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

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

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

Conization before radical hysterectomy in patients with early-stage cervical cancer: A Korean multicenter study (COBRA-R).

OBJECTIVE: To investigate the impact of conization on survival outcomes and to identify a specific population that might benefit from conization before radical hysterectomy (RH) in patients with early-stage cervical cancer. METHODS: From six institutions in Korea, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who underwent primary type C RH between 2006 and 2021. The patients were divided into multiple groups based on tumor size, surgical approach, and histology. We performed a series of independent 1:1 propensity score matching and compared the survival outcomes between the conization and non-conization groups. RESULTS: In total, 1254 patients were included: conization (n = 355) and non-conization (n = 899). Among the matched patients with a tumor size of >2 cm, the conization group showed a significantly better 3-year disease-free survival (DFS) rate compared with the non-conization group when RH was conducted via minimally invasive surgery (MIS), in those with squamous cell carcinoma (96.3% vs. 87.4%, P = 0.007) and non-squamous cell carcinoma (97.0% vs. 74.8%, P = 0.021). However, no difference in DFS was observed between the two groups among the matched patients with a tumor size of ≤2 cm, regardless of surgical approach or histological type. In patients who underwent MIS RH, DFS significantly worsened as the residual tumor size increased (P < 0.001). CONCLUSION: Cervical conization was associated with a lower recurrence rate in patients with early-stage cervical cancer with a tumor size of >2 cm who underwent primary MIS RH. Cervical conization may be performed prior to MIS RH to minimize the uterine residual tumor.

Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers. METHOD: A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics. RESULTS: A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival. CONCLUSION: Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer. STUDY REGISTRATION: The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).

Application of Immune Checkpoint Inhibitors in Gynecological Cancers: What Do Gynecologists Need to Know before Using Immune Checkpoint Inhibitors?

Standard treatments for gynecological cancers include surgery, chemotherapy, and radiation therapy. However, there are limitations associated with the chemotherapeutic drugs used to treat advanced and recurrent gynecological cancers, and it is difficult to identify additional treatments. Therefore, immune checkpoint inhibitor (ICI) therapy products, including PD-1/PD-L1 inhibitors and CTLA-4 inhibitors, are in the spotlight as alternatives for the treatment of advanced gynecological cancers. Although the ICI monotherapy response rate in gynecological cancers is lower than that in melanoma or non-small cell lung cancer, the response rates are approximately 13-52%, 7-22%, and 4-17% for endometrial, ovarian, and cervical cancers, respectively. Several studies are being conducted to compare the outcomes of combining ICI therapy with chemotherapy, radiation therapy, and antiangiogenesis agents. Therefore, it is critical to determine the mechanism underlying ICI therapy-mediated anti-tumor activity and its application in gynecological cancers. Additionally, understanding the possible immune-related adverse events induced post-immunotherapy, as well as the appropriate management of diagnosis and treatment, are necessary to create a quality environment for immunotherapy in patients with gynecological cancers. Therefore, in this review, we summarize the ICI mechanisms, ICIs applied to gynecological cancers, and appropriate diagnosis and treatment of immune-related side effects to help gynecologists treat gynecological cancers using immunotherapy.

Long-term risks of coronary heart disease and cerebrovascular disease in ovarian, uterine and cervical cancer survivors: a nationwide study in Korea.

Only few studies have evaluated the incidence of coronary heart disease (CHD) and cerebrovascular disease (CVD) among gynaecologic cancer survivors. We selected 26,880 gynaecologic cancer patients who underwent health check-ups within 2 years after diagnosis using the Korean National Health Insurance Service Database. They were compared with 79,830 non-cancer controls. Cox regression models were used to estimate hazard ratios (HRs). There was no significant relationship between gynaecologic cancer survivors and CHD or CVD events. However, 10 years after diagnosing cancers, the risk of angina increased in cancer survivors (adjusted HR = 1.193, 95% CI: 1.013-1.406). After 1 year of diagnosis, cancer patients with no initial comorbidities showed an increased risk of all CHD and CVD events (adjusted HR = 1.101, 95% CI: 1.020-1.189) and CHD alone (adjusted HR = 1.168, 95% CI: 1.055-1.293) compared with controls. CHD risk was also higher in the cancer group with no comorbidities after 10 years of diagnosis (adjusted HR = 1.284, 95% CI: 1.020-1.615). Overall, the risk of CHD or CVD did not increase in gynaecologic cancer survivors. However, cancer patients without any comorbidities showed a higher risk of CHD compared with control, the risk persisting until 10 years after cancer diagnosis.Impact StatementWhat is already known on this subject? Cardiovascular risk and the incidence of stroke increase after cancer diagnosis.What do the results of this study add? The risk of coronary heart disease (CHD) and cerebrovascular disease did not increase in Asian (especially Korean) gynaecologic cancer survivors compared with the general population. However, cancer patients without any comorbidities showed a higher risk of CHD compared with the non-cancer population.What are the implications of these findings for clinical practice and/or further research? Our results imply the importance of surveillance of cardiovascular risks among patients with gynaecologic cancer without comorbidities.

Pregnancy Outcomes Following Laparoscopic and Open Surgery in Pelvis during Pregnancy: a Nationwide Population-based Study in Korea.

BACKGROUND: Non-obstetric surgery during pregnancy is associated with adverse obstetric and fetal outcomes. The aim of this study was to investigate the risk of adverse pregnancy outcomes for women who underwent non-obstetric pelvic surgery during pregnancy compared with that of women that did not undergo surgery. METHODS: Study data from women who gave birth in Korea were collected from the Korea National Health Insurance claims database between 2006 and 2016. We identified pregnant women who underwent abdominal non-obstetric pelvic surgery by laparoscopy or laparotomy from the database. Pregnancy outcomes including preterm birth, low birth weight (LBW), cesarean section (C/S), gestational hypertension, gestational diabetes, and postpartum hemorrhage were identified. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the pregnancy outcomes were estimated by multivariate regression models. RESULTS: Data from 4,439,778 women were collected for this study. From 2006-2016, 9,417 women from the initial cohort underwent non-obstetric pelvic surgery (adnexal mass resection, appendectomy) during pregnancy. Multivariate logistic regression analysis indicated that preterm birth (HR, 2.01; 95% CI, 1.81-2.23), LBW (HR, 1.62; 95% CI, 1.46-1.79), C/S (HR, 1.13; 95% CI, 1.08-1.18), and gestational hypertension (HR, 1.35; 95% CI, 1.18-1.55) were significantly more frequent in women who underwent non-obstetric surgery during pregnancy compared to pregnant women who did not undergo surgery. When the laparoscopic and laparotomy groups were compared for risk of fetal outcomes, the risk of LBW was significantly decreased in laparoscopic adnexal resection during pregnancy compared to laparotomy (odds ratio, 0.62; 95% CI, 0.40-0.95). CONCLUSION: Non-obstetric pelvic surgery during pregnancy was associated with a higher risk of preterm birth, LBW, gestational hypertension, placenta previa, placental abruption, and C/S. Although the benefits and safety of laparoscopy during pregnancy appear similar to those of laparotomy in regard to pregnancy outcomes, laparoscopic adnexal mass resection was associated with a lower risk of LBW.

Exploring the prognostic significance of preoperative high normocalcemia in epithelial ovarian carcinoma.

PURPOSE: We investigated the association between serum ionized calcium and prognosis of EOC and determined the optimal cutoff value of ionized calcium level to predict the prognosis of EOC. METHODS: The medical records of patients who were newly diagnosed with EOC from 2001 to 2016 were retrieved. Preoperative ionized calcium test was performed within 2 weeks before surgery, and the cutoff of high normocalcemia was defined based on the receiver operating characteristic (ROC) curve for recurrence. Cox proportional hazards regression models were used to identify independent prognostic factors for progression-free survival (PFS). RESULTS: From 2001 to 2016, 83 patients diagnosed with EOC were identified at a single institution. The optimal cutoff value was set to 4.7 mg/dL (high normocalcemia vs. control group) by plotting the ROC curve for recurrence. Stages III/IV were more frequent in high normocalcemia, with borderline significance (72.9% vs. 52.2%, p = 0.053). Recurrence (67.6% vs. 43.5%, p = 0.029) and death (46.0% vs. 15.2%, p < 0.01) were significantly more frequent in the high normocalcemia group. In multivariate analysis, high normocalcemia (HR 1.9, 95% CI 1.03-3.61, p = 0.04), age (HR 1.04, 95% CI 1.01-1.08, p = 0.02), stage (HR 3.67, 95% CI 1.13-11.92, p = 0.03), residual tumor > 1 cm (HR 3.79, 95% CI 1.61-8.95, p < 0.01), and lymph node metastasis (HR 2.46, 95% CI 1.27-4.78, p < 0.01) were independent risk factors for recurrence. CONCLUSION: This study showed positive association between relatively high level of ionized calcium level and recurrence risk of EOC. High normocalcemia showed the potential as a biomarker for prognosis of EOC.

The Effectiveness of Anti-Apoptotic Agents to Preserve Primordial Follicles and Prevent Tissue Damage during Ovarian Tissue Cryopreservation and Xenotransplantation.

The purpose of this study is to investigate the effectiveness of sphingosine-1-phosphate (S1P) and Z-VAD-FMK (Z-VAD) as anti-apoptotic agents to preserve ovarian function and prevent tissue damage during ovarian tissue cryopreservation and transplantation. This study consisted of two steps, in vitro and in vivo. In the first step, human ovarian tissues were cryopreserved using slow-freezing media alone, S1P, or Z-VAD (control, S1P, Z-VAD group); based on the outcomes in these groups, Z-VAD was selected for subsequent xenotransplantation. In the second step, human frozen/thawed ovarian tissues were grafted into fifty mice divided into three groups: slow-freezing/thawing and transplantation without an anti-apoptotic agent (Trans-control) and xenotransplantation with or without Z-VAD injection (Trans-Z-VAD-positive and Trams-Z-VAD-negative groups, respectively). In the first step, the Z-VAD group had a significantly higher primordial follicular count than the S1P (p = 0.005) and control groups (p = 0.04). Transplanted ovarian tissues were obtained 4 weeks after transplantation (second step). Angiogenesis was significantly increased in the Z-VAD-negative (p = 0.03) and -positive (p = 0.04) groups compared to the control group. This study demonstrated that slow-freezing and transplantation with Z-VAD is an effective method for preserving primordial follicle counts, decreasing double-strand DNA breaks, and increasing angiogenesis in a mouse model. Further molecular and clinical studies are needed to confirm these results.

The impact of previous cesarean section (C/S) on the risk for post-molar gestational trophoblastic neoplasia (GTN).

OBJECTIVE: To investigate the relationship between previous cesarean section (C/S) and risk for post-molar gestational trophoblastic neoplasia (GTN). METHODS: Data from patients who were treated for hydatidiform moles between 1995 and 2016 were retrospectively reviewed. Patient age, gravidity, parity, abortion history, gestational age, pretreatment beta-human chorionic gonadotropin (HCG), previous molar pregnancy, clinical symptoms, enlarged uterus, theca lutein cyst, type of GTN, World Health Organization risk score, chemotherapy, and mode of delivery were recorded. Hazard ratios (HR) and 95% confidence intervals (CI) for variables associated with the occurrence of post-molar GTN and invasive mole were estimated by univariate and multivariate Cox proportional hazards models. RESULTS: From 1995 to 2016, 182 patients were diagnosed with molar pregnancy and underwent treatment. Patients with previous C/S (C/S group) had higher age (37.0 vs 32.8. p = 0.004), gravidity (3.1 vs 2.0, p < 0.001), and parity (1.6 vs 0.9, p < 0.001) than patients without previous C/S (non-C/S group). Post-molar GTN (43.5 vs 26.5%, p < 0.001), invasive mole (21.7 vs 3.7%, p < 0.001), hysterectomy (28.3 vs 6.6%, p < 0.001), and chemotherapy (45.7 vs 28.7%, p = 0.03) were more frequent in the C/S group. In multivariate analysis, independent risk factors for post-molar GTN were previous C/S (HR 5.1, 95% CI 2.1-12.7), abortion history (HR 6.3, 95% CI 2.5-15.6), and pretreatment ß-hCG (HR 1.3, 95% CI 1.1-1.6). CONCLUSIONS: In this study, C/S was a strong risk factor for occurrence of post-molar GTN and invasive mole. Aggressive treatment, such as multi-agent chemotherapy or hysterectomy, can be considered for hydatidiform moles in patients with a C/S history.

Advances in the Treatment and Prevention of Chemotherapy-Induced Ovarian Toxicity.

Due to improvements in chemotherapeutic agents, cancer treatment efficacy and cancer patient survival rates have greatly improved, but unfortunately gonadal damage remains a major complication. Gonadotoxic chemotherapy, including alkylating agents during reproductive age, can lead to iatrogenic premature ovarian insufficiency (POI), and loss of fertility. In recent years, the demand for fertility preservation has increased dramatically among female cancer patients. Currently, embryo and oocyte cryopreservation are the only established options for fertility preservation in women. However, there is growing evidence for other experimental techniques including ovarian tissue cryopreservation, oocyte in vitro maturation, artificial ovaries, stem cell technologies, and ovarian suppression. To prevent fertility loss in women with cancer, individualized fertility preservation options including established and experimental techniques that take into consideration the patient's age, marital status, chemotherapy regimen, and the possibility of treatment delay should be provided. In addition, effective multidisciplinary oncofertility strategies that involve a highly skilled and experienced oncofertility team consisting of medical oncologists, gynecologists, reproductive biologists, surgical oncologists, patient care coordinators, and research scientists are necessary to provide cancer patients with high-quality care.

Doctor and patient awareness of treatment options for cervical intraepithelial neoplasia 1 (CIN 1): a survey questionnaire approach.

The purpose of this study was to investigate doctors' and patients' perceptions of cervical intraepithelial neoplasia 1 (CIN 1) and its treatment methods. A survey questionnaire was offered to obstetrics and gynaecology doctors and patients with CIN 1 in 2017. Only 43% of patients knew of this disease. Regarding perceptions of its aetiology, 64% of the patients perceived human papillomavirus infection to be the main cause of CIN 1. Patients' most preferred treatments were medication (20%), followed by alternative treatment (14%). Among doctors, regular follow-up was the most preferred method for managing CIN 1. The survey showed that current treatment modalities for CIN 1 were satisfactory to only half of doctors (50%) and patients (53%). Overall, 70% of doctors responded that new drug development for CIN 1 is needed. Although, CIN 1 is a low-grade lesion, doctors and patients expressed the desire for new therapeutic agents to manage it.IMPACT STATEMENTWhat is already known on this subject? In general, treatment is not recommended for CIN 1 because lesions are considered indicative of transient HPV infection and spontaneously regress in most patients.What do the results of this study add? Regular follow-up for CIN 1 were satisfactory to only half of doctors and patients. Thirty-six percent of patients wanted active treatment instead of regular follow-up. In addition, 70% of doctors responded that new drug development for CIN 1 is needed.What are the implications of these findings for clinical practice and/or further research? Our results support the need for therapeutic agents for CIN 1.

CXC chemokine ligand 1 mediates adiponectin-induced angiogenesis in ovarian cancer.

OBJECTIVES: Adiponectin is a cytokine secreted from adipose tissue that regulates energy homeostasis, inflammation, and cell proliferation. Obesity is associated with increased risk of various cancers, including ovarian cancer. Adipokines, including adiponectin, have been implicated as a factor linking obesity and carcinogenesis. The oncogenic role of adiponectin is not known with regard to various cancer types. We sought to determine the role of adiponectin in angiogenesis in ovarian cancer in vitro. METHODS: We transfected SKOV3 cells with vascular endothelial growth factor small interfering RNA in order to identify the independent angiogenic role of adiponectin in ovarian cancer. The vascular endothelial growth factor knockdown SKOV3 cell lines were treated with adiponectin for 48 h. The cytokines involved in adiponectin-mediated angiogenesis were explored using the human angiogenesis cytokine array and were verified with the enzyme-linked immunosorbent assay. The angiogenic effect of adiponectin was evaluated using the human umbilical vein endothelial cell tube formation assay. We also investigated the effects of adiponectin treatment on the migration and invasion of SKOV3 cells. RESULTS: The number of tubes formed by human umbilical vein endothelial cell decreased significantly after knockdown of vascular endothelial growth factor (via transfection of vascular endothelial growth factor small interfering RNA into SKOV3 cells). When these vascular endothelial growth factor knockdown SKOV3 cells were treated with adiponectin, there was an increase in the number of tubes in a tube formation assay. Following adiponectin treatment, the CXC chemokine ligand 1 secretion increased in a cytokine array. This was confirmed by both enzyme-linked immunosorbent assay and Western blot. The increased secretion of CXC chemokine ligand 1 by adiponectin occurred regardless of vascular endothelial growth factor knockdown. In addition, the induction of migration and invasion of SKOV3 cells were significantly stronger with adiponectin treatment than they were without. CONCLUSION: Adiponectin treatment of ovarian cancer cells induces angiogenesis via CXC chemokine ligand 1 independently of vascular endothelial growth factor. These findings suggest that adiponectin may serve as a novel therapeutic target for ovarian cancer.

Clinical indications for hysteroscopic removal of uterine masses: Time, age at diagnosis, and mass size.

AIM: The aim of this study was to investigate clinical factors associated with abnormal pathologies of uterine masses resected via hysteroscopy. METHODS: Women who underwent hysteroscopic surgery for presumptive diagnoses of abnormal endometrial or endocervical masses, such as polyps or leiomyomas on ultrasonography, between January 2012 and April 2015, were enrolled. Clinical and pathologic data were retrospectively reviewed. RESULTS: Among 189 patients, pathologic diagnoses of the uterine mass were abnormal in 172 (91.0%) cases, including polyps in 119 (63.0%), leiomyomas in 49 (26.0%), endometrial hyperplasia in two (1.0%), and endometrial cancer in two (1.0%). Seventeen (9.0%) women who underwent hysteroscopic removal showed unremarkable results on pathology, and the most common finding among them was the proliferative phase of the normal endometrium. Women aged over 40 years with uterine masses and a time since last menstrual period of over 15 days are four times more likely to be diagnosed with neoplastic masses than others (odds ratio [OR], 4.39, 95% confidence interval [CI], 1.33-14.48 and OR, 4.22, 95%CI, 1.35-13.21, respectively); those with masses over 1.5 cm in size are three times more likely to be neoplastic than others (OR, 3.08, 95%CI, 1.04-9.12). CONCLUSION: Large mass size, longer time after last menstrual period, and older age are risk factors for abnormal histologies of uterine masses resected via hysteroscopy. Clinicians should take particular care when contemplating hysteroscopic removal for women younger than 40 years, and those with masses of <1.5 cm in size in the proliferative phase of the endometrium to avoid an unnecessary surgery.

Short-term Impact of Hormone Replacement Therapy on Risk of Breast Cancer in BRCA Mutation Carriers: A Nationwide Study in South Korea.

PURPOSE: BRCA1/2 mutations are well-known risk factors for breast and ovarian cancers in women. Risk-reducing salpingo-oophorectomy (RRSO) is the standard treatment for preventing ovarian cancer with BRCA mutations. Postmenopausal syndrome (symptoms after RRSO can be alleviated by hormone replacement therapy (HRT); however, the use of HRT in carriers of BRCA mutations has been controversial because of the concern that HRT increases the risk of breast cancer. This study aimed to evaluate the effects of HRT in BRCA mutation carriers who underwent RRSO. MATERIALS AND METHODS: A total of 151 carriers, who underwent RRSO between 2013 and 2020 after the diagnosis of BRCA1 or BRCA2 mutations were selected and followed up for a median of 3.03 years. Patients were divided into two groups: those who received HRT after RRSO (n=33) and those who did not (n=118). We compared the incidence of breast cancer over time between these two groups. RESULTS: There was no significant difference in the incidence of breast cancer between women who received HRT and those who did not (p=0.229). Multivariate logistic regression analysis, adjusted for age and parity revealed no significant difference in the risk of breast cancer between these two groups (hazard ratio, 0.312; 95% confidence interval, 0.039 to 2.480; p=0.278). CONCLUSION: In this study, we found no relationship between post-RRSO HRT and breast cancer in the population with BRCA mutations. Therefore, healthcare providers may consider the alleviation of symptoms of postmenopausal syndrome through HRT in patients who underwent RRSO.

Optimal Dietary Intake of Riboflavin Associated with Lower Risk of Cervical Cancer in Korea: Korean National Health and Nutrition Examination Survey 2010-2021.

BACKGROUND: This study aimed to evaluate the association between the dietary intake of vitamin B complex (thiamine, riboflavin, and niacin) and cervical cancer in Korea. METHODS: The data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2021 were analyzed, which included 28,306 participants who were categorized into non-cervical cancer and cervical cancer groups. The following dietary intake threshold levels of thiamine, riboflavin, and niacin were identified based on the recommended daily allowances (RDAs): thiamine, 1.1 mg/day; riboflavin, 1.2 mg/day; and niacin, 14 mg/day. RESULTS: Among 28,306 participants, 27,976 were in the non-cervical cancer group and 330 were in the cervical cancer group. Riboflavin intakes of more than 1.2 mg/day but less than 2.4 mg/day were associated with a significantly reduced risk of cervical cancer, whereas intakes of above 2.4 mg/day were not associated with cervical cancer. Thiamine and niacin intakes were not significantly related to the risk of cervical cancer. CONCLUSIONS: The results of this study suggest that an intake of riboflavin of 1.2-2.4 mg/day may contribute to a lower risk of cervical cancer.

Detection of metastatic lymph node and sentinel lymph node mapping ​using mannose receptor targeting in in vivo mouse footpad tumor models and rabbit uterine cancer models.

BACKGROUND: This study aimed to evaluate the effectiveness of neo-mannosyl human serum albumin-indocyanine green (MSA-ICG) for detecting metastatic lymph node (LN) and mapping sentinel lymph node (SLN) using mouse footpad uterine tumor models. Additionally, the authors assessed the feasibility of MSA-ICG in SLN mapping in rabbit uterine cancer models. MATERIALS AND METHODS: The authors compared the LN targeting ability of MSA-ICG with ICG. Six mouse footpad tumor models and two normal mice were each assigned to MSA-ICG and ICG, respectively. After the assigned tracers were injected, fluorescence images were taken, and the authors compared the signal-to-background ratio (SBR) of the tracers. A SLN biopsy was performed to confirm LN metastasis status and CD206 expression level. Finally, an intraoperative SLN biopsy was performed in rabbit uterine cancer models using MSA-ICG. RESULTS: The authors detected 14 groin LNs out of 16 in the MSA-ICG and ICG groups. The SBR of the MSA-ICG group was significantly higher than that of the ICG group. The metastatic LN subgroup of MSA-ICG showed a significantly higher SBR than that of ICG. CD206 was expressed at a high level in metastatic LN, and the signal intensity difference increased as the CD206 expression level increased. SLN mapping was successfully performed in two of the three rabbit uterine cancer models. CONCLUSIONS: MSA-ICG was able to distinguish metastatic LN for an extended period due to its specific tumor-associated macrophage-targeting property. Therefore, it may be a more distinguishable tracer for identifying metastatic LNs and SLNs during uterine cancer surgery. Further research is needed to confirm these results.

Assessing the New 2020 ESGO/ESTRO/ESP Endometrial Cancer Risk Molecular Categorization System for Predicting Survival and Recurrence.

This study aimed to evaluate the efficacy of the 2020 European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines for endometrial cancer (EC). Additionally, a novel risk category incorporating clinicopathological and molecular factors was introduced. The predictive value of this new category for recurrence and survival in Korean patients with EC was assessed, and comparisons were made with the 2013 and 2016 European Society of Medical Oncology (ESMO) risk classifications. Patients with EC were categorized into the POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), p53-aberrant (P53abn), and nonspecific molecular profile (NSMP) subtypes. Recurrence, survival, and adjuvant therapy were assessed according to each classification. Notably, patients with the POLEmut subtype showed no relapse, while patients with the P53abn subtype exhibited higher recurrence (31.8%) and mortality rates (31.8%). Regarding adjuvant therapy, 33.3% of low-risk patients were overtreated according to the 2020 ESGO/ESTRO/ESP guidelines. Overall and progression-free survival differed significantly across molecular classifications, with the POLEmut subtype showing the best and the P53abn subtype showing the worst outcomes. The 2020 ESGO molecular classification system demonstrated practical utility and significantly influenced survival outcomes. Immunohistochemistry for TP53 and MMR, along with POLE sequencing, facilitated substantial patient reclassification, underscoring the clinical relevance of molecular risk categories in EC management.

A phase 1/2a, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet in healthy women and patients with cervical intraepithelial neoplasia 2.

OBJECTIVE: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). METHODS: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women. In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. RESULTS: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (-98.61%; 95% confidence interval=-99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. CONCLUSION: The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02139267.

Chemotherapy response score no longer predicts survival outcomes in high-grade serous ovarian cancer patients with BRCA mutation and/or maintenance therapy.

OBJECTIVE: We aimed to revalidate the chemotherapy response score (CRS) system as a prognostic factor for ovarian cancer patients with breast cancer gene (BRCA) mutations or those receiving frontline poly-ADP ribose polymerase (PARP) inhibitors or bevacizumab as maintenance therapy. METHODS: A retrospective analysis was performed using medical records of patients with high-grade serous carcinoma who received neoadjuvant chemotherapy followed by interval debulking surgery between January 2007 and December 2021 at 5 tertiary medical institutions in South Korea. At each hospital, pathologists independently assessed each slide of omental tissues obtained from surgery using the CRS system. Progression-free survival (PFS) and overall survival (OS) values were obtained using Kaplan-Meier analysis to evaluate the effect of BRCA mutation, maintenance therapy, and CRS on survival time. RESULTS: Of 466 patients, BRCA mutations were detected in 156 (33.5%) and 131 (28.1%) were treated with maintenance therapy; 98 (21.0%) and 42 (9.0%) were treated with PARP inhibitors or bevacizumab, respectively. Patients with CRS3 had significantly longer PFS than those with CRS1 or 2 (24.7 vs. 16.8 months, p<0.001). However, there was no significant difference in PFS improvement between CRS3 patients and those with CRS1 or 2 with BRCA mutation (22.0 vs. 19.3 months, p=0.193). Moreover, no significant PFS prolongation was observed in CRS3 patients compared to CRS1 or 2 patients treated with PARP inhibitors or bevacizumab (24.3 vs. 22.4 months, p=0.851; 27.5 vs. 15.7 months, p=0.347, respectively). CONCLUSION: CRS may not be a prognostic factor in patients with BRCA mutations and those receiving frontline maintenance therapy.

Current treatment strategies for ovarian cancer in the East Asian Gynecologic Oncology Trial Group (EAGOT).

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.