hospitalization. 3 patients had decreases in CA-125 after treatment but none met criteria for partial response. Treatment with denileukin diftitox (ONTAK) decreased regulatory T cells in peripheral blood and ascites. Treated patients did not show any significant changes in IL-8, TGF-β, sIL2Ra in ascites or peripheral blood. ConclusionsDenileukin diftitox (ONTAK) can be safely administered intraperitoneally to recurrent refractory ovarian cancer patients. Regulatory T cells were reduced in ascites and peripheral blood, but there were no significant changes in cytokine levels.Clinical Trial Registration:ClinicalTrials.gov # NCT00357448

Comparison of 68Ga-FAPI-04 and 18F-FDG PET/CT in diagnosing ovarian cancer.

This study assesses the diagnostic performance of 68Ga-FAPI-04 PET/CT compared to 18F-FDG PET/CT in primary, recurrent, and metastatic ovarian cancer. Seventy-nine ovarian cancer patients who performed 68Ga-FAPI-04 and 18F-FDG PET/CT were recruited. The target-to-background ratio (TBR), maximum standardized uptake value (SUVmax), the number of positive lesions, visual assessment, the peritoneal cancer index (PCI) score, staging/restaging, and treatment strategies were compared from the corresponding PET/CT. Additionally, we analyzed and contrasted the diagnostic efficacy in both scans. Among all patients, 6 were assessed for initial assessment and 73 for recurrence and metastasis detection. For all lesions, 68Ga-FAPI-04 PET/CT demonstrated greater TBR than 18F-FDG PET/CT. 68Ga-FAPI-04 PET/CT demonstrated higher sensitivity for peritoneal metastases including patient-based and lesion-based analysis (95.00% vs. 83.33%, P = 0.065; 90.16% vs. 60.66%, P < 0.001) and a higher PCI score [median PCI: 6 (4, 12) vs. 4 (2, 8), P < 0.001]. According to the visual assessment, 68Ga-FAPI-04 PET revealed larger extent metastases in 55.93% (33/59) of the patients with peritoneal metastases. 68Ga-FAPI-04 was upstaged in 7 patients (8.86%, 7/79) and discrepancies in both scans caused treatment strategies to change in 11 patients (13.92%, 11/79). 68Ga-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in identifying metastases and can be a potential supplement for managing ovarian cancer patients.

Potential shared gene signatures and molecular mechanisms between recurrent pregnancy loss and ovarian cancer

Potential shared gene signatures and molecular mechanisms between recurrent pregnancy loss and ovarian cancer

Innovative 3D Imaging in Pre-Operative Evaluation for Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer: A Pilot Study.

The efficacy of secondary cytoreductive surgery (SCS) in recurrent ovarian cancer remains controversial, necessitating meticulous preoperative planning. While 3D imaging has transformed surgical approaches in various disciplines, its application in gynaecologic oncology is nascent. This study introduces a novel investigation employing preoperative 3D modeling in SCS preparation. A retrospective analysis was undertaken at a university affiliated tertiary medical center, examining patients who underwent SCS for recurrent ovarian cancer between 2017 and 2022. Patients were stratified into two cohorts: those with pre-operative CT-based 3D imaging (Group A) and those without (Group B). Demographic profiles, clinical data, and surgical outcomes were compared between the groups. Among the 76 identified patients, 18 were deemed suitable for surgery, with 7 in Group A undergoing preoperative 3D modeling. Demographics encompassing age and performance status were consistent across both groups, while Serous histology was more prominent in Group B. Although operative metrics and collaborative endeavors exhibited no statistically significant variance, the attainment of optimal debulking with no residual disease (R0) was substantially higher in Group A (100%) compared to Group B (54%), with a significance level of P = 0.05. CT-based 3D modeling in the preoperative phase of secondary cytoreductive surgery for ovarian cancer shows potential for enhancing surgical planning. While this pioneering research highlights the potential benefits of integrating 3D imaging into gynaecologic oncology, the limitations of this retrospective study imply that these findings are primarily hypothesis-generating. Further prospective studies are necessary to validate impact.

Secondary cytoreductive surgery with HIPEC: a promising therapeutic option for recurrent ovarian cancer.

Secondary cytoreductive surgery with HIPEC: a promising therapeutic option for recurrent ovarian cancer.

Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial.

Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer. The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m2 in 2 L/m2 of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing trial is registered with ClinicalTrials.gov, NCT01376752. Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1-8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56-0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9-61·7) with HIPEC versus 45·8 months (38·9-54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] vs 30 [14%]), hepatotoxicity (23 [11%] vs 18 [9%]), electrolyte disturbance (28 [14%] vs two [1%]), and renal failure (20 [10%] vs three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group. Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When treating patients with late first relapse of high-grade serous or high-grade endometrioid ovarian cancer amenable to complete cytoreductive surgery at specialist centres, platinum-based HIPEC should be considered to extend overall survival. French National Cancer Institute and French League Against Cancer.

What are the harms and benefits of using pegylated liposomal doxorubicin in women with recurrent epithelial ovarian cancer, alone or in combination with other drugs? (Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review)

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Newhouse R, Nelissen E, El-Shakankery KH, Rogozińska E, Bain E, Veiga S, Morrison J. Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer. Cochrane Database of Systematic Reviews 2023, Issue 7. Art. No.: CD006910. DOI: 10.1002/14651858.CD006910.pub3.

Machine learning for epithelial ovarian cancer platinum resistance recurrence identification using routine clinical data

BackgroundMost epithelial ovarian cancer (EOC) eventually develops recurrence. Identification of high-risk patients can prompt earlier intervention and improve long-term outcomes. We used laboratory and clinical data to create models based on machine learning for EOC platinum resistance recurrence identification.MethodsThis study was designed as a retrospective cohort analysis. Initially, we identified 1,392 patients diagnosed with epithelial ovarian cancer who underwent platinum-based chemotherapy at Yunnan Cancer Hospital between January 1, 2012, and June 30, 2022. We collected data on the patients’ clinicopathologic characteristics, routine laboratory results, surgical information, details of chemotherapy regimens, and survival outcomes. Subsequently, to identify relevant variables influencing the recurrence of platinum resistance, we screened thirty potential factors using two distinct variable selection methods: Lasso regression and multiple logistic regression analysis. Following this screening process, five machine learning algorithms were employed to develop predictive models based on the selected variables. These included decision tree analysis (DTA), K-Nearest neighbor (KNN), support vector machine (SVM), random forest (RF), and eXtreme gradient boosting (XGBoost). The performance of these models was compared against that of traditional logistic regression. To ensure robust internal validation and facilitate comparison among model performance metrics, a five-fold cross-validation method was implemented. Key performance indicators for the models included the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and average accuracy. Finally, we will visualize these models through nomograms, decision tree diagrams, variable importance plots, etc., to assist clinicians in their practice.ResultsMultiple logistic regression analysis identified eight variables associated with platinum resistance recurrence. In the lasso regression, seven variables were selected. Based on the findings from both Lasso regression and multiple logistic regression analysis, models were developed using these 7 and 8 factors. Among these, the XGBoost model derived from multiple logistic regression exhibited superior performance and demonstrated good discrimination during internal validation, achieving an AUC of 0.784, a sensitivity of 0.735, a specificity of 0.713, an average accuracy of 80.4%, with a cut-off value set at 0.240. Conversely, the LR model based on lasso regression yielded commendable results as well; it achieved an AUC of 0.738, a sensitivity of 0.541, a specificity of 0.836, with a cut-off value established at 0.154 and an accuracy rate of 79.6%. Finally, we visualized both models through nomograms to illustrate the significance of each variable involved in their development.ConclusionsWe have successfully developed predictive models for platinum-resistant recurrence of epithelial ovarian cancer, utilizing routine clinical and laboratory data. Among these models, the XGBoost model—derived from variables selected through multiple logistic regression—demonstrated the best performance. It exhibited high AUC values and average accuracy during internal validation, making it a recommended tool for clinical use. However, due to variations in time and context, influencing factors may change over time; thus, continuous evolution of the model is necessary. We propose a framework for this ongoing model adaptation.

CD1a affects the recurrence and prognosis of ovarian cancer.

Explored the correlation between CD1a expression in recurrence and prognosis of ovarian cancer (OV). The CD1a expression profile in OV, recurrent OV, and normal tissues, as well as corresponding clinical data, were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), and Genotype Tissue Expression (GTEx) databases. Meanwhile, immunohistochemical detection of CD1a expression in normal and OV tissues. Kaplan-Meier curves were plotted to estimate the hazard ratio (HR) of survival in OV. In addition, the correlation between CD1a and immune cells in OV, as well as the CD1a expression profile and corresponding survival time in pan-cancer were obtained from TCGA database. CD1a was overexpressed in OV and was significantly under-expressed in recurrent OV (TCGA-OV, p < 0.0001 and ICGC-OV, p < 0.0001). CD1a immunohistochemistry is significantly overexpressed in OV compared to normal tissue (p < 0.05). Recurrent OV (ICGC, p < 0.001; GSE17260, p < 0.001; GSE32062, p < 0.05). The prognosis in OV was significantly better when CD1a is overexpressed compared to under-expressed (HR [low], 1.426: 95% confidence interval [CI], 0.912-2.128; p = 0.050). Meanwhile, the overexpression of CD1a has a better prognosis than low expression in OV and recurrent OV (p = 0.004, HR [low] = 2.462, 95%CI [1.346-4.504] and p = 0.011, HR [low] = 2.199, 95%CI [1.202-4.024]). In addition, CD1a expression was closely correlated with immune cells, the CD8+ T cells, macrophages, and NK cells, while uncharacterized cells were significantly different (p = 2.65e-6, p = 7.52e-13, p = 8.28e-12, and p = 5.89e-8, respectively). Moreover, CD1a expression affected the prognosis in various other cancers. CD1a expression affected the recurrence and prognosis of OV and is closely related to various immune cell levels.

Efficacy and safety of antiangiogenic therapy (bevacizumab or apatinib) plus chemotherapy in patients with platinum‑resistant recurrent ovarian cancer: A retrospective study

Efficacy and safety of antiangiogenic therapy (bevacizumab or apatinib) plus chemotherapy in patients with platinum‑resistant recurrent ovarian cancer: A retrospective study

Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging in Magnetic Resonance in the Assessment of Peritoneal Recurrence of Ovarian Cancer in Patients with or Without BRCA Mutation

Background: The aim of this study was to determine the differences in diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE) parameters between patients with peritoneal high-grade serous ovarian cancer (HGSOC) recurrence with BRCA mutations (BRCAmut) or BRCA wild type (BRCAwt). Materials and Methods: We retrospectively analyzed the abdominal and pelvic magnetic resonance (MR) images of 43 patients suspected of having recurrent HGSOC, of whom 18 had BRCA1/2 gene mutations. Patients underwent MRI examination via a 1.5 T MRI scanner, and the analyzed parameters were as follows: apparent diffusion coefficient (ADC), time to peak (TTP) and perfusion maximum enhancement (Perf. Max. En.). Results: The mean ADC in patients with BRCAwt was lower than that in patients with BRCAmut: 788.7 (SD: 139.5) vs. 977.3 (SD: 103), p-value = 0.00002. The average TTP value for patients with BRCAwt was greater than that for patients with mutations: 256.3 (SD: 50) vs. 160.6 (SD: 35.5), p-value &lt; 0.01. The Perf. Max. En. value was lower in the BRCAwt group: 148.6 (SD: 12.3) vs. 233.6 (SD: 29.2), p-value &lt; 0.01. Conclusion: Our study revealed a statistically significant correlation between DWI and DCE parameters in examinations of peritoneal metastasis in patients with BRCA1/2 mutations. Adding DCE perfusion to the MRI protocol for ovarian cancer recurrence in patients with BRCAmut may be a valuable tool.

The Efficacy and Safety of Folate Receptor α-Targeted Antibody-Drug Conjugate Therapy in Patients With High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers: A Systematic Review and Meta-Analysis.

Antibody-drug conjugates (ADC) have emerged as a highly promising systemic option in the treatment of recurrent ovarian cancer. The present study aimed to evaluate the treatment efficacy of folate receptor α (FRα)-targeting ADCs, associated treatment-related adverse events (TRAEs), and their impact on treatment safety. We conducted an electronic search to identify prospective trials of single-agent ADCs targeting FRα and those combined with chemotherapy in recurrent ovarian cancer. Information regarding the objective response rate (ORR) and TRAEs was collectively analyzed, and differences in subgroups based on FRα receptor expression levels were investigated. The protocol was registered with PROSPERO (CRD42023491151). Ten studies with a total of 940 patients (859 treated with Mirvetuximab soravtansine-gynx (MIRV)), 45 with Farletuzumab Ecteribulin (MORAb-202), and 36 with Luveltamab Tazevibulin (STRO-002) were included in this meta-analysis. Based on the pooled data, the ORR of the entire cohort was 37% (95% CI: 0.30-0.43), while that of the high-FRα expression group was 34% (95% CI: 0.26-0.42). The incidence of grade ≥ 3 adverse events was 27% (95% CI: 0.19-0.36). FRα-targeting ADCs, including MIRV, demonstrated definite efficacy and good safety as novel choices for second-line and beyond treatment of advanced or recurrent ovarian cancer. Patients with high FRα expression showed ORR and PFS benefits similar to those in the overall cohort.

GOG-3084: A phase II trial of ADP-A2M4CD8 TCR-T cell therapy, alone or in combination with nivolumab, among patients with recurrent ovarian cancers

GOG-3084: A phase II trial of ADP-A2M4CD8 TCR-T cell therapy, alone or in combination with nivolumab, among patients with recurrent ovarian cancers

A phase I/II study of ubamatamab (REGN4018), a MUC16xCD3 bispecific antibody, administered alone or in combination with cemiplimab (anti-PD-1) in patients with recurrent ovarian cancer or MUC16+ endometrial cancer: Trial in progress update

A phase I/II study of ubamatamab (REGN4018), a MUC16xCD3 bispecific antibody, administered alone or in combination with cemiplimab (anti-PD-1) in patients with recurrent ovarian cancer or MUC16+ endometrial cancer: Trial in progress update

The impact of financial hardship on symptoms and quality of life in recurrent ovarian cancer

The impact of financial hardship on symptoms and quality of life in recurrent ovarian cancer

Exposure-biomarker analyses for cytokine release syndrome or infusion-related reaction, pain, and cytokine concentrations in serum during treatment with ubamatamab, a MUC16xCD3 bispecific antibody, among patients with recurrent ovarian cancer

Exposure-biomarker analyses for cytokine release syndrome or infusion-related reaction, pain, and cytokine concentrations in serum during treatment with ubamatamab, a MUC16xCD3 bispecific antibody, among patients with recurrent ovarian cancer

Supervised machine learning with a novel set of 20 genes predicts the likelihood of early or late recurrence of high-grade serous ovarian cancer

Supervised machine learning with a novel set of 20 genes predicts the likelihood of early or late recurrence of high-grade serous ovarian cancer

A phase III, randomized trial evaluating avutometinib plus defactinib compared with investigator's choice of therapy among patients with recurrent low-grade serous ovarian cancer: GOG-3097/ENGOT-OV81/NCRI/RAMP 301

A phase III, randomized trial evaluating avutometinib plus defactinib compared with investigator's choice of therapy among patients with recurrent low-grade serous ovarian cancer: GOG-3097/ENGOT-OV81/NCRI/RAMP 301

COPANIRA: Phase Ib trial of copanlisib (PI3K inhibitor) and niraparib (PARP inhibitor) in recurrent ovarian and endometrial cancer

COPANIRA: Phase Ib trial of copanlisib (PI3K inhibitor) and niraparib (PARP inhibitor) in recurrent ovarian and endometrial cancer

Avutometinib plus defactinib in recurrent low-grade serous ovarian cancer: A subgroup analysis of ENGOT-OV60/GOG-3052/RAMP 201 Part A

Avutometinib plus defactinib in recurrent low-grade serous ovarian cancer: A subgroup analysis of ENGOT-OV60/GOG-3052/RAMP 201 Part A