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Background: The Platinum-based combination has been proven to have an outstanding effect on patients with platinum-sensitive recurrent ovarian cancer (PSROC), but the best scientific combination has not been established yet. The present study is aimed to seek the best treatment plan for PSROC. Methods: We did a systematic review and Bayesian network meta-analysis, during which lite before March 2022 were retrieved on PubMed, Embase, Web of Science, and Cochrane Central Registry of Controlled databases. We included randomized controlled clinical trials comparing chemotherapy combinations with other treatments for patients with PSROC. The important outcomes concerned were progression-free survival (PFS) (the primary outcome), overall survival (OS), objective response rate (ORR), adverse events (AEs), and AEs-related discontinuation. All outcomes were ranked according to the surface under the cumulative ranking curve. Results: 26 trials involving 10441 patients were retrieved in this study. For the initial treatment of PSROC, carboplatin plus pegylated liposomal doxorubicin (PLD) plus bevacizumab had the best PFS [hazard ratio (HR) 0.59, 95% credible interval (CI) 0.51–0.68]; Carboplatin plus paclitaxel plus bevacizumab resulted in the best OS (HR 1.22, 95% CI 1.09–1.35) and ORR [odds ratio (OR) 1.22, 95% CI 1.09–1.35]. For the maintenance therapy in PSROC, poly (ADP-ribose) polymerase inhibitors (PARPi) following platinum-based chemotherapy provided the best PFS (HR 0.64, 95% CI 0.61–0.68), the highest frequency of adverse events of grade three or higher (OR 0.18, 95% CI 0.07–0.44) but the treatment discontinuation was generally low. Subgroup analysis suggested that trabectedin plus PLD was comparable to single platinum in prolonging PFS in the platinum-free interval (6–12 months). Conclusion: Both platinum-based chemotherapy plus PARPi and platinum-based chemotherapy plus bevacizumab had higher survival benefits than other treatments in PSROC. Trabectedin plus PLD might be a potential alternative treatment strategy for the partially platinum-sensitive subpopulation with intolerance to platinum. Systematic Review Registration : [ https://www.crd.york.ac.uk/prospero/display_record.php? ], identifier [CRD42022326573].

Ovarian cancer is one of the most aggressive gynaecologic malignancies in women worldwide. The lack of proper screening programs and the characteristic abdominal spreading with minimal clinical symptoms give rise of its high lethality. Most patients show advanced disease at diagnosis and have a poor prognosis. The surveillance of ovarian cancer patients after initial treatment is a challenging question in clinical practice and there is no consensus in literature about the most appropriate follow-up strategy for these women. The role of Imaging has become increasingly important, allowing to properly monitor patients, distinguishing the different relapse patterns, thus guiding the correct management and therapy. In this review, we report and analyze the scientific evidence about the role of the different imaging modalities now available in the follow-up strategy and management of Epithelial Ovarian Cancer patients with recurrent disease.

The use of angiogenesis inhibitors and poly ADP-ribose polymerase inhibitors following multi-agent chemotherapy, including platinum-based agents, has become the standard treatment for platinum-sensitive recurrent ovarian cancer (PSROC). However, the optimal maintenance therapy and selection criteria for these patients remain unclear. Thus, this study aimed to optimize the treatment options and selection criteria for patients with PSROC. The clinical data of 51 patients with PSROC admitted to Nippon Medical School Chiba Hokusoh Hospital and Nippon Medical School Hospital were retrospectively collected. The log-rank test was used for the survival analysis, and Cox proportional hazard regression analysis was used for the multivariate survival analysis. Of the 51 patients, 17 received maintenance therapy with bevacizumab (Bev), and 34 received olaparib (Ola). Recurrence-free survival (RFS) was significantly prolonged in the Ola group (27 months; 95% confidence interval (CI), 19–NA months) compared with that in the Bev group (9 months; 95% CI, 5–22 months; p = 0.000103). The efficacy of Ola was independent of background factors, including response to previous chemotherapy, homologous recombination status, histological type, or laboratory data. Ola is superior to Bev as PSROC maintenance therapy, especially in Japanese and Asian populations.

Epithelial ovarian cancer (EOC) is usually diagnosed late at an advanced stage. Though EOC initially responds to treatment, the recurrence rate is pretty high. The efficacy of different targeted therapies reduces with each recurrence. Hence there is need of effective maintenance therapy in recurrent EOC. Recently, polyADP-ribose polymerase (PARP) inhibitors (PARPi) have been approved both for initial treatment of EOC and as its maintenance treatment. PARPi have also been found to act regardless of BRCA status or homologous recombination (HR) deficiency. Several trials testing PARPi early in maintenance therapy are in progress and their results will shed light on the optimal timing of maintenance therapy that gives the most benefit with least toxicity. Right patient selection for maintenance treatment is also a challenge. Hence, though PARPi are emerging as a promising maintenance treatment in recurrent EOC with prolongation of progression free survival (PFS), results from further trials and overall survival (OS) data from current trials are awaited to fulfill the gaps in understanding the role of this pathway in treatment of EOC. This review discusses the current therapies for EOC, challenges in the treatment of recurrent EOC, recent developments and trials in recurrent EOC maintenance with special focus on PARPi and future perspectives.

Background and AimWe report the results of an international consensus on hyperthermic intraperitoneal chemotherapy (HIPEC) regimens for epithelial ovarian cancer (EOC) performed with the following goals:To define the indications for HIPECTo identify the most suitable HIPEC regimens for each indication in EOCTo identify areas of future research on HIPECTo provide recommendations for some aspects of perioperative care for HIPECMethodsThe Delphi technique was used with two rounds of voting. There were three categories of questions: evidence-based recommendations [using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system with the patient, intervention, comparator, and outcome (PICO) method], an opinion survey, and research recommendations.ResultsSeventy-three (67.5%) of 108 invited experts responded in round I, and 68 (62.9%) in round II. Consensus was achieved for 34/38 (94.7%) questions. However, a strong positive consensus that would lead to inclusion in routine care was reached for only 6/38 (15.7%) questions. HIPEC in addition to interval cytoreductive surgery (CRS) received a strong positive recommendation that merits inclusion in routine care. Single-agent cisplatin was the only drug recommended for routine care, and OVHIPEC-1 was the most preferred regimen. The panel recommended performing HIPEC for a minimum of 60 min with a recommended minimum intraabdominal temperature of 41°C. Nephroprotection with sodium thiosulfate should be used for cisplatin HIPEC.ConclusionsThe results of this consensus should guide clinical decisions on indications of HIPEC and the choice and various parameters of HIPEC regimens and could fill current knowledge gaps. These outcomes should be the basis for designing future clinical trials on HIPEC in EOC.

Abstract Background Based on results of randomized clinical trials, polyADP‐ribose polymerase inhibitors (PARPi) have become the standard of care in patients with platinum-sensitive recurrent ovarian cancer (OvC) in patients responding to platinum chemotherapy. However, little is known about their impact on survival in a real-world setting. Patients and methods This retrospective French multicenter observational study included women with platinum-sensitive recurrent OvC (not limited to the first platinum-sensitive relapse) receiving PARPi as maintenance after response to platinum-based chemotherapy. They were compared to patients with similar characteristics undergoing observation after chemotherapy completion. Data were collected in the Ovarian Cancer Epidemiological Strategy and Medical Economics (ESME-OC) database between 2011 and 2021. We explored progression-free survival (PFS) and overall survival (OS) benefits with PARPi maintenance. Results One hundred and twenty-three patients matching the selection criteria were included in the PARPi group and 397 patients in the control group. Median PFS was 19.9 months (95CI [15.0-21.9]) in the PARPi group vs 13.4 months (95CI [11.8-15.0]) in the control group, with a HR = 0.71 (95CI [0.55-0.93]), P = .01). Median OS was 82.0 months (95CI [48.6-Not Estimable]) in the PARPi group vs 44.7 months (95CI [38.8-53.7]) in the control group (HR = 0.47, 95CI [0.30-0.74], P < .001). Multivariate analyses including performance status, histological subtype, achievement of cytoreductive surgery at relapse, and platinum-free interval, confirmed the independent prognostic impact of PARPi treatment. Conclusion This first national study focusing on the efficacy of PARPi in a real-world population shows similar benefits than in randomized clinical trials, supporting their use in clinical routine practice. Database registration clinicaltrials.gov Identifier NCT03275298.

Background Efforts have been made to investigate the role of salvage radiotherapy (RT) in treating recurrent ovarian cancer (ROC). Stereotactic ablative radiation therapy (SABR) is a state-of-the-art therapy that uses intensity modulation to increase the fractional dose, decrease the number of fractions, and target tumors with high precision. Methods The SABR-ROC trial is a phase 3, multicenter, randomized, prospective study to evaluate whether the addition of SABR to the standard of care significantly improves the 3-year overall survival (OS) of patients with ROC. Patients who have completed the standard treatment for primary epithelial ovarian cancer are eligible. In addition, patients with number of metastases ≤ 10 and maximum diameter of each metastatic site of gross tumor ≤ 5 cm are allowed. Randomization will be stratified by (1) No. of the following clinical factors met, platinum sensitivity, absence of ascites, normal level of CA125, and ECOG performance status of 0–1; 0–3 vs. 4; (2) site of recurrence; with vs. without lymph nodes; and (3) PARP inhibitor; use vs. non-use. The target number of patients to be enrolled in this study is 270. Participants will be randomized in a 1:2 ratio. Participants in Arm 2 will receive SABR for recurrent lesions clearly identified in imaging tests as well as the standard of care (Arm 1) based on treatment guidelines and decisions made in multidisciplinary discussions. The RT fraction number can range from 1 to 10, and the accepted dose range is 16–45 Gy. The RT Quality Assurance (QA) program consists of a three-tiered system: general credentialing, trial-specific credentialing, and individual case reviews. Discussion SABR appears to be preferable as it does not interfere with the schedule of systemic treatment by minimizing the elapsed days of RT. The synergistic effect between systemic treatment and SABR is expected to reduce the tumor burden by eradicating gross tumors identified through imaging with SABR and controlling microscopic cancer with systemic treatment. It might also be beneficial for quality-of-life preservation in older adults or heavily treated patients. Trial registration This trial was registered at ClinicalTrials.gov (NCT05444270) on June 29th, 2022.

Purpose:The DESKTOP I trial proposed a score for the prediction of complete cytoreduction in recurrent ovarian cancer. Resectability was assumed if 3 factors were present: (1) complete resection at first surgery, (2) good performance status, and (3) absence of ascites. The DESKTOP II trial was planned to verify this hypothesis prospectively in a multicenter setting.Methods:Participating centers prospectively enrolled all consecutive patients with platinum-sensitive first or second relapse. The score was applied to all patients, but centers were free to decide on therapy. All further therapies were documented, and the outcome of patients was analyzed. A 75% complete resection rate in 110 prospectively classified patients had to be achieved to confirm a positive predictive value of 2 or higher of 3 with 95% probability.Results:A total of 516 patients were screened within 19 months; of these, 261 patients (51%) were classified as score positive, and 129 patients with a positive score and first relapse were operated on. The rate of complete resection was 76%, thus confirming the validity of this score regarding positive prediction of complete resectability in 2 or more of 3 patients. Complication rates were moderate including second operations in 11% and perioperative mortality in 0.8%.Conclusions:This score is the first prospectively validated instrument to positively predict surgical outcome in recurrent ovarian cancer. It can aid in the selection of patients who might benefit from secondary cytoreductive surgery and will be enrolled in the recently started randomized prospective DESKTOP III trial investigating the role of surgery in recurrent platinum-sensitive ovarian cancer.

Background Recurrent ovarian cancer is often treated with chemotherapy, but many patients experience multiple recurrences with progressively shorter intervals and poorer prognosis. Repeated chemotherapy reduces patients’ quality of life. Stereotactic Ablative Radiation Therapy for Recurrent Ovarian Cancer (SABR-ROC) (KGOG3064/KROG 2204) is an ongoing trial investigating the clinical efficacy of stereotactic ablative radiation therapy (SABR) for recurrent ovarian cancer. This study aimed to assess treatment planning consistency and protocol adherence in a prospective, randomized, multicenter phase III trial. Methods In this dummy run study of a prospective, randomized, multicenter phase III trial (SABR-ROC), we examined the variability in target delineation, dose prescription, and treatment planning among 10 centers participating in the SABR-ROC trial. Four representative cases, each presenting with different anatomical sites and treatment challenges, were selected for evaluation. Target volume consistency was measured using the Dice similarity coefficient, and treatment plans were reviewed to follow predefined goals and constraints in the protocol. Results Overall agreement in target delineation was low, with mean Dice similarity coefficients of 0.278 and 0.255 for gross tumor volume and planning target volume, respectively. Consistency was higher for cases involving lymph node and lung metastases but significantly lower for intraperitoneal and liver seeding metastases due to challenges in target delineation. Treatment plans generally adhered to protocol dose prescriptions, with minor deviations in planning target volume coverage, particularly in cases with multiple small metastases. Deviations from organ-at-risk constraints frequently occurred in cases involving small bowel proximity. Conclusions This study highlights the challenges in standardizing SABR for recurrent ovarian cancer, particularly in achieving a consensus on target delineation and balancing treatment efficacy with organ-at-risk safety. Clinician discretion remains essential in complex cases. The insights from this study will guide the development of standardized protocols to improve outcomes and reduce adverse effects in patients with recurrent ovarian cancer. Trial registration This trial was registered with ClinicalTrials.gov under the identifier NCT05444270 on June 29, 2022.

Immunotherapies have revolutionized the treatment of a variety of cancers. Epithelial ovarian cancer is the most lethal gynecologic malignancy, and the rate of advanced tumor progression or recurrence is as high as 80%. Current salvage strategies for patients with recurrent ovarian cancer are rarely curative. Recurrent ovarian cancer is a “cold tumor”, predominantly due to a lack of tumor antigens and an immunosuppressive tumor microenvironment. In trials testing programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) blockade as a monotherapy, the response rate was only 8.0-22.2%. In this review, we illustrate the status of cold tumors in ovarian cancer and summarize the existing clinical trials investigating PD-1/PD-L1 blockade in recurrent ovarian cancer. Increasing numbers of immunotherapy combination trials have been set up to improve the response rate of EOC. The current preclinical and clinical development of immunotherapy combination therapy to convert an immune cold tumor into a hot tumor and their underlying mechanisms are also reviewed. The combination of anti-PD-1/PD-L1 with other immunomodulatory drugs or therapies, such as chemotherapy, antiangiogenic therapies, poly (ADP-ribose) polymerase inhibitors, adoptive cell therapy, and oncolytic therapy, could be beneficial. Further efforts are merited to transfer these results to a broader clinical application.