Advanced Stage Ovarian Cancer Patients Research Articles

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.

Survival in Advanced-Stage Epithelial Ovarian Cancer Patients with Cardiophrenic Lymphadenopathy Who Underwent Cytoreductive Surgery: A Systematic Review and Meta-Analysis.

Simple SummaryFavorable survival outcomes for patients with advanced-stage ovarian cancer are associated with complete cytoreduction. Enlarged cardiophrenic lymph node (CPLN) is commonly observed in advanced-stage epithelial ovarian cancer (AEOC); however, the prognostic impact of CPLN adenopathy is inconclusive. In this study, we evaluate the clinical outcomes of CPLN adenopathy in AEOC patients who underwent cytoreductive surgery. This systematic review and meta-analysis demonstrated that enlarged CPLN in preoperative imaging is highly associated with metastatic involvement. Patients with CPLN adenopathy had a significantly increased risk of recurrence of disease and dying from the disease in comparison to those without adenopathy, a finding likely related to more advanced disease in this group. Currently, there are no data that definitively demonstrate a therapeutic benefit of CPLN resection. Further randomized controlled trials should be conducted to definitively demonstrate whether CPLN resection at the time of cytoreductive surgery is beneficial.Purpose: To evaluate the clinical outcomes of enlarged cardiophrenic lymph node (CPLN) in advanced-stage epithelial ovarian cancer (AEOC) patients who underwent cytoreductive surgery. Methods: The Embase, Medline, Web of Science, Cochrane Library, and Google Scholar databases were searched for articles from the database inception to June 2021. Meta-analysis was conducted to determine the prognostic impact of surgical outcome, postoperative complication, and survival using random-effects models. Results: A total of 15 studies involving 727 patients with CPLN adenopathy and 981 patients without CPLN adenopathy were included. The mean size of preoperative CPLN was 9.1± 3.75 mm. Overall, 82 percent of the resected CPLN were histologically confirmed pathologic nodes. Surgical outcomes and perioperative complications did not differ between both groups. The median OS time was 42.7 months (95% CI 10.8–74.6) vs. 47.3 months (95% CI 23.2–71.2), in patients with and without CPLN adenopathy, respectively. At 5 years, patients with CPLN adenopathy had a significantly increased risk of disease recurrence (HR 2.14, 95% CI 1.82–2.52, p < 0.001) and dying from the disease (HR 1.74, 95% CI 1.06–2.86, p = 0.029), compared with those without CPLN adenopathy. CPLN adenopathy was significantly associated with ascites (OR 3.30, 95% CI 1.90–5.72, p < 0.001), pleural metastasis (OR 2.58, 95% CI 1.37–4.82, p = 0.003), abdominal adenopathy (OR 2.30, 95% CI 1.53–3.46, p < 0.001) and extra-abdominal metastasis (OR 2.30, 95% CI 1.61–6.67, p = 0.001). Conclusions: Enlarged CPLN in preoperative imaging is highly associated with metastatic involvement. Patients with CPLN adenopathy had a lower survival rate, compared with patients without CPLN adenopathy. Further randomized controlled trials should be conducted to definitively demonstrate whether CPLN resection at the time of cytoreductive surgery is beneficial.

Test me now or, test me later: prospective study of molecular testing in ovarian cancer

Objectives: Advances in molecular tumor profiling through Next-Generation Sequencing (NGS) has led to an increase in available therapeutic options for patients with gynecologic malignancies beyond standard chemotherapy. Specifically, the addition of Poly-(ADP-ribose) Polymerase inhibitors (PARPi) has signaled a paradigm shift in the management of ovarian cancer. The objective of this prospective study was to evaluate how the timing of NGS has affected the implementation of PARPi within a patient's treatment timeline between 2016 and 2019 at a single institution. Methods: Ovarian cancer patients were enrolled in a prospective Personalized Medicine Initiative (PMI) from January 2016 to December 2019 at a single institution. Archival tissue from each patient was sent for NGS testing. Initially, the project included only patients with recurrent or progressive ovarian cancer. This was expanded in a stepwise fashion to now include newly diagnosed high-grade, advanced stage ovarian cancer patients. Primarily, descriptive statistics were used to analyze the data. Results: Of the 308 patients, 251 (81%) had stage III or IV disease; 216 (70%) had high grade serous histology. NGS successfully identified 197 (64%) patients with at least one genetic alteration directed towards an FDA-approved or standard of care therapy. 27 (39%) received a PARPi due to wtBRCA, 25 (36%) for sBRCA, 8 (11%) for gBRCA, and 6 (8%) for LOH+/BRCAwt. The average time between initial diagnosis and NGS decreased from approximately 46 months in 2016-2017 to 30 months in 2018-2019. Likewise, the average number of lines of therapy completed before NGS decreased from 3 in 2016-2017 to 1 in 2018-2019. Furthermore, we found that the time between NGS and PARPi implementation decreased from an average of 12 to 5 months from 2016 to 2019, respectively. Conclusions: Increasingly, early implementation of NGS in the management of ovarian cancers has allowed for more patients to be placed on targeted therapies, including PARPi, for which they otherwise would not be eligible. After 2019, the majority of patients received NGS prior to their second line of treatment. This data suggests early NGS permits PARPi to be used at an earlier time point within a patient's treatment course. Currently, we are testing all newly diagnosed high-grade, advanced stage ovarian cancer patients at as soon as tissue is available to help guide further treatment decisions. In addition, this study demonstrates NGS has a clinically compatible turnaround time, which may guide clinical management of patients with ovarian cancer. Further follow-up studies need to evaluate the impact of earlier PARPi implementation on patient survival.

Evolving trends in ovarian cancer treatment in the US between 2011 and 2019: less surgery and more biologics?

<h3>Objectives:</h3> The surgical and medical treatment landscape of upfront ovarian cancer patients is rapidly evolving. Using real-world population data, we assessed trends in the timing of surgery, initiation of chemotherapy and use of novel biologics in upfront therapy of advanced stage ovarian cancer. <h3>Methods:</h3> Using a real-world electronic health database (Flatiron), we identified all advanced stage ovarian cancer patients diagnosed between 1/1/2011 and 12/31/2019. Flatiron is a longitudinal, demographically and geographically diverse database, which contains health records from more than 280 cancer clinics and 2 million cancer patients in the United States. We calculated descriptive statistics describing patient demographics (age and race), clinico-pathological characteristics (stage and histology), and treatment patterns (utilization of neoadjuvant therapy and bevacizumab). We measured trends over time by comparing averages in three time intervals: 2011-2013, 2014-2016, and 2017-2019. Chi-square tests were used to assess the statistical significance of observed differences and measured trends. <h3>Results:</h3> Of 2,747 patients (median age: 67 years, IQR: 58-75), Whites, Hispanics, Blacks, and Asians, and other/unknown race represented 71%, 7%, 6%, 2% and 14%, respectively. The majority (65%) had stage III and remainder (35%) stage IV cancers. 59% had ECOG scores 0-1. Serous, endometrioid, clear, mucinous and other/unknown histology consisted of 74%, 2%, 2%, 1% and 20% of cancers. Over the last 9 years, 15% were treated with bevacizumab within 6 months of diagnosis. The average time from diagnosis to initiation of therapy was 70 days. Comparing data from 2011-2013, 2014-2016, and 2017-2019, the use of neoadjuvant chemotherapy increased from 18.6% to 31.3% to 36.3% (p<0.001) with a corresponding decrease in upfront surgery followed by chemotherapy (64.3% to 50.7% to 41%). Of note, 20% of patients in 2019 did not receive any surgery. In addition, the incorporation of bevacizumab to chemotherapy increased from 7% to 11% to 24% (p<0.001) in the study periods. More specifically, the use of this biologic increased from 7% to 8% to 28% (p<0.001) in neoadjuvant patients; from 7% to 9% to 20% (p<0.001) in primary surgery patients and from 8% to 18% to 26% (p<0.001) in the no surgery group. Much of this increase occurred following FDA approval of bevacizumab in 2018, with utilization growing from 26% to 46% and 19% to 32% between 2018 and 2019 in the neoadjuvant and primary surgery groups. <h3>Conclusions:</h3> Our real-world analysis shows that the adoption of neoadjuvant chemotherapy in advanced stage ovarian cancer patients has increased to more than one-third of patients, and that nearly half received bevacizumab in 2019. Further research is warranted to study the outcomes of the large fraction (>20%) of patients that did not undergo surgery.

Towards a functional model of drug sensitivity in advanced-stage ovarian cancer: clinical correlation of drug sensitivity assays in organoid tissue cultures

Objectives: Though many ovarian cancer patients respond to primary treatment, a significant portion will not respond and are considered ‘platinum resistant/refractory.’ Such patients experience a significantly worse prognosis relative to those who are ‘platinum sensitive.’ Pre-treatment prediction of platinum sensitivity has eluded scientists, which forces clinicians to undergo a ‘trial and error’ method of treatment by which resistant patients are forced to try and fail a futile line of therapy. Patient-derived organoid (PDO) cultures represent a potentially powerful functional model which preserves tumor heterogeneity (Hill et al, 2018). Here, we describe the successful culture of 4 PDOs from patients with advanced stage ovarian carcinoma and their correlation with clinical treatment outcome. Methods: Fresh tissue was obtained from the patients’ debulking surgery. It was digested, and a cell pellet was created. The pellet was washed several times, re-suspended in Matrigel, plated, and grown at 37oC over several days. PDOs were treated with standard doses of carboplatin (1 µM) and paclitaxel (10 nM). The percent of viable cells at 72 hours was measured using the CellTiter-Glo 3D platform (Promega, Madison, WI). The patients’ clinical charts were then reviewed 6 months after the completion of primary chemotherapy to determine clinical platinum sensitivity as defined by clinical parameters. Results: PDOs were successfully obtained from each of the four patients with advanced stage ovarian carcinoma. Three patients had primary disease, and 1 patient was being treated for a recurrence. The patient with recurrent disease received chemotherapy immediately prior to her debulking surgery, and the rest underwent primary debulking surgery with chemotherapy to follow. Three patients had high grade serous histology, and 1 patient had low grade serous histology. Three patients ultimately had platinum resistant disease, and their PDOs all demonstrated >50% cell viability in response to carboplatin and paclitaxel with 2 resistant PDOs demonstrating a remarkable 90% and 95% cell viability. The PDO from the patient with platinum sensitive disease by clinical criteria demonstrated 49% cell viability in response to treatment (Table 1). Download : Download high-res image (123KB) Download : Download full-size image Conclusions: We describe the successful creation of PDOs from fresh tissue obtained from debulking surgery in advanced stage ovarian cancer patients. If we use ≥50% cell viability as our initial, preliminary sensitivity threshold, results from the PDO drug sensitivity assay correlate with clinical platinum sensitivity in this pilot feasibility. We propose to confirm the predictability of drug sensitivity thresholds in future, larger studies using PDOs. Currently, there is no standardized drug sensitivity assay or response parameters defined as predictable for PDOs. Such work will be integral in the formation of a functional model of drug sensitivity, which can be used in the clinic to predict platinum sensitivity without requiring a patient to try and fail futile treatments.

Predictors of the timing of interval cytoreduction based on the number of cycles of neoadjuvant chemotherapy: a retrospective cohort

Objectives: To identify pretreatment clinical variables in ovarian cancer patients undergoing neoadjuvant chemotherapy that predict a delayed interval cytoreductive surgery. Methods: We performed an (institutional review board) IRB-approved retrospective cohort study of advanced-stage ovarian cancer patients at a single, academic, tertiary-referral center. Patients from 2008-2017 with stage III or IV disease who received NACT were included in the study. Patients without a pathologic or cytologic diagnosis, those who did not have treatment records, and those who underwent surgery at another institution were excluded. Patients who underwent interval cytoreduction (IDS) prior to their 4th cycle were compared against those who required 4 or more cycles, as our institution's practice is to undergo cytoreduction after 3 cycles if an optimal debulking is achievable. Chi-square and t-tests were used to compare clinical, radiographic, laboratory, and pathologic variables between the groups. Results: A total of 123 patients were included in the study: 70 (56.9%) patients underwent surgery at <4 cycles and 53 (43.1%) required 4 or more cycles. There was no difference in terms of age, renal function, or primary tumor size at time of diagnosis (Table 1) per number of cycles of NACT prior to IDS for either group. Patients also had a similar decrease in their Ca-125 values as measured by pre-op nadir (283.3 vs 356.6, p=0.69). Patients who underwent interval debulking surgery at <4 cycles were more likely to have a lower Charlson Comorbidity index (5.3 compared to 6.3, p=0.007) and a higher albumin (3.33 compared to 3.00, p=0.007). Not surprisingly, patients with IDS after fewer cycles received their chemotherapy in a shorter mean time period (47.2 vs 103.7 days, p<0.0001). Both groups restarted chemotherapy in a similar time frame after IDS. Conclusions: Patients with increased Charlson Comorbidity Index and a lower baseline albumin were more likely to require 4 or more cycles prior to proceeding with surgery after neoadjuvant chemotherapy for ovarian carcinoma. Ongoing assessment of these variables and other variables prior to initiating NACT may provide guidance regarding anticipated patient outcomes. To identify pretreatment clinical variables in ovarian cancer patients undergoing neoadjuvant chemotherapy that predict a delayed interval cytoreductive surgery. We performed an (institutional review board) IRB-approved retrospective cohort study of advanced-stage ovarian cancer patients at a single, academic, tertiary-referral center. Patients from 2008-2017 with stage III or IV disease who received NACT were included in the study. Patients without a pathologic or cytologic diagnosis, those who did not have treatment records, and those who underwent surgery at another institution were excluded. Patients who underwent interval cytoreduction (IDS) prior to their 4th cycle were compared against those who required 4 or more cycles, as our institution's practice is to undergo cytoreduction after 3 cycles if an optimal debulking is achievable. Chi-square and t-tests were used to compare clinical, radiographic, laboratory, and pathologic variables between the groups. A total of 123 patients were included in the study: 70 (56.9%) patients underwent surgery at <4 cycles and 53 (43.1%) required 4 or more cycles. There was no difference in terms of age, renal function, or primary tumor size at time of diagnosis (Table 1) per number of cycles of NACT prior to IDS for either group. Patients also had a similar decrease in their Ca-125 values as measured by pre-op nadir (283.3 vs 356.6, p=0.69). Patients who underwent interval debulking surgery at <4 cycles were more likely to have a lower Charlson Comorbidity index (5.3 compared to 6.3, p=0.007) and a higher albumin (3.33 compared to 3.00, p=0.007). Not surprisingly, patients with IDS after fewer cycles received their chemotherapy in a shorter mean time period (47.2 vs 103.7 days, p<0.0001). Both groups restarted chemotherapy in a similar time frame after IDS. Patients with increased Charlson Comorbidity Index and a lower baseline albumin were more likely to require 4 or more cycles prior to proceeding with surgery after neoadjuvant chemotherapy for ovarian carcinoma. Ongoing assessment of these variables and other variables prior to initiating NACT may provide guidance regarding anticipated patient outcomes.

Exploring the malnutrition status and impact of total parenteral nutrition on the outcome of patients with advanced stage ovarian cancer

BackgroundOvarian cancer is a common cancer type in women and is often associated with onset of malnutrition. Total parenteral nutrition (TPN) is a nutritional intervention method that has been reported to have controversial effect on cancer patients. In the present retrospective study, we sought to explore the prevalence of malnutrition assessed by the Nutritional Risk Index (NRI) and its association with survival in advanced stage ovarian cancer patients. We also compared the post-operative outcome of the malnourished patients treated with either TPN or conservative management.ResultsA total of 415 patients with advanced stage ovarian cancer were separated into 4 nutrition groups based on the NRI scores. We found that a number of factors were significantly different among the 4 nutrition groups, including age, serum albumin level, BMI and NRI; among which serum albumin level and NRI were identified to be independent predictors of progression-free and overall survival. In the moderately and severely malnourished patients, those who were treated with TPN had significantly shorter hospitalization period, lower serum albumin level and lower BMI after surgery. In addition, serum albumin level, use of TPN and number of patients with complications were closely related to the hospital stay duration.ConclusionMalnutrition status is closely associated with survival of advanced stage ovarian cancer patients. These patients may benefit from TPN treatment for reduced hospitalization, especially with the onset of hypoalbuminemia.

Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer.

Fluid accumulation in the abdominal cavity is commonly found in advanced-stage ovarian cancer patients, which creates a specialized tumor microenvironment for cancer progression. Using single-cell RNA sequencing (scRNA-seq) of ascites cells from five patients with ovarian cancer, we identified seven cell types, including heterogeneous macrophages and ovarian cancer cells. We resolved a distinct polarization state of macrophages by MacSpectrum analysis and observed subtype-specific enrichment of pathways associated with their functions. The communication between immune and cancer cells was predicted through a putative ligand-receptor pair analysis using NicheNet. We found that CCL5, a chemotactic ligand, is enriched in immune cells (T cells and NK cells) and mediates ovarian cancer cell survival in the ascites, possibly through SDC4. Moreover, SDC4 expression correlated with poor overall survival in ovarian cancer patients. Our study highlights the potential role of T cells and NK cells in long-term survival patients with ovarian cancer, indicating SDC4 as a potential prognostic marker in ovarian cancer patients.

Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting.

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.

Prognostic value of E-Cadherin and its tumor suppressor role in Saudi women with advanced epithelial ovarian cancer

ABSTRACT The extracellular matrix (ECM) disruption and cytoskeleton reorganization are crucial events in tumor proliferation and invasion. E-Cadherin (E-CAD) is a member of cell adhesion molecules involved in cell-cell junctions and ECM stability. The loss of E-CAD expression is associated with cancer progression and metastasis. This retrospective study aimed to assess E-CAD protein expression in ovarian cancer (OC) tissues and to evaluate its prognostic value. Patients and Methods: 143 formalin-fixed and paraffin-embedded (FFPE) blocks of primary advanced stages OC were retrieved and used to construct Tissue microarrays. Automated immunohistochemistry technique was performed to evaluate E-CAD protein expression patterns in OC. Results: E-CAD protein expression was significantly correlated with OC histological subtype (p < 0.0001), while borderline significant correlations were observed with both tumor grade (p = 0.06) and stage (p = 0.07). Interestingly, Kaplan-Meier survival analysis showed that OC patients with membranous E-CAD expression survived longer than those with no E-CAD expression mainly those at advanced stages (p < 0.009). Further in silico analysis confirms the key roles of E-CAD in OC molecular functions. Conclusion: we reported a prognosis value of membranous E-CAD in advanced stage OC patients. Further validation using larger cohorts is recommended to extract clinically relevant outcomes towards better OC management and individualized oncology.

IL-10 Signaling in the Tumor Microenvironment of Ovarian Cancer.

Unlike other malignancies, ovarian cancer (OC) creates a complex tumor microenvironment with distinctive peritoneal ascites consisting of a mixture of several immunosuppressive cells which impair the ability of the patient's immune system to fight the disease. The poor survival rates observed in advanced stage OC patients and the lack of effective conventional therapeutic options have been attributed in large part to the immature dendritic cells (DCs), IL-10 secreting regulatory T cells, tumor-associated macrophages, myeloid-derived suppressor cells, and cancer stem cells that secrete inhibitory cytokines. This review highlights the critical role played by the intraperitoneal presence of IL-10 in the generation of an immunosuppressive tumor microenvironment. Further, the effect of antibody neutralization of IL-10 on the efficacy of DC and chimeric antigen receptor T-cell vaccines will be discussed. Moreover, we will review the influence of IL-10 in the promotion of cancer stemness in concert with the NF-κB signaling pathway with regard to OC progression. Finally, understanding the role of IL-10 and its crosstalk with various cells in the ascitic fluid may contribute to the development of novel immunotherapeutic approaches with the potential to kill drug-resistant OC cells while minimizing toxic side effects.

Feature Selection is Critical for 2-Year Prognosis in Advanced Stage High Grade Serous Ovarian Cancer by Using Machine Learning.

IntroductionAccurate prediction of patient prognosis can be especially useful for the selection of best treatment protocols. Machine Learning can serve this purpose by making predictions based upon generalizable clinical patterns embedded within learning datasets. We designed a study to support the feature selection for the 2-year prognostic period and compared the performance of several Machine Learning prediction algorithms for accurate 2-year prognosis estimation in advanced-stage high grade serous ovarian cancer (HGSOC) patients.MethodsThe prognosis estimation was formulated as a binary classification problem. Dataset was split into training and test cohorts with repeated random sampling until there was no significant difference (p = 0.20) between the two cohorts. A ten-fold cross-validation was applied. Various state-of-the-art supervised classifiers were used. For feature selection, in addition to the exhaustive search for the best combination of features, we used the-chi square test of independence and the MRMR method.ResultsTwo hundred nine patients were identified. The model's mean prediction accuracy reached 73%. We demonstrated that Support-Vector-Machine and Ensemble Subspace Discriminant algorithms outperformed Logistic Regression in accuracy indices. The probability of achieving a cancer-free state was maximised with a combination of primary cytoreduction, good performance status and maximal surgical effort (AUC 0.63). Standard chemotherapy, performance status, tumour load and residual disease were consistently predictive of the mid-term overall survival (AUC 0.63–0.66). The model recall and precision were greater than 80%.ConclusionMachine Learning appears to be promising for accurate prognosis estimation. Appropriate feature selection is required when building an HGSOC model for 2-year prognosis prediction. We provide evidence as to what combination of prognosticators leads to the largest impact on the HGSOC 2-year prognosis.

Long-term survival outcome of advanced epithelial ovarian cancer: A single institutional study.

A number of patients with advanced-stage epithelial ovarian cancer do survive beyond 5 years. The long-term follow-up data are limited, especially for the Indian setting. We evaluated the 10-year survival outcome and influencing clinicopathological factors. A retrospective analysis of advanced-stage epithelial ovarian cancer patients who underwent primary cytoreductive surgery (PCS) or interval cytoreductive surgery (ICS) from 2005 to 2008 was conducted. Survival analysis was performed with the Kaplan-Meier method, and the Cox proportional hazards model was used for prognostic clinicopathological factors analysis. Ninety-four patients with a median age of 54.5 (18-79) years were evaluated. The median follow-up period was 11.2 years. The overall survival (OS) rates at 5, 7, and 10 years were 37%, 23%, and 18%, respectively. The median OS (MOS) was 46 (95% confidence interval [CI], 36-55.8) months and progression-free survival (PFS) was 19.5 (15.3-23.6) months. Long-term survival was significantly predicted by R0 resection (complete cytoreduction with no macroscopic residual disease) and PFS >20 months while prolonged PFS was influenced by age ≤55 years and R0 resection. For the R0 resection group, patients who underwent PCS had better overall survival in comparison with ICS [72.1(25.2-119) months vs 47.4 (34.9-59.9)months] on 10 years follow-up but was not significant statistically. Patients with age ≤55 years, R0 resection, PFS >20 months have a better 10-year survival outcome. Among R0 resection, patients undergoing PCS have clinically a better outcome on 10-year follow-up.

Upfront or intermediate treatment of advanced ovarian cancer patients with cytoreduction plus HIPEC: Results of a retrospective study.

Newly diagnosed advanced-stage ovarian cancer patients are treated with neoadjuvant chemotherapy, primary or intermediate cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study is to evaluate the optimal timing of cytoreduction plus HIPEC for advanced ovarian cancer patients. Advanced ovarian cancer patients treated with cytoreductive surgery plus HIPEC at three different hospitals between 2005 and 2019 were subgrouped regarding their time of management with cytoreduction plus HIPEC, upfront or intermediate. We retrospectively assessed the overall survival (OS), the progression-free survival (PFS), and the disease-free survival (DFS) of these groups. A total of 112 ovarian cancer patients were contained. Of whom, 47 patients were in the upfront group with 24 (51.1%) to be alive, while 65 patients were included in the intermediate group with 34 (52.3%) to be alive. OS (48 vs. 30 months) and DFS (42 vs. 20 months) indicated no significant difference. Although the same median PFS was observed in both groups (10 months), a higher mean PFS was observed in the upfront group (11.9 vs. 9 months, p = 0.023). The treatment of advanced ovarian cancer patients with upfront cytoreductive surgery plus HIPEC is feasible with the same survival results. Further, larger prospective studies need to verify our results.

Chemotherapy response score is a prognostic tool in advanced stage endometrial cancer patients treated with neoadjuvant chemotherapy

Chemotherapy response score (CRS) applied to omental metastases obtained at the time of interval debulking surgery (IDS) has been used to quantify response to neoadjuvant chemotherapy (NACT) in advanced stage ovarian cancer patients. The score has been correlated with both progression free survival (PFS) and overall survival (OS). This CRS score has not been studied in advanced stage endometrial cancer. The objectives of the current study are 1) to apply the CRS to omental and adnexal metastases obtained at IDS of advanced stage endometrial cancer patients and 2) to investigate the association between the CRS score and surgical outcome, PFS and OS.

Predictive value of CIRS severity index on survival in elderly women (>= 70 years) with advanced epithelial ovarian cancer

Objective: This study assessed the predictive value of age and Cumulative Illness Rating Scale (CIRS) severity index on the management of advanced-stage epithelial ovarian cancer (EOC) patients 70 years or older.

A real-world study on characteristics, treatments and outcomes in US patients with advanced stage ovarian cancer

BackgroundDetailed epidemiologic descriptions of large populations of advanced stage ovarian cancer patients have been lacking to date. This study aimed to describe the patient characteristics, treatment patterns, survival, and incidence rates of health outcomes of interest (HOI) in a large cohort of advanced stage ovarian cancer patients in the United States (US).MethodsThis cohort study identified incident advanced stage (III/IV) ovarian cancer patients in the US diagnosed from 2010 to 2018 in the HealthCore Integrated Research Database (HIRD) using a validated predictive model algorithm. Descriptive characteristics were presented overall and by treatment line. The incidence rates and 95% confidence intervals for pre-specified HOIs were evaluated after advanced stage diagnosis. Overall survival, time to treatment discontinuation or death (TTD), and time to next treatment or death (TTNT) were defined using treatment information in claims and linkage with the National Death Index.ResultsWe identified 12,659 patients with incident advanced stage ovarian cancer during the study period. Most patients undergoing treatment received platinum agents (75%) and/or taxanes (70%). The most common HOIs (> 24 per 100 person-years) included abdominal pain, nausea and vomiting, anemia, and serious infections. The median overall survival from diagnosis was 4.5 years, while approximately half of the treated cohort had a first-line time to treatment discontinuation or death (TTD) within the first 4 months, and a time to next treatment or death (TTNT) from first to second-line of about 6 months.ConclusionsThis study describes commercially insured US patients with advanced stage ovarian cancer from 2010 to 2018, and observed diverse treatment patterns, incidence of numerous HOIs, and limited survival in this population.

Abstract 2941: Functional proteomic aberrations post-chemotherapy with paclitaxel and carboplatin in patients with advanced ovarian cancer

Abstract Background: High-grade serous ovarian cancer (HGSOC) remains the leading cause of death from gynecologic malignancies. Here, we examined tumoral proteome changes following neoadjuvant chemotherapy (NACT) to identify potential predictive and prognostic biomarkers of response to primary chemotherapy. Methods: A total of 65 tissue specimens from 10 patients with advanced-stage HGSOC were collected from matched pre- and post-NACT (3 cycles of dose-dense paclitaxel and carboplatin). Protein expression was assessed using reverse-phase protein arrays (RPPA). All relative protein levels using 297 antibodies were normalized by the expression level of pre-treatment samples, and then protein expression alterations and functional analyses were performed by Reactome pathway analysis followed by statistical analysis. Results: The protein expression patterns of samples tended to cluster according to the time point (pre- and post-treatment) by a non-supervised clustering analysis using all the proteins assessed in the RPPA panel. Five differentially expressed proteins among 239 proteins (adj. p&amp;lt;0.1, log2FC≥1) were identified by RPPA. We identified XBP1, MYH11, and S100A4 as being upregulated and CCNB1 and TFRC were down-regulated post-treatment compared to pre-treatment. We also observed significant enrichment of specific functional and signaling pathways by pathway analysis; these included PI3K/AKT signaling, necrosis and programmed cell death (upregulated, p&amp;lt;0.05, FDR&amp;lt;1), and cell cycle and homology-directed repair (HDR) through homologous recombination repair and G2/M checkpoints (down-regulated, p&amp;lt;0.02, FDR&amp;lt;0.5) in post-treatment compared to pre-treatment. Interestingly, cell cycle, DNA damage, and G2 checkpoint pathways at post-treatment exhibited significantly lower pathway scores than pre-treatment. Conclusion: Our findings identified significant proteomic alterations following NACT, and could provide insights into interval proteomic alterations following induction chemotherapy in advanced-stage ovarian cancer patients. These data present information to optimize future clinical trial designs for patients with ovarian cancer. Citation Format: Sanghoon Lee, Li Zhao, Joseph Celestino, Kelly M. Rangel, Richard A. Hajek, Mark S. Kim, Sara E. Sharafi, Jinsong Liu, Nicole D. Fleming, Karen H. Lu, Jianhua Zhang, P. Andrew Futreal, Gordon B. Mills, Shannon N. Westin, Anil K. Sood, Amir A. Jazaeri, Robert L. Coleman. Functional proteomic aberrations post-chemotherapy with paclitaxel and carboplatin in patients with advanced ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2941.

Preoperative neutrophil-to-lymphocyte ratio predicts 30 day postoperative morbidity and survival after primary surgery for ovarian cancer

ObjectiveThe preoperative neutrophil-to-lymphocyte ratio has been found to be an independent prognostic indicator for perioperative complications and survival outcomes in patients undergoing oncologic surgery for several malignancies. The objective of...