Advanced Stage Ovarian Cancer Patients Research Articles

Developing a novel image marker to predict the clinical outcome of neoadjuvant chemotherapy (NACT) for ovarian cancer patients

ObjectiveNeoadjuvant chemotherapy (NACT) is one kind of treatment for advanced stage ovarian cancer patients. However, due to the nature of tumor heterogeneity, the clinical outcomes to NACT vary significantly among different subgroups. Partial responses to NACT may lead to suboptimal debulking surgery, which will result in adverse prognosis. To address this clinical challenge, the purpose of this study is to develop a novel image marker to achieve high accuracy prognosis prediction of NACT at an early stage. MethodsFor this purpose, we first computed a total of 1373 radiomics features to quantify the tumor characteristics, which can be grouped into three categories: geometric, intensity, and texture features. Second, all these features were optimized by principal component analysis algorithm to generate a compact and informative feature cluster. This cluster was used as input for developing and optimizing support vector machine (SVM) based classifiers, which indicated the likelihood of receiving suboptimal cytoreduction after the NACT treatment. Two different kernels for SVM algorithm were explored and compared. A total of 42 ovarian cancer cases were retrospectively collected to validate the scheme. A nested leave-one-out cross-validation framework was adopted for model performance assessment. ResultsThe results demonstrated that the model with a Gaussian radial basis function kernel SVM yielded an AUC (area under the ROC [receiver characteristic operation] curve) of 0.806 ± 0.078. Meanwhile, this model achieved overall accuracy (ACC) of 83.3%, positive predictive value (PPV) of 81.8%, and negative predictive value (NPV) of 83.9%. ConclusionThis study provides meaningful information for the development of radiomics based image markers in NACT treatment outcome prediction.

Association between alteration of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, cancer antigen-125 and surgical outcomes in advanced stage ovarian cancer patient who received neoadjuvant chemotherapy

IntroductionOptimal resection significantly influences the prognosis of advanced-stage epithelial ovarian cancer (EOC) patients undergoing debulking surgery. In patients who received neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), the determination of the ideal timing for surgery remains a challenge. Inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and CA-125 levels, have been recognized as potential predictive markers. ObjectiveThis study aims to evaluate the predictive value of changes in NLR, PLR, and CA-125 levels following NACT, specifically assessing their impact on surgical outcomes during IDS for advanced-stage EOC. MethodsA retrospective cohort study enrolled advanced-stage EOC patients who underwent NACT followed by IDS at Vajira Hospital in Thailand from January 2009 to June 2023. Data on clinical, surgical, and inflammatory markers were collected, and the predictive value of these markers for suboptimal resection outcomes was assessed. ResultsAmong the 65 patients, 98.5 % exhibited radiologic responses post-NACT, while 29.2 % experienced suboptimal resections. Univariate analysis did not reveal significant associations between suboptimal resection and NLR changes after the first NACT cycle or alterations in NLR, PLR, and CA-125 levels at the end of NACT. Subsequent analysis suggested that an NLR decrease exceeding 70 % after the first cycle and NACT completion might predict suboptimal resection, yet statistical analyses showed limited prognostic efficacy (AuROC = 0.608 and 0.597). ConclusionOur study does not support that changes in NLR, PLR, platelet count, and CA-125 levels after NACT reliably predict IDS outcomes. Additional prospective investigations using larger cohorts or a combination of evaluation methods, rather than relying solely on NLR, are recommended.

Visualization of tumor-associated neutrophils in malignant ascites of ovarian cancer with aptamer-decorated AIE probes

Neoadjuvant chemotherapy followed by interval debulking surgery is a recommended treatment for advanced-stage ovarian cancer (OC) patients to avoid bowel and spleen resection. Pre-operative chemotherapy requires ascites from OC patients for cytopathological examinations based on hematoxylin & eosin staining to detect tumor cells, whose low ratio make them difficult to be detected in ascites. Sensitive detection of tumor-related immunocytes (TRI) in ascites is not only indicative of underlying malignant ascites, but also could predict chemoresistance and poor overall survival of OC patients. The antibodies can only recognize immunocytes but cannot distinguish TRI. Herein, we identified an aptamer99 (Apt-99) using a fluorescence-activated cell sorting-based aptamer selection strategy, which could target tumor-related neutrophils (TRNs) with high binding affinity. In contrast, FAM-labeled Apt-99 couldn’t distinguish the neutrophils in the smears of other patients’ derived ascites or peritoneal lavages, such as metastatic ovarian cancer from colon carcinoma and myomas of the uterus. LC-MS/MS analysis, and the molecular docking experiments demonstrated that the target molecule of Apt-99 were S100A8&A9 heterodimers. Moreover, Apt-99-labeled aggregation-induced emission dots were facilely prepared and used for specifically visualizing the TRNs in the ascites smears. The findings indicated the diagnostic potential of Apt-99 and the possibility of further clinical trials.

Evaluating the Effectiveness of 2D and 3D CT Image Features for Predicting Tumor Response to Chemotherapy.

Background and Objective: 2D and 3D tumor features are widely used in a variety of medical image analysis tasks. However, for chemotherapy response prediction, the effectiveness between different kinds of 2D and 3D features are not comprehensively assessed, especially in ovarian-cancer-related applications. This investigation aims to accomplish such a comprehensive evaluation. Methods: For this purpose, CT images were collected retrospectively from 188 advanced-stage ovarian cancer patients. All the metastatic tumors that occurred in each patient were segmented and then processed by a set of six filters. Next, three categories of features, namely geometric, density, and texture features, were calculated from both the filtered results and the original segmented tumors, generating a total of 1403 and 1595 features for the 2D and 3D tumors, respectively. In addition to the conventional single-slice 2D and full-volume 3D tumor features, we also computed the incomplete-3D tumor features, which were achieved by sequentially adding one individual CT slice and calculating the corresponding features. Support vector machine (SVM)-based prediction models were developed and optimized for each feature set. Five-fold cross-validation was used to assess the performance of each individual model. Results: The results show that the 2D feature-based model achieved an AUC (area under the ROC curve (receiver operating characteristic)) of 0.84 ± 0.02. When adding more slices, the AUC first increased to reach the maximum and then gradually decreased to 0.86 ± 0.02. The maximum AUC was yielded when adding two adjacent slices, with a value of 0.91 ± 0.01. Conclusions: This initial result provides meaningful information for optimizing machine learning-based decision-making support tools in the future.

Hyponatremia as a Prognostic Factor in Advanced Stage Ovarian Cancer Patients.

Background: hyponatremia represents one of the most commonly encountered conditions in hospitalized patients, multiple mechanisms being cited so far, neoplastic syndromes being an important cause. The aim of the current paper is to analyse the presence and influence of the short- and long-term outcomes of hyponatremia on ovarian cancer patients submitted to surgery for advanced stage ovarian cancer. Method: 57 patients diagnosed with advanced stage ovarian cancer were submitted to surgery between 2014-2020. The patients were further classified according to the preoperative value of sodium into two groups. Results: there were 21 cases with preoperative normal values of sodium and respectively 36 cases with hyponatremia. Patients with preoperative hyponatremia associated a significantly higher rate of early postoperative complications and a significantly poorer long-term outcome. Therefore, cases with hyponatremia reported a mean disease-free survival of 10.8 months and respectively a mean overall survival of 18.5 months while cases with normal natrium levels reported a mean disease-free survival of 31.4 months and respectively a mean overall survival of 49.7 months (p=0.0001 and p 0.001). Conclusions: patients with lower preoperative values of sodium have a higher risk of developing postoperative complications and a significantly poorer outcome when compared to cases presenting normal levels of sodium preoperatively.

Neutrophil to lymphocyte ratio as a prognostic marker for advanced stage ovarian cancer

Ovarian cancer remains one of the most aggressive malignancies which is frequently diagnosed in advanced stages of the disease, when disseminated lesions are already present. In order to maximize the rates of complete debulking surgery, different prognostic markers have been investigated. The aim of the current paper is to investigate the prognostic value of neutrophil to lymphocyte ratio in advanced stage ovarian cancer patients submitted to debulking surgery.

Cytoreductive Surgery with the PlasmaJet Improved Quality-of-Life for Advanced Stage Ovarian Cancer Patients.

Knowledge of quality-of-life after cytoreductive surgery is important to counsel patients with advanced-stage epithelial ovarian cancer prior to surgery. The aim of this study was to determine whether the use of the PlasmaJet Surgical device during cytoreductive surgery has an effect on the quality-of-life of patients with advanced epithelial ovarian cancer. Data included in this prospective observational study were derived from the PlaComOv study, in which patients with advanced epithelial ovarian cancer were randomly assigned to have cytoreductive surgery with or without adjuvant use of the PlasmaJet. Quality-of-life was measured before surgery and one, six, 12, and 24 months after surgery with three questionnaires: the EORTC QLQ-C30, QLQ-OV28, and EQ-5D-5L. Between 2018 and 2020, 326 patients were enrolled in the trial. The overall response rate was high, with the lowest response rate at 24 months of 77%. At 6 months, quality-of-life was higher in the intervention group (95%CI 0.009; 0.081, p = 0.045). At 12 months, quality-of-life was higher in the intervention group with fewer symptoms of fatigue, appetite loss, and diarrhea (95%CI 0.6; 10,0, p = 0.027); similarly, patients in the intervention group reported a better body image (95%CI -14.2; -3.0, p = 0.003) and a higher score on the visual analog scale (95%CI 1.99; 11.15, p = 0.005). At 24 months postoperatively, no further difference was found between the two groups except for pain (95%CI -12.9; -0.8, p = 0.027) and body image (95%CI -13.808; -0.733, p = 0.029). A higher quality-of-life in the intervention group was partially explained by the mediator 'surgery outcome'. This study demonstrated knowledge of patients' quality-of-life until two years after cytoreductive surgery. The use of the PlasmaJet Surgical device during cytoreductive surgery leads to a higher quality-of-life than conventional surgery with electrocoagulation alone. Even after adjustment for the mediator of surgical outcome, a higher quality-of-life was seen in patients who had surgery with the use of the PlasmaJet device.

Prediction of the survival of patients with advanced-stage ovarian cancer patients undergoing interval cytoreduction with the use of computed tomography reevaluation after neoadjuvant chemotherapy.

To predict ovarian cancer patients' survival by computed tomography (CT) reevaluation after neoadjuvant chemotherapy. In this retrospective single-center cohort study, all patients with advanced epithelial ovarian cancer underwent platinum-based chemotherapy followed by interval cytoreductive surgery. Assessment of abdominal and pelvic lesions before and after chemotherapy using CT scoring criteria. Meanwhile, the progression-free survival and overall survival times were obtained. The Kaplan-Meier method was used to estimate survival curves. Univariate analysis of continuous and categorical variables was performed for prognostic significance using the Cox proportional hazards model. Variables with p < 0.10 on univariate analysis were then included in a multivariate forward stepwise Cox regression analysis. A total of 162 patients were included, with a median age of 52 years (range, 20-72 years). One hundred seven patients (66.0%) underwent suboptimal cytoreduction, and there was no statistically significant difference in patient survival between surgical procedures (log-rank p = 0.092). Six radiographic features were hazard factors for suboptimal cytoreduction. Four features in the postchemotherapy CT images were assigned as predictive criteria by the stepwise regression model (area under the curve [AUC] = 0.689). As compared with a higher AUC (0.713) in the model involving two clinical variables (age and postsurgery CA-125) and two postchemotherapy CT features, the model considering the CT score changes before and after chemotherapy had the highest diagnostic accuracy (AUC = 0.843). CT reevaluation after neoadjuvant chemotherapy is essential for ovarian cancer, the changes of CT feature and score are potential great tools to predict patient survival.

Metastatic pattern of ovarian cancer delineated by tracing the evolution of mitochondrial DNA mutations

Ovarian cancer (OC) is the most lethal gynecologic tumor and is characterized by a high rate of metastasis. Challenges in accurately delineating the metastatic pattern have greatly restricted the improvement of treatment in OC patients. An increasing number of studies have leveraged mitochondrial DNA (mtDNA) mutations as efficient lineage-tracing markers of tumor clonality. We applied multiregional sampling and high-depth mtDNA sequencing to determine the metastatic patterns in advanced-stage OC patients. Somatic mtDNA mutations were profiled from a total of 195 primary and 200 metastatic tumor tissue samples from 35 OC patients. Our results revealed remarkable sample-level and patient-level heterogeneity. In addition, distinct mtDNA mutational patterns were observed between primary and metastatic OC tissues. Further analysis identified the different mutational spectra between shared and private mutations among primary and metastatic OC tissues. Analysis of the clonality index calculated based on mtDNA mutations supported a monoclonal tumor origin in 14 of 16 patients with bilateral ovarian cancers. Notably, mtDNA-based spatial phylogenetic analysis revealed distinct patterns of OC metastasis, in which a linear metastatic pattern exhibited a low degree of mtDNA mutation heterogeneity and a short evolutionary distance, whereas a parallel metastatic pattern showed the opposite trend. Moreover, a mtDNA-based tumor evolutionary score (MTEs) related to different metastatic patterns was defined. Our data showed that patients with different MTESs responded differently to combined debulking surgery and chemotherapy. Finally, we observed that tumor-derived mtDNA mutations were more likely to be detected in ascitic fluid than in plasma samples. Our study presents an explicit view of the OC metastatic pattern, which sheds light on efficient treatment for OC patients.

Homologous recombination inquiry through ovarian malignancy investigations: JGOG3025 Study.

The Cancer Genome Atlas (TCGA) network has clarified that ~50% of high-grade serous ovarian cancers show homologous recombination deficiency (HRD). However, the frequency of HRD in Japanese patients with ovarian cancer remains unclear. We aimed to identify the frequency of HR-associated gene mutations in Japanese patients with ovarian cancer. The JGOG3025 study is a multicenter collaborative prospective observational study involving 65 study sites throughout Japan. We recruited 996 patients who were clinically diagnosed with ovarian cancer before surgery from March 2017 to March 2019, and 701 patients were eligible according to the criteria. We used frozen tumor tissues to extract DNA and performed next-generation sequencing for 51 targeted genes (including 29 HR-associated genes) in 701 ovarian cancers (298 high-grade serous cases, 189 clear cell cases, 135 endometrioid cases, 12 mucinous cases, 3 low-grade serous cases, and 64 others). HRD was defined as positive when at least one HR-associated gene was mutated. The frequencies of HRD and tumor BRCA1/2 mutations were 45.2% (317/701) and 18.5% (130/701), respectively, in the full analysis set. Next, we performed multivariate Cox proportional hazards regression analysis for progression-free survival (PFS) and overall survival (OS). Advanced-stage ovarian cancer patients with HRD had adjusted hazard ratios of 0.72 (95% CI, 0.55-0.94) and 0.57 (95% CI, 0.38-0.86) for PFS and OS, respectively, compared with those without HRD (p=0.016 and 0.007). Our study demonstrated that mutations in HR-associated genes were associated with prognosis. Further studies are needed to investigate the prognostic impact of each HR-associated gene in ovarian cancer.

Abstract 2865: IL4I1, IDO1 and other amino acid-metabolizing enzymes in high-grade serous ovarian cancer

Abstract Ovarian cancer is among the most lethal malignancies in women, and breakthrough immunotherapies including anti-PD-1/PD-L1 and anti-CTLA4 have thus far not been able to significantly ameliorate patient outcomes. In various tumor types, amino acid-metabolizing enzymes such as indoleamine 2,3-dioxygenase 1 (IDO1) and arginase 1 (ARG1) have been found to be among the culprits responsible for generation of an immunosuppressive tumor microenvironment. More recently, interleukin 4 induced 1 (IL4I1) was put forward as a promising anticancer drug target, whereas its expression may also contribute to resistance against IDO1 inhibition. Similar to IDO1, IL4I1 can metabolize tryptophan (Trp) resulting in the formation of AhR agonists, although phenylalanine (Phe) and tyrosine (Tyr) are also major substrates of IL4I1. Plasma and ascites (i.e., peritoneal fluid buildup) were collected from advanced-stage high-grade serous ovarian cancer (HGSOC) patients to determine whether aberrant metabolism by amino acid-metabolizing enzymes occurs in these patients and to evaluate ascites as a potential source of biomarkers related to these enzymes. Activity of the enzymes was indirectly determined through measurement of relevant amino acids and metabolites by targeted metabolomics using LC-MS/MS, while levels of secreted IL4I1 were determined by ELISA. Amino acid, metabolite and enzyme concentrations were compared to healthy control subjects and were examined for correlations with clinicopathological characteristics and clinical outcomes. Pleural effusions from non-small cell lung cancer patients were included to evaluate whether the results could be extended towards another type of cancer-related fluid buildup. Metabolism of Trp was significantly elevated in HGSOC patients compared to control subjects, likely attributable to increased IDO1 expression. Kynurenine (Kyn) levels and Kyn/Trp ratios were higher in ascites compared to plasma samples, demonstrating the value of utilizing this fluid for biomarker detection. Whereas elevated metabolism of Trp by IL4I1 could not be detected in the patients, high levels of Phe- and Tyr-derived metabolites associated with IL4I1 activity were found in their ascites. Levels of these metabolites significantly correlated with the concentration of IL4I1. Moreover, enhanced metabolism of Phe and Tyr correlated with disease stage, suggesting a role for IL4I1 in HGSOC progression. Elevated levels of IL4I1-associated metabolites were also found in the pleural effusions of a subset of non-small cell lung cancer patients, demonstrating that enhanced IL4I1 activity is not limited to ovarian cancer ascites. In conclusion, our results suggest that IL4I1 may be involved in HGSOC progression, indicating this enzyme as a potential therapeutic target. The levels of IL4I1- and IDO1-generated metabolites in ascites may additionally serve as valuable diagnostic or predictive biomarkers. Citation Format: Yvonne Grobben, Judith E. den Ouden, Cristina Aguado, Anne M. van Altena, Aletta D. Kraneveld, Guido J. Zaman. IL4I1, IDO1 and other amino acid-metabolizing enzymes in high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2865.

Preliminary outcomes of five-year survival for ovarian malignancies in profiled Serbian Oncology Centre

ObjectiveThe present study purposed to determine characteristics of ovarian carcinoma and to analyze predictors of survival in patients with ovarian carcinoma. MethodA retrospective cohort study was conducted including the patients with diagnosed ovarian carcinoma treated at the Clinic for Operative Oncology, Oncology Institute of Vojvodina in the period from January 2012 to December 2016. Seventy-two women with ovarian carcinoma were included in the analysis. The data about the histological type of tumor, disease stage, treatment, lymphatic infiltration, and surgical procedure were collected retrospectively, using the database of the institution where the research was conducted (BirPis 21 SRC Infonet DOO ‒ Information System Oncology Institute of Vojvodina). Descriptive statistics and multivariate analysis using Cox proportional hazards model were performed. ResultsThe univariate Cox regression analysis identified histology, tumor grade, FIGO (International Federation of Gynecology and Obstetrics) stage, NACT (Neoadjuvant Chemotherapy), number of therapy cycles, type of surgery, and chemotherapy response as independent predictors of mortality. Finally, the type of tumor and chemotherapy response had an increased hazard ratio for mortality in the multivariate Cox regression model. Herewith, the percentage of high-grade, advanced-stage ovarian cancer patients with complete response to chemotherapy, absence of recurrent disease, and lymphovascular space invasion were significant predictors of survival in patients with ovarian carcinoma. ConclusionsHerein, emerging data regarding precision medicine and molecular-based personalized treatments are promising and will likely modify the way the authors provide multiple lines of treatments in the near future.

The effects of neutral argon plasma versus electrocoagulation on tissue in advanced-stage ovarian cancer: a case series

BackgroundThe aim of surgery for advanced-stage ovarian cancer is a complete cytoreduction, because this is the most important independent prognostic factor for prolonged survival. Yet this can be difficult to achieve when there are micrometastases on the intestinal mesentery or intestines. The PlasmaJet device is an instrument to remove these micrometastases, but little is known about the depth of damage in human tissue compared to electrocoagulation devices.MethodsA prospective study was performed for the ex-vivo comparison of the histological depth of thermal damage of neutral argon plasma (PlasmaJet®) and electrocoagulation devices, in a series of 106 histological slides of 17 advanced-stage ovarian cancer patients. Depending on the tissue types resected during complete cytoreductive surgery, samples were collected from reproductive organs (uterus, ovaries), intestines (ileum, colon, rectum) and omentum, intestinal mesentery and peritoneum.ResultsAverage thermal damage depth was 0.15 mm (range 0.03–0.60 mm) after use of neutral argon plasma and 0.33 mm (range 0.08–1.80 mm) after use of electrocoagulation (p < 0.001). Greater disruption of the tissue surface was often observed after electrocoagulation.ConclusionOur case series suggests that the use of neutral argon plasma during cytoreductive surgery produces significantly less thermal damage than electrocoagulation treatment. It is therefore considered a thermally safe alternative, aiding in the achievement of cytoreductive surgery.

Does sarcopenia predict perioperative mortality in patients with advanced ovarian cancer?

The aim of this study was to assess prognostic value of frailty for the prediction of surgical complications and mortality in women with end-stage ovarian cancer subjected to curative oncological surgery and its value for long-term follow-up. A total of 75 advanced-stage consecutive ovarian cancer patients who underwent elective surgery were investigated. The demographic data and clinical information related to the oncologic treatment were collected in the electronic and physical case records and included the following: age, ethnic group, comorbidities, staging of cancer, surgical procedure details, lymphadenectomy, American Society of Anesthesiology (ASA) grade, anesthetic technique, operative blood loss, operative time, and residual disease. A radiologist, who was blinded to patient outcomes, performed quantitative assessment of psoas muscle areas using the available computed tomography scan images at the caudal end of the third lumbar vertebra. The mean age was 61.2 ± 18.2 years, and the percentage of patients over 65 years was 78%. Comorbidities (hypertension, diabetes, chronic obstructive pulmonary disease, renal insufficiency) were seen in 37 patients (49%). Histological types were adenocarcinoma in all patients (0) mostly serous adenocarcinoma (62%) and stage 3 (58%). According to psoas muscle measurement, 55 patients (73%) were nonsarcopenic and 20 patients (26%) were sarcopenic. Debulking procedures were performed on all patients. Also, bowel resection was applied in 40% of patients. Preoperative anesthetic examinations had shown that they were mostly ASA score 2 (44 patients). Moreover, 26 patients were ASA score 3. Generally, total operative time was between 121-240 minutes, and total blood loss was generally under 500 ml. Postoperative complications were seen in 26% of the patients. Non-surgical complications were observed in 14% of the patients, while non-surgical complications were observed in 12%. Length of the hospital stay >10 days was seen in 10 patients. Mortality was seen in 1 patient 30 days after operation. Nonsurgical complications (pneumonia, urinary tract infections, cardiac complications) were significantly higher in comparison to nonsarcopenic patients. However surgical complications were comparable between each group. Mortality after hospitalization and length of hospital stay were significantly higher in sarcopenic patients in comparison with the nonsarcopenic group. The use of the value of the psoas muscle region is considered to be a method to predict the in-hospital mortality when there is an available abdominal CT scan that has already been performed for ovarian cancer patients with a significant comparable clinical and laboratory background. According to the findings, patients had worse surgical outcomes and higher postoperative nonsurgical complication rate when sarcopenic patients were compared to nonsarcopenic patients. Moreover, postoperative mortality and length of hospital stay were significantly higher in sarcopenic patients in comparison to non-sarcopenic group.

Stratification of Length of Stay Prediction following Surgical Cytoreduction in Advanced High-Grade Serous Ovarian Cancer Patients Using Artificial Intelligence; the Leeds L-AI-OS Score

(1) Background: Length of stay (LOS) has been suggested as a marker of the effectiveness of short-term care. Artificial Intelligence (AI) technologies could help monitor hospital stays. We developed an AI-based novel predictive LOS score for advanced-stage high-grade serous ovarian cancer (HGSOC) patients following cytoreductive surgery and refined factors significantly affecting LOS. (2) Methods: Machine learning and deep learning methods using artificial neural networks (ANN) were used together with conventional logistic regression to predict continuous and binary LOS outcomes for HGSOC patients. The models were evaluated in a post-hoc internal validation set and a Graphical User Interface (GUI) was developed to demonstrate the clinical feasibility of sophisticated LOS predictions. (3) Results: For binary LOS predictions at differential time points, the accuracy ranged between 70-98%. Feature selection identified surgical complexity, pre-surgery albumin, blood loss, operative time, bowel resection with stoma formation, and severe postoperative complications (CD3-5) as independent LOS predictors. For the GUI numerical LOS score, the ANN model was a good estimator for the standard deviation of the LOS distribution by ± two days. (4) Conclusions: We demonstrated the development and application of both quantitative and qualitative AI models to predict LOS in advanced-stage EOC patients following their cytoreduction. Accurate identification of potentially modifiable factors delaying hospital discharge can further inform services performing root cause analysis of LOS.

Single-arm phase II trial of carboplatin and mirvetuximab soravtansine as neoadjuvant chemotherapy (NACT) for advanced- stage ovarian, fallopian tube or primary peritoneal cancer (EOC) who are folate receptor α positive (NCT04606914) (578)

Objectives: The primary objective is to assess the feasibility and safety of obtaining tissue, assessing alpha-folate receptor status, and initiating treatment based on this data using a 21-day schedule in the advanced-stage ovarian, fallopian tube, or peritoneal cancer patients, without an unacceptable interval debulking surgery (IDS) delay. Secondary objectives include assessing progression-free survival, percentage of disease-free survival at two years, ORR prior to IDS per iRECIST 1.1 and GCIG CA-125 criteria, and percentage of optimal cytoreduction and pathological complete response (pCR) at IDS. Methods: This is a phase II study design with carboplatin and mirvetuximab (FRa receptor monoclonal antibody.) Patients with biopsy-confirmed, newly diagnosed, advanced-stage serous epithelial ovarian cancer appropriate for NACT will have centralized tumor evaluation via immunohistochemistry for FRa receptor overexpression. IHC staining is 2+ in 75% of cells will define eligibility. Patients will receive NACT with one lead-in cycle of single-agent carboplatin AUC 5/6, physician’s choice), followed by AUC 5 carboplatin and Mirvetuximab 6mg/kg adjusted to ideal body weight every 21days for three cycles prior to interval cytoreductive surgery (iCRS.) Patients eligible for surgery will undergo an iCRS no sooner than three weeks but no later than six weeks following the completion of cycle 3. Postoperatively, patients will complete three additional cycles of carboplatin-mirvetuximab for a total of 6 intended cycles. A total of 70 patients will be included. Patients with BRCA mutations are not excluded from this trial and may receive standard of care maintenance therapy, including bevacizumab and/or PARP inhibitors per physician’s choice in the adjuvant setting. After completion of adjuvant treatment, participants will be assessed approximately every 12 weeks by radiologic imaging to monitor disease status using RECIST 1.1 criteria. Objectives: The primary objective is to assess the feasibility and safety of obtaining tissue, assessing alpha-folate receptor status, and initiating treatment based on this data using a 21-day schedule in the advanced-stage ovarian, fallopian tube, or peritoneal cancer patients, without an unacceptable interval debulking surgery (IDS) delay. Secondary objectives include assessing progression-free survival, percentage of disease-free survival at two years, ORR prior to IDS per iRECIST 1.1 and GCIG CA-125 criteria, and percentage of optimal cytoreduction and pathological complete response (pCR) at IDS. Methods: This is a phase II study design with carboplatin and mirvetuximab (FRa receptor monoclonal antibody.) Patients with biopsy-confirmed, newly diagnosed, advanced-stage serous epithelial ovarian cancer appropriate for NACT will have centralized tumor evaluation via immunohistochemistry for FRa receptor overexpression. IHC staining is 2+ in 75% of cells will define eligibility. Patients will receive NACT with one lead-in cycle of single-agent carboplatin AUC 5/6, physician’s choice), followed by AUC 5 carboplatin and Mirvetuximab 6mg/kg adjusted to ideal body weight every 21days for three cycles prior to interval cytoreductive surgery (iCRS.) Patients eligible for surgery will undergo an iCRS no sooner than three weeks but no later than six weeks following the completion of cycle 3. Postoperatively, patients will complete three additional cycles of carboplatin-mirvetuximab for a total of 6 intended cycles. A total of 70 patients will be included. Patients with BRCA mutations are not excluded from this trial and may receive standard of care maintenance therapy, including bevacizumab and/or PARP inhibitors per physician’s choice in the adjuvant setting. After completion of adjuvant treatment, participants will be assessed approximately every 12 weeks by radiologic imaging to monitor disease status using RECIST 1.1 criteria.

Primary versus interval debulking surgery in the management of ovarian cancer patients, current data summary

Objective: Optimal management of ovarian cancer patients have been investigated by several centers and have been discussed in a great number of published articles. Aim of this article is the review of current data regarding this lethal malignancy treatment. Moreover, we discuss the ongoing trials regarding primary or interval cytoreductive surgery after neoadjuvant chemotherapy. Mechanism: We reviewed the relevant literature regarding ovarian cancer treatment via primary debulking surgery (PDS) as well as neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Findings in Brief: Our findings suggest that Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) are alternative treatments for advanced-stage ovarian cancer patients where optimal debulking surgery is considered unfeasible, while some studies indicate that NACT/IDS offer similar oncological outcomes with fewer postoperative complications. The prediction of optimal debulking probability can be evaluated by CA-125 level ≥500 U/mL, performance status ≥2, suprarenal paraaortic or supradiaphragmatic nodes &gt;1 cm, Porta hepatis disease, diffuse serosal bowel carcinomatosis, bowel mesenteric involvement or a PIV score ≥8 if a laparoscopy is performed. Conclusions: Regarding the management of advanced ovarian cancer patientswho receive neoadjuvant interval debulking surgery seems to be as efficacient as primary cytoreduction. The patients that are more eligible and could benefit from this treatment strategy should be specified through larger, double-blind randomized control trials.

Combination microRNA-based cellular reprogramming with paclitaxel enhances therapeutic efficacy in a relapsed and multidrug-resistant model of epithelial ovarian cancer

Most advanced-stage ovarian cancer patients, including those with epithelial ovarian cancer (EOC), develop recurrent disease and acquisition of resistance to chemotherapy, leading to limited treatment options. Decrease in Let7b miRNA levels in clinical ovarian cancer has been associated with chemoresistance, increased proliferation, invasion, and relapse in EOC. We have established a murine EOC relapsed model by administering paclitaxel (PTX) and stopping therapy to allow for tumor regrowth. Global microRNA profiling in the relapsed tumor showed significant downregulation of Let7b relative to untreated tumors. Here, we report the use of hyaluronic acid (HA)-based nanoparticle formulation that can deliver Let7b miRNA mimic to tumor cells and achieve cellular programming both in vitro and in vivo. We demonstrate that a therapeutic combination of Let7b miRNA and PTX leads to significant improvement in anti-tumor efficacy in the relapsed model of EOC. We further demonstrate that the combination therapy is safe for repeated administration. This novel approach of cellular reprogramming of tumor cells using clinically relevant miRNA mimic in combination with chemotherapy could enable more effective therapeutic outcomes for patients with advanced-stage relapsed EOC.

Overall Survival and Related Factors of Advanced-stage Epithelial Ovarian Cancer Patients Underwent Debulking Surgery in Jakarta, Indonesia: A Single-center Experience

AIM: The worrisome prognosis of advanced-stage epithelial ovarian cancer (EOC) needs a new perspective from developing countries. Thus, we attempted to study the 5-year overall survival (OS) of advanced-stage EOC patients who underwent debulking surgery in an Indonesian tertiary hospital. METHODS: A retrospective study recruited forty-eight subjects between 2013 and 2015. We conducted multiple logistic regression analyses to predict risk factors leading to unwanted disease outcomes. The OS was evaluated through the Kaplan–Meier curve and Log-rank test. Cox proportional hazards regression examined prognostic factors of patients. RESULTS: Prominent characteristics of our patients were middle age (mean: 51.9 ± 8.9 years), obese, with normal menarche onset, multiparous, not using contraception, premenopausal, with serous EOC, and FIGO stage IIIC. The subjects mainly underwent primary debulking surgery (66.8%), with 47.9% of all individuals acquiring optimal results, 77.1% of patients treated had the residual disease (RD), and 52.1% got adjuvant chemotherapy. The risk factor for serous EOC was menopause (odds ratio [OR] = 4.82). The predictors of suboptimal surgery were serous EOC (OR = 8.25) and FIGO stage IV (OR = 11.13). The different OS and median survival were observed exclusively in RD, making it an independent prognostic factor (hazard ratio = 3.50). 5-year A five year OS and median survival for patients with advanced-stage EOC who underwent debulking surgery was 37.5% and 32 months, respectively. Optimal versus suboptimal debulking surgery yielded OS 43.5% versus 32% and median survival of 39 versus 29 months. Both optimal and suboptimal debulking surgery followed with chemotherapy demonstrated an OS 40% lower than those not administered (46.2% and 20%, respectively). The highest 5-year OS was in serous EOC (50%). Meanwhile, the most extended median survival was with mucinous EOC (45 months). CONCLUSION: Chemotherapy following optimal and suboptimal debulking surgery has the best OS among approaches researched in this study. RD is a significant prognostic factor among advanced-stage EOC. Suboptimal surgery outcomes can be predicted by stage and histological subtype.

Translational and pharmacological principles of hyperthermic intraperitoneal chemotherapy for ovarian cancer.

The long-term survival of advanced-stage ovarian cancer patients remains poor, despite extensive cytoreductive surgery, chemotherapy, and the recent addition of poly (ADP-ribose) polymerase inhibitors (PARPi). Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown survival benefit by specifically targeting peritoneal metastases, the primary site of disease recurrence. Different aspects of how HIPEC exerts its effect remain poorly understood. Improved understanding of the effects of hyperthermia on ovarian cancer cells, the synergy of hyperthermia with intraperitoneal chemotherapy, and the pharmacological and pharmacokinetic properties of intraperitoneally administered cisplatin may help identify ways to optimize the efficacy of HIPEC. This review provides an overview of these translational and pharmacological principles of HIPEC and aims to expose knowledge gaps that may direct further research to optimize the HIPEC procedure and ultimately improve survival for women with advanced ovarian cancer.