Efficacy of immune-checkpoint inhibitors combined with cytotoxic chemotherapy in advanced or recurrent endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. METHODS: We conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). FINDINGS: Four trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62-0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63-0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26-0.43; OS; HR, 0.37; 95% CI, 0.22-0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54-0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56-0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19-0.81) over PD-L1 negative population. INTERPRETATION: ICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes.

Psychosocial barriers and facilitators for cascade genetic testing in hereditary breast and ovarian cancer: a scoping review.

Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.

Prognostic impact of erythropoietin-stimulating agent use during front-line chemotherapy in patients with ovarian cancer: A Korean multicenter cohort study.

OBJECTIVE: To evaluate whether treatment with erythropoiesis-stimulating agents (ESAs) for chemotherapy-induced anemia affects progression-free survival (PFS) in patients receiving front-line chemotherapy following surgery for ovarian cancer (OC). METHODS: We retrospectively reviewed all consecutive patients who received front-line chemotherapy after surgery between 2013 and 2019 at six institutions. The patients were divided according to the use of ESAs during front-line chemotherapy. The primary endpoint was PFS. The secondary endpoint was the occurrence of thromboembolism. Propensity score matching (PSM) analysis was used to compare survival between matched cohorts. RESULTS: Overall, 2147 patients (433 receiving ESA and 1714 for no-ESA) were identified, with a median follow-up of 44.0 months. The ESA group showed a significantly higher proportion of stage III/IV disease (81.8% vs 61.1%; P < 0.001) and postoperative gross residual disease (32.3% vs 21.2%; P < 0.001) than the no-ESA group. In the multivariable Cox regression analysis, the use of ESAs did not affect PFS (adjusted hazard ratio, 1.03; 95% confidence interval [CI]: 0.89-1.20; P = 0.661). The incidence of thromboembolism was 10.2% in the ESA group and 4.6% in the no-ESA group (adjusted odds ratio, 6.58; 95% CI: 3.26-13.28; P < 0.001). When comparing the well-matched cohorts after PSM, PFS did not differ between the ESA (median PFS 23.5 months) and no-ESA groups (median PFS 22.2 months) (P = 0.540, log-rank test). CONCLUSIONS: The use of ESAs during front-line chemotherapy did not negatively affect PFS in patients with OC after surgery but increased the risk of thromboembolism.

Efficacy and safety of BVAC-C in HPV type 16- or 18-positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study.

Background: BVAC-C, a B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV-positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16- or 18-positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy. Patients and methods: Patients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1-not reported), the median PFS was 5.8 months (95% CI 4.2-10.3), and the median OS was 17.7 months (95% CI 12.0-not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses. Conclusion: BVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response. Clinical trial registration: ClinicalTrials.gov, identifier NCT02866006.

Determination of ovarian transposition through prediction of postoperative adjuvant therapy in young patients with early stage cervical cancer undergoing surgery: a Korean multicenter retrospective study (KGOG 1042).

OBJECTIVE: We aimed to predict the risk of postoperative adjuvant therapy using preoperative variables in young patients with early stage cervical cancer. The predicted risk can guide whether ovarian transposition should be performed during surgery. METHODS: In total, 886 patients with stage IB1-IIA cervical cancer aged 20-45 years who underwent modified radical or radical hysterectomy between January 2000 and December 2008 were included. Preoperative variables, preoperative laboratory findings, International Federation of Gynaecology and Obstetrics stage, tumor size, and pathological variables were collected. Patients with high risk factors or those who met the Sedlis criteria were considered adjuvant therapy risk (+); others were considered adjuvant therapy risk (-). A decision-tree model using preoperative variables was constructed to predict the risk of adjuvant therapy. RESULTS: Of 886 patients, 362 were adjuvant therapy risk (+) (40.9%). The decision-tree model with four distinct adjuvant therapy risks using tumor size and age were generated. Specifically, patients with tumor size ≤2.45 cm had low risk (49/367; 13.4%), those with tumor size ≤3.85 cm and >2.45 cm had moderate risk (136/314; 43.3%), those with tumor size >3.85 cm and age ≤39.5 years had high risk (92/109; 84.4%), and those with tumor size >3.85 cm and age >39.5 years had the highest risk (85/96; 88.5%). CONCLUSION: The risk of postoperative adjuvant therapy in young patients with early stage cervical cancer can be predicted using preoperative variables. We can decide whether ovarian transposition should be performed using the predicted risk.

Development of an Automatic Rule-Based Algorithm for the Detection of Ovarian Cancer Recurrence From Electronic Health Records.

PURPOSE: As the onset of cancer recurrence is not explicitly recorded in the electronic health record (EHR), a high volume of manual chart review is required to detect the cancer recurrence. This study aims to develop an automatic rule-based algorithm for detecting ovarian cancer (OC) recurrence on the basis of minimally preprocessed EHR data. METHODS: The automatic rule-based recurrence detection algorithm (Auto-Recur), using notes on image reading (positron emission tomography-computed tomography [PET-CT], CT, magnetic resonance imaging [MRI]), biomarker (CA125), and treatment information (surgery, chemotherapy, radiotherapy), was developed to detect the first OC recurrence. Auto-Recur contains three single algorithms (images, biomarkers, treatments) and hybrid algorithms (combinations of the single algorithms). The performance of Auto-Recur was assessed using sensitivity, specificity, and accuracy of the recurrence time detected. The recurrence-free survival probabilities were estimated and compared with the retrospective chart review results. RESULTS: The proposed Auto-Recur considerably reduced human resources and time; it saved approximately 1,340 days when scaled to 100,000 patients compared with the conventional retrospective chart review. The hybrid algorithm on the basis of a combination of image, biomarker, and treatment information was the most efficient (sensitivity: 93.4%, specificity: 97.4%) and precisely captured recurrence time (average time error: 8.5 days). The estimated 3-year recurrence-free survival probability (44%) was close to the estimates by the retrospective chart review (45%, log-rank P value = .894). CONCLUSION: Our rule-based algorithm effectively captured the first OC recurrence from large-scale EHR while closely approximating the recurrence-free survival estimates obtained by conventional retrospective chart reviews. The study findings facilitate large-scale EHR analysis, enhancing clinical research opportunities.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Prospective analysis of pre and postoperative laboratory parameters associated with thrombosis in patients with ovarian cancer.

Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate pre and post operative biomarkers associated with thrombosis including deep vein thrombosis and pulmonary thromboembolism in patients treated for ovarian cancer. We collected pre and post operative blood samples from 133 patients undergoing surgery for ovarian cancer between December 2021 and August 2022. The measured parameters were white blood cell count, hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, antithrombin III, protein C, protein S, plasminogen, plasminogen activator inhibitor 1, homocysteine, N-terminal pro-brain natriuretic peptide, interleukin 6, thrombopoietin, soluble P-selectin and granulocyte stimulating factor. Body mass index of patients were collected. Differences between patients who developed thrombosis and those without were compared with Wilcoxon rank-sum test and we analyzed the continuous variables using logistic regression. Twenty-one (15.8%) patients developed thrombosis ranging from 6 to 146 days (median 15 days) after surgery. Pre operative values of homocysteine (p = 0.033) and IL-6 (p = 0.043) were significantly increased and post operative aPTT (p = 0.022) was prolonged and plasminogen (p = 0.041) was decreased in patients with thrombosis. It is important to find novel biomarkers for thrombosis to carefully manage patients who are prone to develop thrombosis despite preventive measures were applied.

Clinical guidelines for ovarian cancer: the Korean Society of Gynecologic Oncology guidelines.

Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.

Surgery for Recurrent Epithelial Ovarian Cancer.

PURPOSE OF REVIEW: To review evidence around the value and challenges of surgery for recurrent epithelial ovarian cancer (ROC). Both cytoreductive and palliative aspects will be addressed RECENT FINDINGS: Prospective and retrospective evidence demonstrates a significantly longer remission derived from the combination of surgical and systemic modalities as opposed to systemic treatment alone in carefully selected ROC-patients who have relapsed more than 6 months from the end of their 1st line platinum-based chemotherapy. Nevertheless, this benefit appears to be limited when total macroscopic tumor clearance is not achieved. Selection algorithms to identify optimal surgical candidates are of paramount importance to prevent surgical morbidity without the equivalent oncological benefit. In the palliative setting, the risks and benefits of salvage surgery need to be counterbalanced with the advances of conservative techniques for optimal care. Well-defined selection algorithms to identify those who will benefit from surgery in the relapsed setting appear to be the key to oncologic and surgical success.

Incidence and treatment outcomes of ovarian carcinosarcoma from the national cancer registry of Korea.

OBJECTIVE: To investigate the incidence and survival outcomes of ovarian carcinosarcoma in Korea between 1999 and 2018. METHODS: Patients diagnosed with ovarian carcinosarcoma between 1999 and 2018 were identified from the Korea Central Cancer Registry (KCCR) and their information was collected. Age-standardized incidence rates (ASRs), annual percent changes (APC), and relative survival rates of ovarian carcinosarcoma were calculated and compared to those of epithelial ovarian cancer. RESULTS: According to the KCCR, 458 cases of ovarian carcinosarcoma were detected, and accounted for 1.5% (458/30,679) of all epithelial ovarian cancers in Korea between 1999 and 2018. The ASR of ovarian carcinosarcoma between 1999 and 2018 was 0.064 per 100,000 women. The incidence rate of ovarian carcinosarcoma increased during the study period, with an ASR of 0.029 per 100,000 in 1999 and 0.073 per 100,000 in 2018. The APC of ovarian carcinosarcoma during 1999-2018 was 5.86 (p<0.001). The median overall survival (OS) of patients with ovarian carcinosarcoma was 39 months, and the 5-year OS rate was 42.5%. Among ovarian carcinosarcomas, patients with localized stages showed better clinical outcomes than those with regional or distant stages (5-year OS, 60.8%, 57.9%, and 32.8%, respectively; p<0.001). In addition, younger (<50 years) patients showed better OS than older (≥50 years) patients (5-year OS, 52.6% vs. 40.2%; p<0.001). CONCLUSION: Our nationwide registry-based study demonstrated that the incidence of ovarian carcinosarcoma increased from 1999 to 2018 in Korea. Patients with advanced-stage disease and older age (≥50 years) had poorer survival outcomes.

Adherence of PARP inhibitor for frontline maintenance therapy in primary epithelial ovarian cancer: a cross-sectional survey.

OBJECTIVE: To identify the adherence rate to poly (ADP-ribose) polymerase (PARP) inhibitors and identify factors contributing to the deterioration of adherence at our institution. METHODS: The adherence rate to PARP inhibitors was calculated using self-reported Adherence to Refills and Medications Scale questionnaires from a cross-sectional survey. Multivariable logistic regression analysis was performed to identify the factors that affected adherence. RESULTS: Of the 131 respondents, 32 (24.4%) showed non-adherence to PARP inhibitors. In the multivariable logistic regression analysis, unemployed or retired status (odds ratio [OR]=4.878; 95% confidence interval [CI]=1.528-15.572; p=0.008), patients receiving niraparib (OR=3.387; 95% CI=1.283-8.940; p=0.014), and a lower score on the quality-of-life assessment (EORTC-QLQ-OV28), which reflects a better quality of life (QOC) with a lower symptom burden (OR=1.056; 95% CI=1.027-1.086; p<0.001) were associated with high adherence to PARP inhibitors. CONCLUSION: Approximately one-fourth of patients with ovarian cancer are non-adherent to PARP inhibitors as maintenance treatment for newly diagnosed advanced ovarian cancer. The occupational status, type of PARP inhibitor, and QOC may affect adherence to PARP inhibitors.

Comparison of survival outcomes between olaparib and niraparib maintenance therapy in BRCA-mutated, newly diagnosed advanced ovarian cancer.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Trends in the incidence and survival outcomes of endometrial cancer in Korea: a nationwide population-based cohort study.

OBJECTIVE: To evaluate trends in the incidence and survival outcomes of endometrial cancer (EC) based on the year of diagnosis, stage, age, and histologic types. METHODS: Women with primary EC diagnosed between 1999 and 2018, and who were followed up with until 2019, were identified from the Korea Central Cancer Registry using the International Classification of Diseases, 10th revision. The age-standardized rates (ASRs) of incidence, annual percent changes (APCs), and survival were estimated according to age, stage, histology, and year of diagnosis. RESULTS: The ASR for EC increased from 2.38 per 100,000 in 1999 to 7.29 per 100,000 in 2018 across all histologic types (APCs of 9.82, 15.97, and 7.73 for endometrioid, serous, and clear cell, respectively, p<0.001). There were significant differences in the 5-year survival rates based on histology (90.9%, 55.0%, and 68.5% for endometrioid, serous, and clear cell, respectively, p<0.001), stage (93.4%, 77.0%, and 31.0% for localized, regional, and distant, respectively, p<0.001), and age (93.0% for <50 years and 80.6% for ≥50 years, p<0.001). The 5-year survival was significantly better in the group diagnosed between 2000 and 2018 (85.9%) than that in the 1999-2008 group (83.3%) (p<0.001). This trend was only observed for endometrioid cancer (p<0.001). CONCLUSION: The incidence of EC increased across the all 3 subtypes. Survival of patients with endometrioid histology improved over the past two decades, but remained static for serous or clear cell histology. Healthcare strategies to prevent EC incidence in at-risk populations and apply effective treatments for high-risk histology are needed.

Excellent Outcomes in Children, Adolescents, and Young Adults with Ovarian Germ Cell Tumors Treated by Either Reduced- or Standard-Dose Bleomycin.

To investigate the outcomes of children, adolescents, and young adults (AYAs) with malignant ovarian germ cell tumors (MOGCTs), we analyzed the data of 61 patients aged ≤39 years diagnosed with MOGCT between 2006 and 2022. Among 59 patients who received chemotherapy after initial diagnosis, 57 received BEP (standard dose of bleomycin with 30 units per week, n = 13) or bEP (reduced dose of bleomycin with 15 units/m2 on day 1, n = 44). The 5-year overall survival (OS) and event-free survival (EFS) rates were 98.3% and 84.9%, respectively. Reduced bleomycin dose did not adversely affect survival. Normalization of tumor markers within 3 months after surgery was significantly associated with better EFS (p < 0.01). Of the 59 surviving patients, 8 experienced surgery-related menopause, while 49 demonstrated menstrual recovery. After completion of chemotherapy, there was no significant difference in pulmonary function regarding bleomycin dose, and no overt nephrotoxicity. Approximately 60% and 25% of survivors experienced peripheral neuropathy at the end of chemotherapy and after 1 year, respectively (p < 0.01). Children and AYAs with MOGCT have favorable survival rates with minimal long-term toxicity, which are not influenced by a reduced bleomycin dose. Rapid normalization of tumor markers is associated with improved outcomes.

Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysis.

OBJECTIVES: This meta-analysis was undertaken to systematically evaluate the effects of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy on the survival of newly diagnosed advanced epithelial ovarian cancer (EOC) patients. METHODS/MATERIALS: A systematic literature search revealed 3,227 studies. A subsequent selection process identified seven suitable randomized studies that assessed the survival outcomes in newly diagnosed advanced EOC patients administered PARPi (n = 1921; the PARPi group) or placebo (n = 1150; the placebo group). The survival outcomes were compared with respect to the PARPi treatment regardless of bevacizumab maintenance therapy. All adverse events ≥ grade 3 were analyzed. Review Manager Version 5.4.1 software was used for the meta-analysis. RESULTS: The two-year progression-free survival (PFS) was significantly better in the PARPi group than the placebo (Hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41 to 0.68). Furthermore, patients in the PARPi group with the BRCA1/2 mutation (BRCAm), BRCA wild type, homologous-recombination deficiency (HRD), or HRD without BRCAm, but not with homologous-recombination proficiency had a significantly better two-year PFS than the patients in the placebo group. The five-year overall survival (OS) was comparable in the two groups, but patients in the PARPi group with BRCAm had a significantly better five-year OS than those in the placebo group (HR, 0.57; 95% CI, 0.44 to 0.74). In addition, the adverse event rate (≥ grade 3) was significantly higher in the PARPi group than in the placebo group (HR, 2.94; 95% CI, 1.13 to 7.63). CONCLUSIONS: In patients with newly diagnosed advanced EOC, PARPi maintenance therapy was significantly more effective in terms of survival than no PARPi treatment. However, the risk of serious adverse events was higher for patients who received PARPi maintenance therapy.

Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers. METHOD: A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics. RESULTS: A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival. CONCLUSION: Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer. STUDY REGISTRATION: The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).

Characteristics of second primary breast cancer after ovarian cancer: a Korea central cancer registry retrospective study.

Background: Second primary cancer has become an important issue among cancer survivors. This study sought to determine the differences in clinicopathologic outcomes between second primary breast cancer (SPBC) after ovarian cancer and primary breast cancer (PBC) in the Republic of Korea. Methods and materials: We searched the Korea Central Cancer Registry and identified 251,244 breast cancer cases that were diagnosed between 1999 and 2017. The incident rate and standardized incidence ratio (SIR) were calculated. Demographic and clinical characteristics and overall survival (OS) rates were estimated according to age, histological type, and cancer stage. Results: Among the 228,329 patients included, 228,148 were patients with PBC, and 181 patients had SPBC diagnosed after ovarian cancer (OC). The mean ages at diagnosis were 56.09 ± 10.81 years for SPBC and 50.65 ± 11.40 years for PBC. Patients with SPBC were significantly less likely than patients with PBC to receive adjuvant radiotherapy (14.92% vs. 21.92%, p = 0.02) or adjuvant chemotherapy (44.75% vs. 55.69%, p < 0.01). Based on the age-standardized rate (ASR), the incidence of SPBC after OC was 293.58 per 100,000 ovarian cancer patients and the incidence of PBC was 39.13 per 100,000 women. The SIR for SPBC was 1.27 (1.09-1.46, 95% Confidence interval) in the patients overall. The 5-year OS rates were 72.88% and 89.37% for SPBC and PBC (p < 0.01). The OS rate in SPBC decreased significantly with advanced stage and older age. Conclusion: The incidence of breast cancer is about 1.27 times higher in ovarian cancer patients than in healthy people. The survival outcomes were worse for SPBC than for PBC and were related to older age and advanced stage. Active screening for breast cancer is necessary in ovarian cancer patients.

Phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer: primary analysis in the original cohort of KGOG3046/TRU-D.

BACKGROUND: This study assessed the antitumor activity and safety of durvalumab plus tremelimumab combined with neoadjuvant chemotherapy (NAC) in patients newly diagnosed with advanced ovarian cancer. Here, we report the primary endpoint of the original cohort of the KGOG 3046/TRU-D study. METHODS: In this investigator-initiated single-arm, phase II trial, patients with stage IIIC-IVB ovarian cancer were administered three cycles of durvalumab (1500 mg) and tremelimumab (75 mg) with NAC, followed by interval debulking surgery (IDS). After surgery, three cycles of durvalumab (1120 mg) and adjuvant chemotherapy followed by durvalumab maintenance (1120 mg [total 12 cycles]) were administered. The primary endpoint of the study was 12-month progression-free survival (PFS) rate. RESULTS: Twenty-three patients were enrolled. The median patient age was 60 years (range 44-77 years), and most patients presented with high-grade serous carcinoma (87.0%) and stage IV disease (87.0%). At the time of data cut-off on January 17, 2023, the median follow-up duration was 29.2 months (range 12.0-42.2). The 12-month, 24-month, and 30 month PFS rates were 63.6%, 45.0%, and 40.0%, respectively. All patients underwent IDS, with an R0 resection rate of 73.9%, and 17.4% achieved pathological complete response. Skin rashes were the most common treatment-related adverse events (TRAEs, 69.6%). However, all TRAEs completely resolved after steroid use. CONCLUSION: This study showed promising activity with a durable clinical response, supporting the potential of NAC with dual immune checkpoint blockade in advanced-stage ovarian cancer. TRIAL REGISTRATION NUMBER: NCT03899610.

Acceptability and Usability of the Family Gene Toolkit for Swiss and Korean Families Harboring BRCA1/BRAC2 Pathogenic Variants: A Web-Based Platform for Cascade Genetic Testing.

The study adapted the Family Gene Toolkit and developed a customized web application for Swiss and Korean families harboring BRCA1 or BRCA2 pathogenic variants to support family communication of genetic testing results and promote cascade genetic testing among at-risk relatives. In the first step, narrative data from 68 women with BRCA1/BRCA2 pathogenic variants and clinician feedback informed a culturally sensitive adaptation of the content consistent with current risk management guidelines. In the second step, the Information Technology team developed the functions and the interface of the web application that will host the intervention. In the third step, a new sample of 18 women from families harboring BRCA1/BRCA2 pathogenic variants tested the acceptability and usability of the intervention using "think-aloud" interviews and a questionnaire. Participants expressed high levels of satisfaction with the intervention. They provided positive feedback for the information regarding active coping, strategies to enhance family communication, interactive elements, and illustrative stories. They reported that the information was useful and the web application was easy to navigate. Findings suggest that the Family Gene Toolkit is well-designed and can increase rates of cascade testing among at-risk relatives. Its efficacy will be tested in a subsequent randomized trial.