Heterogeneous treatment effect of dose-dense paclitaxel plus carboplatin therapy for advanced ovarian cancer.

A Japanese clinical trial (JGOG3016) showed that dose-dense weekly paclitaxel in combination with carboplatin extensively prolonged overall survival (OS) in patients with advanced ovarian cancer. However, in other clinical trials, dose-dense paclitaxel regimens were not superior to triweekly paclitaxel regimens. In this study, causal tree analysis was applied to explore subpopulations with different treatment effects of dose-dense paclitaxel in a data-driven approach. The 587 participants with stage II-IV ovarian cancer in the JGOG3016 trial were used for model development. The primary endpoint was treatment effect in terms of 3-year OS in patients receiving dose-dense vs. conventional paclitaxel therapies. In patients <50 years, the 3-year OS was similar in both groups; however, it was higher in the dose-dense group in patients ≥50 years. Dose-dense paclitaxel showed strong positive treatment effects in patients ≥50 years with stage II/III disease, BMI <23 kg/m2, non-CC/MC, and residual tumor ≥1 cm. In contrast, although there was no significant difference in OS; the 3-year OS rate was 23% lower in dose-dense paclitaxel than conventional paclitaxel in patients ≥60 years with stage IV cancer. Patients in this group had a particularly lower performance status than other groups. Our causal tree analysis suggested that poor prognosis groups represented by residual tumor tissue ≥1 cm benefit from dose-dense paclitaxel, whereas elderly patients with advanced disease and low-performance status are negatively impacted by dose-dense paclitaxel. These subpopulations will be of interest to future validation studies. Personalized treatments based on clinical features are expected to improve advanced ovarian cancer prognosis.

Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants.

Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).

Pretreatment systemic inflammatory markers predict survival in endometrial cancer: A Japanese Gynecologic Oncology Group 2043 exploratory data analysis.

OBJECTIVE: We investigated whether pretreatment systemic inflammatory markers are associated with survival outcomes in patients with endometrial cancer (EC). METHODS: Data from the Japanese Gynecologic Oncology Group 2043 were analyzed. Patients who did not receive chemotherapy or were lost to follow-up were excluded. Associations of pretreatment systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, with progression-free survival (PFS) and overall survival (OS) were analyzed. The optimal NLR, PLR, and HALP score cutoff values for PFS and OS were determined. Survival estimates were calculated and compared using the Kaplan-Meier method and log-rank test. RESULTS: We included 712 patients (median age: 55 [range, 28-74] years; body mass index [BMI]: 21.1 [15.2-38.6] kg/m2). For PFS, optimal NLR, PLR, and HALP score cutoff values were 1.48, 0.017, and 35.52, respectively, and for OS, the values were 1.88, 0.026, and 19.87, respectively. At optimal PFS-related cutoff values, NLR was associated with BMI; PLR with age, BMI, and clinical stage; and HALP score with BMI, clinical stage, and lymph node metastasis. At optimal OS-related cutoff values, NLR was associated with BMI, PLR, and BMI; the HALP score was associated with age and BMI. The HALP score was a prognostic factor for PFS (p = 0.025), while PLR and HALP scores were prognostic factors for OS (both p = 0.028). CONCLUSIONS: Pretreatment systemic inflammatory markers are associated with survival outcomes in patients with EC, with the HALP score being a prognostic factor for PFS and OS.

Prognostic significance of adjuvant chemotherapy in stage I-II endometrial carcinoma patients who underwent lymphadenectomy.

BACKGROUND: Endometrial carcinoma, the most common gynecologic carcinoma, has an excellent prognosis post-surgery when diagnosed early. The role of postoperative adjuvant chemotherapy in stages I-II endometrial carcinoma remains controversial. This study assesses the efficacy of adjuvant chemotherapy in improving prognosis for these patients. METHODS: A retrospective analysis was conducted on 1223 stage I-II endometrial carcinoma patients who underwent surgical treatment including total hysterectomy, bilateral salpingo-oophorectomy, and lymph-node biopsy or dissection across four Jikei University School of Medicine-affiliated facilities between 2001 and 2018. Patients were divided into low intermediate risk (LIR) and high intermediate risk (HIR) groups based on recurrence risk. Propensity score matching adjusted for various covariates was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received adjuvant chemotherapy and those who did not. RESULTS: The study included 443 eligible patients, with 288 in the LIR group and 155 in the HIR group. Post propensity score matching, no significant difference in PFS or OS was observed between the observation and adjuvant chemotherapy groups within both risk categories. Notably, the 5-year OS for LIR was 97.6% in the observation group and 96.7% in the chemotherapy group; for HIR, the 5-year OS was similarly high with no significant difference. CONCLUSIONS: The findings suggest that postoperative adjuvant chemotherapy does not significantly contribute to the improvement of recurrence or prognosis in patients with stage I-II endometrial carcinoma who are categorized outside the low-risk group and have no lymph-node metastasis.

Therapeutic effect of dose-dense paclitaxel plus carboplatin with or without bevacizumab for Japanese patients with epithelial ovarian cancer.

BACKGROUND: Evidence regarding chemosensitivity to different therapeutic regimens in epithelial ovarian cancer (EOC) remains limited. This study aimed to investigate EOC implementation in daily clinical practice and reveal favorable regimens for EOC among Japanese patients. METHODS: We retrospectively collected clinical data of patients newly diagnosed with EOC from 2012 to 2021 at our affiliated institutions. We evaluated overall survival (OS) and progression-free survival (PFS) of conventional paclitaxel plus carboplatin (TC) vs. dose-dense TC (ddTC) according to the eligibility of GOG262 and JGOG3016 and those with bevacizumab (BEV) vs. without BEV based on GOG218. Further, we evaluated OS and PFS of ddTC and ddTC + BEV to TC + BEV among patients with stage III/IV. RESULTS: The ddTC group (n = 402) demonstrated longer PFS and OS than the TC group (n = 165) (adjusted hazard ratios [aHRs] [95% confidential intervals (CIs)]: 0.69 [0.55-0.88] and 0.67 [0.50-0.90], respectively). The group with BEV (n = 158) demonstrated a longer PFS than those without BEV (n = 296) (0.74 [0.57-0.95]), but not for OS (0.84 [0.60-1.17]). The ddTC and ddTC + BEV groups (n = 259 and 117) demonstrated no statistically significant differences in PFS and OS than the TC + BEV group (n = 75) (1.09 [0.79-1.50] and 0.74 [0.52-1.08] for PFS and 0.89 [0.59-1.34] and 0.73 [0.50-1.05] for OS, respectively). CONCLUSION: Our study may indicate ddTC, BEV, and their combination regimen as the promising first-line chemotherapy option among Japanese patients with advanced EOC.

Homologous recombination inquiry through ovarian malignancy investigations: JGOG3025 Study.

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

Prognostic relevance of HRDness gene expression signature in ovarian high-grade serous carcinoma; JGOG3025-TR2 study.

BACKGROUND: This study aimed to evaluate the homologous recombination repair pathway deficiency (HRD) in ovarian high-grade serous carcinoma (HGSC). METHODS: In the ovarian cancer data from The Cancer Genome Atlas, we identified genes differentially expressed between tumours with and without HRD genomic scars and named these genes "HRDness signature". We performed SNP array, RNA sequencing, and methylation array analyses on 274 HGSC tumours for which targeted sequencing of 51 genes and clinical data were available to generate JGOG3025-TR2 dataset. The HRDness signature was tested on external datasets, including the JGOG3025-TR2 cohort, by computational scoring and machine-learning prediction. RESULTS: High scores and positive predictions of the HRDness signature were significantly associated with BRCA alterations, genomic scar scores, and better survival. On the other hand, among cases with high scores and/or positive predictions, those with BRCA1 methylation showed poorer survival. In the JGOG3025-TR2 cohort, HRD status was significantly associated with the use of olaparib after relapse and progression-free survival after its initiation. CONCLUSIONS: The HRDness gene expression signature is associated with a good prognosis, while BRCA1 methylation is associated with a poor prognosis. The newly generated JGOG3025-TR2 dataset will be useful in future HGSC studies.

Paclitaxel sensitizes homologous recombination-proficient ovarian cancer cells to PARP inhibitor via the CDK1/BRCA1 pathway.

OBJECTIVE: An effective treatment strategy for epithelial ovarian cancer (EOC) with homologous recombination (HR)-proficient (HRP) phenotype has not been established, although poly (ADP-ribose) polymerase inhibitors (PARPi) impact the disease course with HR-deficient (HRD) phenotype. Here, we aimed to clarify the cellular effects of paclitaxel (PTX) on the DNA damage response and the therapeutic application of PTX with PARPi in HRP ovarian cancer. METHODS: Two models with different PTX dosing schedules were established in HRP ovarian cancer OVISE cells. Growth inhibition and HR activity were analyzed in these models with or without PARPi. BRCA1 phosphorylation status was examined in OVISE cells by inhibiting CDK1, which was reduced by PTX treatment. CDK1 expression was evaluated in EOC patients treated with PTX-based neoadjuvant chemotherapy. RESULTS: PTX suppressed CDK1 expression resulting in impaired BRCA1 phosphorylation in OVISE cells. The reduced CDK1 activity by PTX could decrease HR activity in response to DNA damage and therefore increase the sensitivity to PARPi. Immunohistochemistry showed that CDK1 expression was attenuated in samples collected after PTX-based chemotherapy compared to those collected before chemotherapy. The decrease in CDK1 expression was greater with dose-dense PTX schedule than with the conventional PTX schedule. CONCULSIONS: PTX could act synergistically with PARPi in HRP ovarian cancer cells, suggesting that the combination of PTX with PARPi may be a novel treatment strategy extending the utility of PARPi to EOC. Our findings provide cules for future translational clinical trials evaluating the efficacy of PTX in combination with PARPi in HRP ovarian cancer.

Delivery-Dependent Shift in Oxytocin-Responsive Cell Population in the Central Amygdala of the Female Rat.

INTRODUCTION: Despite its recent reputation as prosocial neurohormone, the most important physiological role of oxytocin (OT) is stimulating uterine contractions. Though it is well known that plasma OT concentrations change drastically during delivery, it remains unexplored whether and how OT receptors in the maternal brain are activated. We examined whether the responses of cells in the central amygdala (CeA), an OT receptor-rich limbic site involved in pain and fear memory regulation, to exogenously applied OT analogue, Thr-Gly-OT (TGOT), vary depending on delivery. METHODS: Intracellular Ca2+ dynamics of the CeA cells were visualized in brain slices from female rats at virgin (VG), during pregnancy term (PT) days 16-21, within 24 h after delivery (G0), and within 1-3 days after delivery (G3). The Ca2+ responses to 1 µM TGOT, 20 mM KCl (high K), and 300 µM ADP were compared. RESULTS: We found that fraction of cells responding to TGOT, high K, and ADP differed significantly between the four delivery-associated terms. In particular, the fraction of cells responding to TGOT (TGOT responders) significantly increased from VG and PT at G0 and G3. Furthermore, the significant positive correlation between TGOT and high K response in TGOT and high K responders was reduced at G0, while that between TGOT and ADP responses in TGOT and ADP responders was increased at G0. CONCLUSION: These results indicate that the responses of CeA cells to an OT receptor agonist markedly change around delivery, which might play a role in controlling the labor-related pain and post-delivery emotional complications.

Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine.

Rapid advances are being made in cancer drug therapy. Since molecularly targeted therapy has been introduced, personalized medicine is being practiced, pathological tissue from malignant tumors obtained during routine practice is frequently used for genomic testing. Whereas cytological specimens fixed mainly in alcohol are considered to be more advantageous in terms of preservation of the nucleic acid quality and quantity. This article is aimed to share the information for the proper handling of cytological specimens in practice for genomic medicine based on the findings established in "Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine (in Japanese)" published by the Japanese Society of Clinical Cytology in 2021. The three-part practical guidelines are based on empirical data analyses; Part 1 describes general remarks on the use of cytological specimens in cancer genomic medicine, then Part 2 describes proper handling of cytological specimens, and Part 3 describes the empirical data related to handling of cytological specimens. The guidelines indicated proper handling of specimens in each fixation, preparation, and evaluation.

Evaluation of non-hematologic toxicity in patients with cervical cancer after Type 3 radical hysterectomy followed by concurrent chemoradiotherapy: a retrospective study.

OBJECTIVE: To investigate the safety of concurrent chemoradiotherapy after Type 3 radical hysterectomy, focusing on non-hematologic toxicity. METHODS: Between January 2010 and December 2017, 236 patients diagnosed with cervical cancer Stages IB1-II (FIGO2008) and who had undergone Type 3 radical hysterectomy at the Jikei Medical University School-related four hospitals were included. Of these 236 patients, 134 had undergone adjuvant concurrent chemoradiotherapy after Type 3 radical hysterectomy (radical hysterectomy + concurrent chemoradiotherapy group), and 102 received no adjuvant therapy after Type 3 radical hysterectomy (radical hysterectomy group). The frequency of non-hematologic toxicities, especially lymphedema, pelvic infection, renal dysfunction, ileus and diarrhea, was investigated in the radical hysterectomy + concurrent chemoradiotherapy and radical hysterectomy groups using univariate and multivariate analyses. In these analyses, age, extent of lymph node dissection and preoperative clinical stage were included as risk factors for five complications. The risk factors for grade ≤ 2 adverse events were statistically evaluated. RESULTS: The frequency of lower extremity lymphedema (22 vs. 10%), renal dysfunction (13 vs. 3%), and diarrhea (13 vs. 0%) was significantly higher in the radical hysterectomy + CRRT group than that in the radical hysterectomy group. Logistic regression analysis revealed that adjuvant concurrent chemoradiotherapy significantly affected the occurrence of grade ≥ 2 lymphedema (P < 0.01) and renal dysfunction (P < 0.01). CONCLUSIONS: Concurrent chemoradiotherapy after Type 3 radical hysterectomy is associated with a higher incidence of renal dysfunction, lower extremity lymphedema and diarrhea. A more appropriate adjuvant therapy needs to be established.

Genetic characteristics of platinum-sensitive ovarian clear cell carcinoma.

OBJECTIVE: Most ovarian clear cell carcinomas are resistant to platinum-based chemotherapy, while a small subset shows a positive response. The aim of this study was to clarify the clinical, pathological and genetic characteristics of platinum-sensitive ovarian clear cell carcinomas. METHODS: The study included 53 patients with stage III-IV ovarian clear cell carcinoma who had residual tumours after primary surgery and received platinum-based therapy between 2009 and 2018. A retrospective examination of platinum sensitivity was performed using the criterion of ≥6 months from the last day of first-line platinum therapy until recurrence/progression. Cases determined to be platinum-sensitive were subjected to immunohistochemical staining, genomic analyses using target sequencing (i.e. NCC Oncopanel) and homologous recombination deficiency (myChoice® HRD Plus) assays. RESULTS: Of the 53 stage III-IV ovarian clear cell carcinoma cases, 11 (21%) were platinum-sensitive. These cases showed better progression-free and overall survival than platinum-resistant cases (hazard ratio = 0.16, P < 0.001). Among the seven sensitive cases whose tumour tissues were available for molecular profiling, five were pure ovarian clear cell carcinoma based on pathological and genetic features, whereas the remaining two cases were re-diagnosed as high-grade serous ovarian carcinoma. The pure ovarian clear cell carcinomas lacked BRCA1 and BRCA2 mutations, consistent with the absence of the homologous recombination deficiency phenotype, whereas two cases (40%) had ATM mutations. By contrast, the two high-grade serous ovarian carcinoma cases had BRCA1 or BRCA2 mutations associated with the homologous recombination deficiency phenotype. CONCLUSION: The subset of platinum-sensitive ovarian clear cell carcinomas includes a majority with pure ovarian clear cell carcinoma features that lack the homologous recombination deficiency phenotype.

Short- and long-term morbidity of total parietal peritonectomy for advanced ovarian cancer.

OBJECTIVE: Total parietal peritonectomy is gradually being recognized as a surgical option for advanced ovarian cancer; however, evidence regarding its efficacy and safety remains insufficient. Herein, we aimed to assess the short- and long-term post-operative safety profiles of total parietal peritonectomy. METHODS: We reviewed the medical records of post-operative morbidity and mortality of patients who underwent cytoreductive surgery with total parietal peritonectomy for stage III and IV ovarian cancer between April 2018 and January 2023. RESULTS: Fifty patients were enrolled in the study: 31 who underwent primary cytoreductive surgery and 19 who underwent interval cytoreductive surgery. The median age of all patients was 57 (range, 23-74) years. The median follow-up period was 22 (range, 3-59) months. Of 44 patients (88%) with stage IIIC/IV, 38 patients (76%) had high-grade serous carcinoma. The complete resection rates were 94%, 91%, and 100% in all patients, the primary cytoreductive surgery group, and the interval cytoreductive surgery group, respectively. There were 63 post-operative complication events overall, including 17 (27%) major complication events in 15 patients within 1 year post-operatively. Ten major complications occurred within 30 days of surgery, mainly in the primary cytoreductive surgery group (9 cases). Regarding complication type, the most frequent major event was pleural effusion (3 cases, 7%). After 30 days, there were a total of 17 all-grade complication events, of which ileus and hydronephrosis were major complications in 3 cases each (18%). There were no mortalities related to cytoreductive surgery. The scheduled adjuvant chemotherapy could be completed in 96% of patients. CONCLUSIONS: Total parietal peritonectomy is a feasible procedure for managing advanced ovarian cancer. Short- and long-term complications may include pleural effusion and ileus/hydronephrosis, respectively.

COVID-19 mRNA vaccination status and concerns among pregnant women in Japan: a multicenter questionnaire survey.

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

Ovarian serous borderline tumors with recurrent or extraovarian lesions: a Japanese, retrospective, multi-institutional, population-based study.

BACKGROUND: Ovarian serous borderline tumors (SBT) are typically unilateral and are primarily treated using hysterectomy and bilateral salpingooophorectomy (SO). However, most young patients prefer fertility-sparing surgeries (FSS) with tumorectomy or unilateral SO. Micropapillary morphology and invasive implants have been designated as histopathological risk indicators for recurrence or metastasis, but their clinical impact remains controversial because of limitations like diagnostic inconsistency and incomplete surgical staging. METHODS: A nationwide multi-institutional population-based retrospective surveillance was conducted with a thorough central pathology review to reveal the clinical features of SBT. Of 313 SBT patients enrolled in the Japanese Society of Clinical Oncology's Surveillance of Gynecologic Rare Tumors, 289 patient records were reviewed for clinical outcomes. The glass slides of patients at stage II-IV or with recurrence or death were re-evaluated by three gynecological pathologists. RESULT: The 10-year overall and progression-free survival (PFS) rates were 98.6% and 92.3%. The median recurrence period was 40 months and 77.0% was observed in the contralateral ovary within 60 months. Patients aged ≤ 35 years underwent FSS more frequently and relapsed more (p < .001). A clinic-pathological analysis revealed diagnosis during pregnancy, FSS, and treatment at non-university institutes as well as advanced stage and large diameter were independent risk factors of recurrence. Among patients having pathologically confirmed SBTs, PFS was not influenced by the presence of micropapillary pattern or invasive implants. CONCLUSION: The recurrence rate was lower in this cohort than previous reports, but the clinical impacts of incomplete resection and misclassification of the tumor were still significant on the treatment of SBT.

Veliparib with frontline chemotherapy and as maintenance in Japanese women with ovarian cancer: a subanalysis of efficacy, safety, and antiemetic use in the phase 3 VELIA trial.

BACKGROUND: The phase 3 VELIA trial evaluated veliparib with carboplatin/paclitaxel and as maintenance in patients with high-grade serous ovarian carcinoma. METHODS: Patients with previously untreated stage III-IV high-grade serous ovarian carcinoma were randomized 1:1:1 to control (placebo with carboplatin/paclitaxel and placebo maintenance), veliparib-combination-only (veliparib with carboplatin/paclitaxel and placebo maintenance), or veliparib-throughout (veliparib with carboplatin/paclitaxel and veliparib maintenance). Randomization stratification factors included geographic region (Japan versus North America or rest of the world). Primary end point was investigator-assessed median progression-free survival. Efficacy, safety, and pharmacokinetics were evaluated in a subgroup of Japanese patients. RESULTS: Seventy-eight Japanese patients were randomized to control (n = 23), veliparib-combination-only (n = 30), and veliparib-throughout (n = 25) arms. In the Japanese subgroup, median progression-free survival for veliparib-throughout versus control was 27.4 and 19.1 months (hazard ratio, 0.46; 95% confidence interval, 0.18-1.16; p = 0.1 [not significant]). In the veliparib-throughout arm, grade 3/4 leukopenia, neutropenia, and thrombocytopenia rates were higher for Japanese (32%/88%/32%) versus non-Japanese (17%/56%/28%) patients. Grade 3/4 anemia rates were higher in non-Japanese (65%) versus Japanese (48%) patients. Early introduction of olanzapine during veliparib monotherapy maintenance phase may help prevent premature discontinuation of veliparib, via its potent antiemetic efficacy. CONCLUSIONS: Median progression-free survival was numerically longer in Japanese patients in the veliparib-throughout versus control arm, consistent with results in the overall study population. Pharmacokinetics were comparable between Japanese and non-Japanese patients. Data for the subgroup of Japanese patients were not powered to show statistical significance but to guide further investigation.

Gestational glycosuria, proteinuria, and borderline hypertension in pregnancy are predictors for the later onset of maternal chronic disease.

AIM: Although hypertensive disorders of pregnancy and gestational diabetes mellitus (DM) are risk factors for hypertension, DM, and kidney disease in later life, the association of gestational glycosuria, proteinuria, and borderline hypertension with these chronic diseases has been unclear. METHODS: This cross-sectional study was conducted between April 2017 and November 2020 at a Japanese tertiary hospital. Three variables listed in the Maternal and Child Health Handbook were analyzed: glycosuria, proteinuria, and systolic blood pressure (<130, 130-139, and ≥ 140 mmHg) during pregnancy. The incidences of DM, kidney disease, and hypertension self-reported by mothers of pregnant women on a questionnaire were assessed with logistic regression analysis. RESULTS: The 312 women completed the questionnaires an average of 35.8 ± 4.2 years after delivering their daughters. Risk for DM was significantly increased among women with glycosuria (adjusted odds ratio [aOR], 3.62; 95% confidence interval [CI], 1.21-10.9), and risk for kidney disease was significantly increased among women with proteinuria (aOR, 4.07; 95% CI, 1.29-12.9). Risk for hypertension was significant in women whose blood pressures were ≥ 140 mmHg (aOR, 4.26; 95% CI, 1.96-9.24), but the association between blood pressures of 130-139 mmHg and hypertension was not significant (aOR, 1.72; 95% CI, 0.95-3.11); however, a significant positive trend (p < 0.001) between increasing blood pressure and hypertension was observed. CONCLUSIONS: Gestational glycosuria, proteinuria, and increased blood pressure were associated with the development of maternal chronic diseases. These standard and inexpensive assessments may improve lifelong health management in women.

Study of the effects of in-person attendance at academic conferences on the health of the attendees under COVID-19 pandemic.

OBJECTIVE: To analyze the effects of in-person attendance at an academic conference held during the Covid-19 pandemic on the health of the attendees, as assessed based on symptoms such as fever and cough attributed to infection with the Covid-19 virus. METHODS: A questionnaire was used to survey the members of the Japan Society of Obstetrics and Gynecology (JSOG) about their health during the period from August 7 to August 12, 2022, after the 74th Annual Congress of the JSOG, which was held August 5 to 7. RESULTS: Our survey yielded responses from 3054 members (1566 of whom had attended the congress in person and 1488 of whom had not attended in person); 102 (6.5%) of the in-person attendees and 93 (6.2%) of the people who did not attend in person reported problems with their health. No statistically significant difference was found between these two groups (p = 0.766). In a univariate analysis of factors affecting the presence of health problems, attendees with age ≥60 years had significantly fewer health problems than attendees who were in their 20s (odds ratio: 0.366 [0.167-0.802; p = 0.0120]). In a multivariate analysis, attendees who had received four vaccine shots had significantly fewer health problems than attendees who had received three shots (odds ratio: 0.397 [0.229-0.690, p = 0.0010]). CONCLUSION: Congress attendees who took precautions at the congress to avoid being infected and who had a high vaccination rate did not develop significantly more health problems associated with in-person attendance at the congress.

Association between fetal sex and pregnancy outcomes among women with twin pregnancies: a multicenter cross-sectional study.

PURPOSE: To examine the frequency and to what extent fetal sex is associated with pregnancy outcomes among twin pregnancies, stratified by chorionicity. METHODS: This registry-based multicenter cross-sectional study was conducted using the Japan Society of Obstetrics and Gynecology perinatal database between 2007 and 2016. The sample population was restricted to women with twin pregnancies. The main pregnancy-related outcomes included preterm birth, very preterm birth, extremely preterm birth, preeclampsia, twin-to-twin transfusion syndrome (TTTS), and selective intrauterine growth restriction (s-IUGR). Birth weight, small for gestational age (SGA), and fetal death were also investigated. RESULTS: The primary analysis was performed based on 37,953 women, including 23,804 women with dichorionic diamniotic (DD) twins and 14,149 women with monochorionic diamniotic (MD) twins. Women with male/male DD twins had a significantly higher risk of preterm birth (adjusted risk ratio [aRR]: 1.07, 95% confidence interval [CI]: 1.03-1.10) and a lower risk of preeclampsia (aRR: 0.74, 95% CI: 0.62-0.88) than women with female/female DD twins. Women with male/male MD twins also had a significantly higher risk of preterm birth (aRR: 1.06, 95% CI: 1.04-1.09) than women with female/female MD twins. Risks of preeclampsia, TTTS, and s-IUGR did not differ by sex among MD pregnancies. Male SGA risk was significantly higher among male/male twins than among male/female DD twins. Among MD twins, risks of SGA and fetal death were significantly higher in male/male fetuses. CONCLUSIONS: This study demonstrated significant associations between fetal sex and several pregnancy outcomes in twin pregnancies, some of which differed by chorionicity.

Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup.

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer.