Prognostic impact of suspicious extraabdominal lymph nodes on patient survival in advanced ovarian cancer.

OBJECTIVE: To evaluate the clinical impact of suspicious extra-abdominal lymph nodes (EALNs) identified preoperatively on CT and/or PET/CT images in advanced ovarian cancer. METHODS: A retrospective study was conducted with 122 patients diagnosed with stage III or IV ovarian cancer with preoperative CT and/or PET/CT images from 2006 to 2022. Imaging studies were evaluated for the presence, size and location of suspicious EALNs. Suspicious lymph node enlargement was defined by a cut-off ≥5mm short-axis dimension on CT and/or lesions with maximum standardized uptake values of ≥2.5 on PET/CT. This study only included patients who did not have their EALNs surgically removed. RESULTS: A total 109 patients met the inclusion criteria; 36 (33%) had suspicious EALNs and were categorized as "node-positive". The median overall survival (OS) was 45.73 months for the "node-positive" and 46.50 months for the "node-negative" patients (HR 1.17, 95% CI 0.68-2.00, p = 0.579). In multivariate analysis, after adjusting for other variables selected by process of backward elimination using a significance level of p<0.20, suspicious EALNs still showed no clinical significance on OS (aHR 1.20, 95% CI 0.67-2.13, p = 0.537) as well as progression-free survival (aHR 1.43, 95% CI 0.85-2.41, p = 0.174). Old age (aHR 2.23, 95% CI 1.28-3.89, p = 0.005) and platinum resistance (aHR 1.92, 95% CI 1.10-3.36, p = 0.023) affects adversely on OS. CONCLUSION: Suspicious EALNs did not worsen the prognosis of patients with advanced ovarian cancer. However, its impact on survival is not yet clarified. Further investigation is required to assess the clinical significance of suspicious EALNs on preoperative imaging studies.

Risk Factors and Prognosis of Stroke in Gynecologic Cancer Patients.

Increased life expectancy and cancer prevalence rates expose patients to a higher risk of developing other comorbidities such as stroke. This study aimed to evaluate the risk factors for and prognosis of stroke in patients with gynecological cancers. A single-center retrospective cohort study was conducted on patients with cervical, endometrial, and epithelial ovarian cancers. Patients were classified into three groups based on the period of stroke onset: at least one year before cancer diagnosis, within one year before cancer diagnosis to six months after the last treatment date, and six months after the last treatment date. Among the 644 patients, stroke occurred in 54 (8.4%). In univariate analysis, stroke was significantly associated with overall survival. In contrast, in multivariate analysis, stroke was significantly associated with age and hypertension, but not with overall survival. Age, pulmonary thromboembolism/deep vein thrombosis, histological grade, and tumor stage were significantly associated with overall survival. Therefore, it is important to establish an appropriate examination and treatment plan for patients with gynecologic cancers using a multidisciplinary approach that incorporates the patient's age, medical condition, and tumor characteristics rather than excessively considering the adverse effects of stroke on cancer prognosis.

Sedative-Hypnotic Effects of Glycine max Merr. Extract and Its Active Ingredient Genistein on Electric-Shock-Induced Sleep Disturbances in Rats.

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders.

Role of diagnostic laparoscopy in deciding primary treatment in advanced-stage ovarian cancer.

OBJECTIVE: We evaluated the usefulness of preoperative diagnostic laparoscopy for treatment planning in patients with advanced-stage ovarian cancer. METHODS: We retrospectively analyzed 614 patients diagnosed with advanced-stage ovarian cancer between January 2010 and May 2018. Primary debulking surgery (PDS) or neoadjuvant chemotherapy (NAC) followed by interval debulking surgery were selected based on preoperative laparoscopic (Group 1, n=192) and computed tomography findings (Group 2, n=422). The primary outcomes in the PDS and NAC groups were suboptimal cytoreduction (residual disease >1 cm) rate and non-high-grade serous carcinoma (non-HGSC) rate, respectively. RESULTS: The patients who underwent PDS in group 1 and group 2 were 49 (25.5%) and 279 (66.1%), respectively. The suboptimal cytoreduction rate after PDS was lower in Group 1 than in Group 2 (2.0% vs 11.1%, p=0.023). Moreover, Group 1 showed a tendency toward a lower proportion of non-HGSC patients who underwent NAC than that in Group 2 (9.1% vs. 15.4%, p=0.069). Further, Group 1 showed lower rates of postoperative morbidity than Group 2 (5.2% vs. 10.4%, p=0.033). However, Kaplan-Meier analysis showed no significant differences in survival outcomes between the 2 groups. CONCLUSION: Diagnostic laparoscopy reduced the suboptimal cytoreduction rate in the PDS group and the implementation rate of NAC in non-HGSC patients. Moreover, it reduced postoperative morbidity without affecting survival in both groups. Thus, diagnostic laparoscopy is a valuable diagnostic tool for determining the primary treatment.

Sprayable nanomicelle hydrogels and inflammatory bowel disease patient cell chips for development of intestinal lesion-specific therapy.

All-in-one treatments represent a paradigm shift in future medicine. For example, inflammatory bowel disease (IBD) is mainly diagnosed by endoscopy, which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels. Furthermore, molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy. This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component. These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy. Next, peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions, specifically by nanomicelles. The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation. Hence, the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5 (TLR5) as the main target of flagellin binding and Notch-1. The peptide binding potently suppressed inflammatory signaling without drug loading, where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha. The results were produced using a human colorectal cell line, clinical IBD patient cells, gut-on-a-chip, a mouse IBD model, and pig experiments to validate the translational utility.

Incidence of postoperative thrombotic events in ovarian cancer patients with a de-escalated prophylactic strategy: A retrospective cohort study.

OBJECTIVE: This study aimed to determine the incidence of thrombotic events in ovarian cancer patients following a de-escalated prophylactic strategy and to stratify risk groups. METHODS: We reviewed the records of patients who underwent debulking surgery for ovarian cancer at a single institution between January 2007 and May 2019. We identified clinically diagnosed and radiologically confirmed cases of thrombotic events-classified as pulmonary thromboembolism (PE), deep vein thrombosis (DVT), and other thrombotic events-within 6 months of debulking surgery. RESULTS: After excluding 13 patients diagnosed with thromboembolism at the baseline or during neoadjuvant chemotherapy, 799 were analyzed. Since the introduction of medical prophylaxis at our institution in 2009, 482 patients (60%) received medical prophylaxis with subcutaneous injection of low molecular weight heparin for 5 days with mechanical prophylaxis, whereas 317 (40%) received mechanical prophylaxis only. After debulking surgery, thrombotic events occurred in 28 patients (3.5%) including PE (n = 11), DVT (n = 10), and other thrombotic events (n = 7). Multivariable analysis identified age, body mass index (BMI), and operative duration as independent risk factors associated with thrombotic events. A thrombotic event was an independent prognostic factor for overall survival (HR 2.17, 95% CI 1.16-4.1). A cut-off analysis for pre-operative identifiable risk factors showed age < 57 years and BMI < 21 could help define low-risk groups. One patient from 172 low-risk patients (0.58%) experienced a thrombotic event. CONCLUSIONS: The thrombotic event incidence was low in our cohort. A de-escalated prophylaxis strategy may be considered in young (age < 57 years) and lean (BMI < 21) patients.

Prognostic value of complete metabolic response on ¹8F-FDG-PET/CT after three cycles of neoadjuvant chemotherapy in advanced high-grade serous ovarian cancer.

OBJECTIVE: We investigated the prognostic value of complete metabolic response (CMR) on ¹8F-fluorodeoxyglucose positron emission tomography/computed tomography (¹8F-FDG-PET/CT) after 3 cycles of neoadjuvant chemotherapy (NAC) in advanced high-grade serous ovarian cancer (HGSC). METHODS: PET/CT at baseline and after 3 cycles of NAC were performed; peak standardized uptakes were measured. PET parameters were compared with NAC parameter: cancer antigen-125 (CA-125) normalization before interval debulking surgery (IDS) and chemotherapy response score (CRS) to predict platinum-sensitivity. Kaplan-Meier analysis was used to determine correlations between PET parameters and survival. Prognostic factors were obtained by multivariate Cox regression analysis. RESULTS: Between 2007 and 2020, 102 patients were recruited: 19 (18.6%) were designated as CMR group and 83 (81.4%) as non-CMR group. CMR after 3 cycles of NAC showed the highest accuracy in predicting platinum-sensitivity (area under the curve [AUC]=0.729; 95% confidence interval [CI]=0.552-0.823; p=0.017), compared with CA-125 normalization before IDS (AUC=0.626; 95% CI=0.542-0.758; p=0.010) and CRS (AUC=0.613; 95% CI=0.490-0.735; p=0.080). CMR demonstrated better prognosis than non-CMR in progression-free survival (PFS) (median PFS, 23.9 months vs. 16.4 months; p=0.021) and overall survival (OS) (median OS, not reached vs. 69.7 months; p=0.025). In multivariate analysis, CMR was associated with a lower risk of recurrence (adjusted hazard ratio [aHR]=0.50; 95% CI=0.27-0.92; p=0.027) and death (aHR=0.23; 95% CI=0.05-0.99; p=0.048). CONCLUSION: CMR after 3 cycles of NAC can be a prognostic factor for both recurrence and death in advanced HGSC.

Cancer Patient Tissueoid with Self-Homing Nano-Targeting of Metabolic Inhibitor.

The current paradigm of cancer medicine focuses on patient- and/or cancer-specific treatments, which has led to continuous progress in the development of patient representatives (e.g., organoids) and cancer-targeting carriers for drug screening. As breakthrough concepts, i) living cancer tissues convey intact profiles of patient-specific microenvironmental signatures. ii) The growth mechanisms of cancer mass with intense cell-cell interactions can be harnessed to develop self-homing nano-targeting by using cancer cell-derived nanovesicles (CaNVs). Hence, a tissueoid model of ovarian cancer (OC) is developed by culturing OC patient tissues in a 3D gel chip, whose microchannel networks enable perfusion to maintain tissue viability. A novel model of systemic cancer responses is approached by xenografting OC tissueoids into ischaemic hindlimbs in nude mice. CaNVs are produced to carry general chemotherapeutics or new drugs under pre/clinical studies that target the BRCA mutation or energy metabolism, thereby increasing the test scope. This pioneer study cross-validates drug responses from the OC clinic, tissueoid, and animal model by demonstrating the alignment of results in drug type-specific efficiency, BRCA mutation-dependent drug efficiency, and metabolism inhibition-based anti-cancer effects. Hence, this study provides a directional foundation to accelerate the discovery of patient-specific drugs with CaNV application towards future precision medicine.

Hormone autocrination by vascularized hydrogel delivery of ovary spheroids to rescue ovarian dysfunctions.

The regeneration potential of implantable organ model hydrogels is applied to treat a loss of ovarian endocrine function in women experiencing menopause and/or cancer therapy. A rat ovariectomy model is used to harvest autologous ovary cells while subsequently producing a layer-by-layer form of follicle spheroids. Implantation of a microchannel network hydrogel with cell spheroids [vascularized hydrogel with ovarian spheroids (VHOS)] into an ischemic hindlimb of ovariectomized rats significantly aids the recovery of endocrine function with hormone release, leading to full endometrium regeneration. The VHOS implantation effectively suppresses the side effects observed with synthetic hormone treatment (i.e., tissue overgrowth, hyperplasia, cancer progression, deep vein thrombosis) to the normal levels, while effectively preventing the representative aftereffects of menopause (i.e., gaining fatty weight, inducing osteoporosis). These results highlight the unprecedented therapeutic potential of an implantable VHOS against menopause and suggest that it may be used as an alternative approach to standard hormone therapy.

Effects of Korean Red Ginseng (Panax ginseng C.A. Meyer) on Menopausal Symptoms in Premenopausal Women After Gynecologic Cancer Surgery: A Double-Blind, Randomized Controlled Trial.

Objectives: Korean red ginseng (KRG) has been widely used as an alternative medicine to relieve menopausal symptoms. However, there is still a lack of clinical studies showing the effects of KRG on menopausal symptoms after gynecologic cancer surgery. Therefore, the authors investigated the effects of KRG on surgical menopause symptoms in premenopausal women with gynecologic cancer. Design: A double-blind, randomized, placebo-controlled clinical trial was conducted. Settings/Location: The study was performed at Severance Hospital at the Yonsei University College of Medicine in Seoul, Korea. Subjects: Fifty-five premenopausal women diagnosed with gynecologic cancer were enrolled in the study. Interventions: Patients were randomly assigned to a KRG (n = 29) or a placebo control group (n = 26). Subjects were administered either KRG (a total of 3 g per day) or placebo supplements for 12 weeks. Outcome measures: Patients' physical measurements (height, weight, and blood pressure) and blood samples (lipid profiles, hormone profiles, biochemical profiles, and neutrophil-to-lymphocyte ratio) at baseline and at 12 weeks were compared. Changes in menopausal symptoms based on the Menopause Rating Scale (MRS) were also compared between these two time points and two groups. Results: After 12 weeks, the MRS score was significantly reduced in each group (p = 0.001 and p = 0.001, respectively), but there were no significant differences between the two groups (p = 0.661). No adverse events were observed in either group. After comparing 11 MRS symptoms between the two groups, the KRG group seemed to be superior to the placebo group on the subscale of sexual complaints (p < 0.05). Conclusions: Through the study, KRG did not show absolute relief of surgical menopause symptoms in premenopausal women after gynecologic cancer surgery. However, the study did demonstrate that KRG may be effective in reducing sexual complaints. Further studies are required to evaluate the long-term effects of KRG in a larger patient population.

Mismatch repair status influences response to fertility-sparing treatment of endometrial cancer.

BACKGROUND: Patients younger than 40 years usually present with early-stage endometrial cancer with favorable prognosis. However, such patients are usually in their childbearing age and may desire fertility-sparing options. The identification of biomarkers may improve the clinical outcomes in these patients and aid in fertility-sparing management; however, there has been no reports on biomarker analysis so far. OBJECTIVE: This study aimed to evaluate the prognostic significance of Proactive Molecular Risk Classifier for Endometrial Cancer in the fertility-sparing management of endometrial cancer. STUDY DESIGN: A total of 57 endometrial biopsy specimens obtained before hormone therapy were evaluated, and patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer molecular subtypes (mismatch repair deficiency, DNA polymerase epsilon mutation, wild-type p53, and abnormal p53). The primary endpoint was the response rate after hormone therapy. The secondary endpoint was the recurrence rate after the complete response, hysterectomy rate owing to treatment failure, and upstaged diagnosis rate after hysterectomy. RESULTS: Of 57 patients, 9 (15.8%) had mismatch repair deficiency, 2 (3.5%) had DNA polymerase epsilon mutation, 45 (78.9%) had wild-type p53, and 1 (1.8%) had abnormal p53. Overall, the complete response rate was 75.4% after hormone therapy. Patients with mismatch repair deficiency had a significantly lower complete response or partial response rate than those with wild-type p53 in terms of the best overall response (44.4% [95% confidence interval, 4.0-85.0] vs 82.2% [95% confidence interval, 71.0-94.0]; P=.018) and complete response rate at 6 months (11.1% [95% confidence interval, 0.2-37.0] vs 53.3% [95% confidence interval, 38.0-68.0]; P=.010). Among patients with mismatch repair deficiency, 4 underwent immediate hysterectomy because of treatment failure and 3 presented upstaged diagnosis after hysterectomy. CONCLUSION: The Proactive Molecular Risk Classifier for Endometrial Cancer molecular classification has prognostic significance in the fertility-sparing management of endometrial cancer, thereby enabling early stratification and risk assignment to direct care. Mismatch repair status could be used as a predictive biomarker for selecting patients who could benefit from hormone therapy. These findings need to be validated in larger studies.

Impact of subcutaneous negative pressure drains on surgical wound healing in ovarian cancer.

INTRODUCTION: Subcutaneous negative pressure wound drains have been used to reduce wound complication rates in various surgical procedures. However, research on the benefits of subcutaneous drains on wound healing after ovarian cancer surgery is limited. The aim of this study was to assess the effects of subcutaneous negative pressure drains on wound healing after abdominal surgery for ovarian cancer. METHODS: Patients who underwent surgery with a midline incision for ovarian cancer between February 2015 and May 2019 were retrospectively examined. Patients were divided into two groups according to the presence (group 1; n=99) or absence (group 2; n=213) of subcutaneous wound drains. The primary endpoint was the incidence of wound complications within 8 weeks after abdominal surgery. The secondary endpoints were time interval from surgery to adjuvant chemotherapy and survival. RESULTS: Patients in group 1 were older (mean 58.5 vs 55.4 years; p=0.02), and had higher rates of previous abdominal surgery (66.7% vs 47.9%; p=0.002), bowel surgery (47.5% vs 34.3%; p=0.026), and had a high surgical complexity score (53.5% vs 33.8%; p<0.001) compared with patients in group 2. Median body mass index was not different between the two groups: group 1, 22.9 kg/m2 (range 16.0 to 33.3) and group 2, 22.8 kg/m2 (range 16.4 to 37.5) (p=0.858). A higher rate of clear wound healing (82.8% vs 71.8%; p=0.036) and a lower rate of seroma formation (6.1% vs 16.0%; p=0.015) were observed in group 1 compared with group 2. After multivariate analysis, subcutaneous wound drain placement was identified as an independent predictive factor for preventing wound complications (adjusted odds ratio 0.43; 95% confidence interval 0.21 to 0.87). Time interval from surgery to adjuvant treatment was significantly longer in patients with wound complications than in those with clear wound healing (mean 23.6 vs 19.2 days; p=0.003). Kaplan-Meier analysis, however, showed no significant differences in progression free or overall survival between the two groups (p=0.35 and p=0.96, respectively). CONCLUSION: The prophylactic use of subcutaneous negative pressure drains after abdominal surgery for ovarian cancer significantly reduced the incidence of wound complications in this study.

Early Assessment of Response to Neoadjuvant Chemotherapy with 18F-FDG-PET/CT in Patients with Advanced-Stage Ovarian Cancer.

PURPOSE: The aim of this study was to evaluate the ability of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after one cycle of neoadjuvant chemotherapy (NAC) to predict chemotherapy response before interval debulking surgery (IDS) in advanced-stage ovarian cancer patients. MATERIALS AND METHODS: Forty consecutive patients underwent 18F-FDG-PET/CT at baseline and after one cycle of NAC. Metabolic responses were assessed by quantitative decrease in the maximum standardized uptake value (SUVmax) with PET/CT. Decreases in SUVmax were compared with cancer antigen 125 (CA-125) level before IDS, response rate by Response Evaluation Criteria in Solid Tumors criteria before IDS, residual tumor at IDS, and I chemotherapy response score (CRS) at IDS. RESULTS: A 40% cut-off for the decrease in SUVmax provided the best performance to predict CRS 3 (compete or near-complete pathologic response), with sensitivity, specificity, and accuracy of 81.8%, 72.4%, and 72.4%, respectively. According to this 40% cut-off, there were 17 (42.5%) metabolic responders (≥ 40%) and 23 (57.5%) metabolic non-responders (< 40%). Metabolic responders had higher rate of CRS 3 (52.9% vs. 8.7%, p=0.003), CA-125 normalization (< 35 U/mL) before IDS (76.5% vs. 39.1%, p=0.019), and no residual tumor at IDS (70.6% vs. 31.8%, p=0.025) compared with metabolic non-responders. There were significant associations with progression-free survival (p=0.021) between metabolic responders and non-responders, but not overall survival (p=0.335). CONCLUSION: Early assessment with 18F-FDG-PET/CT after one cycle of NAC can be useful to predic response to chemotherapy before IDS in patients with advanced-stage ovarian cancer.

Doenjang, A Korean Traditional Fermented Soybean Paste, Ameliorates Neuroinflammation and Neurodegeneration in Mice Fed a High-Fat Diet.

Obesity is considered a risk factor for neurodegeneration. Because fermentation of soybean increases contents of various bioactive compounds with anti-obesity and anti-diabetic activities, we investigated the protective effect of doenjang, a Korean traditional fermented soybean paste, against neuroinflammation and neurodegeneration in the cortex and hippocampus of mice fed a high-fat (HF) diet. C57BL/6J mice were fed a low-fat diet, an HF diet, an HF-containing steamed soybean diet, or an HF-containing doenjang (DJ) diet for 11 weeks. Doenjang consumption alleviated hippocampal neuronal loss, which was increased by the HF diet. Accordingly, we observed higher cell proliferation and neurotrophic factor mRNA levels in the DJ group. Contents of oxidative metabolites and mRNA levels of oxidative stress- and neuroinflammation-related genes were lower in the DJ group compared to the HF group. Dietary doenjang reduced ß-amyloid peptide (Aß) levels by regulating gene expressions involved in Aß production and degradation. Furthermore, doenjang consumption reduced tau hyperphosphorylation induced by HF feeding. Overall, doenjang was more effective than steamed soybean in suppressing neuroinflammation and neurodegeneration in mice fed an HF diet. These results suggest that bioactive compounds produced during the fermentation and aging of soybean may be involved in the enhanced neuroprotective effects of doenjang.

Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708).

BACKGROUND: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer. METHODS: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes. RESULTS: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively). CONCLUSIONS: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.

Pretreatment lymphocytopenia is an adverse prognostic biomarker in advanced-stage ovarian cancer.

The aim of this study was to investigate the prognostic significance of lymphocytopenia in advanced-stage ovarian cancer. We retrospectively reviewed 506 patients with advanced-stage ovarian cancer at Yonsei Cancer Hospital. This study included two cohorts of patients: a neoadjuvant chemotherapy (NAC) group (N = 247) and a primary debulking surgery (PDS) group (N = 259). The absolute lymphocyte count was recorded before treatment. A receiver operating characteristic (ROC) curve analysis was used to determine the cutoff for defining lymphocytopenia in the NAC cohort and followed by multivariate analysis. Subsequently, lymphocytopenia was assessed in the PDS cohort by multivariate analysis. A further analysis was performed to evaluate the absolute lymphocyte count as a continuous variable. An absolute lymphocyte count of 1.49 × 109/L was determined as the cutoff for the ROC curve analysis in the NAC cohort, and the multivariate analysis revealed that lymphocytopenia was an independent prognostic factor for poor progression-free survival (PFS) [hazard ratio (HR), 1.50; 95% confidence interval (CI), 1.07-2.11] and overall survival (OS) (HR, 2.02; 95% CI, 1.21-3.40). In the PDS cohort, the multivariate analysis showed that lymphocytopenia was an independent prognostic factor for poor PFS (HR, 1.73; 95% CI, 1.20-2.49) and OS (HR, 1.87; 95% CI, 1.27-2.75). The absolute lymphocyte count was a significant factor when analyzed as a continuous variable in both the NAC and PDS cohorts. Pretreatment lymphocytopenia is an independent adverse prognostic factor in patients with advanced-stage ovarian cancer.

Prognostic significance of CA-125 re-elevation after interval debulking surgery in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy.

AIMS: We evaluated the prognostic significance of postoperative re-elevation of cancer antigen-125 (CA-125) levels in patients with ovarian cancer and preoperative normalization of CA-125 levels after neoadjuvant chemotherapy (NAC). METHODS: The data of 103 patients with preoperative CA-125 normalization after NAC at the Yonsei Cancer Hospital (2006-2017) were analyzed. We compared the clinical characteristics and survival outcomes among patients with normal postoperative CA-125 levels and those with re-elevated CA-125 levels after interval debulking surgery (IDS). CA-125 elevation was defined as levels >35 U/mL. RESULTS: Among 103 patients, 52 (50.5%) and 51 (49.5%) had normal and re-elevated CA-125 levels after IDS, respectively. Patients with CA-125 re-elevation underwent more radical surgeries during IDS than those with normal CA-125 levels (p = 0.018). We found no significant differences in progression-free survival (PFS; p = 0.726) or overall survival (OS; p = 0.293) between the two groups. Moreover, patients with persistent CA-125 elevation (3 weeks after IDS) did not have inferior PFS (p = 0.171 and p = 0.208, respectively) or OS (p = 0.128 and p = 0.095, respectively) compared to patients with early normalization (within 3 weeks of IDS) or normal CA-125 levels. Multivariate regression showed that CA-125 re-elevation had no effect on recurrence (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.43-1.30) or death (HR, 0.99; 95% CI, 0.33-2.98). CONCLUSION: Among patients with preoperative CA-125 normalization after NAC, postoperative CA-125 re-elevation had no prognostic value. Novel and reliable biomarkers reflecting the tumor response after IDS should be identified.

Outcomes of Non-High Grade Serous Carcinoma after Neoadjuvant Chemotherapy for Advanced-Stage Ovarian Cancer: Single-Institution Experience.

PURPOSE: Outcomes in patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied; however, there is limited information on responses to chemotherapy among patients with non-HGSC. The aim of this study was to compare the survival outcomes of patients with advanced-stage non-HGSC and HGSC treated with NAC. MATERIALS AND METHODS: This study was a retrospective analysis of patients with advanced-stage ovarian cancer treated at Yonsei Cancer Hospital between 2006 and 2017. The demographics, chemotherapy response, and survival rates were compared between patients with non-HGSC and those with HGSC. RESULTS: Among 220 patients who underwent NAC, 25 (11.4%) patients had non-HGSC histologic subtypes, and all received a taxane-platinum combination regimen for NAC. Patients with non-HGSC had lower baseline cancer antigen-125 levels (p<0.001), poorer response rates (p<0.001), lower rates of optimal cytoreduction (p=0.003), and poorer progression-free survival (PFS) (median PFS 10.3 months vs. 18.3 months; p=0.009) and overall survival (OS) (median OS 25.5 months vs. 60.6 months; p<0.001), compared to those with HGSC. In multivariate analysis, non-HGSC was a negative prognostic factor for both PFS [hazard ratio (HR), 3.19; 95% confidence interval (CI), 1.73-5.88] and OS (HR, 4.22; 95% CI, 2.07-8.58). CONCLUSION: In this study, poorer survival outcomes were observed in patients who underwent NAC for treatment of non-HGSC versus those treated for HGSC. Different treatment strategies are urgently required to improve survival outcomes for patients with non-HGSC undergoing NAC.

Evaluation of various kinetic parameters of CA-125 in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy.

Various kinetic parameters of serum CA-125 have been reported to have better correlation with outcomes for patients treated with neoadjuvant chemotherapy (NAC). This study aimed to compare the available kinetic parameters of serum CA-125 in an external cohort of advanced-stage ovarian cancer. Using the cancer registry databases from the Yonsei Cancer Hospital, we retrospectively reviewed 210 patients with advanced-stage ovarian cancer, treated with NAC followed by interval debulking surgery. We compared area under the receiver-operating characteristics curves (AUCs), false negative rate, and negative predictive value (NPV) using 10 different models for optimal cytoreduction and platinum resistance. In addition, we compared incremental AUC for progression-free survival (PFS) and overall survival (OS). No gross residual tumor was observed in 37.0% and residual tumors <1 cm in 82.2% of patients. No model using CA-125 kinetic parameters had an AUC higher than >0.6 for predicting optimal cytoreduction. After adjusting for age, BMI, disease stage, and histologic subtypes, all models had an AUC >0.70 for predicting platinum resistance. However, no model had a high enough NPV (highest value = 82.0%) to avoid chemotherapy futility. For survival outcomes, no model had an incremental AUC >0.70 for predicting either PFS or OS. None of the proposed serum CA-125 kinetic parameters showed high accuracy in predicting optimal cytoreduction, platinum resistance, or survival in patients receiving NAC. For advanced-stage ovarian cancer treated with NAC, there is a need to discover reliable biomarkers to better stratify patient response groups for optimal treatment decision-making.