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.

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.

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.

OPERA: a phase II trial of oregovomab plus non-platinum chemotherapy in PARP inhibitor/platinum-resistant ovarian cancer.

A consensus regarding subsequent therapeutic strategies for patients with platinum- and poly (ADP-ribose) polymerase inhibitor (PARPi)-resistant ovarian cancer is lacking. These patients typically receive non-platinum-based chemotherapy; however, survival outcomes remain poor. Compared with chemotherapy alone, combination therapy with novel target agents can provide additional benefits to these patients. Oregovomab, an investigational murine monoclonal antibody against CA-125, has shown promising efficacy in a phase II study in patients with recurrent ovarian cancer. Herein, we described the rationale and design of OPERA/KGOG 3065/APGOT-OV6, a multicenter, investigator-initiated, two-cohort, single-arm phase II trial, aimed at examining the efficacy of oregovomab plus non-platinum-based chemotherapy in patients with PARPi/platinum-resistant ovarian cancer. The primary end point was the objective response rate, according to RECIST 1.1.Clinical Trial Registration: NCT05407584 (ClinicalTrials.gov).

OPERA/KGOG 3065/APGOT-OV6 is a promising phase II studies that test new drug (oregovomab) on the patients with poly (ADP-ribose) polymerase inhibitor (PARPi)/platinum-resistant epithelial ovarian cancer. PARPis have changed the treatment landscape of ovarian cancer in a relatively short time. PARPi/platinum-resistant epithelial ovarian cancer refer to a subtype of recurrent epithelial cancer of ovarian, tubal or peritoneal origin who experienced disease progression despite treatment with a PARPi or platinum-based chemotherapy drugs. Although various new drugs have been tested to improve the treatment response in resistant patients, a consensus regarding the international standard of treatment is yet to be established, despite the poor survival outcomes of these patients. OPERA/KGOG 3065/APGOT-OV6 has been designed to add oregovomab, a murine monoclonal antibody to cancer antigen-125 (CA-125), to non-platinum chemotherapy (pegylated liposomal doxorubicin or paclitaxel) for patients with ovarian cancer determined as PARPi/platinum-resistant and ineligible for bevacizumab treatment. The results of this study will aid in developing effective treatment strategies for patients with PARPi/platinum-resistant ovarian cancer.

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.

Cost-effectiveness of hyperthermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III-IV ovarian cancer from a randomized controlled phase III trial in Korea (KOV-HIPEC-01).

BACKGROUND: To evaluate the cost-effectiveness of the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) following interval cytoreductive surgery (ICS) for stage III-IV ovarian cancer from a randomized controlled phase III trial. METHODS: A comparative cost-effective analysis was performed using a Markov health-state transition model derived from the current trial cohort (ClinicalTrials.gov Identifier: NCT01091636). The incremental cost-effectiveness ratio (ICER) was evaluated by dividing the incremental costs by incremental quality-adjusted life-years (QALYs) with a time horizon of 10 years. Costs were calculated from the perspective of Korean healthcare, and health utility values were extracted from published sources. RESULTS: Based on data from the trial, the mean QALY in the ICS group was 7.16 compared to 10.8 in ICS followed by the HIPEC group. With an incremental QALY of 3.64, the ICS followed by HIPEC, was estimated to obtain an ICER of KRW 954,598 (USD 708.3) per QALY. CONCLUSION: The findings of the study suggest that ICS followed by HIPEC, is cost-effective with a significant gain in QALYs. These results may support the current reimbursement of HIPEC from Korean insurance services and the management of long-term conditions.

Impact of warm saline irrigation, hyperthermic intraperitoneal chemotherapy on postoperative pain in primary ovarian cancer from the KOV-HIPEC-01 randomized trial.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a treatment option at the time of cytoreductive surgery after neoadjuvant chemotherapy. The effect of active warming of HIPEC on postoperative pain needs to be investigated. This study aimed to investigate whether HIPEC reduces postoperative pain. METHODS: From the KOV-HIPEC-01 trial, a randomized controlled trial of HIPEC for advanced primary ovarian cancer, 184 patients with a residual tumor size <1 cm were randomly assigned to the HIPEC and control groups at a 1:1 ratio. The consumption of analgesics and pain scales were analyzed. Hyperthermic intraperitoneal chemotherapy was administered after cytoreductive surgery. The primary objective was to compare the consumption of opioids measured in morphine milligram equivalents and non-opioids measured as the maximum daily dose between the HIPEC and control groups. The secondary objective was to compare the minimum and maximum pain intensities on numeric rating scales between the two groups using a linear mixed model. RESULTS: Lesser consumption of non-opioids, with a lower mean maximum daily dose on postoperative days 1 and 2, was observed. The HIPEC group also experienced lower maximum pain intensities on postoperative day 1. No overall differences in the minimum or maximum pain intensities were observed on postoperative day 7. CONCLUSION: The addition of HIPEC to cytoreductive surgery did not lead to increased postoperative pain, as demonstrated by a reduction in the use of analgesics and lower scores on postoperative pain scales during the early postoperative period.

NIRVANA-1: maintenance therapy with niraparib versus niraparib-bevacizumab in patients with advanced ovarian cancer.

Following the results of the PRIMA and PAOLA-1 trials, the most effective maintenance strategy for International Federation of Gynecology and Obstetrics stage III patients is still debated, raising the question which of those two maintenance strategies is the most effective: PARP inhibitors alone or PARP inhibitors in combination with bevacizumab. The ongoing NIRVANA-1 study will try to answer this question by assessing the efficacy and safety of niraparib + bevacizumab in comparison with niraparib alone after adjuvant chemotherapy for completely resected stage III patients. Stratification factors include tumor BRCA status, International Federation of Gynecology and Obstetrics stage (IIIA vs IIIB/IIIC) and the use of hyperthermic intraperitoneal chemotherapy during surgery - within the OVHIPEC-2 trial. The primary end point will be progression-free survival rate at 24 months. Safety, median progression-free survival and overall survival will also be studied.

In many patients with ovarian cancer who are treated with platinum-based chemotherapy after surgery, the tumor comes back several months later. In order to minimize this risk, one treatment approach that has shown promising results is PARP inhibitors. This treatment works by inhibiting cancer cells' ability to repair themselves after DNA damage. One of the PARP inhibitors approved by medical authorities is niraparib, used as a solo therapy after surgery and chemotherapy. Nevertheless, the most effective maintenance strategy for patients in this setting is still debated. In a worldwide clinical trial called NIRVANA-1, researchers are investigating how niraparib would work if combined with another treatment called bevacizumab, which stops the growth of new blood vessels in tumors. Patients who participate in this trial will be randomly assigned to one of two treatment groups: the combination of niraparib + bevacizumab or niraparib by itself. The main purpose of NIRVANA-1 is to understand whether the combination of niraparib and bevacizumab prevents the cancer from returning in patients with completely resected stage III ovarian cancer. The trial will also assess the safety of this combination compared with niraparib alone. At the time of this writing, NIRVANA-1 is open for new patients to join. Sponsored by ARCAGY-GINECO, the NIRVANA-1 trial is currently recruiting patients from France, Spain, Italy, Belgium, Japan and Korea. The duration of the inclusion period is estimated to be around 36 months. The study is registered on ClinicalTrial.gov with registration number NCT05183984.

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).

Oral contraceptives and risk of breast cancer and ovarian cancer in women with a BRCA1 or BRCA2 mutation: a meta-analysis of observational studies.

It remains inconclusive whether the use of oral contraceptives (OCs) alters the risks of breast or ovarian cancer in women with a breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) mutation. We investigated the association between OC use and the risks of breast or ovarian cancer in this group by using a meta-analysis. PubMed and EMBASE were searched using keywords until February 2021 to identify relevant studies that evaluated the association between OC ever use and the risks of breast or ovarian cancer in women with a BRCA1 or BRCA2 mutation. Twelve studies for breast cancer and eight studies for ovarian cancer were identified. In the random-effects meta-analysis, the ever use of OCs was significantly associated with an increased risk of breast cancer [odds ratio (OR), relative risk (RR) or hazard ratio (HR) = 1.24; 95% confidence interval (CI) 1.08-1.41] and a decreased risk of ovarian cancer (OR/RR/HR = 0.53, 95% CI 0.41-0.67). Consistent findings were observed when BRCA1 and BRCA2 mutation carriers were analyzed separately. The increased risk of breast cancer was observed only in the long-term (>5 years) users of OCs, while the decreased risk of ovarian cancer was observed regardless of the duration of OC use. The current study suggests that the ever use of OCs in BRCA mutation carriers is significantly associated with an increased risk of breast cancer and a decreased risk of ovarian cancer. Therefore, the use of OCs as chemoprevention of ovarian cancer should be cautious in BRCA mutation carriers.

A predictive model based on site-specific risk factors of recurrence regions in endometrial cancer patients.

OBJECTIVE: This study investigated site-specific differences in clinical factors for recurrence in patients who were newly diagnosed and treated for endometrial cancer. A model for predicting recurrence sites was generated. METHODS: Electronic medical records' data were retrieved from January 2006 to December 2018 for patients who were diagnosed with endometrial cancer at the National cancer center in Korea. Recurrence sites were classified as local, regional, or distant. We used multinomial logistic regression models that modeled the log-odds for the three recurrence sites relative to non-recurrence as a linear combination of possible risk factors for the recurrence of endometrial cancer. RESULTS: The data of 611 patients were selected for analysis; there were 20, 12, and 25 cases of local, regional, and distant recurrence, respectively, and 554 patients had no recurrence. High-grade disease was associated with local recurrence; non-endometrioid histology and parametrial invasion were risk factors for regional recurrence; additionally, parametrial invasion and no lymphadenectomy were associated with distant metastasis. CONCLUSION: We identified different risk factors specific for each type of recurrence site. Using these risk factors, we suggest that individually tailored adjuvant treatments be introduced for patients.

Clinical implications of neoadjuvant chemotherapy in advanced endometrial cancer: a multi-center retrospective cohort study.

BACKGROUND: The mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer. METHODS: From the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC-IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients' clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed. RESULTS: Overall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P < 0.001 and 5.934; P = 0.001, respectively). Multivariate analysis for OS could not be conducted because of the small number of events, although non-endometrioid histology was the only factor associated with worse OS in univariate analysis (adjusted HR, 4.523; P = 0.032). CONCLUSIONS: NAC-IDS may be a treatment option for unresectable metastatic endometrial cancer. Tumor histology and the possibility of complete cytoreduction are the primary considerations for NAC-IDS.

Surgical outcomes of ureteral reconstruction during cytoreductive surgery for ovarian cancer: a retrospective cohort study.

BACKGROUND: Ureteral reconstruction is required after surgical resection of the tumor invading the urinary tract in ovarian cancer with low incidence. There are no currently reported surgical outcomes of ureteral reconstruction during cytoreductive surgery. The aim of the study is to investigate the clinical features and surgical outcomes of ureteral reconstruction during primary, interval and secondary cytoreductive surgery for ovarian cancer.  METHODS: A total of 3226 patients who underwent primary, interval or secondary cytoreductive surgery for ovarian cancer between January 2000 and May 2021 were reviewed. Fifty-six patients who underwent ureteral reconstruction during cytoreductive surgery were included in the analysis.  RESULTS: Ureteral reconstruction was required in 1.7% (56/3226) of ovarian cancer patients. Of the 56 patients who underwent ureteral reconstruction during cytoreductive surgery, 35 (62.5%) had primary ovarian cancer, and 21 (37.5%) had recurrent ovarian cancer. The median tumor size invading the lower urinary tract was 2.0 cm (range, 0.4-9.5 cm). Ureteroneocystostomy with direct implantation (51.8%) and psoas hitch (8.9%), transureteroureterostomy (7.1%), and ureteroureterostomy (32.1%) were required as part of cytoreductive surgery. Complete cytoreduction with ureteral reconstruction was achieved in 83.9% (47/56) and the rest of the patient population (16.1%) achieved a gross residual tumor size of less than 1 cm. All complications, including hydronephrosis (33.9%), were managed, none resulting in long-term sequelae. In primary ovarian cancer, the 5-year disease-free survival and overall survival were 50.0% and 89.5%, respectively. In patients with recurrent ovarian cancer, the 5-year disease-free survival and overall survival were 23.6% and 64.0%, respectively. CONCLUSIONS: Ureteral reconstruction as a part of cytoreductive surgery for ovarian cancer could be performed with acceptable morbidities. Complete cytoreduction by a multidisciplinary surgical team, including urologic oncologists, should be pursued for the surgical management of ovarian cancer. TRIAL REGISTRATION: Retrospectively registered.

Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol.

BACKGROUND: The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. METHODS: This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. DISCUSSION: We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery. TRIAL REGISTRATION: ClinicalTrials.gov ; NCT04370496 ; registration date, May 2020.

Predicting the risk of the distant recurrence of cervical cancer after concurrent chemoradiation: A validation study of the Korean Gynecologic Oncologic Group (KGOG)-1024 model.

BACKGROUND: This study aimed to validate the performance of the Korean Gynecologic Oncologic Group (KGOG)-1024 risk model in predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer (LACC). METHODS: In a retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, individual risk was calculated using the KGOG-1024 risk model. The cohort was categorized into three risk groups (low-, intermediate-, and high-risk groups) according to the calculated risk. The means of the calculated and observed risks were compared within each group. RESULTS: The study population was classified into low-, intermediate-, and high-risk groups according to the KGOG-1024 risk model (27.2%, 49.3%, and 23.5% of patients, respectively). The calculated and observed 5-year cumulative incidence rates were 12.4% vs. 16.4% in the low-risk group, 23.2% vs. 25.9% in the intermediate-risk group, and 50.7% vs. 36.3% in the high-risk group. Overall, the calculated and observed risk was 26.7% vs. 25.6%. CONCLUSIONS: The KGOG-1024 risk assessment model accurately predicted distant recurrence after chemoradiation in patients with LACC, especially in the low- and intermediate-risk groups. The model may be helpful for identifying patients for future trials assessing the possible benefit of adjuvant systemic treatment after chemoradiation.

Clinical outcomes of BRCA1/2 pathogenic variants in ovarian cancer cluster region in patients with primary peritoneal, epithelial ovarian, and fallopian tube cancer.

OBJECTIVE: An "ovarian cancer cluster region" (OCCR) has been reported in both BRCA1 and BRCA2. However, the clinical significance of the OCCR of BRCA1/2 has not yet been investigated. METHODS: The medical records of 991 patients with epithelial ovarian, primary peritoneal, and fallopian tube cancer who underwent genetic testing for BRCA1 and/or BRCA2 from January 1, 2006, to August 31, 2019, were retrospectively reviewed. Sanger and next-generation sequencing analyses were used to test the BRCA1 and BRCA2 mutation status. Progression-free survival (PFS) and overall survival (OS) were compared according to the mutation location (OCCR vs. non-OCCR region). Survival outcomes were determined using Kaplan-Meier survival analysis. RESULTS: A total of 162 patients had BRCA1 pathogenic variants (PVs), and 76 had BRCA2 PVs. Patients with BRCA1 PV that in the OCCR region showed shorter PFS than those with BRCA1 PV outside the OCCR (22.6 months vs. 27.6 months, P = 0.038). In the platinum-sensitive subgroup of BRCA1, patients with BRCA1 PV in the OCCR region showed shorter PFS than those in the non-OCCR group (P = 0.0197). On the other hand, BRCA2 variants did not exhibit any particular trend (32.8 months vs. 27.9 months, P = 0.468). However, no significant differences were detected in OS between patients with BRCA1/2 PVs, regardless of the location of the variants. CONCLUSIONS: Patients with BRCA1 PV in the OCCR had shorter PFS than those outside the OCCR. This tendency was more pronounced in the platinum-sensitive subgroup. To our knowledge, this is the first study of BRCA1/2 mutations based on the OCCR.

Impact of bevacizumab and secondary cytoreductive surgery on survival outcomes in platinum-sensitive relapsed ovarian clear cell carcinoma: A multicenter study in Korea.

OBJECTIVE: This study investigated survival outcomes for platinum-sensitive relapsed ovarian clear cell carcinoma (OCCC) by treatment method. METHODS: OCCC patients with platinum-sensitive recurrence that received secondary treatment at five institutions between July 2007 and June 2021 were included. Patient characteristics and survival outcomes were compared according to the use of bevacizumab (BEV) during second-line chemotherapy and secondary cytoreductive surgery (CRS). RESULTS: 138 patients were included. The BEV (n = 36) and non-BEV (n = 102) groups had similar initial FIGO stages and proportions of secondary CRS. The BEV group showed improved progression-free survival (PFS; median, 15.4 vs. 7.5 months; P = 0.042) and overall survival (OS; P = 0.043) compared to the non-BEV group. In multivariate analyses, BEV was identified as an independent prognostic factor for PFS (adjusted hazard ratio [aHR], 0.571; 95% confidence interval [CI], 0.354-0.921; P = 0.022) and OS (aHR, 0.435; 95%CI, 0.195-0.970; P = 0.042). The secondary CRS group (n = 42) had early-stage disease at diagnosis more frequently (P = 0.009) and multi-site metastasis (P < 0.001) at recurrence less frequently than the no surgery group (n = 96). The secondary CRS group showed significantly better PFS (median, 33.7 vs. 7.2 months; P < 0.001) and OS (P < 0.001). Secondary CRS was associated with a significantly improved PFS (aHR, 0.297; 95% CI, 0.183-0.481; P < 0.001) and OS (aHR, 0.276; 95% CI, 0.133-0.576; P = 0.001). The BEV and non-BEV groups showed similar PFS and OS among the patients who underwent secondary CRS. In contrast, the BEV group showed improved PFS and OS among patients who did not undergo surgery. CONCLUSIONS: The use of BEV during second-line chemotherapy and secondary CRS may improve PFS and OS in patients with platinum-sensitive relapsed OCCC. Further prospective studies are warranted.

Hyperthermic intraperitoneal chemotherapy for epithelial ovarian cancer: A meta-analysis.

BACKGROUND: The value of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of cytoreductive surgery (CRS) for epithelial ovarian cancer (EOC) is controversial and its use remains experimental in most national and international guidelines. We wished to systematically evaluate all available evidence. METHODS: A comprehensive review of data from MEDLINE, EMBASE, and Cochrane Library databases was conducted from the first report on HIPEC in EOC till April 3, 2022. Progression-free survival (PFS) and overall survival (OS) were compared between the HIPEC and control groups. This meta-analysis was registered with PROSPERO (CRD42021265810). RESULTS: Fifteen studies (10 case-control studies and 5 randomized controlled trials [RCTs]) were included in the present meta-analysis. Based on the time interval between the last systemic chemotherapy exposure and timing of CRS +/- HIPEC, all studies and patients' cohorts we classified into recent (<6 months; n = 9 studies/patients cohorts) and non-recent (≥6 months, n = 8 studies/patients cohorts) chemotherapy exposure groups. In the recent chemotherapy exposure group, HIPEC was associated with improvement of both PFS (HR, 0.585; 95% CI, 0.422-0.811) and OS (HR, 0.519; 95% CI, 0.346-0.777). On the contrary, in the non-recent chemotherapy exposure group, HIPEC failed to significantly affect PFS (HR, 1.037; 95% CI, 0.684-1.571) or OS (HR, 0.932; 95% CI, 0.607-1.430). Consistent results were observed in subsequent sensitivity analyses. CONCLUSION: Our present meta-analysis demonstrates that the value of HIPEC at CRS for EOC appears to depend on the timing of the last systemic chemotherapy exposure. Future trials are awaited to define the role of HIPEC in EOC.

Learning curve analysis of multiport robot-assisted hysterectomy.

PURPOSE: The purpose of this study was to evaluate the surgical outcomes and learning curve of multiport robot-assisted hysterectomy. METHODS: Eighty-eight patients were identified who underwent multiport robot-assisted surgery for hysterectomy. A retrospective analysis was performed. The cumulative summation technique (CUSUM) was used to investigate the learning curve in surgical proficiency by analyzing total operative, docking, and console times. RESULTS: The patients' median age was 51 years. In addition, the median operative time was 120.5 min (range 56-344 min). The most common indication for surgery was myoma (33.0%). The median estimated blood loss was 30 mL (range 5-200 mL). There was no conversion to laparoscopic or open surgery. No transfusion was required, and only one complication including umbilical incisional hernia was reported. A tendency of decline in total operative time following the first 23 cases was found. The CUSUM graph for total operative time indicated the generation of three distinct performance phases: learning (n = 23), competence (n = 36), and mastery (n = 29). The median docking time was 3 min (range 1-10 min) and median console time was 70 min (range 24-298 min). CONCLUSION: The multiport robot-assisted surgery is an easy and safe procedure with minimal postoperative complications and can be quickly learned. The learning curve was 23 cases to significantly decrease the operative time.

Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial.

BACKGROUND: Although most patients with epithelial ovarian cancer respond to frontline platinum-based chemotherapy, around 70% will relapse within 3 years. The phase 3 JAVELIN Ovarian 100 trial compared avelumab (anti-PD-L1 monoclonal antibody) in combination with chemotherapy followed by avelumab maintenance, or chemotherapy followed by avelumab maintenance, versus chemotherapy alone in patients with treatment-naive epithelial ovarian cancer. METHODS: JAVELIN Ovarian 100 was a global, open-label, three-arm, parallel, randomised, phase 3 trial run at 159 hospitals and cancer treatment centres in 25 countries. Eligible women were aged 18 years and older with stage III-IV epithelial ovarian, fallopian tube, or peritoneal cancer (following debulking surgery, or candidates for neoadjuvant chemotherapy), and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1:1) via interactive response technology to receive chemotherapy (six cycles; carboplatin dosed at an area under the serum-concentration-time curve of 5 or 6 intravenously every 3 weeks plus paclitaxel 175 mg/m2 every 3 weeks or 80 mg/m2 once a week [investigators' choice]) followed by avelumab maintenance (10 mg/kg intravenously every 2 weeks; avelumab maintenance group); chemotherapy plus avelumab (10 mg/kg intravenously every 3 weeks) followed by avelumab maintenance (avelumab combination group); or chemotherapy followed by observation (control group). Randomisation was in permuted blocks of size six and stratified by paclitaxel regimen and resection status. Patients and investigators were masked to assignment to the two chemotherapy groups without avelumab at the time of randomisation until completion of the chemotherapy phase. The primary endpoint was progression-free survival assessed by blinded independent central review in all randomly assigned patients (analysed by intention to treat). Safety was analysed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02718417. The trial was fully enrolled and terminated at interim analysis due to futility, and efficacy is no longer being assessed. FINDINGS: Between May 19, 2016 and Jan 23, 2018, 998 patients were randomly assigned (avelumab maintenance n=332, avelumab combination n=331, and control n=335). At the planned interim analysis (data cutoff Sept 7, 2018), prespecified futility boundaries were crossed for the progression-free survival analysis, and the trial was stopped as recommended by the independent data monitoring committee and endorsed by the protocol steering committee. Median follow-up for progression-free survival for all patients was 10·8 months (IQR 7·1-14·9); 11·1 months (7·0-15·3) for the avelumab maintenance group, 11·0 months (7·4-14·5) for the avelumab combination group, and 10·2 months (6·7-14·0) for the control group. Median progression-free survival was 16·8 months (95% CI 13·5-not estimable [NE]) with avelumab maintenance, 18·1 months (14·8-NE) with avelumab combination treatment, and NE (18·2 months-NE) with control treatment. The stratified hazard ratio for progression-free survival was 1·43 (95% CI 1·05-1·95; one-sided p=0·99) with the avelumab maintenance regimen and 1·14 (0·83-1·56; one-sided p=0·79) with the avelumab combination regimen, versus control treatment. The most common grade 3-4 adverse events were anaemia (69 [21%] patients in the avelumab maintenance group, 63 [19%] in the avelumab combination group, and 53 [16%] in the control group), neutropenia (91 [28%], 99 [30%], and 88 [26%]), and neutrophil count decrease (49 [15%], 45 [14%], and 59 [18%]). Serious adverse events of any grade occurred in 92 (28%) patients in the avelumab maintenance group, 118 (36%) in the avelumab combination group, and 64 (19%) in the control group. Treatment-related deaths occurred in one (<1%) patient in the avelumab maintenance group (due to atrial fibrillation) and one (<1%) patient in the avelumab combination group (due to disease progression). INTERPRETATION: Although no new safety signals were observed, results do not support the use of avelumab in the frontline treatment setting. Alternative treatment regimens are needed to improve outcomes in patients with advanced epithelial ovarian cancer. FUNDING: Pfizer and Merck KGaA, Darmstadt, Germany.