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To examine the efficacy and safety of minimally invasive surgery (MIS) and conventional abdominal surgery for epithelial ovarian cancer (EOC), stratified by treatment type. A systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Ovarian Cancer Committee. Several academic databases, including PubMed/MEDLINE, Cochrane Database, and Ichushi were searched by the Japan Medical Library Association on November 11, 2023, using the keywords "epithelial ovarian cancer", "minimally invasive surgery", "laparoscopic", and "robot-assisted". Articles describing MIS treatment for EOC compared with conventional abdominal surgery were independently assessed by two authors. The primary outcomes were survival and perioperative adverse events. After screening 1114 studies, 35 articles were identified, including primary staging surgery (PSS) for early-stage EOC EOC (n = 20) and neoadjuvant chemotherapy following interval debulking surgery (NACT-IDS; n = 10) and upfront primary debulking surgery (PDS; n = 5) for advanced-stage EOC. These studies included 29,888 patients (7661 undergoing MIS and 22,227 undergoing abdominal surgery). Patients receiving MIS and abdominal surgery had similar overall survival (PSS: odds ratio [OR] 1.02, 95% confidence interval [CI] 0.75–1.37; NACT-IDS: OR 0.93, 95%CI 0.25–3.44 and PDS: OR 0.66, 95%CI 0.36–1.22, all P > 0.05). MIS showed perioperative complication rates comparable to those of abdominal surgery (intraoperative and postoperative, all treatment types P ≥ 0.05). However, the rate of lymph node dissection in early-stage EOC (PSS: OR 0.49, 95%CI0.26–0.91) and multivisceral resections in advanced-stage EOC (NACT-IDS: OR 0.27 95%CI 0.16–0.44 and PDS: OR 0.27, 95%CI 0.16–0.44) was lower in MIS than in abdominal surgery (all P < 0.05). MIS did not negatively impact the survival and perioperative complications of patients with EOC compared to abdominal surgery. While MIS is a viable option, varied case selection and surgical procedures suggest potential bias, requiring further validation studies. • MIS for gynecologic cancer is increasing, but clear EOC indications lack high-quality evidence. • Meta-analysis shows no significant OS or perioperative complication differences between MIS and abdominal surgery for EOC. • MIS for EOC is viable, but varied case selection and procedures suggest potential bias. [ABSTRACT FROM AUTHOR]

Background: Extensive surgery on advanced-stage epithelial ovarian cancer is associated with increased postoperative morbidity, which may cause a delay in or omission of chemotherapy. We examined postoperative complications and their effects on adjuvant treatment in patients undergoing primary debulking surgery (PDS). Methods: Stage IIIC-IV epithelial ovarian cancer patients who underwent PDS between January 2013 and December 2020 were included. Patients were divided into two groups according to the radicality of the operation, i.e., extensive or standard surgery, and their outcomes were compared. Results: In total, 172 patients were included; 119 underwent extensive surgery, and 53 had standard surgery. Clavien–Dindo grade 3–5 (CDC 3+) complications were detected in 41.2% of patients after extensive operations and in 17% after standard surgery (p = 0.002). The most common CDC 3+ complication was pleural effusion. Despite the difference in the complication rates, the delay in chemotherapy did not differ between the extensive and standard groups (p = 0.98). Conclusions: Complications are common after PDS. Extensive surgery increases the complication rate, but most complications can be treated effectively; therefore, a delay in adjuvant treatment is rare.

Simple Summary: Upfront surgery to resect all visible tumors, followed by adjuvant chemotherapy, is the cornerstone of treating advanced ovarian cancer. In this retrospective study, 172 patients underwent primary debulking surgery; we analyzed the postoperative complications and complication rates and examined the effects of complications on adjuvant treatment. This study shows that complications are common after extensive surgery; however, most complications can be treated effectively, and delay in adjuvant treatment is rare. Background: Extensive surgery on advanced-stage epithelial ovarian cancer is associated with increased postoperative morbidity, which may cause a delay in or omission of chemotherapy. We examined postoperative complications and their effects on adjuvant treatment in patients undergoing primary debulking surgery (PDS). Methods: Stage IIIC-IV epithelial ovarian cancer patients who underwent PDS between January 2013 and December 2020 were included. Patients were divided into two groups according to the radicality of the operation, i.e., extensive or standard surgery, and their outcomes were compared. Results: In total, 172 patients were included; 119 underwent extensive surgery, and 53 had standard surgery. Clavien–Dindo grade 3–5 (CDC 3+) complications were detected in 41.2% of patients after extensive operations and in 17% after standard surgery (p = 0.002). The most common CDC 3+ complication was pleural effusion. Despite the difference in the complication rates, the delay in chemotherapy did not differ between the extensive and standard groups (p = 0.98). Conclusions: Complications are common after PDS. Extensive surgery increases the complication rate, but most complications can be treated effectively; therefore, a delay in adjuvant treatment is rare. [ABSTRACT FROM AUTHOR]

This article provides a literature review on tubal carcinoma to offer an updated insight into its preventative strategies, diagnosis, treatment and oncological surveillance. In addition to the search string utilized, the authors' focus extended to key scientific studies, consensus statements, guidelines and relevant case reports essential for the proper clinical management of the disease, providing a methodologically well-structured literature review combined with practical expertise in the oncological field. This article also includes two special clinical cases that emphasize the importance of understanding the physiopathology and the current state of the art in the anatomopathological advancements in tubal/ovarian/peritoneal carcinoma, often assimilated into a single clinical entity and to which many of the concepts extracted from the literature can apply. [ABSTRACT FROM AUTHOR]

To evaluate procedures performed during primary debulking surgery (PDS) and interval debulking surgery (IDS) for ovarian cancer. Patients surgically treated at our institution for newly diagnosed stage IIIC/IV epithelial ovarian cancer between 6/1/2015–12/31/2021 were identified using a prospectively collected database. Patients were triaged to PDS or neoadjuvant chemotherapy (NACT) followed by IDS using an institutional algorithm. Data on specific procedures performed, including consultants called, were collected from operative and pathology reports. Appropriate statistical analyses were applied. Overall, 467 patients underwent PDS and 434 underwent IDS; 76% (PDS) and 71% (IDS) of cases achieved complete gross resection. Comparing PDS vs IDS cohorts, median age was 63 years (range, 23–86) vs 67 years (range, 35–95), 79% vs 86% of patients had high-grade serous histology, and 38% vs 70% had stage IV disease. Most procedures (except ostomy, distal pancreatectomy) were more common during PDS (P <.05). Bowel surgery was performed during 65% of PDS and 33% of IDS, and upper abdominal surgery during 72% of PDS and 52% of IDS; both were more common during PDS (P <.001). Estimated blood loss (median, 500 mL [PDS] vs 300 mL [IDS]) and operative time (median, 362 min [PDS] vs 267 min [IDS]) were higher for PDS (P <.001). A consulting surgeon was utilized during 31% of PDS and 18% of IDS, with hepatopancreaticobiliary as the most commonly called service (61% and 65%, respectively). In our study of patients with advanced-stage ovarian cancer, while most procedures were more often performed during PDS, NACT did not obviate the need for radical surgical resection. Thus, advanced surgical skills remain essential. • Complete gross resection was achieved at the time of primary or interval debulking surgery in >70% of patients • Most advanced surgical procedures were more common during primary than interval debulking surgery • Bowel and upper abdominal surgery were performed often during both primary and interval debulking surgery • Neoadjuvant chemotherapy did not obviate need for radical surgical resection; advanced surgical skills remain essential [ABSTRACT FROM AUTHOR]

Background: The newest clinical evidence that the relationship between the peritoneal cancer index (PCI) and the postoperative prognosis of advanced ovarian cancer patients remains controversial, and there are no large-sample and multicenter studies to clarify this matter. Therefore, in this paper, we used meta-analysis to systematically assess the postoperative prognostic value of PCI in subjects with advanced ovarian cancer to provide individualized treatment plans and thus improve the prognosis of patients. Methods: Literature on the correlation between PCI and the postoperative prognosis in subjects with advanced OC undergoing cytoreductive surgery (CRS) was searched in the Cochrane Library, Pubmed, Embase, and Web of Science from the database inception to April 20, 2023. The search was updated on February 28, 2024. We only included late-stage (FIGO stage: III-IV) patients who did not undergo neoadjuvant chemotherapy (NACT) or hyperthermic intraperitoneal chemotherapy (HIPEC). Afterwards, literature screening and data extraction were conducted using Endnote20 software. The literature quality was assessed using the Newcastle-Ottawa Scale (NOS). Lastly, statistical analysis was performed with STATA 15.0 software. Results: Five studies with 774 patients were included. The result indicated that patients with high PCI had a worse prognosis than those with low PCI. The combined hazard ratio was 2.79 [95%CI: (2.04, 3.82), p<0.001] for overall survival (OS) in patients with high PCI. Further subgroup analysis by the FIGO staging revealed that in stage III [HR: 2.61, 95%CI: (2.00, 3.40), p<0.001] and stage III-IV patients [HR: 2.69, 95%CI: (1.66, 4.36), p<0.001], a high PCI score was significantly associated with a worse prognosis. The PCI score had a greater impact on the OS of patients with higher stages. The combined hazard ratio was 1.89 [95%CI: (1.51, 2.36), p<0.001] for progression-free survival (PFS) in patients with high PCI. Conclusion: PCI may be used as a postoperative prognosis indicator in patients with advanced OC on primary debulking surgery. High PCI indicates a worse prognosis. However, further research is warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008–2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0–21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0–21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS. • Time to chemotherapy after PDS for advanced EOC does not influence 5-year survival. • Time to chemotherapy is associated with 2-year survival in patients with no residual disease (R0) after PDS. • Time to chemotherapy >42 days is associated with excess mortality in patients with FIGO stage IV and R0 after PDS. • Time to chemotherapy is not associated with survival in patients with advanced EOC and residual disease after PDS. [ABSTRACT FROM AUTHOR]

Standard treatment for advanced ovarian cancer (OC) consists of a combination of chemotherapy and cytoreductive surgery, but practice varies depending on the order of these 2 procedures: neoadjuvant chemotherapy followed by interval debulking surgery or primary cytoreduction followed by adjuvant chemotherapy. The aim of the work is to evaluate methods of treatment of OC of stages III, IV according to FIGO.The literature review includes publications in English from the PubMed, CochraneLibrary and Google Scholar databases on the use of neoadjuvant therapy and primary cytoreduction in late stages of OC (FIGO III–IV). 6 randomized controlled trials, 8 meta-analyses, 8 systematic reviews, 1 case report were identified. Data from publications were distributed according to the criteria for assessing the effectiveness of the treatment: overall and relapse-free survival, perioperative complications, quality of life of patients and the grade of cytoreduction.Neoadjuvant chemotherapy + interval debulking surgery is not inferior to primary debulking surgery + adjuvant chemotherapy in terms of survival outcomes in selected patients, but treatment with neoadjuvant chemotherapy + interval debulking surgery improves perioperative outcomes and optimal cytoreduction rates. It is needed to focus on finding optimal criteria for selecting patients in both groups in future studies of this issue. It is necessary to take into account X-ray, histological studies, the molecular subtype of the tumor, the patient’s condition, the qualifications of the surgical team, the drugs included in chemotherapy.

Abstract Objective The aim of this study was to establish a preoperative model to predict the outcome of primary debulking surgery (PDS) for advanced ovarian cancer (AOC) patients by combing Suidan predictive model with HE4, CA125, CA153 and ROMA index. Methods 76 AOC Patients in revised 2014 International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent PDS between 2017 and 2019 from Yunnan Cancer Hospital were included. Clinical data including the levels of preoperative serum HE4, CA125, CA153 and mid-lower abdominal CT-enhanced scan results were collected. The logistics regression analysis was performed to find factors associated with sub-optimal debulking surgery (SDS). The receiver operating characteristic curve was used to evaluate the predictive performances of selected variables in the outcome of primary debulking surgery. The predictive index value (PIV) model was constructed to predict the outcome of SDS. Results Optimal surgical cytoreduction was achieved in 61.84% (47/76) patients. The value for CA125, HE4, CA153, ROMA index and Suidan score was lower in optimal debulking surgery (ODS) group than SDS group. Based on the Youden index, which is widely used for evaluating the performance of predictive models, the best cutoff point for the preoperative serum HE4, CA125, CA153, ROMA index and Suidan score to distinguish SDS were 431.55 pmol/l, 2277 KU/L, 57.19 KU/L, 97.525% and 2.5, respectively. Patients with PIV≥5 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing SDS were 73.7%, 82.9%, 62.9% and 72.3%, respectively. In the constructed model, the AUC of the SDS prediction was 0.770 (95% confidence interval: 0.654-0.887), P

Simple Summary: Minimally invasive laparoscopic surgeries improve surgical recovery with shorter hospital stays and lower complications. However, the role of minimally invasive surgery in advanced and recurrent ovarian cancer has remained confined to small case series. This retrospective study reports the highest number of patients with advanced and recurrent ovarian cancers undergoing laparoscopic surgery in a single referral center. A rigorous algorithm for the selection of patients has been applied to confirm the feasibility of laparoscopy for primary debulking surgery and broadened its application to interval and secondary debulking surgery. Our study showed that minimally invasive surgery is feasible in select patients with favorable postoperative and oncological outcomes, consistent with other cohorts reported in the literature undergoing traditional laparotomic approach. Objective: To report the feasibility of laparoscopic cytoreduction surgery for primary and recurrent ovarian cancer in a select group of patients. Methods: A retrospective analysis was conducted on a cohort of patients with FIGO stage IIIA-IV advanced ovarian cancer who underwent laparoscopic primary debulking surgery (PDS), interval debulking surgery (IDS), or secondary debulking surgery (SDS) between June 2008 and January 2020. The primary endpoint was achieving optimal cytoreduction, defined as residual tumor less than 1 cm. Secondary endpoints included evaluating surgical complications and long-term survival, assessed at three-month intervals during the initial two years and then every six months. Results: This study included a total of 108 patients, among whom, 40 underwent PDS, 44 underwent IDS, and 24 underwent SDS. Optimal cytoreduction rates were found to be 95.0%, 97.7%, and 95.8% for the PDS, ISD, and SDS groups, respectively. Early postoperative complications (<30 days from surgery) occurred in 19.2% of cases, with 7.4% of these cases requiring reintervention. One patient died following postoperative respiratory failure. Late postoperative complications (<30 days from surgery) occurred in 9.3% of cases, and they required surgical reintervention only in one case. After laparoscopic optimal cytoreduction with a median follow-up time of 25 months, the overall recurrence rates were 45.7%, 38.5%, and 39.3% for PDS, ISD, and SDS, respectively. The three-year overall survival rates were 84%, 66%, and 63%, respectively, while the three-year disease-free survival rates were 48%, 51%, and 71%, respectively. Conclusions: Laparoscopic cytoreduction surgery is feasible for advanced ovarian cancer in carefully selected patients, resulting in high rates of optimal cytoreduction, satisfactory peri-operative morbidity, and encouraging survival outcomes. Future studies should focus on establishing standardized selection criteria and conducting well-designed investigations to further refine patient selection and evaluate long-term outcomes. [ABSTRACT FROM AUTHOR]

To compare the impact of primary debulking surgery (PDS) and interval debulking surgery (IDS) on the long-term survival of patients with advanced ovarian cancer. Patients with advanced epithelial ovarian cancer (stage III-IVB) who underwent surgery (PDS/IDS) in the Gynecology Department of The First Affiliated Hospital of University of USTC from January 2018 to June 2018 were collected. The two types of surgery were compared in terms of survival time (OS) and incidence of serious surgical complications. Kaplan-Meier method was used to analyze the survival curve, log-rank test was used to compare the survival differences, and Cox proportional hazards regression model was used to analyze the risk factors affecting survival. A total of 76 patients were included, including 24 cases in the IDS group, and 52 cases in the PDS group. There were no statistically significant differences between the two groups in terms of age, nutritional score, preoperative hemoglobin (Hb) levels, histopathological types, clinical stages, etc(P>0.05). The intraoperative bleeding volume in the IDS group was significantly lower than that in the PDS group (1045.83± 981.91 mL vs 1628.85± 1168.72 mL, P<0.01). The incidence of serious surgical complications in the IDS group was significantly lower than that in the PDS group (12.5% vs 36.5%, P<0.05). During follow-up, there were 9 deaths in the IDS group, and 16 deaths in the PDS group. The median OS in the IDS group was 47.0 months, and the median OS in the PDS group was 38.0 months, and there was no significant difference in OS between the two groups (P=0.17). Multivariate Cox regression analysis showed that intraoperative bleeding volume(HR=1.001, 95%CI=1.000-1.002, P=0.03) and severe surgical complications (HR=2.345,95%CI=1.123-4.902, P=0.02) were independent risk factors affecting OS, while the operation type (PDS/IDS) was not an independent risk factor affecting OS (HR=0.667,95% CI=0.302-1.473, P=0.32). In patients with advanced ovarian cancer, IDS compared with PDS can reduce intraoperative bleeding volume and the incidence of serious surgical complications, but has no significant effect on long-term survival. Intraoperative bleeding volume and severe surgical complications are independent risk factors for long-term survival, and should be avoided. [ABSTRACT FROM AUTHOR]

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis, and it holds promise as a therapeutic strategy, but its role remains elusive. The aim of this study was to assess the existing evidence for the use or not of HIPEC in primary debulking surgery (PDS), interval debulking surgery (IDS), and recurrent ovarian cancer (ROC), evaluated in terms of survival rates and post-surgical morbidity. Methods: Medline, Pubmed, Cochrane, and Medscape were systematically searched for any article comparing the use of HIPEC treatment with any other therapy in patients with ovarian cancer in PDS, IDS, and ROC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. We only considered English-language published studies. Results: We included 14 studies, including two RCTs with a total of 1813 women, published between 2003 and 2023 with a recruitment period between 1998 and 2020. In PDS, there were no differences in progression-free survival (PFS) between HIPEC and controls [MD −5.53 months [95% CI −19.91 to 8.84 months]; I2 = 96%]. Conversely, in patients treated with NACT, pooled results showed a significant survival advantage in terms of progression-free survival (PFS) and overall survival (OS) in the combined HIPEC plus IDS group rather than surgery alone [PFS: MD 4.68 months (95% CI 3.49 to 5.86 months, I2 = 95%); OS: MD 11.81 months (95% CI 9.34 to 14.27 months); I2 = 97%]. Concerning ROC patients, pooled MD did not show either a significant PFS difference between intervention and controls [MD 2.68 months (95% CI 433 to 9.70 months); I2 = 95%], and OS significant difference (MD 6.69 months [95% CI −9.09 to 22.47 months]; I2 = 98%). Severe post-operative complications (≥grade 3) were available in 10 studies, accounting for 1108 women. Overall, there was a slightly but significantly increased risk with the combined approach compared to controls [RR 1.26 (95% CI 1.02 to 1.55); I2 = 0%]. Conclusions: The combination of HIPEC with cytoreductive surgery prolongs OS and PFS in advanced epithelial ovarian cancer after NACT with acceptable morbidity. However, additional trials are still needed to determine the effectiveness of HIPEC in primary and recurrence settings. In the era of personalized medicine, the correlation between the efficacy of HIPEC and biological and molecular findings represents a challenge for the future of ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective: To assess compliance with the 2019 regional recommendation to centralize epithelial ovarian cancer (EOC) patients and to assess whether the COVID‐19 pandemic has affected the quality of care for EOC patients. Methods: We compared data from EOC patients treated before the introduction of the 2019 regional recommendation (2018‐2019) with data obtained from EOC patients treated after the regional recommendation was adopted during the first 2 years of the COVID‐19 pandemic (2020‐2021). Data were retrieved from the Optimal Ovarian Cancer Pathway records. R software version 4.1.2 (the R Foundation for Statistical Computing, Vienna, Austria) was used for the statistical analysis. Results: 251 EOC patients were centralized. The number of EOC patients centralized increased from 2% to 49% despite the COVID‐19 pandemic. During the COVID‐19 pandemic, there was an increase in the use of neoadjuvant chemotherapy and interval debulking surgery. There was an improvement in the percentage of Stage III patients without gross residual disease following both primary and interval debulking surgery. The percentage of EOC cases discussed by the multidisciplinary tumor board (MTB) increased from 66% to 89% of cases. Conclusion: Despite the COVID‐19 pandemic, centralization has increased and the quality of care has been preserved thanks to the MTB. Synopsis: Centralization of ovarian cancer patients was the key to ensuring effective treatment despite the COVID‐19 pandemic. The multidisciplinary tumor board ensured the quality of care. [ABSTRACT FROM AUTHOR]

Introduction: Primary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes. Methods: We conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC. All patients underwent a germline multigene panel for BRCA1/2 evaluation. Results: Among the 83 patients who underwent PDS, a TTC ≥ 60 days was associated with a shorter PFS (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.04--3.93, p = 0.038), although this association lost statistical significance when adjusting for residual disease (HR 1.52, 95% CI 0.75-3.06, p = 0.244, for TTC and HR 2.73, 95% CI 1.50-4.96, p = 0.001, for residual disease). Among 52 IDS patients, we found no evidence of an association between TTC and clinical outcomes. Ascites, type of chemotherapy, or germline BRCA1/2 mutational status did not influence TTC and were not associated with clinical outcomes in PDS or IDS patients. Discussion: In conclusion, longer TTC seems to negatively affect prognosis in patients undergoing PDS, especially those with residual disease. [ABSTRACT FROM AUTHOR]

To compare outcomes of patients with high-grade epithelial ovarian cancer (EOC) who underwent secondary cytoreduction surgery (SCS) after up-front treatment with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) versus primary debulking surgery (PDS). Patients with high-grade EOC who underwent SCS from 2/1/2004–10/31/2021 were classified by up-front treatment. Clinical and treatment characteristics were compared between cohorts. Progression-free survival (PFS2) and overall survival (OS2) following SCS were compared using a Cox model adjusted for stage, age at SCS, and number of years between end of chemotherapy and SCS. Of 374 patients, 62 (17%) underwent NACT-IDS and 312 (83%) PDS. Justification for NACT was disease extent (n = 57, 92%), comorbidities (n = 3, 5%), and thromboembolism (n = 2, 3%). The NACT-IDS cohort had a higher median age at SCS (64 years [IQR: 56–70] vs 59 years [IQR: 53–66]; P =.03), higher proportion of stage III/IV disease (100% vs 81%; P <.001), and shorter median interval between end of chemotherapy and SCS (1.5 years [IQR: 1.1–2.3] vs 1.9 years [IQR: 1.3–3.1]; P =.01). Achievement of complete gross resection at SCS did not differ between NACT-IDS and PDS (84% vs 88%; P =.18). PFS2 (HR: 1.19, 95% CI: 0.83–1.71) and OS2 (HR: 0.96, 95% CI: 0.57–1.63) did not vary by primary treatment modality after adjusting for clinically relevant covariates. Despite more extensive disease at presentation, patients with high-grade EOC who recur after NACT-IDS seem to have similar surgical and survival outcomes after SCS compared to patients who recur after PDS, suggesting that prior NACT-IDS should not preclude SCS. • Patients with SCS after NACT-IDS were older, had higher stage at diagnosis, and less time from end of chemotherapy to SCS. • Recurrence and overall survival after SCS did not differ by primary treatment modality (NACT-IDS vs PDS). • Prior treatment modality should not preclude consideration for SCS at time of recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice. Patients and methods: We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy. Results: Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93). Conclusions: NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS. [ABSTRACT FROM AUTHOR]

Background: Preoperative assessment of whether a successful primary debulking surgery (PDS) can be performed in patients with advanced high‐grade serous ovarian carcinoma (HGSOC) remains a challenge. A reliable model to precisely predict resectability is highly demanded. Purpose: To investigate the value of diffusion‐weighted MRI (DW‐MRI) combined with morphological characteristics to predict the PDS outcome in advanced HGSOC patients. Study Type: Prospective. Subjects: A total of 95 consecutive patients with histopathologically confirmed advanced HGSOC (ranged from 39 to 77 years). Fields Strength/Sequence: A 3.0 T, readout‐segmented echo‐planar DWI. Assessment: The MRI morphological characteristics of the primary ovarian tumor, a peritoneal carcinomatosis index (PCI) derived from DWI (DWI‐PCI) and histogram analysis of the primary ovarian tumor and the largest peritoneal carcinomatosis were assessed by three radiologists. Three different models were developed to predict the resectability, including a clinicoradiologic model combing MRI morphological characteristic with ascites and CA125 level; DWI‐PCI alone; and a fusion model combining the clinical‐morphological information and DWI‐PCI. Statistical Tests: Multivariate logistic regression analyses, receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI) were used. A P < 0.05 was considered to be statistically significant. Results: Sixty‐seven cases appeared as a definite mass, whereas 28 cases as an infiltrative mass. The morphological characteristics and DWI‐PCI were independent factors for predicting the resectability, with an AUC of 0.724 and 0.824, respectively. The multivariable predictive model consisted of morphological characteristics, CA‐125, and the amount of ascites, with an incremental AUC of 0.818. Combining the application of a clinicoradiologic model and DWI‐PCI showed significantly higher AUC of 0.863 than the ones of each of them implemented alone, with a positive NRI and IDI. Data Conclusions: The combination of two clinical factors, MRI morphological characteristics and DWI‐PCI provide a reliable and valuable paradigm for the noninvasive prediction of the outcome of PDS. Evidence Level: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Purpose: In this study, we aimed to put forth the factors that contribute to the recurrence of mucinous ovarian cancer. Materials and Methods: Forty-four mucinous ovarian cancer patients who have presented to our clinic between February 2006 and May 2018 took part in the study. In order to predict the factors that contribute to recurrence, the univariate and the multivariate logistic regressions were utilized. The Kaplan--Meier survival analysis was utilized for survival and the log-rank test was used for the discrepancies between the groups. In the analysis of the data, the Statistical Package for the Social Sciences 22 program was used. It was acknowledged to have statistical meaning when the P value in all the tests was lower than 0.05. Findings: Recurrence was detected in 20 out of 44 patients who participated in the study. The ages of the patients who did not experience recurrence were significantly lower (P = 0.001). The patients were detected mostly in Stage 1 (36.4%). In the group of patients without recurrence, systemic lymphadenectomy (43.2%) was greater (P = 0.019). Lymph node metastasis was three times higher in the group that experienced recurrence (P = 0.047). When the two groups were compared, the platinum resistance was considerably greater in the group with recurrence (P = 0.005). In terms of residual tumor, the rate of complete resection was (9%) better in the group that experienced recurrence compared to the group that did not experience recurrence, with a rate of 45.5%. While 12 patients who experienced recurrence died, 6 people died in the other group. From the factors that contribute to recurrence, in terms of residual tumor quantity, this was grouped as complete (R0) resection and optimal + suboptimal (R1 + R2) resection and the following were determined: odds ratio (OR) - 5.7 (95% confidence interval [CI]: 1.56-20.9) and P = 0.008 for R1 + R2. In univariate analysis, the OR was determined as 1.16 (95% CI: 1.06-1.27) for age. Possessing a Stage 2 and higher disease statistically contributed considerably to the recurrence compared to Stage 1 disease (OR: 6.33; 95% CI: 1.59-25.22; P = 0.009). Age was determined as an independent prognostic risk factor in the multivariate analysis (OR: 1.10 [95% CI: 1.04-1.25]), P = 0.018. Furthermore, the OR for the advanced-stage (Stage 2 or higher) patients in the multivariate analysis was determined as 7.88 (95% CI: 0.78-78.8) and was found to be statistically significant at limits (P = 0.079). Results: We have put forth that the genetic, biological, and clinical characteristics of mucinous ovarian cancers differ from that of other epithelial ovarian cancers, and that age, advanced stage, and residual tumor quantity are prognostic risk factors in terms of recurrence, and that age is an independent prognostic risk factor. Conclusion: Biological and clinical characteristics of mucinous ovarian cancers differ from those of other epithelial ovarian cancers, and we observed that the age, advanced stage, and the amount of residual tumor regarding recurrence are prognostic risk factors, while age was determined as an independent prognostic risk factor. [ABSTRACT FROM AUTHOR]

IntroductionPrimary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes.MethodsWe conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC. All patients underwent a germline multigene panel for BRCA1/2 evaluation.ResultsAmong the 83 patients who underwent PDS, a TTC ≥ 60 days was associated with a shorter PFS (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.04–3.93, p = 0.038), although this association lost statistical significance when adjusting for residual disease (HR 1.52, 95% CI 0.75–3.06, p = 0.244, for TTC and HR 2.73, 95% CI 1.50–4.96, p = 0.001, for residual disease). Among 52 IDS patients, we found no evidence of an association between TTC and clinical outcomes. Ascites, type of chemotherapy, or germline BRCA1/2 mutational status did not influence TTC and were not associated with clinical outcomes in PDS or IDS patients.DiscussionIn conclusion, longer TTC seems to negatively affect prognosis in patients undergoing PDS, especially those with residual disease.

Purpose: To develop and validate an MRI-based radiomics nomogram for the preoperative prediction of miliary changes in the small bowel mesentery (MCSBM) in advanced high-grade serous ovarian cancer (HGSOC). Materials and methods: One hundred and twenty-eight patients with pathologically proved advanced HGSOC (training cohort: n = 91; validation cohort: n = 37) were retrospectively included. All patients were initially evaluated as MCSBM-negative by preoperative imaging modalities but were finally confirmed by surgery and histopathology (MCSBM-positive: n = 53; MCSBM-negative: n = 75). Five radiomics signatures were built based on the features from multisequence magnetic resonance images. Independent clinicoradiological factors and radiomics-fusion signature were further integrated to construct a radiomics nomogram. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves and clinical utility. Results: Radiomics signatures, ascites, and tumor size were independent predictors of MCSBM. A nomogram integrating radiomics features and clinicoradiological factors demonstrated satisfactory predictive performance with areas under the curves (AUCs) of 0.871 (95% CI 0.801–0.941) and 0.858 (95% CI 0.739–0.976) in the training and validation cohorts, respectively. The net reclassification index (NRI) and integrated discrimination improvement (IDI) revealed that the nomogram had a significantly improved ability compared with the clinical model in the training cohort (NRI = 0.343, p = 0.002; IDI = 0.299, p < 0.001) and validation cohort (NRI = 0.409, p = 0.015; IDI = 0.283, p = 0.001). Conclusion: Our proposed nomogram has the potential to serve as a noninvasive tool for the prediction of MCSBM, which is helpful for the individualized assessment of advanced HGSOC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In women affected by advanced ovarian cancer, complete cytoreductive surgery is of paramount important to achieve the best oncological outcomes. In this study, we compared radiologic, laparoscopic, and laparotomic scoring assessments to identify the best strategy to predict the achievement of complete cytoreductive surgery, both in upfront surgery and in neoadjuvant chemotherapy and subsequent surgery. We found that laparoscopic score assessment had a high accuracy for optimal cytoreduction in women affected by advanced ovarian cancer who need to undergo surgical management. Objective: To identify the best method among the radiologic, laparoscopic and laparotomic scoring assessment to predict the outcomes of cytoreductive surgery in patients with advanced ovarian cancer (AOC). Methods: Patients with AOC who underwent pre-operative computed tomography (CT) scan, laparoscopic evaluation, and cytoreductive surgery between August 2016 and February 2021 were retrospectively reviewed. Predictive Index (PI) score and Peritoneal Cancer Index (PCI) scores were used to estimate the tumor load and predict the residual disease in the primary debulking surgery (PDS) and interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT) groups. Concordance percentages were calculated between the two scores. Results: Among 100 eligible patients, 69 underwent PDS, and 31 underwent NACT and IDS. Complete cytoreduction was achieved in 72.5% of patients in the PDS group and 77.4% in the IDS. In patients undergoing PDS, the laparoscopic PI and the laparotomic PCI had the best accuracies for complete cytoreduction (R0) [area under the curve (AUC) = 0.78 and AUC = 0.83, respectively]. In the IDS group, the laparotomic PI (AUC = 0.75) and the laparoscopic PCI (AUC= 0.87) were associated with the best accuracy in R0 prediction. Furthermore, radiological assessment, through PI and PCI, was associated with the worst accuracy in either PDS or IDS group (PI in PDS: AUC = 0.64; PCI in PDS: AUC = 0.64; PI in IDS: AUC = 0.46; PCI in IDS: AUC = 0.47). Conclusion: The laparoscopic score assessment had high accuracy for optimal cytoreduction in AOC patients undergoing PDS or IDS. Integrating diagnostic laparoscopy in the decision-making algorithm to accurately triage AOC patients to different treatment strategies seems necessary. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to find the risk factors for major intraoperative blood loss (MBL) of primary debulking surgery (PDS) for ovarian cancer. Methods: Patients with ovarian cancer who underwent PDS in our hospital, from 2010 to 2017, were enrolled. The association between risk factors and MBL was modeled with the use of logistic regression. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive value of the logistic regression model. Results: A total of 346 patients met the inclusion criteria. There were 150 patients with MBL. Tumor stage 3/4 (P ​

Objective To investigate the impact of serum albumin (at diagnosis and pre-operatively) on survival in patients undergoing cytoreductive surgery for advanced ovarian cancer(AOC) and whether improvement in albumin achieved following neoadjuvant chemotherapy (NACT) affects overall survival (OS). Methods Outcomes of 441 patients who underwent cytoreduction for AOC were reviewed. Albumin was recorded at diagnosis and pre-operatively. Further analysis was performed if patients were hypoalbuminaemic at diagnosis.Analysis was stratified according to whether the patientreceived primary debulking surgery (PDS) or interval debulking surgery (IDS) and if their albumin was corrected. Results 308 patients had a serum albumin level at diagnosis and 400 patients had a pre-operative albumin available for analysis. For patients with an albumin at diagnosis ≤ 35g/L and ≥36 g/L, median OS was 31.5 (95% CI 23.5–39.5) and 50.4 (95% CI 38.9–61.9) months respectively (P = 0.003). Followingmultivariate analysis (MVA), albumin at diagnosis remained statistically significant as an independent marker for survival, even after adjusting for cytoreductive outcome, stage and grade(p = 0.04, Hazard ratio 1.38, 95% CI 1.01–1.89). Hypoalbuminaemic patients at diagnosis achieved complete cytoreduction in 53% of cases.For PDS patients, median OS was 19.7 months (95% CI 11.5–27.9). For IDS patients, median OS was 27.9 months (n = 1).IDS patients with a corrected albumin had a median OS of 42.9 months (95% CI 31.5–54.3) (p > 0.05). Conclusion Hypoalbuminaemia at diagnosis is a poor prognostic factor in AOC. Normalization of serum albumin after NACT is a potential predictor of survival.

Background & Objectives Ultra-radical (UR) procedures, including splenectomy, are utilized to increase complete cytoreduction rates during Cytoreductive Surgery (CRS) performed with the aim of complete macroscopic clearance of disease. The purpose of this study was to investigate if splenectomy negatively impacts survival when undertaken during CRS for advanced ovarian cancer (AOC) and compare published splenectomy and cytoreduction rates. Methods A retrospective review of all consecutive patients who underwent cytoreductive surgery for AOC between 16/05/2013-28/01/2019. Survival, baseline patient characteristics, complications and surgical parameters were recorded. Propensity scored matching (PSM) was performed to reduce bias. Results 154 patients identified over 71 months. 97 underwent standard, 57 underwent UR surgery, 27 patients received splenectomy (17.5%) No difference was seen in overall survival (OS) between all patients (median OS 34 months (95%CI 25.9–41.1) and patients who underwent splenectomy (median OS not yet reached) (p = >0.05). After PSM for various baseline covariates, no significant difference in splenectomy versus non-splenectomy patients (3-year survival 54% compared to 56%) (P > 0.05). Three splenectomy specific complications occurred; one each of pancreatic tail injury, left pleural effusion and streptococcal pharyngitis during chemotherapy. We found wide variation in utilization of splenectomy in published case series; from 9% to 35%. Conclusions Splenectomy performed as part of CRS is not detrimental to survival in AOC. There is a wide variation in utilization of splenectomy in published case series with little correlation with cytoreduction rates.

Aim: Surgery for advanced ovarian cancer (AOC) has evolved over the past decade to ingeminate the need to offer maximum effort surgery (MES). The aim of this study is to analyze the implementation of a paradigm shift in the surgical management of women with AOC at the University Hospitals of Leicester NHS Trust (UHL) in 2015, until 2020, compared to 2011–2014. Methods: Retrospective cohort study of women with AOC who underwent cytoreductive surgery (CRS) in the UHL. The two groups were: 153 women from January 2011 to December 2014 (group 1), 136 women from January 2015 to January 2020 (group 2). Results: In group 1, the 1, 3, and 5 years overall survival rates (OS) were, 90.4%, 33.7%, and 19.3%, compared to 90.2%, 55.4%, and 29.7%, respectively, in group 2 (p = 0.012). Significantly more women had CRS in group 2: 45—Primary debulking surgery (PDS) and 57—interval debulking surgery (IDS) versus 17—PDS & 67—IDS in group 1 (p < 0.001). Surgical complexity score (modified Aletti score) was higher in group 2 compared to group 1 (p = <0.001). No significant difference was noted in the postoperative complications, in group 2, in women who underwent PDS versus IDS, yet PDS was associated with higher OS. Conclusions: MES/CRS in women with AOC significantly improves OS. Our data highlights the importance of a dedicated team to implement this change in cancer centers. Where possible, suitable women with AOC likely to have complete cytoreduction based on preoperative assessment, should be offered PDS. [ABSTRACT FROM AUTHOR]

Objective: To explore the impact of the primary treatment sequence (primary debulking surgery, PDS, versus neoadjuvant chemotherapy and interval debulking surgery, NACT‐IDS) on post‐relapse survival (PRS) and recurrence characteristics of recurrent epithelial ovarian cancer (REOC). Design: Real‐world retrospective study. Setting: Tertiary hospitals in China. Population: A total of 853 patients with REOC at International Federation of Gynaecology and Obstetrics stages IIIC–IV from September 2007 to June 2020. Overall, 377 and 476 patients received NACT‐IDS and PDS, respectively. Methods: Propensity score‐based inverse probability of treatment weighting (IPTW) was performed to balance the between‐group differences. Main Outcome Measures: Clinicopathological factors related to PRS. Results: The overall median PRS was 29.3 months (95% CI 27.0–31.5 months). Multivariate analysis before and after IPTW adjustment showed that NACT‐IDS and residual R1/R2 disease were independent risk factors for PRS (p < 0.05). Patients with diffuse carcinomatosis and platinum‐free interval (PFI) ≤ 12 months had a significantly worse PRS (p < 0.001). Logistic regression analysis revealed that NACT‐IDS was an independent risk factor for diffuse carcinomatosis (OR 1.36, 95% CI 1.01–1.82, p = 0.040) and PFI ≤ 12 months (OR 1.59, 95% CI 1.08–2.35, p = 0.019). In IPTW analysis, NACT‐IDS was still significantly associated with diffuse carcinomatosis (OR 1.29, 95% CI 1.05–1.58, p = 0.015) and PFI ≤ 12 months (OR 1.90, 95% CI 1.52–2.38, p < 0.001). Conclusions: The primary treatment sequence may affect the PRS of patients with REOC by altering the recurrence pattern and PFI duration. [ABSTRACT FROM AUTHOR]

Introduction: Complete resection after debulking surgery is strongly associated with prolonged survival for advanced serous ovarian cancer (ASOC). Though positron emission tomography/computed tomography (PET/CT) is more advantageous than computed tomorgraphy (CT) for detecting metastases, studies on the PET/CT prediction model for incomplete resection for ovarian cancer are insufficient. We analyzed and compared the predictive value of preoperative PET/CT score, CT score, metabolic parameters, tumor markers and hematological markers for incomplete resection after debulking surgery for ASOC.Material and Methods: A total of 62 ASOC patients who underwent preoperative [18 F]FDG PET/CT and debulking surgery were retrospectively analyzed. PET/CT and CT scores were based on the Suidan model. The predictive value of PET/CT score, CT score, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) for incomplete resection were analyzed and compared.Results: Preoperative PET/CT score had the highest predictive value for incomplete resection in primary debulking surgery group (sensitivity: 65.0%, specificity: 88.9%, area under the ROC curve (AUC): 0.847, p < 0.001), however, in secondary debulking surgery group, preoperative PET/CT score and CT score had the same and highest predictive value for incomplete resection (sensitivity: 80.0%, specificity: 94.7%, AUC: 0.853, p = 0.017), compared with preoperative metabolic parameters SUVmax and MTV, tumor markers HE4 and CA125, and hematological markers LMR, PLR and NLR. Preoperative PET/CT score ≥ 3 (Suidan model) and preoperative PET/CT score ≥ 2 predicted a high risk of incomplete resection after primary and secondary debulking surgeries, respectively. There was no statistical difference between primary and secondary debulking surgery groups in predictive value of PET/CT score for incomplete resection (p = 0.971). There were significant differences between PET/CT scores and CT scores in primary debulking surgery group and no significant differences in secondary debulking surgery group.Conclusions: A high PET/CT score predicted a high risk of incomplete resection. The preoperative PET/CT score had an identical predictive value in primary and secondary debulking surgery groups. PET/CT score was more accurate in the detection of metastases than CT score was. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether neoadjuvant chemotherapy (NACT) confers superior outcomes compared to primary debulking surgery (PDS) in patients with stage III and IV epithelial ovarian, tubal or peritoneal cancer as well as in patients with high tumour load. Methods: We searched the electronic databases PubMed, Cochrane Central Register of Controlled trials, and Scopus from inception to March 2021. We considered randomised controlled trials (RCTs) comparing NACT with PDS for women with epithelial ovarian cancer (EOC) stages III and IV. The primary outcomes were overall survival and progression-free survival. Secondary outcomes were optimal cytoreduction rates, perioperative adverse events, and quality of life. Results: Six RCTs with a total of 1901 participants were included. Meta-analysis demonstrated similar overall survival (HR = 0.96, 95% CI [0.86–1.07]) and progressionfree survival (HR = 0.98, 95% CI [0.89–1.08]) between NACT and PDS. Subgroup analyses did not demonstrate higher survival for stage IV patients (HR = 0.88, 95% CI [0.71–1.09]) nor for patients with metastatic lesions >5 cm(HR = 0.86, 95% CI [0.69–1.08]) treated with NACT, albeit with some uncertainty due to imprecision. Similarly, no survival benefit was observed in the subgroup of patients with metastatic lesions >10 cm (HR = 0.94, 95% CI [0.78–1.12]). NACT was associated with significantly higher rates of complete cytoreduction (RR = 2.34, 95% CI [1.48–3.71]). Severe peri-operative adverse events were less frequent in the NACT arm (RR = 0.34, 95% CI [0.16–0.72]. Conclusion: Patients with stage III and IV epithelial ovarian cancer undergoing NACT or PDS have similar overall survival. NACT is likely associated with higher rates of complete cytoreduction and lower risk of severe adverse events and peri-operative death. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the seventh most common cancer in women worldwide and the eighth most common cause of cancer death. Due to the lack of effective early detection strategies and the unspecific onset of symptoms, it is diagnosed at an advanced stage in 75% of cases. The cancer antigen (CA) 125 is used as a prognostic marker and its level is elevated in more than 85% of women with advanced stages of epithelial ovarian cancer (EOC). The standard treatment is primary debulking surgery (PDS) followed by adjuvant chemotherapy (ACT), but the later approach is neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Several studies have been conducted to find out whether preoperative CA-125 serum levels influence treatment choice, surgical resection and survival outcome. The aim of our study was to analyse experience of single institution as Cancer comprehensive center with preoperative usefulness of CA-125.

Complete resection of all visible lesions during primary debulking surgery is associated with the most favorable prognosis in patients with advanced high-grade serous ovarian cancer. An accurate preoperative assessment of resectability is pivotal for tailored management. This study aimed to assess the potential value of a modified model that integrates the original 8 radiologic criteria of the Memorial Sloan Kettering Cancer Center model with imaging features of the subcapsular or diaphragm and mesenteric lesions depicted on diffusion-weighted magnetic resonance imaging and growth patterns of all lesions for predicting the resectability of advanced high-grade serous ovarian cancer. This study included 184 patients with high-grade serous ovarian cancer who underwent preoperative diffusion-weighted magnetic resonance imaging between December 2018 and May 2023 at 2 medical centers. The patient cohort was divided into 3 subsets, namely a study cohort (n=100), an internal validation cohort (n=46), and an external validation cohort (n=38). Preoperative radiologic evaluations were independently conducted by 2 radiologists using both the Memorial Sloan Kettering Cancer Center model and the modified diffusion-weighted magnetic resonance imaging–based model. The morphologic characteristics of the ovarian tumors depicted on magnetic resonance imaging were assessed as either mass-like or infiltrative, and transcriptomic analysis of the primary tumor samples was performed. Univariate and multivariate statistical analyses were performed. In the study cohort, both the scores derived using the Memorial Sloan Kettering Cancer Center (intraclass correlation coefficients of 0.980 and 0.959, respectively; both P <.001) and modified diffusion-weighted magnetic resonance imaging–based models (intraclass correlation coefficients of 0.962 and 0.940, respectively; both P <.001) demonstrated excellent intra- and interobserver agreement. The Memorial Sloan Kettering Cancer Center model (odds ratio, 1.825; 95% confidence interval, 1.390–2.395; P <.001) and the modified diffusion-weighted magnetic resonance imaging–based model (odds ratio, 1.776; 95% confidence interval, 1.410–2.238; P <.001) independently predicted surgical resectability. The modified diffusion-weighted magnetic resonance imaging–based model demonstrated improved predictive performance with an area under the curve of 0.867 in the study cohort and 0.806 and 0.913 in the internal and external validation cohorts, respectively. Using the modified diffusion-weighted magnetic resonance imaging–based model, patients with scores of 0 to 2, 3 to 4, 5 to 6, 7 to 10, and ≥11 achieved complete tumor debulking rates of 90.3%, 66.7%, 53.3%, 11.8%, and 0%, respectively. Most patients with incomplete tumor debulking had infiltrative tumors, and both the Memorial Sloan Kettering Cancer Center and the modified diffusion-weighted magnetic resonance imaging–based models yielded higher scores. The molecular differences between the 2 morphologic subtypes were identified. When compared with the Memorial Sloan Kettering Cancer Center model, the modified diffusion-weighted magnetic resonance imaging–based model demonstrated enhanced accuracy in the preoperative prediction of resectability for advanced high-grade serous ovarian cancer. Patients with scores of 0 to 6 were eligible for primary debulking surgery. [ABSTRACT FROM AUTHOR]

The rationale behind the use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery is the association between pharmacological activity of chemotherapy delivered to the peritoneal cavity with the enhanced cytotoxic effect of hyperthermia. Data on the efficacy of HIPEC in the primary debulking surgery (PDS) setting are still controversial and limited by the small sample size of most of the studies, the inclusion of different treatment settings and chemotherapy regimens. Among the ongoing prospective trials, only the OVHIPEC-2 trial is investigating exclusively patients submitted to PDS ± HIPEC with cisplatin 100 mg/m2 and results are expected by 2026. On the interval debulking surgery (IDS) setting high quality data are coming from the result of the OVHIPEC-1 trial, which demonstrated a survival advantage of nearly 4 months in median progression-free survival (PFS) (14.2 months vs. 10.7 months; p = 0.003) and almost 12 months in median overall survival (OS) (45.7 months vs. 33.9 months; p = 0.02) for HIPEC treated patients (cisplatin 100 mg/m2) compared to no-HIPEC group, with comparable morbidity. However, due to some criticisms raised to the results of OVHIPEC-1 trial, the ESMO-ESGO guidelines recommended not to consider HIPEC as standard therapy until results from ongoing randomized control trials (RCTs) are provided. On the contrary, for the National Comprehensive cancer network (NCCN) guidelines HIPEC can be considered at the time of IDS. Similarly, data supporting the role of HIPEC in association with surgery in case of recurrent disease appear to be controversial in terms of patients and selection and intraperitoneal chemotherapy regimen. Indeed, despite the positive results coming from a prospective randomized trial, they appear to be biased by the inclusion of both platinum sensitive and resistant disease and the lack of information on PFS. Those results are in contrast with data coming from another prospective trial, which failed to demonstrate a survival gain of recurrent ovarian cancer patients treated with secondary cytoreductive surgery + HIPEC with carboplatin (800 mg/m2 for 90 min) compared to women submitted to cytoreduction only. Again, in this subgroup of patients data of ongoing RCTs are awaited to assess the impact on survival of HIPEC administration in case of recurrent disease. [ABSTRACT FROM AUTHOR]

Primary debulking surgery (PDS) has remained the only treatment of ovarian cancer with survival advantage since its development in the 1970s. However, survival advantage is only observed in patients who are optimally resected. Neoadjuvant chemotherapy (NACT) has emerged as an alternative for patients in whom optimal resection is unlikely and/or patients with comorbidities at high risk for perioperative complications. The purpose of this review is to summarize the evidence to date for PDS and NACT in the treatment of stage III/IV ovarian carcinoma. We systematically searched the PubMed database for relevant articles. Prior to 2010, NACT was reserved for non-surgical candidates. After publication of EORTC 55971, the first randomized trial demonstrating non-inferiority of NACT followed by interval debulking surgery, NACT was considered in a wider breadth of patients. Since EORTC 55971, 3 randomized trials—CHORUS, JCOG0602, and SCORPION—have studied NACT versus PDS. While CHORUS supported EORTC 55971, JCOG0602 failed to demonstrate non-inferiority and SCORPION failed to demonstrate superiority of NACT. Despite conflicting data, a subset of patients would benefit from NACT while preserving survival including poor surgical candidates and inoperable disease. Further randomized trials are needed to assess the role of NACT. [ABSTRACT FROM AUTHOR]

To investigate the impact of serum albumin (at diagnosis and pre-operatively) on survival in patients undergoing cytoreductive surgery for advanced ovarian cancer(AOC) and whether improvement in albumin achieved following neoadjuvant chemotherapy (NACT) affects overall survival (OS). Outcomes of 441 patients who underwent cytoreduction for AOC were reviewed. Albumin was recorded at diagnosis and pre-operatively. Further analysis was performed if patients were hypoalbuminaemic at diagnosis.Analysis was stratified according to whether the patientreceived primary debulking surgery (PDS) or interval debulking surgery (IDS) and if their albumin was corrected. 308 patients had a serum albumin level at diagnosis and 400 patients had a pre-operative albumin available for analysis. For patients with an albumin at diagnosis ≤ 35g/L and ≥36 g/L, median OS was 31.5 (95% CI 23.5–39.5) and 50.4 (95% CI 38.9–61.9) months respectively (P = 0.003). Followingmultivariate analysis (MVA), albumin at diagnosis remained statistically significant as an independent marker for survival, even after adjusting for cytoreductive outcome, stage and grade(p = 0.04, Hazard ratio 1.38, 95% CI 1.01–1.89). Hypoalbuminaemic patients at diagnosis achieved complete cytoreduction in 53% of cases.For PDS patients, median OS was 19.7 months (95% CI 11.5–27.9). For IDS patients, median OS was 27.9 months (n = 1).IDS patients with a corrected albumin had a median OS of 42.9 months (95% CI 31.5–54.3) (p > 0.05). Hypoalbuminaemia at diagnosis is a poor prognostic factor in AOC. Normalization of serum albumin after NACT is a potential predictor of survival. [ABSTRACT FROM AUTHOR]

Background: Whether neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) against primary debulking surgery (PDS) has a differential effect on prognosis due to Breast Cancer Susceptibility Genes (BRCA)1/2 mutations has not been confirmed by current studies. Methods: All patients included in this retrospective study were admitted to Qilu Hospital of Shandong University between January 2009 and June 2020, and germline BRCA1/2 mutation were tested. Patients in stage IIIB, IIIC, and IV, re-staged by International Federation of Gynecology and Obstetrics (FIGO) 2014, were selected for analysis. All patients with NAC received 1-5 cycles of platinum-containing (carboplatin, cisplatin, or nedaplatin) chemotherapy. Patients who received maintenance therapy after chemotherapy were not eligible for this study. All relevant medical records were collected. Results: A total of 322 patients were enrolled, including 112 patients with BRCA1/2 mutations (BRCAmut), and 210 patients with BRCA1/2 wild-type (BRCAwt). In the two groups, 40 BRCAmut patients (35.7%) and 69 BRCAwt patients (32.9%) received NAC. The progression-free survival (PFS) of BRCAmut patients was significantly reduced after NAC (median: 14.9 vs. 18.5 months; p=0.023); however, there was no difference in overall survival (OS) (median: 75.1 vs. 72.8 months; p=0.798). Whether BRCAwt patients received NAC had no significant effect on PFS (median: 13.5 vs. 16.0 months; p=0.780) or OS (median: 54.0 vs. 56.4 months; p=0.323). Multivariate analyses in BRCAmut patients showed that the predictors of prolonged PFS were PDS (p=0.001), the absence of residual lesions (p=0.012), and FIGO III stage (p=0.020); Besides, PARP inhibitor was the independent predictor for prolonged OS in BRCAmut patients (p=0.000), for BRCAwt patients, the absence of residual lesions (p=0.041) and history of PARP inhibitors (p=0.000) were beneficial factors for OS prolongation. Conclusions: For ovarian cancer patients with FIGO IIIB, IIIC, and IV, NAC-IDS did not adversely affect survival outcomes due to different BRCA1/2 germline mutational status. [ABSTRACT FROM AUTHOR]

Ultra-radical (UR) procedures, including splenectomy, are utilized to increase complete cytoreduction rates during Cytoreductive Surgery (CRS) performed with the aim of complete macroscopic clearance of disease. The purpose of this study was to investigate if splenectomy negatively impacts survival when undertaken during CRS for advanced ovarian cancer (AOC) and compare published splenectomy and cytoreduction rates. A retrospective review of all consecutive patients who underwent cytoreductive surgery for AOC between 16/05/2013-28/01/2019. Survival, baseline patient characteristics, complications and surgical parameters were recorded. Propensity scored matching (PSM) was performed to reduce bias. 154 patients identified over 71 months. 97 underwent standard, 57 underwent UR surgery, 27 patients received splenectomy (17.5%) No difference was seen in overall survival (OS) between all patients (median OS 34 months (95%CI 25.9–41.1) and patients who underwent splenectomy (median OS not yet reached) (p = >0.05). After PSM for various baseline covariates, no significant difference in splenectomy versus non-splenectomy patients (3-year survival 54% compared to 56%) (P > 0.05). Three splenectomy specific complications occurred; one each of pancreatic tail injury, left pleural effusion and streptococcal pharyngitis during chemotherapy. We found wide variation in utilization of splenectomy in published case series; from 9% to 35%. Splenectomy performed as part of CRS is not detrimental to survival in AOC. There is a wide variation in utilization of splenectomy in published case series with little correlation with cytoreduction rates. [ABSTRACT FROM AUTHOR]

To examine clinical trends in Denmark for younger and older epithelial ovarian cancer (EOC) patients, focusing on incidence, treatment, and survival changes. We included a nationwide cohort diagnosed with EOC from 2005 to 2018. We described age-standardized incidence, surgical patterns, residual disease trends, and cancer-specific survival stratified by age (<70 and ≥ 70 years), stage, and period (2005–09, 2010–13, 2014–18). We included 7522 patients. The incidence decreased from 16.3 (2005) to 11.4 (2018) per 100,000 woman-years, driven by the younger cohort. While the proportion of patients with stage IIIC-IV disease undergoing primary debulking surgery (PDS) decreased, the proportion of patients having interval debulking surgery (IDS) and no debulking surgery increased significantly. In 2014–18, 36% and 24% had PDS for younger and older patients, respectively, compared to 72% and 62% in 2005–09. In both age cohorts, the proportion of patients debulked to no residual disease increased significantly among patients with stage IIIC-IV and in the total cohort. Two-year cancer-specific survival increased from 75% (2005–09) to 84% (2014–18) for younger patients and from 53% to 66% for older patients. After adjusting for potential confounders, age ≥ 70 was associated with a 1.4-fold increased risk of cancer-specific death (95% confidence interval: 1.2,1.5). The proportion of patients with advanced EOC not undergoing PDS or IDS increased significantly. During the same period, patients debulked to no residual disease, and cancer-specific survival increased. However, a survival gap in favor of the younger patients remains after adjusting for potential confounders. • Incidence of EOC in Denmark decreased among women <70 years of age but was stable for women ≥70 years during 2005–2018. • The proportion of patients with advanced EOC not undergoing debulking surgery increased from 2005 to 2018. • During the same period, the proportion of patients having 0 cm residual disease after debulking surgery increased. • During the same period, cancer-specific survival increased for both younger and older EOC patients. [ABSTRACT FROM AUTHOR]

Can He,1 Niresh Thapa,1,2 Yang Wang,1 Ziye Song,1 Jing Yang,1 Mengfei Xu,1 Na Zuo,1 Hongbing Cai1 1Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan 430071, Hubei, People’s Republic of China; 2Karnali Academy of Health Sciences, Jumla, NepalCorrespondence: Can He; Hongbing Cai Email 631448785@qq.com; chb2195@163.comObjective: This study aimed to evaluate the roles of the ratio of log(serum CA125 level)/PCI in epithelial ovarian cancer.Methods: This is a retrospective study. Data were retrieved for patients with epithelial ovarian cancer who received primary debulking surgeries (PDS) between January 2014 and December 2017 in Zhongnan Hospital of Wuhan University. The PCI and CA125 were determined retrospectively using surgical reports, histological findings, and intraoperative photographic documentation. Survival analysis and ROC curves were applied to evaluate the roles of the ratio of log(serum CA125 level)/PCI in epithelial ovarian cancer.Results: A total of 69 patients were included. Of these, serous ovarian cancer and mucinous carcinoma accounted for 63.8% (n=44) and 31.9% (n=22), respectively. The remaining patients had clear cell carcinoma (2.9%, n=2) and endometrioid carcinoma ( 1.4%, n= 1). Kaplan–Meier survival analysis showed that log(serum CA125 level)/PCI (log-rank p=0.018) were prognostic factors for OS. Cox regression analysis, otherwise, suggested that only stages were an independent factor of PFS (P=0.02, 95% CI 0.043– 0.763); outcomes of cytoreductive surgery could only affect OS significantly (P=0.009, 95% CI 1.639– 31.016). Binary logistic regression discovered that only log(serum CA125 level)/PCI was an independent risk factor of PDS. We further used the ROC curve to find that log(serum CA125 level)/PCI could correctly predict the resectability of PDS with AUC 0.781.Conclusion: The ratio of log(CA125)/PCI that combined the tumor burden and characteristics of peritoneal carcinoma of ovarian origin can predict the resectability of PDS in epithelial ovarian cancer.Keywords: epithelial ovarian cancer, peritoneal carcinomatosis index, resectability, cancer antigen 125, primary debulking surgery

BackgroundWhether neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) against primary debulking surgery (PDS) has a differential effect on prognosis due to Breast Cancer Susceptibility Genes (BRCA)1/2 mutations has not been confirmed by current studies.MethodsAll patients included in this retrospective study were admitted to Qilu Hospital of Shandong University between January 2009 and June 2020, and germline BRCA1/2 mutation were tested. Patients in stage IIIB, IIIC, and IV, re-staged by International Federation of Gynecology and Obstetrics (FIGO) 2014, were selected for analysis. All patients with NAC received 1-5 cycles of platinum-containing (carboplatin, cisplatin, or nedaplatin) chemotherapy. Patients who received maintenance therapy after chemotherapy were not eligible for this study. All relevant medical records were collected.ResultsA total of 322 patients were enrolled, including 112 patients with BRCA1/2 mutations (BRCAmut), and 210 patients with BRCA1/2 wild-type (BRCAwt). In the two groups, 40 BRCAmut patients (35.7%) and 69 BRCAwt patients (32.9%) received NAC. The progression-free survival (PFS) of BRCAmut patients was significantly reduced after NAC (median: 14.9 vs. 18.5 months; p=0.023); however, there was no difference in overall survival (OS) (median: 75.1 vs. 72.8 months; p=0.798). Whether BRCAwt patients received NAC had no significant effect on PFS (median: 13.5 vs. 16.0 months; p=0.780) or OS (median: 54.0 vs. 56.4 months; p=0.323). Multivariate analyses in BRCAmut patients showed that the predictors of prolonged PFS were PDS (p=0.001), the absence of residual lesions (p=0.012), and FIGO III stage (p=0.020); Besides, PARP inhibitor was the independent predictor for prolonged OS in BRCAmut patients (p=0.000), for BRCAwt patients, the absence of residual lesions (p=0.041) and history of PARP inhibitors (p=0.000) were beneficial factors for OS prolongation.ConclusionsFor ovarian cancer patients with FIGO IIIB, IIIC, and IV, NAC-IDS did not adversely affect survival outcomes due to different BRCA1/2 germline mutational status.

Introduction: The role of a molecular pattern predictive of hyperthermic intraperitoneal chemotherapy (HIPEC) efficacy in advanced ovarian cancer (AOC) patients has been poorly investigated. We aimed to assess the effect of HIPEC after primary debulking surgery (PDS) in AOC according to patient's Breast Cancer Gene (BRCA) mutational status. Methods: This is a retrospective, single center, case-control study. Data on AOC patients receiving HIPEC at the end of PDS as previously enrolled in a phase II monocentric trial (HIPEC group), were retrieved and matched for clinical and surgical characteristics with a group of cases who underwent PDS without receiving HIPEC between 01/2010 and 01/2015 (No HIPEC group). Patients with International Federation of Gynecology and Obstetrics (FIGO) stage ≥IIIB disease, aged between 18 and 70 years, with a laparoscopic Predictive Index value (PIV) ≤8 and residual disease ≤2.5 mm were included. Results: 70 patients were included. With the except of age (p = 0.012), the populations were balanced for the main characteristics. At a median follow-up of 48 months, no differences in Progression Free Survival (PFS) (p = 0.968) and Overall Survival (OS) (p = 0.789) were recorded. Survival analysis according to HIPEC administration and BRCA mutational status showed an improved PFS (p = 0.011) and OS (p = 0.003) in BRCA mutated compared to wild-type patients when HIPEC was not administered, whilst they were superimposable in case of HIPEC administration (p = 0.857 vs p = 0.372; respectively). No differences in terms of neither intra-operative (p = 1.0) nor early post-operative complications (p = 0.920) were detected. Conclusions: Our results show that HIPEC in AOC may be a promising treatment in BRCA wild-type patients, as it seems to balance their decreased chemosensitivity compared to mutation carriers.

Objective: The primary treatment of patients with advanced ovarian cancer is selected from whether primary debulking surgery or neoadjuvant chemotherapy. We investigated whether pretreatment serum microRNA profiles are useful for selecting patients with advanced high-grade serous ovarian cancer who obtain better outcomes from undergoing primary debulking surgery or neoadjuvant chemotherapy., Methods: Consecutive patients with clinical stage IIIB-IVB and serum microRNA data were selected. Patients who underwent primary debulking surgery or neoadjuvant chemotherapy were subjected to 1:1 propensity score matching before comparing their progression-free survival using Cox modelling. Progression-free probabilities for the selected microRNA profiles were calculated, and the estimated progression-free survival with the recommended primary treatment was determined and compared with the actual progression-free survival of the patients., Results: Of the 108 patients with stage IIIB-IVB disease, the data of 24 who underwent primary debulking surgery or neoadjuvant chemotherapy were compared. Eleven and three microRNAs were independent predictors of progression-free survival in patients who underwent primary debulking surgery and neoadjuvant chemotherapy, respectively. Two microRNAs correlated significantly with complete resection of the tumours in primary debulking surgery. No differences were found between the actual and estimated progression-free survival in the primary debulking surgery and neoadjuvant chemotherapy groups (P > 0.05). The recommended and actual primary treatments were identical in 27 (56.3%) of the 48 patients. The median improved survival times between recommended and actual treatment were 11.7 and 32.6 months for patients with actual primary debulking surgery and neoadjuvant chemotherapy, respectively., Conclusions: Pretreatment microRNA profiles could be used to select subgroups of patients who benefited more from primary debulking surgery or neoadjuvant chemotherapy and might contribute to selecting the optimal primary treatment modality in advanced high-grade serous ovarian cancer patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The newest clinical evidence that the relationship between the peritoneal cancer index (PCI) and the postoperative prognosis of advanced ovarian cancer patients remains controversial, and there are no large-sample and multicenter studies to clarify this matter. Therefore, in this paper, we used meta-analysis to systematically assess the postoperative prognostic value of PCI in subjects with advanced ovarian cancer to provide individualized treatment plans and thus improve the prognosis of patients., Methods: Literature on the correlation between PCI and the postoperative prognosis in subjects with advanced OC undergoing cytoreductive surgery (CRS) was searched in the Cochrane Library, Pubmed, Embase, and Web of Science from the database inception to April 20, 2023. The search was updated on February 28, 2024. We only included late-stage (FIGO stage: III-IV) patients who did not undergo neoadjuvant chemotherapy (NACT) or hyperthermic intraperitoneal chemotherapy (HIPEC). Afterwards, literature screening and data extraction were conducted using Endnote20 software. The literature quality was assessed using the Newcastle-Ottawa Scale (NOS). Lastly, statistical analysis was performed with STATA 15.0 software., Results: Five studies with 774 patients were included. The result indicated that patients with high PCI had a worse prognosis than those with low PCI. The combined hazard ratio was 2.79 [95%CI: (2.04, 3.82), p<0.001] for overall survival (OS) in patients with high PCI. Further subgroup analysis by the FIGO staging revealed that in stage III [HR: 2.61, 95%CI: (2.00, 3.40), p<0.001] and stage III-IV patients [HR: 2.69, 95%CI: (1.66, 4.36), p<0.001], a high PCI score was significantly associated with a worse prognosis. The PCI score had a greater impact on the OS of patients with higher stages. The combined hazard ratio was 1.89 [95%CI: (1.51, 2.36), p<0.001] for progression-free survival (PFS) in patients with high PCI., Conclusion: PCI may be used as a postoperative prognosis indicator in patients with advanced OC on primary debulking surgery. High PCI indicates a worse prognosis. However, further research is warranted to confirm these findings., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023424010., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Liu, Liu, Guo and Han.)

Objective: To assess epidemiological, pathological and clinical characteristics, therapeutic management patterns and outcomes in the management of advanced ovarian cancer (AOC) in clinical practice. Methods: Multicenter, retrospective, epidemiological, observational real-world study reviewing clinical records from 277 patients diagnosed with AOC between January 2008 and December 2010 who were treated and followed in 31 Spanish hospitals belonging to the Spanish Ovarian Cancer Research Group (GEICO). Survival curves were estimated by Kaplan-Meier and differences analyzed by the log-rank test. Results: Median age at diagnosis was 62 years (range 26-96), 62% of patients had a high-grade serous carcinoma, and 64% and 21% of patients had stage IIIC and stage IV disease, respectively. Overall, 46% of patients underwent primary debulking surgery (PDS), with complete cytoreduction in 63% of procedures, and 34% underwent interval debulking surgery, with complete cytoreduction in 71% of them. Overall, 96% of patients received at least one cycle of front-line chemotherapy. Recurrence occurred in 77% of patients, and 90% of them (69% of total) received a secondline chemotherapy. Median progression-free survival (PFS) was 14 months (95% CI: 13-17) and median overall survival (OS) was 41 months (95% CI: 34-49). PDS and complete cytoreduction had a statistically significant correlation with PFS and OS. Conclusions: This retrospective study provides real-world data of clinical characteristics, therapeutic management, and outcomes in Spanish AOC patients. Primary debulking surgery and complete cytoreduction were favorable prognostic factors in this series. [ABSTRACT FROM AUTHOR]