Japanese Journal of Clinical Oncology

Sentinel lymph node biopsy mapped with carbon nanoparticle suspensions in patients with cervical cancer: a systematic review and meta-analysis

Abstract Background The mapping technique significantly influences the detection rate of sentinel lymph nodes in cervical cancer. This study aims to evaluate the clinical efficacy of carbon nanoparticle suspensions (CNSs) in guiding sentinel lymph node biopsy (SLNB) for cervical cancer patients. Methods Systematic search of China National Knowledge Infrastructure, Cqvip, Wanfang, PubMed, EMBASE, Web of Science, and the Cochrane Library from inception until June 2024. Studies on cervical cancer patients receiving SLNB with CNSs are included. An individual participant data meta-analysis was conducted. The protocol was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42024569290). Results In total, 26 publications involving 1671 patients were analyzed. The overall detection rate of CNSs in SLNB for cervical cancer was 0.92, with bilateral and unilateral detection rates of 0.74 and 0.20, respectively. This detection rate exhibited a correlation with lesion size and the administration of neoadjuvant chemotherapy. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 0.93 (95% CI: 0.88–0.96, I2 = 35.89%), 1.00 (95% CI: 0.98–1.00, I2 = 90.01%), 216.84 (95% CI: 40.47–1161.85, I2 = 77.68%), and 0.07 (95% CI: 0.05–0.12, I2 = 54.96%), respectively. The area under the curve of the summary receiver operating characteristic curve was 0.97. No significant differences were found in subgroup analyses based on the method, time, and dose of CNS injection. However, significant publication bias was detected among the included studies based on Deeks’ funnel plot [Slope (Bias) = −15.61, P = .001]. Nonetheless, sensitivity analysis confirmed the reliability and stability of the results. Conclusions This meta-analysis highlights the accuracy and feasibility of using CNSs for SLNB in patients with cervical cancer, particularly for lesions <2.0 cm and patients untreated with neoadjuvant chemotherapy.

Is standard radical surgery necessary for elderly patients with early-stage epithelial ovarian carcinoma? ~Propensity score matched analysis~

Abstract Objective The impact of ‘standard full-staged radical surgery (SRS)’ on overall survival (OS) in elderly patients with early-stage epithelial ovarian cancer (EOC) remains unclear. In the current study, we investigated the impact of SRS on OS in elderly patients with early-stage EOC in a multicentric analysis using a propensity score (PS)-matching technique. Methods Between 1986 and 2017, 3227 patients with EOC were registered and accumulated by the Tokai Ovarian Tumor Study Group, consisting of 14 collaborating institutions, after a central pathological review. Among them, 204 elderly patients aged older than or equal to 65 years who had a stage I EOC were analyzed, including 72 patients who had received SRS (Group I) and 132 who had undergone non-SRS limited surgery (Group II). Oncologic outcomes were compared between the two groups using a PS-matching technique to adjust for various clinicopathologic risk factors. Results The median follow-up duration of all surviving patients was 55.9 months. Consequently, 54 patients (26.5%) developed recurrence. In addition, 33 patients (16.2%) died of the disease. In the original cohort, the 5-year OS rates of Groups I and II were 95.8 and 82.3%, respectively. We identified a marginally significant difference between the two groups (Log-rank: P = 0.086). In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in OS between the two groups [OS (Group I vs. II), HR: 0.766 (95% CI: 0.271–2.165), P = 0.615]. Conclusions After adjustment for clinicopathologic factors, non-SRS limited surgery may not worsen the oncologic outcome in elderly women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.

Adjuvant treatment of endometrial cancer today

Abstract Endometrial cancer frequently occurs in post-menopausal women, and the endometrium is a well-known site of cancer affecting women. Endometrial cancer is found with genital bleeding and often at an early stage. However, there are some risks of recurrence after hysterectomy. As a medical treatment after the diagnosis of endometrial cancer, appropriate adjuvant therapy is considered to lead to a decrease in the rate of recurrence and improvement of prognosis according to the determination of the cancer stage from the surgical and histopathological results. In this review, we describe post-operative adjuvant therapy administered for endometrial cancer and advanced disease, focusing on chemotherapy, radiation therapy and the combination of both. These treatments are divided according to the risk of recurrence as based primarily on the reported evidence.

Current management of hereditary cancer syndromes in ovarian and endometrial cancer: a Japanese study

Abstract Background To evaluate the current state of hereditary cancer syndrome management in patients with ovarian and endometrial cancer and to identify the barriers to uptake of genetic testing. Methods We conducted a cross-sectional multicenter study at five regional cancer centers in Japan, including 229 patients with ovarian cancer and 454 with endometrial cancer treated between January 2021 and December 2022. We assessed the proportion of patients who received information about hereditary cancer syndromes from gynecologists, underwent genetic counseling with genetic experts, and completed genetic testing; in addition, we explored the barriers to testing uptake. Results Among patients with ovarian cancer, 152 (66.4%) received information about hereditary cancer syndromes from their gynecologists, with 61 (26.6%) subsequently receiving genetic counseling and 58 (25.3%) undergoing genetic testing. By contrast, patients with endometrial cancer demonstrated markedly lower rates: only 76 (16.7%) received initial information, 22 (5.3%) accessed genetic counseling, and 13 (2.9%) completed genetic testing. Among patients who received information about hereditary cancer syndromes from their gynecologists, 38% with ovarian cancer and 14% with endometrial cancer underwent genetic testing. Among patients identified as high-risk for hereditary cancer syndromes through tumor profiling, 27.6% (8/29) with ovarian cancer and 70.6% (12/17) with endometrial cancer did not undergo genetic testing. Patient disinterest was the primary barrier to genetic testing among high-risk individuals. Conclusions The barriers to uptake of genetic testing arise primarily from inadequate provider communication and patient disinterest in hereditary cancer syndromes.

The prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer: a multi-center study with a propensity score-adjusted analysis

Abstract Objective Complete-staging surgery is recommended for stage IA ovarian cancer, but may be omitted for various reasons, including the preservation of fertility and an advanced age. We herein investigated the prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer. Methods We retrospectively collected data on 4730 patients with malignant ovarian tumors from the databases of multiple institutions and ultimately included 293 with stage IA epithelial ovarian cancer. Limited-staging surgery was defined as one that did not involve hysterectomy, systematic retroperitoneal lymphadenectomy or the collection of ascites cytology. We used an inverse probability of treatment weighting analysis with propensity scores and estimated the hazard ratios of recurrence and death with limited-staging surgery. Results In total, 176 out of 293 patients (39.9%) were assigned to the limited-staging surgery group. After propensity score adjustments, no significant differences were observed in recurrence-free survival or overall survival between the limited- and complete-staging surgery groups. Even in the subgroup analysis with age stratification, recurrence-free survival and overall survival were similar in the limited- and complete-staging surgery groups. Conclusions The present results indicate the limited prognostic impact of limited-staging surgery for stage IA epithelial ovarian cancer.

Estrogen/estrogen receptor promotes the proliferation of endometrial carcinoma cells by enhancing hMOF expression

AbstractBackgroundThis study aims to analyse the expression of human MOF in endometrial carcinoma cells and its relationship with estrogen and estrogen receptor and to investigate the effect of estrogen–human MOF on the malignant biological behaviours of endometrial carcinoma cells.MethodsThe expression of human MOF was detected in different endometrial tissues by immunohistochemistry. The effects of human MOF, human MOF combined with estrogen stimulation and estrogen plus anti-human MOF antibody blocking on the proliferation of endometrial carcinoma cells were evaluated by western blotting, real-time polymerase chain reaction, cell proliferation assay and cell cycle distribution. Bioinformatics was used to identify the correlations of human MOF and estrogen and involved pathways.ResultsThe expression levels of human MOF in endometrial carcinoma tissues were significantly higher than that in atypical hyperplasia and normal endometrial tissues. High expression of human MOF was associated with late-stage cancer, lymph node metastasis and short survival time, and it was also an independent prognostic risk factor for endometrial carcinoma. After human MOF knockdown, the proliferation, migration and invasive capacity of Ishikawa cells decreased and cell apoptosis increased. After stimulation with estrogen, the PI3K/Akt and Ras–Raf–MEK–ERK signalling pathways were activated, and the expression of the human MOF protein was increased. human MOF (KAT8) expression showed a positive correlation with ESR1 expression, and KAT8-associated genes were enriched in the cell cycle pathways and splicing pathways.ConclusionHuman MOF was highly expressed in endometrial carcinoma and associated with proliferation. Estrogen/estrogen receptor enhanced human MOF expression; promoted the proliferation, migration and invasion of Ishikawa cells; and inhibited cell apoptosis by activating the PI3K/Akt and Ras–Raf–MEK–ERK signalling pathways.

Clinical characterization of patients with gBRCA1/2 mutation-positive unresectable pancreatic cancer: a multicenter prospective study

Abstract Background Accumulating evidence has demonstrated platinum-based chemotherapy followed by maintenance therapy with a poly Adenosine diphosphate (ADP)-ribose polymerase inhibitor (olaparib) show benefits in unresectable pancreatic cancer with a germline (g)BRCA1/2 mutation. Evaluation of the germline BRCA1 and BRCA2 mutation is essential for making decisions on a treatment strategy for patients with unresectable pancreatic cancer. However, the detection rates of germline BRCA1 and BRCA2 mutations and efficacy of maintenance with olaparib remain undetermined, prospectively, in Japan. Methods & Results In this prospective analysis, the rate of germline BRCA1 and BRCA2 mutations and efficacy of chemotherapy were analyzed in 136 patients with pancreatic cancer who underwent BRACAnalysis® (85 patients) or FoundationOne® CDx (51 patients) between January 2020 and July 2022. A total of six patients (4.4%) had a germline BRCA1 and BRCA2 mutation. Five patients were treated with modified FOLFIRINOX and one with fluorouracil and oxaliplatin. All patients continued platinum-based chemotherapy for ˃4 months and were subsequently treated with olaparib as a maintenance therapy. The response rate to platinum-based chemotherapy in the germline BRCA1 and BRCA2 mutation-positive group was significantly better than that of the germline BRCA1 and BRCA2 mutation-negative group (66% vs 23%, P = 0.04). All patients harbouring a germline BRCA1 and BRCA2 mutation were able to switch to olaparib. The median progression-free survival using olaparib was 5.7 months (range 3.0–9.2). Conclusions The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies. An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.

Genetic characteristics of platinum-sensitive ovarian clear cell carcinoma

AbstractObjectiveMost 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.MethodsThe 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.ResultsOf 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.ConclusionThe 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.

Risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer: a single-institution 10-year experience

Abstract Background For women diagnosed with hereditary breast and ovarian cancer, the clinical guidelines recommend risk-reducing salpingo-oophorectomy at age 35–40 years or after completion of childbearing. However, there is limited information regarding the current status of risk-reducing salpingo-oophorectomy in Japan. Methods To clarify factors influencing decision-making for risk-reducing salpingo-oophorectomy among Japanese women diagnosed with hereditary breast and ovarian cancer and their clinical outcomes, we analyzed the medical records of 157 Japanese women with germline BRCA pathogenic variants (BRCA1 n = 85, BRCA2 n = 71 and both n = 1) at our institution during 2011–21. Specimens obtained from risk-reducing salpingo-oophorectomy were histologically examined according to the sectioning and extensively examining the fimbriated end protocol. Results The risk-reducing salpingo-oophorectomy uptake rate was 42.7% (67/157). The median age at risk-reducing salpingo-oophorectomy was 47 years. Older age, married state and parity were significantly associated with risk-reducing salpingo-oophorectomy (P < 0.001, P = 0.002 and P = 0.04, respectively). History of breast cancer or family history of ovarian cancer did not reach statistical significance (P = 0.18 and P = 0.14, respectively). Multivariate analyses revealed that older age (≥45 years) and married state may be independent factors associated with risk-reducing salpingo-oophorectomy. Interestingly, the annual number of risk-reducing salpingo-oophorectomy peaked in 2016–17 and has increased again since 2020. The rate of occult cancers at risk-reducing salpingo-oophorectomy was 4.5% (3/67): ovarian cancer (n = 2) and serous tubal intraepithelial carcinoma (n = 1). Conclusion Age and marital status significantly affected decision-making for risk-reducing salpingo-oophorectomy. This is the first study to suggest possible effects of Angelina Jolie’s risk-reducing salpingo-oophorectomy in 2015 and the National Health Insurance introduced for risk-reducing salpingo-oophorectomy in 2020. The presence of occult cancers at risk-reducing salpingo-oophorectomy supports clinical guidelines recommending risk-reducing salpingo-oophorectomy at younger ages.

Significance of tumor size and number of positive nodes in patients with FIGO 2018 stage IIIC1 cervical cancer

Abstract Objective This study aimed to investigate the prognostic significance of tumor size and number of positive pelvic lymph nodes (PLN) in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC1 cervical cancer patients. Methods Clinical data from 626 women with cervical cancer treated at Osaka International Cancer Center in 2010–2020 were retrospectively reviewed. Using the cutoff value obtained on the receiver operating characteristic analysis, the prognostic significance of tumor size and number of positive PLN in stage IIIC1 patients was first evaluated via uni- and multivariate analyses. Then, the impact of incorporating tumor size and number of positive PLN into the FIGO staging system was investigated using the Kaplan–Meier method. Results Among 196 women with Stage IIIC1 disease, larger tumors (>4 cm) and multiple PLN metastases (≥4) were independent predictors of progression-free survival (PFS) in patients with stage IIIC1 cervical cancer. The PFS of patients with stage IIIC1 disease was inversely associated with the number of risk factors. Although patients with stage IIIC1 disease had significantly increased survival rates compared to those with stage IIIA or IIIB disease in the original FIGO 2018 staging system, this reversal phenomenon was resolved by incorporating larger tumors (>4 cm) and multiple PLN metastases (≥4) into the revised staging system. Conclusions Incorporating tumor size and number of metastatic lymph nodes into the FIGO staging system allows additional risk stratification for women with stage IIIC1 cervical cancer and improves survival prediction performance.

Upregulation of cyclase-associated actin cytoskeleton regulatory protein 2 in epithelial ovarian cancer correlates with aggressive histologic types and worse outcomes

Abstract Objective Cyclase-associated actin cytoskeleton regulatory protein 2 (CAP2) regulates actin dynamics to control cell cycles and cell migration. CAP2 overexpression contributes to cancer progression in several tumor types; however, the role of CAP2 expression in ovarian cancer remains unclear. This study aimed to clarify the significance of CAP2 expression in epithelial ovarian tumor. Methods We evaluated CAP2 expression in ovarian cancer cell lines using quantitative real-time polymerase chain reaction, western blotting and immunocytochemistry and examined the effect of CAP2 silencing in migration and proliferation assays. CAP2 immunohistochemistry was conducted using tissue specimens from 432 ovarian carcinoma patients; a further 55 borderline and benign 65 lesions were analyzed. CAP2 expression levels were defined as low, intermediate or high, for correlation analysis with clinicopathological factors. Results CAP2 expression was significantly higher in cell lines from Type II ovarian cancer than in those in Type I, and knockdown of CAP2 showed decreased migration and proliferation. Higher levels of CAP2 expression in human tissues were associated with Type II histology, residual lesion, lymph node metastasis, ascites cytology and higher clinical stage. High CAP2 expression levels were observed in 26 (23.4%) of 111 Type II ovarian cancers and in 16 (5.0%) of 321 Type I cancers but not in any borderline or benign lesions. Multivariate analyses showed that CAP2 expression in ovarian cancer is an independent prognostic factor for recurrence-free survival (P = 0.019). Conclusion CAP2 expression is upregulated in aggressive histologic types of epithelial ovarian cancer and serves as a novel prognostic biomarker for patient survival.

Clinical significance of primary debulking surgery and neoadjuvant chemotherapy-interval debulking surgery in advanced ovarian cancer

Abstract Primary debulking surgery followed by platinum-based chemotherapy remains the standard treatment of patients with stage III–IV epithelial ovarian cancer. Neoadjuvant chemotherapy is an alternative treatment regimen that can be considered in selected patients. Complete cytoreduction, both through primary debulking surgery and interval debulking surgery, has a major positive effect on survival and should be the goal, even if this requires extensive surgery. When thorough assessment of tumor spread and performance status of the patient indicates that complete primary cytoreduction is not feasible without unacceptable morbidity, then alternative therapeutic strategies, such as neoadjuvant chemotherapy, must be considered. Such patients can be offered the option of interval debulking surgery after checking their response to neoadjuvant chemotherapy and resolution of the initial obstacles for primary debulking surgery (i.e. complete response of irresectable disease and improvement of the performance status). Current evidence suggests that a selected group of patients with International Federation of Gynecology and Obstetrics stage III–IV ovarian cancer will benefit from NAC-IDS. Research is ongoing to identify patients who might derive the greatest benefit from neoadjuvant chemotherapy followed by interval debulking surgery, instead of primary debulking surgery, on the basis of radiological, genetic, pathological, and immunological variables. In this review, we discuss current knowledge about the clinical significance of primary debulking surgery and neoadjuvant chemotherapy in advanced ovarian cancer and discuss unanswered questions in the field.

Prognosis of BRCA1/2-negative breast cancer patients with HBOC risk factors compared with sporadic breast cancer patients without HBOC risk factors

Abstract Objective Demands for genetic counseling with BRCA1/2 examination have markedly increased. Accordingly, the incidence of uninformative results on BRCA1/2 mutation status has also increased. Because most patients examined for BRCA1/2 mutation have a high risk of hereditary breast and/or ovarian cancer, many patients suffer psychological distress even when the BRCA1/2 result is negative. We compared oncological outcomes between BRCA1/2-negative breast cancer with high risk of hereditary breast and/or ovarian cancer and sporadic breast cancer without risk of hereditary breast and/or ovarian cancer. Methods The criteria for high risk for hereditary breast and/or ovarian cancer were defined as family history of breast and/or ovarian cancer in first- or second-degree relative, early onset breast cancer at <35 years old and bilateral breast cancer. Patients were matched maximally 1:3 into those who identified as negative for BRCA1/2 mutation with risk of hereditary breast and/or ovarian cancer (study group) and those who were not examined for BRCA1/2 mutation without risk for hereditary breast and/or ovarian cancer (control group). Matched variables were pathologic stage, estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status. Results All matching variables were successfully matched. Median follow-up duration was 57.8 months. There was no significant difference between the groups in disease-free survival (log-rank P = 0.197); however, the study group showed significantly better overall survival and breast cancer-specific survival (both P < 0.0001). We conducted subgroup analysis in the middle-aged group (36–54) and showed no significant difference for disease-free survival (P = 0.072) but significantly better overall survival and breast cancer-specific survival in the study group (P = 0.002 and P < 0.0001). Conclusions BRCA1/2-negative breast cancer patients who had hereditary breast and/or ovarian cancer risk factors showed similar disease-free survival and better overall survival and breast cancer-specific survival compared with those with sporadic breast cancer without hereditary breast and/or ovarian cancer risk factors.

The impact of lymphadenectomy on prognosis and survival of clinically apparent early-stage malignant ovarian germ cell tumors

Abstract Objective To determine the impact of lymphadenectomy (LND) on survival of clinically apparent early-stage malignant ovarian germ cell tumors (MOGCTs). Methods We retrospectively analyzed the survival of patients who were diagnosed with the three most common histopathology types of malignant ovarian germ cell tumors (yolk sac tumor, dysgerminoma and immature teratoma) and with clinical stage I and II disease, and treated at Sun Yat-sen University Cancer Center between 1 January 1970 and 30 September 2018. Results There were 227 stage I, 28 stage II and one stage IIIA cases after surgery. One hundred and twenty-six patients underwent lymphadenectomy and 130 did not. Only one lymph node metastasis (0.8%) was found in the lymphadenectomy group. Two hundred and twenty-four out of 256 patients (87.5%) received postoperative chemotherapy. There were five relapses (4.0%) in the lymphadenectomy group and four (3.1%) in the non-lymphadenectomy group. Median follow-up was 68 months (range, 1–388). The 10-year disease-free survival rate in the lymphadenectomy group and non-lymphadenectomy group were 88.2 and 96.4%, respectively (P = 0.412); the 10-year overall survival rate in the two groups were 95.7 and 98.2%; respectively (P = 0.798). The results showed that lymphadenectomy did not improve patient survival. Conclusions Lymphadenectomy may have little impact on survival in patients with clinically apparent early-stage malignant ovarian germ cell tumors and may be omitted in the surgical treatment.

Prognostic impact of pelvic and para-aortic lymphadenectomy on clinically-apparent stage I primary mucinous epithelial ovarian carcinoma: a multi-institutional study with propensity score-weighted analysis

AbstractBackgroundThe exact impact of full-staging lymphadenectomy on patients with primary mucinous epithelial ovarian carcinoma confined to the ovary is still unclear. In this study, we investigated the prognostic impact of lymphadenectomy covering both pelvic and para-aortic lymph nodes in patients with clinically-apparent stage I mucinous epithelial ovarian carcinoma, using data from multi-institutions under a central pathological review system and analyses with a propensity score-based method.MethodsWe conducted a regional multi-institutional retrospective study between 1986 and 2017. Among 4730 patients with malignant ovarian tumors, a total of 186 women with mucinous epithelial ovarian carcinoma were eligible. We evaluated differences in survival outcomes between patients with both pelvic and para-aortic lymphadenectomy and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation. To analyze the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables.ResultsFifty-five patients received both pelvic and para-aortic lymphadenectomy. With PS-based adjustment, both pelvic and para-aortic lymphadenectomy did not have additive effects regarding overall survival (P = 0.696) and recurrence-free survival (P = 0.978). Multivariate analysis similarly showed no significant impact of both pelvic and para-aortic lymphadenectomy on their prognosis.ConclusionsThe effect of pelvic and para-aortic lymphadenectomy is limited for clinically-apparent stage I primary mucinous epithelial ovarian carcinoma as long as full peritoneal and clinical lymph node evaluations are conducted. The results of this study should be used as the basis for additional studies, including prospective trials.

Debulking surgery for malignant tumors: the current status, evidence and future perspectives

Abstract Debulking surgery, also called cytoreductive surgery, is a resection of the tumor as much as possible and an intended incomplete resection for unresectable malignant tumors. Since the most important principle in surgical oncology is complete R0 resection, debulking surgery goes against the basic principle and obscures the concept of operability. However, debulking surgery has been advocated for various types of advanced malignant tumors, including gynecological cancers, urological cancers, gastrointestinal cancers, breast cancers and other malignancies, with or without adjuvant therapy. Positive data from randomized trials have been shown in subsets of ovarian cancer, renal cell carcinoma, colorectal cancer and breast cancer. However, recent trials for renal cell carcinoma, colorectal cancer and breast cancer have tended to show controversial results, mainly according to the survival improvement of nonsurgical systemic therapy alone. On the other hand, debulking surgery still has a therapeutic role for slow-growing and borderline malignant tumors, such as pseudomyxoma peritonei and thymomas. The recent understanding of tumor heterogeneity and clonal evolution responsible for malignancy and drug resistance indicates that select patients may obtain prolonged survival by the synergistic effect of debulking surgery and novel systemic therapy. This review aimed to describe the current status and evidence of debulking surgery in a cross-organ manner and to discuss future perspectives in the current era with advances in systemic therapy.

Clinical implication of psoas muscle mass measurement for predicting death within 3 months in patients with incurable uterine cervical or corpus malignancy

Abstract Objective The aim of this study was to find a clinical marker for identifying refractory cancer cachexia. Methods We analyzed computed tomography imaging data, which included the third lumbar vertebra, from 94 patients who died of uterine cervix or corpus malignancy. The time between the date of examination and date of death was the most important attribute for this study, and the computed tomography images were classified into >3 months before death and ≤ 3 months before death. Psoas muscle mass index was defined as the left–right sum of the psoas muscle areas (cm2) at the level of third lumbar vertebra, divided by height squared (m2). Results A data set of 94 computed tomography images was obtained at baseline hospital visit, and a data set of 603 images was obtained at other times. One hundred (16.6%) of the 603 non-baseline images were scanned ≤3 months before death. Mean psoas muscle mass index change rates at >3 months before death and ≤3 months before death were −1.3 and −20.1%, respectively (P < 0.001). Receiver operating characteristic curve analysis yielded a cutoff value of −13.0%. The area under the curve reached a moderate accuracy level (0.777, 95% confidence interval 0.715–0.838). When we used the cutoff value to predict death within 3 months, sensitivity and specificity were 74.0 and 82.1%, respectively. Conclusions Measuring change in psoas muscle mass index might be useful for predicting cancer mortality within 3 months. It could become a potential tool for identifying refractory cancer cachexia.

Is salvage radiotherapy optimal to patients with occult cervical cancer undergoing inadvertent simple hysterectomy? A propensity score-matched analysis of a nationwide clinical oncology database

Abstract Objective We used National Cancer Institute’s Surveillance, Epidemiology and End Result database to assess the role of salvage radiotherapy for women with unanticipated cervical cancer after simple hysterectomy. Methods Patients with non-metastatic cervical cancer and meeting inclusion criteria were divided into three groups based on treatment strategy: simple hysterectomy, salvage radiotherapy after hysterectomy and radical surgery. Parallel propensity score-matched datasets were established for salvage radiotherapy group vs. simple hysterectomy group (matching ratio 1: 1), and salvage radiotherapy group vs. radical surgery group (matching ratio 1:2). The primary endpoint was the overall survival advantage of salvage radiotherapy over simple hysterectomy or radical surgery within the propensity score-matched datasets. Results In total, 2682 patients were recruited: 647 in the simple hysterectomy group, 564 in the salvage radiotherapy group and 1471 in the radical surgery group. Age, race, histology, grade, FIGO stage, insured and marital status and chemotherapy were comprised in propensity score-matched. Matching resulted in two comparison groups with neglectable differences in most variables, except for black race, FIGO stage III and chemotherapy in first matching. In the matched analysis for salvage radiotherapy vs. simple hysterectomy, the median follow-up time was 39 versus 32 months. In the matched analysis for salvage radiotherapy vs. radical surgery, the median follow-up time was 39 and 41 months, respectively. Salvage radiotherapy (HR 0.53, P = 0.046) significantly improved overall survival compared with simple hysterectomy, while salvage radiotherapy cannot achieve similar overall survival to radical surgery (HR 1.317, P = 0.045). Conclusions This is the largest study of the effect of salvage radiotherapy on overall survival in patients with unanticipated cervical cancer. Salvage radiotherapy can improve overall survival compared with hysterectomy alone, while cannot achieve comparable survival to radical surgery.

Gastric-type adenocarcinoma of the uterine cervix: clinical features and future directions

Abstract The concept of gastric-type mucinous carcinoma of the uterine cervix (GAS) has been accepted worldwide because of its aggressive clinical behaviour and the absence of high-risk human papilloma virus infection. The World Health Organization (WHO) 2020 classification divides cervical tumours into two categories: human papilloma virus-associated and human papilloma virus-independent. Hence, GAS is now classified as an human papilloma virus-independent gastric type. Because clinical studies have reported that GAS is refractory to conventional treatments such as chemotherapy and radiotherapy, especially at an advanced stage, and has aggressive features with widespread dissemination to unusual sites, such as the omentum, peritoneum and distant organs, it is urgent to establish new treatment strategies by comparing the molecular profiles of human papilloma virus-associated adenocarcinomas. A series of genetic mutations characteristic to GAS encourage the development of future treatment strategies such as targeted therapy and immunotherapy.

High cost of chemotherapy for gynecologic malignancies

Abstract Background The prognosis of gynecological malignancies has improved with the recent advent of molecularly targeted drugs and immune checkpoint inhibitors. However, these drugs are expensive and contribute to the increasing costs of medical care. Methods The Japanese Clinical Oncology Group (JCOG) Health Economics Committee conducted a questionnaire survey of JCOG-affiliated facilities from July 2021 to June 2022 to assess the prevalence of high-cost regimens. Results A total of 57 affiliated facilities were surveyed regarding standard regimens for advanced ovarian and cervical cancers for gynecological malignancies. Responses were obtained from 39 facilities (68.4%) regarding ovarian cancer and 37 (64.9%) concerning cervical cancer, with respective case counts of 854 and 163. For ovarian cancer, 505 of 854 patients (59.1%) were treated with regimens that included PARP inhibitors, costing >500 000 Japanese yen monthly, while 111 patients (13.0%) received treatments that included bevacizumab, with costs exceeding 200 000 Japanese yen monthly. These costs are ~20 and ~10 times higher than those of the conventional regimens, respectively. For cervical cancer, 79 patients (48.4%) were treated with bevacizumab regimens costing >200 000 Japanese yen per month, ~10 times the cost of conventional treatments. Conclusions In this survey, >70% of patients with ovarian cancer were treated with regimens that included poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors or bevacizumab; ~50% of patients with cervical cancer were treated with regimens containing bevacizumab. These treatments were ~10 and ~20 times more expensive than conventional regimens, respectively. These findings can inform future health economics studies, particularly in assessing cost-effectiveness and related matters.

Projection of the number of new cases of ovarian cancer in the world

Projection of the number of new cases of uterine cancer in the world

The use of bevacizumab is correlated with improved post-progression survival in advanced recurrent ovarian cancer

Abstract Background The recent improvements in anti-cancer therapy following first-line treatment can potentially impact post-progression survival. We evaluated the factors that influence post-progression survival in advanced recurrent ovarian cancer. Methods Eighty-nine patients who underwent first-line treatment between June 2005 and December 2017 were included. The post-progression survival was defined as the difference between overall survival and initial progression-free survival. The effects of age, histology, stage, optimal surgery, secondary debulking surgery, bevacizumab administration, platinum sensitivity, and olaparib maintenance in recurrence were compared and independent risk factors were determined. Results The median follow-up duration was 60.0 months (range: 2–181). Platinum-sensitive recurrence had longer post-progression survival than platinum-resistant (P < 0.001). Inclusion of bevacizumab in first-line treatment did not produce a significant difference in post-progression survival (P = 0.462). Secondary debulking surgery (P = 0.013), bevacizumab administration (P < 0.001), and olaparib maintenance (P = 0.001) during recurrence increased post-progression survival. In multivariate analysis, histologies other than serous or endometrioid (hazard ratio = 2.389; 95% confidence interval = 1.200–4.754; P = 0.013) and non-bevacizumab usage in recurrence (hazard ratio = 4.484; 95% confidence interval = 1.939–10.370; P < 0.001) were independently correlated with poorer prognosis. Bevacizumab administration beyond progressive disease elicited improved post-progression survival (P < 0.001). In patients receiving bevacizumab in first-line treatment, exclusion of bevacizumab in the recurrent therapy (hazard ratio = 5.507; 95% confidence interval = 2.301–12.124; P < 0.001) was independently correlated with poorer prognosis. Conclusions The continuous use of bevacizumab beyond progressive disease improves post-progression survival suggesting its important role in first-line and recurrence treatment for ovarian cancer.

Expression and prognostic significance of NKD2 in ovarian cancer

AbstractPurposeNaked2 (NKD2) is a negative regulator of Wnt signaling pathway and associates with transforming growth factor secretion. The role of NKD2 in ovarian cancer is unknown.Patients and methodsGene expression profiles were measured and compared in nine patients by RNA sequencing. NKD2 expressions in ovarian cancer were measured by reverse transcription polymerase chain reaction and western blot. Tissue slides of 79 patients were stained and scored for NKD2 expression. In vitro experiments were conducted to explore the role of NKD2 in ovarian cancer. The prognostic role of NKD2 was evaluated by survival analysis.ResultsNKD2 was upregulated in patients with better survival by mRNA and protein expression. Patients were classified as NKD2-high group (n = 30) and NKD2-low group (n = 49) according to immunohistochemical score. High NKD2 was correlated with lower recurrence rate (P = 0.002) and higher percentage of platinum-sensitive recurrence (P = 0.006). Median progression-free survival was significantly longer for NKD2-high patients than NKD2-low patients (49.1 vs.14.1 months, P < 0.001). Accordingly, there was a significantly difference in terms of overall survival time between two groups (hazard ratio: 3.04; 95% confidence interval: 1.58–5.85, P < 0.001). Multivariate regression suggested that NKD2 was independently prognostic factors in terms of progression-free survival (hazard ratio: 2.91; 95% confidence interval: 1.61–5.27, P < 0.001) and overall survival (hazard ratio: 3.6; 95% confidence interval: 1.80–7.21, P < 0.001). In vitro studies further demonstrated that NKD2 suppressed ovarian cancer cell proliferation, colony formation and cell migration.ConclusionNKD2 is a novel prognostic marker and could suppress tumor progression in ovarian cancer.

Retrospective evaluation of risk-reducing salpingo-oophorectomy for BRCA1/2 pathogenic variant carriers among a cohort study in a single institution

Abstract Background Risk-reducing salpingo-oophorectomy is performed for the primary prevention of ovarian cancer in patients with hereditary breast–ovarian cancer syndrome. We performed risk-reducing salpingo-oophorectomy for the first time in Japan in 2008, and we experienced 20 cases of risk-reducing salpingo-oophorectomy through 2019. In the past, the use of risk-reducing salpingo-oophorectomy in Japan was restricted because it was not covered by a Japanese National Health Insurance. Since April 2020, risk-reducing salpingo-oophorectomy has been covered by insurance for patients with breast–ovarian cancer syndrome and pre-existing breast cancer, and this surgery is expected to become more widely implemented in Japan. Methods To contribute to the widespread use of risk-reducing salpingo-oophorectomy in the future, we retrospectively reviewed 20 cases of risk-reducing salpingo-oophorectomy at our hospital cohort study to clarify the issues in its implementation. Results The variant genes for which risk-reducing salpingo-oophorectomy was indicated were BRCA1 and BRCA2 in 13 (65%) and 7 patients (35%), respectively. The median age at which risk-reducing salpingo-oophorectomy was performed was 49 years (range, 38–58), 13 patients (65%) had gone through menopause, and 16 patients (80%) had a history of breast cancer. Of the five patients (25%) with vasomotor symptoms, four received Chinese medicine, and only one received hormone replacement therapy. Occult cancer was detected in the removed ovaries in two patients (10%), although no postoperative peritoneal carcinogenesis has been observed to date. Conclusions Women who paid for risk-reducing salpingo-oophorectomy out of pocket were older than the recommended age at which the procedure should be performed, and this may explain the higher rate of occult cancers than previously reported. We need to perform risk-reducing salpingo-oophorectomy at the recommended age to ensure that the procedure is effective for primary prevention.

Current trends in chemotherapy for advanced ovarian cancer

Abstract Chemotherapy for advanced ovarian cancer has progressed over the past several decades with the introduction of cytotoxic agents. Various methods, including single agents, combination therapy and changes in the method of administration, have been validated in many clinical trials and have been combined in an attempt to improve the prognosis of advanced ovarian cancer. In recent years, molecular-targeted agents have been added to cytotoxic agents as a treatment option for maintenance therapy; however, their efficacy has been limited, and further development of treatment options is expected. The advent of poly(ADP-ribose) polymerase inhibitors has considerably improved prognosis and has affected treatment strategies for advanced ovarian cancer over the past few years. With the addition of the recently introduced immune checkpoint inhibitors, future treatment strategies for advanced ovarian cancer may become more complex. In this review, we introduce the latest advances in chemotherapy for advanced ovarian cancer and discuss future perspectives.

Identification of epigenetic genes for predicting prognosis and immunotherapy response of ovarian cancer

Abstract Background Epigenetic factors play a critical role in tumour development and progression. The aim of this study was to construct and validate a robust epigenetic gene set-based signature for predicting prognosis of ovarian cancer. Methods By using LASSO Cox regression model, we screened out the most useful prognostic epigenetic factors and a prognostic signature was developed based on them. Survival receiver operating characteristic was used to test the prognostic accuracy of signature in training and validation sets. The associations between the risk scores and immune cell infiltration, tumour purity, immune checkpoint inhibitor genes expression were also assessed in ovarian cancer . Results A total of 26 epigenetic factors were identified to develop the prognostic signature. In the training set, the prognosis of high-risk patients was strikingly poorer than that of low-risk patients (hazard ratio: 2.11, 95% confidence interval: 1.65–2.72, P < 0.001). Similar results were further observed in the internal validation set (hazard ratio: 1.69, 95% confidence interval: 1.07–2.63, P = 0.020) and external validation set (hazard ratio:1.95, 95% confidence interval: 1.41–2.69; P < 0.001). Survival receiver operating characteristic at 5 year showed the epigenetic signature (area under the curve = 0.700) performed better than other clinical features in predicting prognosis. Distinct difference in immune activation related pathways, immune cells infiltration, tumour purity reflected by immune and stromal score and immune checkpoint inhibitor genes gene expression was observed between high- and low-risk samples. Conclusions This study constructed an epigenetic signature that was capable of predicting postoperative outcomes and may also serve as potential biomarker for immunotherapy responses for ovarian cancer.

Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy

Abstract Objective To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients. Methods We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues. Results In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230. Conclusion The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.

Risks of extracolonic tumours in patients with Lynch syndrome: a nationwide multicentre cohort study in Japan

Abstract Background Lynch syndrome (LS) is a genetic condition characterized by an increased risk of colorectal cancer and other associated malignancies. With the limited information available regarding extracolonic tumours, this study aimed to explore tumours associated with LS in the Japanese population and discuss the potential differences in causative pathogenic genetic variants and their phenotypic expression compared with Western cohorts. Methods This multicentre retrospective cohort study analysed 316 genetically confirmed LS cases (148 men and 168 women) from 13 institutions. We analysed the incidence of extracolonic LS-associated tumours according to sex and gene variants, including MLH1 (124 cases), MSH2 (139), MSH6 (37), PMS2 (11), and EPCAM (5). Extracolonic tumour types assessed included 88 endometrial, 47 gastric, 27 small intestinal, 21 urothelial, 13 ovarian, 8 biliary tract, 5 brain, three pancreatic, and 18 other cancers. Results The cumulative risk by age 70 was 66% for endometrial cancer, 23% for gastric cancer, 14% for small intestine cancer, 10% for upper urothelial cancer, 9% for ovarian cancer, and 3% for biliary tract cancer. The mean age at diagnosis varied, with gastric and small intestinal cancers presenting later in life than urothelial, endometrial, and ovarian cancers. Men had a higher risk of most cancers, except for gynaecological cancers. Gastric and urothelial cancers were primarily associated with MLH1 and MSH2 pathogenic variants. Conclusion This study highlights the need for tailored surveillance programmes based on cancer type, sex, causative pathogenic genetic variants, and risk profiles to effectively manage LS in Japan.

Current status of vulvar cancer in Japan: analysis of the Japanese Gynecologic Oncology Group nationwide survey study

Abstract This review provides an overview of the current status of vulvar cancer in Japan, focusing specifically on the findings from the Japanese Gynecologic Oncology Group nationwide survey study. The author offers a comprehensive summary of the current status of vulvar cancer in Japan, along with an exploration of the molecular mechanisms underlying the disease. Notably, the review highlights the concerning upward trend of vulvar cancer in older age groups and advanced stages in Japan. The author concludes that addressing these challenges may require the centralization of resources and expertise. By bridging knowledge gaps and identifying areas for improvement, this review contributes to enhancing the understanding and management of vulvar cancer in Japan.

Adjuvant radiotherapy for cervical cancer in South Korea: a radiation oncology survey of the Korean Radiation Oncology Group (KROG 20-06)

Abstract Objective Radiation therapy plays an important role in adjuvant treatment for surgically treated cervical cancer with adverse pathological findings. This was the first study to evaluate current practices of adjuvant radiation therapy among centres affiliated with the Korean Radiation Oncology Group. Methods A survey containing specific questions on the demographics in 2019, indications of adjuvant treatment, radiation therapy field, prescription radiation therapy dose, boost radiation therapy and chemotherapy was sent out by e-mail to 93 centres. Results The overall response rate was 62.4%. Regarding radiation therapy techniques, intensity-modulated radiation therapy was adopted in most institutions (41/58, 70.7%). Various risk group criteria were selected for adjuvant radiation therapy and concurrent chemoradiation therapy. One or two risk factors among tumour size, depth of invasion and lymphovascular invasion were considered for adjuvant radiation therapy by 20.7 and 60.3% of the respondents, respectively. The following criteria for concurrent chemoradiation therapy were considered by 60.3% of the respondents: parametrial extension, positive resection margin or lymph node metastasis. Various upper borders were preferred for pelvic radiation therapy by the institutions, and a total dose of 50.4 Gy in 28 fractions was the most prescribed dose scheme (37/58, 63.8%). Lymph node bed boost radiation therapy and vaginal cuff brachytherapy were considered for selected patients by 22.4% (13/58) and 60.3% (35/58) of the institutions. Conclusion This survey demonstrated the practice patterns of adjuvant treatment that are prevalent in the field of radiation oncology among members of the Korean Radiation Oncology Group. These findings warrant further consensus on radiation therapy guidelines in the context of adjuvant treatment for cervical cancer.

Emerging technologies for cervical cancer screening

Abstract Cervical cancer remains a concern worldwide, and cervical cancer screening plays an important role in reducing the burden of this disease. Although cytology is still the main strategy for cervical cancer screening, it has gradually changed to human papillomavirus testing. The specificity of human papillomavirus testing is lower than that of cytology, which leads to an increased rate of colposcopy after positive results. To decrease colposcopic examinations, an efficient triage method is needed for human papillomavirus screening. New biomarkers have been developed and evaluated for primary screening and triage of abnormal cytology or human papillomavirus-positive results. Their sensitivity and specificity were estimated and compared with those of cytology. In the present study, the following new techniques were examined: p16/Ki67 dual staining, DNA methylation, micro-ribonucleic acid, chromosomal abnormalities, Claudins and DNA ploidy. Evaluation studies of p16/Ki67 dual staining and DNA methylation were more advanced than those of other options. When p16/Ki67 dual staining was used for triage for human papillomavirus testing, the sensitivity of 2 or greater cervical intraepithelial neoplasia (CIN2+) detection was higher than that of cytology without decreased specificity. Although there are several types of DNA methylation, sensitivity and specificity were moderate for detecting CIN2+. S5 classifier is a commercialized product that consists of viral methylation, and high sensitivity with decreased specificity has been reported. Considering its combination with self-sampling, DNA methylation is a highly anticipated technique along with human papillomavirus testing for the next generation of cervical cancer screening. However, the backgrounds for cervical cancer screening differ among countries and further study is needed to identify the best available method.

Regional differences in human papillomavirus type 52 prevalence among Japanese women with cervical intraepithelial neoplasia

Abstract Although geographical differences in the distribution of human papillomavirus genotypes have been observed worldwide, no studies have reported on national differences in the prevalence of human papillomavirus types in Japan. Here, we report a cross-sectional study to explore regional differences in the prevalence of human papillomavirus types among Japanese women with cervical intraepithelial neoplasia or invasive cervical cancer. Using human papillomavirus genotyping data from the nationwide prospective study on human papillomavirus vaccine effectiveness, we compared the frequency of detection of 15 high-risk and two low-risk human papillomavirus types in each disease category between the women who visited hospitals located in eastern Japan and those who visited hospitals located in western Japan. The risk of cervical intraepithelial neoplasia progression was assessed by calculating a prevalence ratio of each human papillomavirus type for cervical intraepithelial neoplasia grade 2/3 versus grade 1. Among the human papillomavirus types studied, human papillomavirus 52 was detected significantly more frequently in western hospitals than in eastern hospitals in cervical intraepithelial neoplasia grade 1 patients, but was less frequent in cervical intraepithelial neoplasia grade 2/3. The prevalence of particular human papillomavirus types was not significantly different between patients in hospitals in eastern Japan and those in hospitals in western Japan for invasive cervical cancer. In both eastern and western hospitals, a higher risk of cervical intraepithelial neoplasia progression was observed in patients infected with human papillomavirus 16, 31 or 58. In contrast, there was a significantly higher prevalence of human papillomavirus 52 infection in women with cervical intraepithelial neoplasia grade 2/3 than in those with cervical intraepithelial neoplasia grade 1 in eastern hospitals (prevalence ratio, 1.93; 95% confidence interval, 1.48–2.58), but not in western hospitals (prevalence ratio, 1.03; 95% confidence interval, 0.83–1.30). Regional differences of human papillomavirus 52 prevalence in cervical intraepithelial neoplasia lesions may exist and emphasize the importance of continuous monitoring of human papillomavirus type prevalence throughout the country in order to accurately assess the efficacy of human papillomavirus vaccines.

Prognostic factors of 2018 FIGO stage IB-IIA cervical cancer with absence of high/ intermediate surgical-pathological risk factors

Abstract Objective This retrospective analysis of a real-world database of open radical hysterectomy in Japan aimed to reveal the clinicopathological findings and clinical outcomes of low-risk patients with stage IB-IIA cervical cancer. Methods A total of 1143 stage IB1, IB2 and IIA1 (reclassified by FIGO 2018 staging system) patients with cervical cancer who underwent radical hysterectomy between January 2004 and December 2008 from the Japanese Gynecologic Oncology Group database were analyzed. Low-risk patients were defined as those without a tumor size exceeding 4 cm, parametrial tumor involvement, deep (outer half) stromal invasion, lymphovascular space invasion or lymph nodal metastasis. Results 61.2% (772/1262) patients with stage IB1, 32.1% (229/932) with stage IB2 and 16.9% (72/294) of stage IIA1 were classified into the low-risk group. The 5-year overall survival and disease-free survival rates were 98.4 and 93.7%, respectively. Histological classification did not affect the survival rates, but stage IIA cases had significantly lower overall survival and disease-free survival (83.5 and 93.8%, respectively) than stage IB cases. The independent prognostic factors for disease-free survival were older age (≧50), histology, clinical stage and clinical stage as independent prognostic factors for overall survival. Regarding recurrence, older age, non-SCC and stage IIA1 were independent risk factors for local recurrence, but stage IIA1 was the only independent risk factor for distant metastasis. Conclusion We found that stage IIA1 was the strongest risk factor for survival and recurrence of low-risk uterine cervical cancer (FIGO, 2018). In low-risk cases, stage IIA1 should be considered separately from stage IB.

Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial

Abstract Objective This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer. Methods Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%. Results Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8–86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3–80.3 Gy) and bladder D2cc was 69.8 Gy (38.9–84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036). Conclusion The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.

A preliminary study on the detection of lymph node metastasis in cervical cancer using a quantitative RT-PCR assay

Abstract Objective This preliminary study aimed to assess the detection accuracy of sentinel lymph node metastasis in cervical cancer using quantitative reverse transcriptase-polymerase chain reaction. Methods We collected cervical cancer tissues and 70 pelvic lymph node samples from patients with cervical cancer. The quantitative reverse transcriptase-polymerase chain reaction assay was performed to investigate the expression of cytokeratin 19 mRNA in cervical cancer tissues and determine the cutoff value of cytokeratin 19 mRNA between the non-metastatic and metastatic lymph nodes. Results The expression of cytokeratin 19 mRNA in cancer tissues was detected in all (71/71) the tumours, with a median copy number of 7.56 × 105/μl of RNA by quantitative reverse transcriptase-polymerase chain reaction. Sixteen lymph nodes were diagnosed as positive by pathological examination. The median copy numbers of cytokeratin 19 mRNA for positive and negative lymph nodes were 43.3 × 104/μl and 121.1/μl, respectively. The expression of cytokeratin 19 mRNA in pathologically positive lymph nodes was higher than that in the negative lymph nodes (P < 0.0001) by quantitative reverse transcriptase-polymerase chain reaction analysis. Using a receiver operating characteristic plot, the maximum sensitivity (100%) and specificity (94.4%) were obtained when the cutoff value was set at 1169 copies/μl. Conclusions After setting the cutoff value at 1169 copies/μl, a quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA showed high accuracy in detecting lymph node metastasis in cervical cancer. We believe that the quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA may be acceptable for lymph node metastasis detection in patients with cervical cancer.

Active small bowel sparing in intracavitary brachytherapy for cervical cancer

Abstract Objective To propose and evaluate an active method for sparing the small bowel in the treatment field of cervical cancer brachytherapy by prone position procedure. Methods The prone position procedure consists of five steps: making bladder empty, prone-positioning a patient on belly board, making the small bowel move to abdomen, filling the bladder with Foley catheter and finally turning the patient into the supine position. The proposed method was applied for the treatment of seven cervical cancer patients. Its effectiveness was evaluated and a correlation between the patient characteristics and the volumetric dose reduction of small bowel was also investigated. Brachytherapy treatment plans were built before and after the proposed method, and their dose-volume histograms were compared for targets and organs-at-risk. In this comparison, all plans were normalized to satisfy the same D90% for high-risk clinical target volume. Results For the enrolled patients, the average dose of small bowel was significantly reduced from 75.2 ± 4.9 Gy before to 60.2 ± 4.0 Gy after the prone position procedure, while minor dosimetric changes were observed in rectum, sigmoid and bladder. The linear correlation to body mass index, thickness and width of abdominopelvic cavity and bladder volume were 76.2, 69.7, 28.8 and −36.3%, respectively. Conclusions The application of prone position procedure could effectively lower the volumetric dose of the small bowel. The dose reduction in the small bowel had a strong correlation with the patient’s obesity and abdominal thickness. This means the patients for whom the proposed method would be beneficial can be judiciously selected for safe brachytherapy.

Hormone replacement therapy in female-specific cancer survivors: considerations beyond cancer cure

Abstract With rapid advances in disease diagnosis and treatment, patients with cancer will achieve longer survival. Among female cancer survivors, oncologic treatments often lead to premature ovarian insufficiency, negatively impacting their health and quality of life. Hormone replacement therapy (HRT) may mitigate these effects; however, concerns remain regarding its impact on oncologic outcomes. Updating the evidence base could help healthcare providers identify patients who may benefit from HRT without an increased risk of recurrence. This review provides an updated overview of HRT in women with a history of cervical, endometrial, ovarian, and breast cancers. For cervical cancer, HRT is not contraindicated in either squamous cell carcinoma or adenocarcinoma, regardless of stage. For endometrial cancer, HRT is not contraindicated in early-stage disease with no residual tumor, although it should be avoided in low-grade endometrial stromal sarcoma. HRT is not contraindicated in epithelial ovarian cancer regardless of stage, except in low-grade serous carcinoma. Currently, HRT is contraindicated for breast cancer. This review highlights the need to promote long-term healthcare strategies for cancer survivors. A shift in focus beyond cancer cure toward lifelong health management is warranted.

Risk-reducing mastectomy and salpingo-oophorectomy in women with hereditary breast and ovarian cancer: a single-institute experience following coverage by Japanese national medical insurance

Abstract Background Risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) are preventive options for women with hereditary breast and ovarian cancer (HBOC). The Japanese national medical insurance began covering RRM and RRSO for patients with HBOC in April 2020. Methods We retrospectively analyzed 59 individuals with pathogenic germline variants (PGVs) from 55 families diagnosed with HBOC between 2010 and 2024 to assess the prevalence of RRM and RRSO after April 2020. Results The median age at diagnosis was 50 years. Ten individuals (16.9%) were diagnosed before April 2020, whereas 49 (83.1%) were diagnosed afterward. PGVs included BRCA1 (28 individuals) and BRCA2 (31 individuals). The most common cancer was breast cancer (74.6%), followed by ovarian (13.6%), and pancreatic cancer (3.3%); 15.3% had no cancer history. RRM was performed in 19 of 41 individuals (46.3%), with the highest rate observed among BRCA1 PGV individuals (55.0%). RRSO was conducted in 30 of 41 individuals (73.1%), with higher rates among BRCA1 and BRCA2 PGV individuals. None of the individuals without a history of breast and/or ovarian cancer underwent these procedures. The median age was 50 for RRM and 49 for RRSO. Most surgeries (64.7% for RRM and 76.0% for RRSO) occurred within a year of genetic testing. Multivariate analysis showed that breast cancer history was strongly associated with RRM. Conclusions National insurance coverage has enhanced access to genetic testing and preventive surgeries, with 46.3% and 73.1% undergoing RRM and RRSO, respectively. However, individuals without a cancer history remain underrepresented.

Evaluation of ovarian cancer prognosis by nomogram model based on prospective cohort study

Abstract Objective Ovarian cancer (OC), accounting for 3.4% of female cancer diagnoses and 4.8% of cancer-related deaths globally, faces high recurrence risks. We aimed to develop a nomogram integrating novel biomarkers to improve prognostic accuracy for OC patients. Methods Clinical data from 1342 OC patients at Chongqing University Cancer Hospital (2019–21) were analyzed. Multivariate Cox regression identified independent prognostic factors to construct the nomogram. Model performance was evaluated via the C-index, time-dependent area under the receiver operating characteristic curve, calibration curves, and decision curve analysis (DCA). Results The independent prognostic factors for OC in this study include the body mass index, International Federation of Gynecology and Obstetrics stage, differentiation, surgery, targeted therapy, hemoglobin, β2 microglobulin, neutrophil-to-lymphocyte ratio, interleukin-6, and keratin 19. In both the training and validation cohorts, the C-indexes were 0.756 (95% CI: 0.718–0.793) and 0.751 (95% CI: 0.697–0.805), respectively. The calibration curve demonstrated a high level of consistency between the predicted and observed probabilities. DCA confirmed that the nomogram model provided a higher net benefit. Conclusions This study established a prognostic nomogram for OC and validated it with rigorous statistical metrics. An online tool was developed to facilitate personalized treatment strategies, offering clinical utility for OC management.

Rare malignant ovarian tumors: a review

Abstract There are many histologic types of gynecologic malignancies. I reviewed three rare ovarian tumor types that have poor prognoses. Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. It is thought to arise from mesonephric duct remnants of the female genital tract and is typically associated with endometriosis. Although MLA has some similarities to endometrioid carcinoma, they have different prognoses. Recurrence of MLA is common, even in early stage cases, and distant metastases, especially in the lungs, are often seen. MLA is characterized by positive immunohistochemical-staining for TTF-1, GATA3, PAX2, and CD10, and negative staining for estrogen and progesterone receptors. Data on treatment for MLA are scarce, and further studies are needed. Adult granulosa cell tumors, the most common type of malignant ovarian sex cord-stromal tumors, have an indolent growth pattern. Chemotherapy, hormone therapy, and radiotherapy have all shown some efficacy. However, debulking surgery remains the most important treatment because tumor disruption or remnants are risk factors for recurrence. Late recurrence is also characteristic of this tumor. Malignant transformations of mature teratoma are suspected when the patient is relatively old and the tumor is large. Squamous cell carcinoma is the most common somatic malignancy. Treatment must be tailored to the transformed histology. Chemotherapy and radiation have shown some efficacy; however, the prognosis is extremely poor in advanced cases. Because these three types of ovarian tumors are rare, research on possible treatments has been difficult, but recent significant advances in drug therapy are expected to lead to the development of effective treatments.

Breast cancer surveillance for epithelial ovarian cancer patients with BRCA1 and BRCA2 pathogenic variants: a single-center retrospective study

Abstract Objectives To identify a method for breast cancer (BC) surveillance in patients with epithelial ovarian cancer (EOC) with germline BRCA1/2 pathogenic variants (gBRCA1/2m) and the incidence of BC after EOC in the era of broad PARP inhibitors use. Methods We retrospectively analyzed the data on EOC patients who had gBRCA1/2m by genetic testing between January 2017 and August 2023 in our single center. Results Of 125 patients with EOC, 33 had gBRCA1/2m. Of these, 27 (81.8%) underwent BC surveillance, 20 ultrasound and/or mammography, and seven magnetic resonance imaging (MRI). The median time from EOC diagnosis to the initiation of BC surveillance was 8 months. EOC recurrence was significantly lower in the group with MRI than in the group without MRI (no case vs. 10 cases, P = .0261). The duration from EOC diagnosis to the start of BC surveillance was longer in the group with MRI than in the group without MRI (21 vs. 7 months, P = .1033). Two (6.1%) patients developed BC after EOC. Both cases were early stage, triple-negative BCs that occurred more than 3 years after the diagnosis of stage III EOC. Conclusions With the advent of PARP inhibitors, long-term survival is expected to increase, and a certain number of patients with EOC after initial treatment may benefit from BC surveillance using MRI. In particular, BC surveillance with MRI may be considered for patients who have not experienced EOC recurrence for more than 2 years.

Trends in 5-year net survival for women diagnosed with breast, cervical or ovarian cancer in Japan, 2000–14 (CONCORD-3)

Abstract Background Breast, cervical and ovarian cancers significantly affect young and middle-aged women, both physically and socially. However, relevant comprehensive stratified analyses are limited. Using Japanese data from CONCORD-3, a global cancer survival surveillance program, we analyzed long-term survival trends. Methods Data from 16 Japanese population-based cancer registries were analyzed for women diagnosed aged 15–99 years during 2000–2014 with a tumor originating in the breast, cervix uteri or ovaries. Follow-up was extended to five years post-diagnosis or until December 31st, 2014. In situ tumors and death-certificate-only registrations were excluded. Five-year net survival was estimated with the Pohar Perme estimator by calendar period of diagnosis, morphology and stage, and age-standardized with International Cancer Survival Standard weights. Results During 2000–2014, 5-year net survival improved for breast cancer from 85.9% (95% CI, 85.2–86.6%) to 89.4% (88.9–89.9%), for cervical cancer from 67.5% (66.3–68.7%) to 71.4% (70.4–72.3%), and for ovarian cancer from 35.5% (33.8–37.2%) to 46.3% (44.9–47.7%). Five-year survival for tumors diagnosed at a localized stage remained consistently high (>98% for breast cancer and > 90% for cervical cancer). Ovarian cancer survival varied greatly according to morphology. Conclusions Five-year net survival for women with cancers of the breast, cervix, and ovary) in Japan improved during 2000–2014, and remained at a globally high level throughout this period. These gains are probably attributable to earlier detection of breast and cervical cancers and advances in multimodal treatment for all cancers. Survival for distant-stage cervical and ovarian cancers remains a challenge, underscoring the need for enhanced screening and treatment strategies.

Impact of the FIGO2023 staging system on endometrial cancer in Japan: differences between next-generation sequencing and simplified surrogate marker analysis

Abstract Background The International Federation of Gynecology and Obstetrics (FIGO) revised the staging system of endometrial cancer in 2023. In this study, we aimed to determine stage transitions and prognosis of endometrial cancer using FIGO2008, FIGO2023 without molecular classification (FIGO2023), and FIGO2023 with molecular classification (FIGO2023m). Methods Eighty-three patients diagnosed with endometrial cancer who underwent surgery and next-generation sequencing (NGS) molecular profiling as part of the Project HOPE cohort study were enrolled. Each case was staged according to the FIGO2008 and FIGO2023 criteria, and we evaluated changes in stage and disease-specific survival (DSS). Molecular classification based on NGS was performed to evaluate FIGO2023m, and the concordance rate with immunohistochemical marker analysis was assessed. Results Transitioning from FIGO2008 to FIGO2023 resulted in the restaging of 18 cases. Conversely, transitioning from FIGO2008 to FIGO2023m led to the restaging of 15 cases. The concordance rate between FIGO2023 and FIGO2023m staging was 96.4%. With FIGO2023m, the 5-year DSS was 97.6% for stage I (95% confidence interval [CI] 83.9–99.7), 83.3% for stage II (95% CI 56.8–94.3), 100% for stage III (95% CI NA), and 25.0% for stage IV (95% CI 0.9–66.5). Discrepancies in disease staging due to discordance between simplified surrogate marker analysis and NGS evaluation occurred in two cases. Conclusions The revision of the staging system from FIGO2008 to FIGO2023 and FIGO2023m resulted in the restaging of several cases, with significant changes between stages I and II.

Potential utility of pretreatment serum miRNAs for optimal treatment selection in advanced high-grade serous ovarian cancer

Abstract Objective The primary treatment of patients with advanced ovarian cancer is selected from whether primary debulking surgery or neoadjuvant chemotherapy. We investigated whether pretreatment serum microRNA profiles are useful for selecting patients with advanced high-grade serous ovarian cancer who obtain better outcomes from undergoing primary debulking surgery or neoadjuvant chemotherapy. Methods Consecutive patients with clinical stage IIIB–IVB and serum microRNA data were selected. Patients who underwent primary debulking surgery or neoadjuvant chemotherapy were subjected to 1:1 propensity score matching before comparing their progression-free survival using Cox modelling. Progression-free probabilities for the selected microRNA profiles were calculated, and the estimated progression-free survival with the recommended primary treatment was determined and compared with the actual progression-free survival of the patients. Results Of the 108 patients with stage IIIB–IVB disease, the data of 24 who underwent primary debulking surgery or neoadjuvant chemotherapy were compared. Eleven and three microRNAs were independent predictors of progression-free survival in patients who underwent primary debulking surgery and neoadjuvant chemotherapy, respectively. Two microRNAs correlated significantly with complete resection of the tumours in primary debulking surgery. No differences were found between the actual and estimated progression-free survival in the primary debulking surgery and neoadjuvant chemotherapy groups (P > 0.05). The recommended and actual primary treatments were identical in 27 (56.3%) of the 48 patients. The median improved survival times between recommended and actual treatment were 11.7 and 32.6 months for patients with actual primary debulking surgery and neoadjuvant chemotherapy, respectively. Conclusions Pretreatment microRNA profiles could be used to select subgroups of patients who benefited more from primary debulking surgery or neoadjuvant chemotherapy and might contribute to selecting the optimal primary treatment modality in advanced high-grade serous ovarian cancer patients.

Evaluation of survival outcomes between minimally invasive and open surgery in the treatment of early-stage endometrial cancer: a population-based study in Osaka Japan

Abstract Objective To compare the oncological outcomes between Japanese women who underwent minimally invasive surgery and those who underwent open surgery for early-stage endometrial cancer. Methods This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2011 to 2018. Surgically treated patients for localized (uterine-confined) endometrial cancer were identified. Patients were classified into two groups according to the type of surgery (minimally invasive surgery group and open-surgery group), pathological risk factors (low-risk and high-risk), and year of diagnosis (Group 1, 2011–14; Group 2, 2015–18). Overall survival was compared between the minimally invasive surgery and open-surgery groups. Results In the analyses including all patients, there was no difference in overall survival between the minimally invasive surgery and open-surgery groups (P = 0.0797). The 4-year overall survival rate was 97.1 and 95.7% in the minimally invasive surgery and open-surgery groups, respectively. When investigated according to pathological risks, there were no differences in overall survival between the minimally invasive surgery and open-surgery groups in both the low- and high-risk groups. In the low-risk group, the 4-year overall survival rates in the minimally invasive surgery and open-surgery groups were 97.7 and 96.5%, respectively. In the high-risk group, the 4-year overall survival rates in the minimally invasive surgery and open-surgery groups were 91.2 and 93.2%, respectively. Similarly, there were no differences in overall survival between the minimally invasive surgery and open-surgery groups in both Group 1 (P = 0.4479 in low-risk and P = 0.1826 in high-risk groups) and Group 2 (P = 0.1750 in low-risk and P = 0.0799 in high-risk groups). Conclusion Our study provides epidemiological evidence that minimally invasive surgery is an effective alternative to open surgery in Japanese patients with early-stage endometrial cancer.

The sarcopenia index measured using the lumbar paraspinal muscle is associated with prognosis in endometrial cancer

Abstract Objective The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer. Methods We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were treated as derivation set and the other 104 patients as validation set. Using preoperative computed tomography images, we measured the horizontal cross-sectional area at the third lumbar spine level: the (i) psoas major, (ii) iliac and (iii) paraspinal muscle. The clinical information including recurrence-free survival and overall survival were retrospectively collected. These results were validated with external data sets of three hospitals. Results The median values of the sarcopenia index (cm2/m2) ± standard deviation with the first data of 90 patients using the psoas, iliac and paraspinal muscle were 3.4 ± 1.0, 1.7 ± 0.6 and 12.6 ± 3.2, respectively. In univariate analyses, the sarcopenia indexes measured using the psoas or paraspinal muscle were associated with recurrence-free survival and overall survival. On the other hand, in multivariate analyses, only the sarcopenia index using paraspinal muscle was significantly related to recurrence-free survival (hazard ratio = 3.78, 95% confidence intervals = 1.29–5.97, P = 0.009) and overall survival (hazard ratio = 3.13, 95% confidence interval = 1.18–8.26, P = 0.022). Paraspinal sarcopenia index was also related to overall survival (hazard ratio = 3.74, 95% confidence interval = 1.31–10.72, P = 0.014) even in patients with advanced stage. Serum albumin was significantly correlated with the sarcopenia index (P = 0.012). Within the analysis of the validation set, sarcopenia index using paraspinal muscle was related to recurrence-free survival (hazard ratio = 2.06, P = 0.045) in multivariate analysis and recurrence-free survival (P = 0.009) in patients with advanced stage. Conclusions The sarcopenia index using the paraspinal muscle, not psoas, could be a suitable index to predict recurrence-free survival and overall survival in patients with type-II endometrial cancer even in advanced stage.

A single-institution retrospective exploratory analysis on the effectiveness and safety of lenvatinib plus pembrolizumab for advanced endometrial cancer: insights from ProMisE molecular classification system

Abstract Background The Proactive Molecular Risk Classifier for Endometrial Cancer has identified four risk groups for the prognosis of endometrial cancer. Lenvatinib plus pembrolizumab was recently approved as a second-line treatment for unresectable endometrial cancer, but reports in clinical practice are lacking. The relationship between the efficacy of lenvatinib/pembrolizumab and Proactive Molecular Risk Classifier for Endometrial Cancer classification is unclear. Methods This single-centre retrospective study included patients who underwent lenvatinib/pembrolizumab therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient, p53 abnormal and no specific molecular profile subtypes using immunohistochemistry. The response rate, progression-free survival and adverse events were evaluated using electronic medical records. The study was approved by the hospital’s ethics committee (approval number: MH2022-093). Results This study enrolled 20 patients, who underwent a median follow-up of 17.8 months (95% confidence interval: 16.6–18.9). The best overall response rate was 60.0% (36.1–80.9), and the median progression-free survival was 11.6 months (2.9–20.3). The median progression-free survival in the p53 abnormal group (n = 9) was 3.4 months (3.0–3.8); however, progression-free survival did not reach the median (P < 0.001) in the mismatch repair-deficient/no specific molecular profile group (n = 11). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and partial responses were observed in all cases. No treatment-related deaths occurred. Conclusion The p53abn group in the Proactive Molecular Risk Classifier for Endometrial Cancer classification has a poor prognosis even after treatment with lenvatinib/pembrolizumab.

Role of clonal lineage analysis via next-generation sequencing in identifying the origin of multiple cancers and guiding treatment options

Abstract Multiple cancers occur in the same individual, such as hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome. Here, we report a patient with HBOC syndrome who developed four different cancer types (pancreatic cancer, right lung adenocarcinoma, prostate cancer, and left lung adenocarcinoma) within a relatively short period of 6.5 years. In HBOC syndrome, the lung adenocarcinoma is rare, and the tumors were initially suspected to be lung metastases from pancreatic cancer, respectively. The pathological analysis results in each of the three lesions were inconsistent. A whole-exome analysis was performed on all three tumors using next-generation sequencing (NGS). The results showed that many of the deletion mutations found in pancreatic cancer were not present in other lung tumors. Homologous recombination is required for the repair of deletion mutations, but this function is impaired in HBOC syndrome. Deletions occurring in the primary tumor are irreversible and should be inherited in metastatic lesions. Therefore, we hypothesized that these three cancers arose independently, that each lung tumor was a primary tumor rather than a metastasis of pancreatic cancer, and that their resection would be curative. This assumption was reasonable, as no new lesions were observed in a 10-year follow-up study since the onset of pancreatic cancer. Tracking genetic traits using NGS helps understand the origins and progression of malignant tumors.

Comparative analysis of surgical outcomes between the hinotori™ surgical robot system and da Vinci® Xi for simple hysterectomy with sentinel lymph node biopsy in low-risk endometrial cancer

Abstract Objectives This study aimed to compare the surgical outcomes of simple hysterectomy with sentinel lymph node biopsy for low-risk endometrial cancer performed using the hinotori™ Surgical Robot System and the da Vinci® Xi system. Materials and Methods We retrospectively analyzed the data of 234 patients who underwent simple hysterectomy with sentinel lymph node biopsy at Kagoshima University Hospital between January 2017 and June 2024. Amongst them, 20 patients underwent surgery using the hinotori™ Surgical Robot System and 214 using the da Vinci® Xi. Surgical factors, including operative time, cockpit/console time, blood loss and sentinel lymph node detection, were evaluated. Statistical analyses included chi-square and Wilcoxon tests, with significance set at P < 0.05. Results The median operative and cockpit/console times were comparable between the two systems. However, the time from roll-in to the start of cockpit/console surgery was significantly longer for the hinotori™ Surgical Robot System than for the da Vinci® Xi (P = 0.0039). No significant differences were observed for blood loss, length of hospital stay, or complication rates. The sentinel lymph node detection rates and number of sentinel lymph nodes resected were similar between the two systems, with metastatic sentinel lymph node rates of 6% in both groups. Conclusion Simple hysterectomy with sentinel lymph node biopsy performed using the hinotori™ Surgical Robot System demonstrated outcomes comparable with those using the da Vinci® Xi system, with no significant differences in key surgical factors. These results suggest that the hinotori™ Surgical Robot System is a viable alternative for minimally invasive surgery in low-risk endometrial cancer. Further studies with larger sample sizes are required to validate these findings.

Potential prognostic predictors of treatment with immune checkpoint inhibitors for advanced endometrial cancer

Abstract Background Prognostic predictors of immunotherapy in patients with advanced endometrial cancer remain unclear. The potential role of inflammatory predictors, including pretreatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet scores, was investigated. Methods Between August 2018 and December 2023, 35 patients were retrospectively analyzed. Prognostic predictors were compared, and optimal cut-off values that exhibited the greatest discrimination for overall response, disease control, progression-free survival and overall survival were determined. Multivariate analysis was used to assess the prognostic significance of the predictors. Results The greatest discrimination for overall response, progression-free survival and overall survival included platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet; the areas under the curve were 0.638, 0.649 and 0.641, respectively. The precise cut-off values of neutrophil-to-lymphocyte ratio for progression-free survival and overall survival were 4.92 and 5.40, respectively. The lower neutrophil-to-lymphocyte ratio group had a significantly longer progression-free survival (P = 0.001, median survival; 4.0 months vs. 19 months) and longer overall survival (P = 0.002, median survival; 5.0 months vs. 21 months). Of the risk factors assessed, neutrophil-to-lymphocyte ratio (hazard ratio = 4.409; 95% CI = 1.10–17.64; P = 0.036) and regimen (hazard ratio = 5.559; 95% CI = 1.26–24.49; P = 0.023) were independently correlated with overall survival. Conclusion In patients with advanced endometrial cancer, pretreatment neutrophil-to-lymphocyte ratio may be a prognostic predictor of those who would benefit from immunotherapy.

A BMI-category distribution pattern of intrinsic and treatment-related prognostic factors in endometrial cancer

Abstract Objective In patients with endometrial cancer, obesity is associated with favorable prognostic characteristics but not with prolonged survival. The aim of this study was to elucidate the reason for this clinical paradox. Methods We retrospectively reviewed 1173 patients with endometrial cancer. Patients were divided into a non-obese group [body mass index (BMI) < 30 kg/m2], class I obesity group (BMI 30–35 kg/m2) and class II obesity group (BMI ≥ 35 kg/m2). The relationship between clinicopathological factors and disease-specific survival (DSS) was analyzed by Cox regression analysis. To correct for three-time significance testing, we used the Bonferroni method, giving the level of probability at which findings were considered significant as P < 0.0167. Results Three disease-intrinsic variables—older age, advanced stage and high-risk histology—and three treatment-related variables—no hysterectomy, no lymphadenectomy and no chemotherapy—were independently associated with poor DSS. DSS was similar among the three groups of patients even though the proportion of patients with plural pretreatment-related unfavorable risk factors significantly decreased with increment of BMI category (40.1 vs. 27.5 vs. 17.6%, P = 0.0003). The proportion of patients with plural treatment-related unfavorable prognostic factors significantly increased with increment of BMI category (21.3 vs. 26.7 vs. 39.3%, P = 0.0072). Conclusions Poor-quality surgical staging in obese women may result in worse than expected survival outcomes.

The first report of surgery for gynecological diseases using the hinotori™ surgical robot system

Abstract Objective This study aimed to report the first surgery for gynecological diseases using a new robotic platform, the hinotori™, and validate its feasibility in clinical settings. Methods The world’s first robot-assisted total hysterectomy for a gynecological ailment was carried out at Kagoshima University Hospital in December 2022 utilizing the hinotori™ surgical robot system. Eleven other patients then underwent comparable procedures. The surgical team was certified to execute the procedure and had undergone official hinotori™ training. Results Preoperative diagnoses indicated five cases of endometrial cancer, four cases of uterine myoma and one case each of atypical endometrial hyperplasia, uterine adenosarcoma and high-grade cervical intraepithelial neoplasia. Median age and body mass index were 51 (range: 38–70) years and 26.9 (range: 17.3–33.3) kg/m2, respectively. Median roll-in, cockpit and operation times were 15 (range: 10–18), 161 (range: 110–225) and 214 (range: 154–287) min, respectively. The median blood loss was 22 (range: 7–83) mL and conversion to laparotomy was not allowed. Only one patient had postoperative pelvic region infection. The median length of hospital stay was 6 (range: 4–10) days. Conclusion Based on our experience with presented 12 cases, robotic surgery with the hinotori™ is a feasible technique of minimally invasive surgery for gynecological diseases.

Current treatment status of older patients with gynecological cancers

Abstract The percentage of older patients with gynecological malignancies has recently been on the rise. Although prospective studies focusing on the treatment of older patients have been conducted for ovarian cancer, mainly in Europe, there have been scarce literature on cervical and endometrial cancers, and information on their treatment is currently lacking. One of the characteristics of older patients is that not only their performance status but also other factors, such as physical, mental and social factors, cause a large variability, and individual differences in their response to treatments. One of the major issues in the treatment of older patients is how to objectively measure these individual differences and link them to the appropriate treatment selection. In this review, clinical evidence for the guided treatment of older patients with gynecological cancer will be reviewed.

Developing a novel DNA methylation risk score for survival and identification of prognostic gene mutations in endometrial cancer: a study based on TCGA data

Abstract Background Few studies have focused on DNA methylation in endometrial cancer. The aim of our study is identify its role in endometrial cancer prognosis. Methods A publicly available dataset was retrieved from The Cancer Genome Atlas. For validation of expression alteration due to methylation, RNA sequencing data were obtained from other independent cohorts. MethSurv was used to search for candidate CpG probes, which were then filtered by least absolute shrinkage and selection operator Cox regression and multivariate Cox regression analyses to identify final set of CpG probes for overall survival. A methylation-based risk model was developed and receiver operating characteristic analysis with area under curve was used for evaluation. Patients were divided into high- and low-risk groups using an optimal cut-off point. Comprehensive bioinformatic analyses were conducted to identify hub genes, key transcription factors, and enriched cancer-related pathways. Kaplan–Meier curve was used for survival analysis. Results A 5-CpG signature score was established. Its predictive value for 5-year overall survival was high, with area under curve of 0.828, 0.835 and 0.816 for the training, testing and entire cohorts. cg27487839 and cg12885678 had strong correlation with their gene expression, XKR6 and PTPRN2, and lower PTPRN2 expression was associated with poorer survival in both The Cancer Genome Atlas and the validation datasets. Low-risk group was associated with significantly better survival. Low-risk group harboured more mutations in hub genes and key transcription factors, and mutations in SP1 and MECP2 represented favourable outcome. Conclusion We developed a methylation-based prognostic stratification system for endometrial cancer. Low-risk group was associated with better survival and harboured more mutations in the key regulatory genes.

Initial screening by immunohistochemistry is effective in universal screening for Lynch syndrome in endometrial cancer patients: a prospective observational study

Abstract Background Few prospective reports of universal screening for Lynch syndrome exist for patients with endometrial cancer. In this study, we performed immunohistochemical staining for DNA mismatch repair-related genes (MLH1, MSH2, MSH6 and PMS2), to determine the extent to which Lynch syndrome can be diagnosed in endometrial cancer patients through universal screening. Methods We recruited 116 consecutive patients assumed to have uterine corpus malignancy from October 2019 to February 2021 in a prospective observational study. We performed immunohistochemical for mismatch repair-related proteins on samples from 100 patients who had surgicopathologically confirmed diagnoses of endometrial cancer. Samples with missing immunohistochemical results for any of the proteins had subsequent universal screening tests for microsatellite instability, DNA methylation of the MLH1 promoter region and mismatch repair genetics. Results We identified 19 (19.0%) patients with lost results for any of the proteins. All 19 patient samples had subsequent screening tests. We identified the microsatellite instability-high phenotype in 84.2% (16/19) of these patients and MLH1 methylation in 57.9% (11/19). Mismatch repair genetic testing detected two pathological variants, in MSH2 and MSH6, which indicated that the prevalence of Lynch syndrome was 2.0% in our cohort. Two cases of unclassified variant (MSH6) and one case of benign variant (PMS2) were also detected. Conclusions Initial screening by immunohistochemical is an effective method in universal screening for Lynch syndrome in endometrial cancer patients.

Clinical issues of surgery for uterine endometrial cancer in Japan

Abstract Objective The mainstay of treatment for uterine endometrial cancer is surgery, and recurrent-risk cases require multidisciplinary treatment, including surgery, chemotherapy and radiation therapy. Methods The standard surgery for uterine endometrial cancer is hysterectomy and bilateral salpingooophorectomy, with additional retroperitoneal lymph node dissection and omentectomy, depending on the case. The appropriate treatment is determined based on the risk classification, such as the depth of invasion into the myometrium, diagnosis of histological type and grade, and risk assessment of lymph node metastasis. Results Recently, minimally invasive surgery has been widely used not only in low-risk patients but also in intermediate- and high-risk patients. In low-risk patients, the possibility of ovarian preservation is discussed from a healthcare perspective for young women. Determining the need for retroperitoneal lymph node dissection based on sentinel lymph node evaluation may contribute in minimizing the incidence of post-operative lymphedema while ensuring accurate diagnosis of lymph node metastasis. Recently, many studies using sentinel lymph nodes have been reported for patients with uterine endometrial cancer, and the feasibility of sentinel lymph node mapping surgery has been proven. Unfortunately, sentinel lymph node biopsy and sentinel lymph node mapping surgery have not been widely adopted in surgery for uterine cancer in Japan. In addition, the search for biomarkers, such as RNA sequencing using The Cancer Genome Atlas, metabolic profile and lipidomic profile for early detection and prognostic evaluation, has been actively pursued. Conclusions Gynecologic oncologists expect to be able to provide uterine endometrial cancer patients with appropriate treatment that preserves their quality of life without compromising oncologic outcomes in the near future.

Does complete-staging lymphadenectomy improve survival outcomes in stage I endometrioid epithelial ovarian carcinoma? A multi-institutional retrospective study with propensity score-weighted analysis

AbstractBackgroundWe investigated the prognostic impact of complete-staging lymphadenectomy on patients with clinically apparent Stage I endometrioid epithelial ovarian carcinoma.MethodsWe conducted a regional multi-institutional retrospective study between 1986 and 2018. Amongst 4897 patients with malignant ovarian tumours diagnosed under central pathological review, 259 women with Stage I endometrioid epithelial ovarian carcinoma were eligible. We evaluated differences in survival of patients with both pelvic and para-aortic lymphadenectomy (Group A) and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation (Group B). To analyse the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables.ResultsIn total, 145 patients (56.0%) received both pelvic and para-aortic lymphadenectomy. With propensity score-based adjustment, estimated survival was better in Group A compared with that in Group B but not significant. Pelvic and para-aortic lymphadenectomy also led to no significant improvement of overall survival in most of the subgroups. However, point estimations of the hazard ratio for lymphadenectomy in patients with an age of 45 or younger (hazard ratio, 0.304; 95% confidence interval, 0.094–0.982), a Grade 1–2 (hazard ratio, 0.441; 95% confidence interval, 0.204–0.954) and T1c2–3 tumour (hazard ratio, 0.449; 95% confidence interval, 0.164–1.231) were better compared with those with the opposite characteristics.ConclusionsComplete-staging lymphadenectomy was not a significant prognostic factor in patients with Stage I endometrioid epithelial ovarian carcinoma, where we still need to explore appropriate candidate for the procedure.

Prospective evaluation of sentinel node navigation surgery in Japanese patients with low-risk endometrial cancer—safety and occurrence of lymphedema

Abstract Objective The present study aimed to clarify the occurrence rate of lymphedema and prognosis in patients with endometrial cancer according to sentinel lymph node biopsy alone with intraoperative histopathological examination. Methods The study included 45 consecutive patients with endometrial cancer treated at Tohoku University Hospital between October 2014 and August 2017. All patients had endometrial carcinoma with endometrioid histology Grade 1 or Grade 2 confirmed by biopsy and stage I on magnetic resonance imaging and/or computed tomography at their preoperative evaluation. Sentinel lymph node detection was performed by radioisotope and dye. Patients who were diagnosed intraoperatively as negative for sentinel lymph node metastasis did not undergo further systematic pelvic lymphadenectomy. The occurrence rate of lymphedema and prognosis was evaluated. Results Bilateral sentinel lymph nodes were detected in 44 of 45 patients (97%). Forty-three patients underwent sentinel lymph node biopsy alone, and only two patients underwent systematic lymphadenectomy. Sentinel lymph node metastases were detected in one patient intraoperatively and two patients postoperatively as ITCs. No patients experienced recurrence. New symptomatic lower-extremity lymphedema was identified in one of 43 patients (2.3%) who underwent sentinel lymph node biopsy alone. Conclusion Sentinel lymph node biopsy alone with intraoperative histopathological diagnosis appears to be a safe and effective strategy to detect lymph node metastasis and to reduce the number of patients with lower-extremity lymphedema among patients with endometrial cancer.

Prevalence and molecular characteristics of DNA mismatch repair deficient endometrial cancer in a Japanese hospital-based population

AbstractBackgroundThe prevalence and molecular characteristics of defective DNA mismatch repair endometrial cancers in the Japanese population have been underexplored. Data supporting clinical management of patients with Lynch-like syndrome and germline variant of uncertain significance of mismatch repair genes are still lacking.MethodsImmunohistochemistry of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary endometrial cancers in 395 women with a median age of 59 years. Genetic and/or epigenetic alterations of the mismatch repair genes were also investigated.ResultsLoss of expression of one or more mismatch repair proteins was observed in 68 patients (17.2%). A total of 17 out of 68 patients (25%, 4.3% of all cases) were identified as candidates for genetic testing for Lynch syndrome after excluding 51 patients with MLH1 hypermethylated cancer. Fourteen of these 17 patients subjected to genetic testing were found to have Lynch syndrome (n = 5), germline variant of uncertain significance (n = 2) or Lynch-like syndrome (n = 7). Compared with patients with Lynch syndrome, those with germline variant of uncertain significance and Lynch-like syndrome tended to demonstrate an older age at the time of endometrial cancer diagnosis (P = 0.07), less fulfillment of the revised Bethesda guidelines (P = 0.09) and lower prevalence of Lynch syndrome-associated tumors in their first-degree relatives (P = 0.01).ConclusionsThis study provides useful information for management in patients with DNA mismatch repair endometrial cancer. Specifically, cancer surveillance as recommended in patients with Lynch syndrome might not be necessary in patients with germline variant of uncertain significance and Lynch-like syndrome and their relatives.

Comparison of survival outcomes between laparoscopic and open surgery in patients with low-risk endometrial cancer

Abstract Objective To evaluate the feasibility, safety and surgical outcomes of laparoscopic surgery for the treatment of low-risk endometrial cancer. Methods Of 155 patients with low-risk endometrial cancer, who were included in this retrospective study between May 2008 and March 2017, 82 and 73 underwent laparoscopic and open surgery, respectively. Clinicopathological and surgical data, recurrence-free survival and overall survival were analyzed. Results No statistically significant differences in median age, final pathological type, International Federation of Gynecology and Obstetrics stage and lymphovascular space involvement were observed between the laparoscopic and open surgery groups. No procedure in the laparoscopic surgery group was converted to open surgery. The median follow-up period was 60 months, with oncologic recurrence identified in three cases (one lung carcinoma and two pelvic cavity carcinomas) in the laparoscopic surgery group. There was no significant between-group difference in 5-year recurrence-free survival (laparoscopic surgery group: 96.3%, open surgery group: 92.6%) and overall survival (laparoscopic surgery group: 100%, open surgery group: 95.4%). Conclusions Laparoscopic surgery is a feasible and safe treatment for endometrial cancer and should be considered as a standard treatment option for low-risk endometrial cancer.

Evaluation of safety and diagnostic performance for flexible hysteroscopy in 1591 outpatient cases

AbstractBackgroundTo date, only few large studies are available concerning the safety and diagnostic concordance rates of outpatient flexible hysteroscopy. In our institution, outpatient hysteroscopy has been routinely and educationally applied Kosuke Tsuji to intrauterine lesions; thus, we retrospectively investigated the institution’s outpatient flexible hysteroscopy cases.MethodsA total of 1591 cases of outpatient flexible hysteroscopy conducted at our institution in 2012–2016 were retrospectively analyzed in terms of their clinical background, complications and diagnostic concordance rates.ResultsA total of 1591 cases included 546 cases of benign tumors (317 endometrial polyps, 168 myomas and 61 endometrial hyperplasia), 361 cases of atypical endometrial hyperplasia, 571 cases of endometrial cancers and 113 cases of other diagnoses. No major complications, including uterine perforation, occurred. However, one patient (0.06%) was diagnosed with septic shock caused by intrauterine infection that required prolonged immunosuppressive drug administration. Meanwhile, 335 patients diagnosed with benign tumors through outpatient flexible hysteroscopy underwent operation, and the diagnostic concordance rate was 74.6% (250 cases). However, this rate included 14 cases (4.2%) diagnosed with malignant tumors postoperatively. In preoperative endometrial cancer cases, the sensitivity and specificity for cervical invasion diagnosis were 39.4 and 90.8%, respectively. In addition, only one patient manifested positive ascites cytology intraoperatively, possibly caused by outpatient hysteroscopy.ConclusionsOutpatient flexible hysteroscopy is highly safe, with a slight negligible effect on ascites cytology. However, the diagnosis should be determined by multidisciplinary approaches, as hysteroscopy alone can miss malignancy.

Four versus six chemotherapy cycles in endometrial carcinoma with a high risk of recurrence: a retrospective study

Abstract Objective This study compared the survival outcomes and the incidence of chemotherapy-related adverse events in endometrial cancer patients who received four and six cycles of adjuvant chemotherapy to examine the optimal number of adjuvant chemotherapy cycles. Methods A total of 112 patients with endometrial cancer with a high risk of recurrence were retrospectively enrolled; 46 patients received four cycles and 66 received six cycles of adjuvant chemotherapy. Between-group differences of overall survival, disease-free survival, hematological and non-hematological toxicities were analyzed. Baseline patient’s background differences were assessed with inverse probability of treatment weighting using propensity score. Results Overall and disease-free survivals between the two groups were not significantly different. Paclitaxel + carboplatin, every 3–4 weeks was the most frequently used chemotherapy regimen in both groups. Patients in the six-cycle chemotherapy group developed neutropenia G4 or febrile neutropenia more frequently than those in the four-cycle group; odds ratio (95% confidence interval) is 4.07 (1.51–10.96). Peripheral sensory neuropathy was the most frequently observed non-hematological toxicity; the incidence of peripheral sensory neuropathy was not significantly different between four- and six-cycle chemotherapy group, P = 0.832. The result was same in the subgroup analysis in patients who received TC regimen, P = 0.455. Conclusion This study implies a possible benefit of fewer cycles of adjuvant chemotherapy in endometrial cancer patients with a high risk of recurrence because of the lower incidence of hematological toxicities without impairing survival outcomes.

Risk factors for lymph node metastasis of ovarian, fallopian tube and primary peritoneal cancer in hereditary breast and ovarian cancer syndrome

Abstract Background To establish an individualized surgical strategy for lymphadenectomy in ovarian cancer patients with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+), we investigated the clinicopathological characteristics that are involved in the increased risk of lymph node metastasis. Methods We retrospectively reviewed the data of Japanese women registered in the database of the Japanese Hereditary Breast and Ovarian Cancer Consortium, who underwent BRCA1 and BRCA2 genetic testing. Results We evaluated the predictors of lymph node metastasis in all patients with the information of age at the diagnosis, disease site, histological subtype, 2014 FIGO stage, personal breast cancer history and family history; 233, 153 and 32 patients in the BRCA− (no pathogenic variant), BRCA1+ and BRCA2+ groups, respectively. The prevalence of lymph node metastasis was not markedly different between BRCA− (20.0%), BRCA1+ (18.4%) and BRCA2+ (26.2%). Multivariate analysis revealed an absence of a family history of ovarian cancer as an independent predictor for an increased risk of lymph node metastasis in BRCA1+, and the prevalence of lymph node metastasis was 11.7 and 42.0% in the groups with and without a family history of ovarian cancer, respectively. This subgroup without a family history of ovarian cancer did not show any correlation with a particular variant of BRCA1, including two common variants of c.188 T > A and c.2800C > T. Conclusions This study suggested that certain genetic factors related to the penetrance of hereditary breast and ovarian cancer syndrome altered the frequency of lymph node metastasis in BRCA1+ ovarian cancer, and family history may be useful to personalize the indication of lymphadenectomy.

A prospective cohort study on the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer

Abstract Objective this prospective cohort study aimed to assess the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer. Methods in this study, 40 Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer selected to receive bevacizumab with chemotherapy were enrolled. Patients in poor general condition were excluded. Each patient was monitored prospectively for adverse events, administration status, disease status and survival. Treatment was continued until intolerable adverse events or disease progression. The primary endpoint was safety. Results bevacizumab plus platinum-based chemotherapy was performed for 30 patients (median cycle; 16.5), while bevacizumab plus non-platinum chemotherapy was performed for 10 patients (median cycle; 5.5). Among bevacizumab-related adverse events, hypertension occurred in 80% of patients, proteinuria in 83%, mucositis in 25%, bleeding in 20%, thromboembolic events in 5.0% and fistula in 2.5%. Gastrointestinal perforation or other life-threatening lethal adverse events were not observed. Response rate and median progression-free survival were 73% and 19.3 months for patients with bevacizumab plus platinum-based chemotherapy, and 30% and 3.9 months for patients with bevacizumab plus non-platinum chemotherapy, respectively. There was no correlation between response rate and occurrence of adverse events such as hypertension or proteinuria. Conclusion bevacizumab combined with chemotherapy was tolerable and effective for Japanese patients with relapsed ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Hypertension and proteinuria are frequently occurred and managed properly for continuing treatment.

Value of adjuvant chemotherapy and informed microscopic examination for occult gynecologic cancer detected upon risk-reducing salpingo-oophorectomy after chemotherapy for BRCA1/2-associated breast cancer: a case report

Abstract BRCA1/2 mutation carriers are at high risk for type II ovarian, fallopian tube or peritoneal cancer. Although risk-reducing salpingo-oophorectomy plays an important role in the prevention of these BRCA1/2-associated gynecological cancers, occult ovarian, fallopian tube, or peritoneal cancer is discovered upon risk-reducing salpingo-oophorectomy in 1–4% of BRCA1/2 mutation carriers. Notably, around 30% of BRCA1/2 mutation carriers who undergo risk-reducing salpingo-oophorectomy have undergone adjuvant chemotherapy for breast cancer. We describe the discovery and treatment of occult cancer at the edge of the left fimbria in a BRCA1 mutation carrier who had, just a short time previously, undergone neoadjuvant paclitaxel plus carboplatin (TC) chemotherapy for triple-negative breast cancer. During subsequent risk-reducing salpingo-oophorectomy, a 5.5-mm nodule was observed at the edge of the left fimbria. Microscopic examination of the tumour tissue revealed high-grade serous carcinoma with degenerate tumour cells and fibrosis. Peritoneal fluid was negative for cancer cells. Two months later, hysterectomy, omentectomy and retroperitoneal lymphadenectomy were performed. The final diagnosis was stage FIGO IA fallopian tube cancer. Adjuvant chemotherapy (TC administered every 3 weeks) was applied, and there has been no evidence of recurrence for 5 years. In applying gynecologic surgery and adjuvant chemotherapy, we followed the general recommendation for stage IA fallopian tube cancer. There is no standard strategy for the treatment of occult fallopian tube cancer detected after chemotherapy for BRCA1-associated triple-negative breast cancer. According to our experience in this case, we believe the clinical value of staging laparotomy in cases of a small occult BRCA1/2-associated gynecological cancer should be further investigated.

Stage III disease of ovarian, tubal and peritoneal cancers can be accurately diagnosed with pre-operative CT. Japan Clinical Oncology Group Study JCOG0602

Abstract Purpose Computed tomography of the abdomen and pelvis is a useful imaging modality for identifying origin and extent of ovarian cancer before primary debulking surgery. However, the International Federation of Gynecology and Obstetrics staging for ovarian cancer is determined based on surgico-pathological findings. The purpose of this study is to determine whether computed tomography staging can be the surrogate for surgico-pathological International Federation of Gynecology and Obstetrics staging in advanced ovarian cancer undergoing neoadjuvant chemotherapy. Methods Computed tomography staging was compared with surgico-pathological International Federation of Gynecology and Obstetrics staging in primary debulking surgery arm patients in a randomized controlled trial comparing primary debulking surgery and neoadjuvant chemotherapy (JCOG0602). The cancer of primary debulking surgery arm was identically diagnosed regarding the origin and extent with the cancer of neoadjuvant chemotherapy arm before accrual, using imaging studies (computed tomography and/or magnetic resonance imaging), cytological examination (ascites, pleural effusion or tumor contents fluid) and tumor marker (CA125 > 200 U/mL and CEA < 20 ng/mL). Institutional computed tomography staging was also compared with computed tomography staging by central review. Results Among 149 primary debulking surgery arm patients, 147 patients who underwent primary debulking surgery immediately were analyzed. Positive predictive values and sensitivity of computed tomography staging for surgical stage III disease (extra-pelvic peritoneal disease and/or retroperitoneal lymph node metastasis) were 99%. Meanwhile, positive predictive values for the presence of small (≤2 cm) extra-pelvic peritoneal disease were low; <20% in omentum. Accuracy of institutional computed tomography staging was comparable with computed tomography staging by central review. Conclusions Preoperative computed tomography staging in each institution can be the surrogate for surgico-pathological diagnosis in stage III disease of ovarian cancer patients undergoing neoadjuvant chemotherapy without diagnostic surgery, but reliability of diagnosis of stage IIIB disease is inadequate. Clinical trial registration: UMIN000000523(UMIN-CTR).

Long-term prognostic significance of ascites cytology in ovarian cancer cases in which R0 resection was achieved in the initial surgery: a multi-institutional retrospective cohort study

Abstract Background In ovarian cancer (OvCa), achieving complete resection (RO) in initial surgery is crucial for improving prognosis. However, patients with undetected microscopic metastasis post-RO surgery often have poorer outcomes. This study explores prognostic factors for OvCa patients who underwent RO surgery, focusing on the role of ascites cytology as an indicator of microscopic peritoneal metastasis. Methods We analyzed data from 975 OvCa cases in the Tokai Ovarian Tumor Study Group database (1986–2019). Excluding patients without chemotherapy or with distant metastasis, we examined prognostic factors using Cox regression analysis. Propensity score (PS) methods balanced the cytology-positive and -negative groups, with subgroup analysis for clinical stage and ascites volume. Results Multivariate analysis identified FIGO stage III and positive ascites cytology as poor prognostic factors for overall and progression-free survival. After PS adjustment, positive ascites cytology also shortened progression-free intervals post-recurrence, especially in cases with peritoneal or lymph node metastasis. Subgroup analysis revealed a more substantial prognostic impact of positive ascites cytology in early-stage cases. Conclusion The present results suggest that in OvCa patients with the R0 status, the presence of tumor cells in ascites is an independent negative prognostic factor and may be an indicator of peritoneal micro-metastasis.

Discontinuation and non-publication of randomized controlled trials on cervical cancer or precancer

Abstract Background Research waste is a considerable problem in clinical trials, with nonpublication being a significant contributor. We aimed to determine the prevalence of discontinuation and nonpublication of randomized controlled trials (RCTs) on cervical cancer or precancer. Methods We searched ClinicalTrials.gov for registered RCTs investigating cervical cancer or precancer that started between January 2000 and December 2020. The primary and secondary outcomes were trial nonpublication and premature discontinuation, respectively. Publication status was determined by systematic searches of peer-reviewed journals using the PubMed and Scopus databases. Results A total of 113 RCTs met the inclusion criteria. Among the 85 trials completed before December 2020, 44 (51.8%) were prematurely discontinued and 40 (47.1%) were unpublished. A single-center design (61.4% vs. 34.1%, P = .012) and lack of external funding (59.1% vs. 36.6%, P = .038) were significantly associated with trial discontinuation. Large-scale (target sample size >400; 46.7% vs. 17.5%, P = .004) and externally funded trials (66.7% vs. 35.0%, P = .004) were more likely to be published. Multivariate logistic analysis revealed that a large sample size [odd ratio (OR): 4.125, 95% confidence interval (CI): 1.511–11.259, P = .006] and presence of external funding (OR: 3.714, 95% CI: 1.513–9.117, P = .004) were independent positive factors for trial publication. Conclusion A significant proportion of RCTs related to cervical cancer or precancer were discontinued early or remain unpublished, resulting in a waste of research resources.

Validation of objective performance metrics via an intelligent medical network in gynecological oncology robotic surgery

Abstract Background Automated performance metrics (APMs) are potentially useful to accurately assess and improve surgeon skills and patient outcomes, while their clinical use is currently limited. We report on the use of the Medicaroid Intelligent Network System (MINS™), a network support system platform used together with the “hinotori” surgical robot system (hinotori™) for the collection of data logs from surgeries, and discuss its potential to improve surgical outcomes. Methods This study prospectively evaluated the efficacy of MINS™ for collecting data logs in gynecologic oncologic robotic surgery between December 2022 and February 2024 in nine patients. MINS™ regularly communicated with the hinotori™ via a secure network to collect and send system logs to a cloud server, quantifying various performance data for the evaluation of surgical outcomes. Results Clinical data on hinotori™ movement were successfully extracted. The number of operation arm (OA) changes was significantly higher in Patient No. 7, who underwent pelvic lymph node dissection. OA3 monopolar was used more frequently than OA1 bipolar for coagulation (mean: 6.7% vs 2.5%, P ˂0.001). The error count and percentage of inactive time associated with OA collisions decreased dramatically after Patient No. 6, following the version upgrade in July 2024. Conclusion MINS™ utilizes technology to connect the hinotori™ to various systems via the Internet, allowing objective evaluations of surgical procedures from data logs. MINS™ is a clinically applicable APM system that objectively analyzes a surgeon's individuality and has the potential to improve surgical techniques and promote standardization.

A comparison of liquid-based and conventional cytology using data for cervical cancer screening from the Japan Cancer Society

Abstract Objective Liquid-based cytology has replaced conventional cytology in cervical cancer screening in many countries. However, a detailed comparison of liquid-based cytology with conventional cytology has not been reported in Japan. Therefore, the aim of the study is to evaluate efficacy of liquid-based cytology in Japan. Methods We first evaluated the prevalence of use of liquid-based cytology and then examined the efficacy of liquid-based cytology and conventional cytology for detecting CIN and the rate of unsatisfactory specimens using data from cancer screening collected by the Japanese Cancer Society from FY2011 to FY2014. A Poisson regression model with random effects analyses was used to classify histological outcomes and unsatisfactory specimens using liquid-based cytology compared to conventional cytology. Results A total of 3 815 131 women were analyzed in the study. The rate of liquid-based cytology increased from approximately 8% in FY2011 to 37% in FY2014. Compared to conventional cytology, the detection rates with liquid-based cytology were significantly higher (1.42 times) for CIN1+ [detection rate ratio (DRR) = 1.42, 95% confidence interval (CI) 1.35–1.48, P < 0.001] and CIN2+ (DRR = 1.16, 95% CI 1.08–1.25, P < 0.001). Positive predictive value ratios of CIN1+ and CIN2+ were also significantly higher for liquid-based cytology than for conventional cytology. However, there was no significant difference between liquid-based cytology and conventional cytology for detection rates and positive predictive values of CIN3+ and cancer. The rate of unsatisfactory specimens was significantly lower with liquid-based cytology compared to conventional cytology (DRR = 0.07, 95% CI 0.05–0.09, P < 0.001). Conclusions In order to avoid the unsatisfactory specimens in cervical cancer screening, the results of this study did indicate that liquid-based cytology was more useful than conventional cytology in practical standpoints.

Use of clinical variables for preoperative prediction of lymph node metastasis in endometrial cancer

Abstract Objective Endometrial cancer is the most common gynaecological cancer, and most patients are identified during early disease stages. Noninvasive evaluation of lymph node metastasis likely will improve the quality of clinical treatment, for example, by omitting unnecessary lymphadenectomy. Methods The study population comprised 611 patients with endometrial cancer who underwent lymphadenectomy at four types of institutions, comprising seven hospitals in total. We systematically assessed the association of 18 preoperative clinical variables with postoperative lymph node metastasis. We then constructed statistical models for preoperative lymph node metastasis prediction and assessed their performance with a previously proposed system, in which the score was determined by counting the number of high-risk variables among the four predefined ones. Results Of the preoperative 18 variables evaluated, 10 were significantly associated with postoperative lymph node metastasis. A logistic regression model achieved an area under the curve of 0.85 in predicting lymph node metastasis; this value is significantly higher than that from the previous system (area under the curve, 0.74). When we set the false-negative rate to ~1%, the new predictive model increased the rate of true negatives to 21%, compared with 6.8% from the previous one. We also provide a spreadsheet-based tool for further evaluation of its ability to predict lymph node metastasis in endometrial cancer. Conclusions Our new lymph node metastasis prediction method, which was based solely on preoperative clinical variables, performed significantly better than the previous method. Although additional evaluation is necessary for its clinical use, our noninvasive system may help improve the clinical treatment of endometrial cancer, complementing minimally invasive sentinel lymph node biopsy.

Efficacy and safety of olaparib, olaparib plus bevacizumab and niraparib maintenance treatment in Japanese patients with platinum-sensitive advanced ovarian cancer

Abstract Objective To investigate whether maintenance treatment could be safely and effectively performed with olaparib, olaparib plus bevacizumab and niraparib in platinum-sensitive advanced ovarian cancer at multiple institutions in Japan. Methods We investigated progression-free survival and adverse events in 117 patients with platinum-sensitive advanced ovarian cancer treated with maintenance therapy. Results The median progression-free survival of 117 patients was 20.1 months. Patients with germline BRCA pathogenic variants had a significantly better prognosis than the other groups (P < 0.001). Furthermore, in the multivariate analysis, stage IV (P = 0.016) and germline BRCA wild-type (P ≤ 0.001) were significantly associated with worse progression-free survival in patients with advanced ovarian cancer. Regarding adverse events, all three types of maintenance treatment were significantly worse than chemotherapy given before maintenance treatment with respect to renal function (olaparib, P = 0.037; olaparib plus bevacizumab, P < 0.001; and niraparib, P = 0.016). Conclusion Maintenance treatment was performed effectively and safely. Renal function deterioration is likely to occur during maintenance treatment, and careful administration is important in platinum-sensitive advanced ovarian cancer.

Clinical perspectives of rare ovarian tumors: clear cell ovarian cancer

AbstractOvarian clear cell carcinoma (OCCC) is a rare and distinct histological type of epithelial ovarian carcinoma in terms of its histopathological, clinical and genetic features. Patients with OCCC are younger and diagnosed at earlier stages than those with the most common histological type—high-grade serous carcinoma. Endometriosis is considered a direct precursor of OCCC. Based on preclinical data, the most frequent gene alternations in OCCC are mutations of AT-rich interaction domain 1A and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. The prognosis of patients with early-stage OCCC is favorable, whereas patients at an advanced stage or who have the recurrent disease have a dismal prognosis due to OCCC’s resistance to standard platinum-based chemotherapy. Despite a lower rate of response due to its resistance to standard platinum-based chemotherapy, the treatment strategy for OCCC resembles that of high-grade serous carcinoma, which includes aggressive cytoreductive surgery and adjuvant platinum-based chemotherapy. Alternative treatment strategies, including biological agents based on molecular characteristics specific to OCCC, are urgently needed. Furthermore, due to its rarity, well-designed collaborative international clinical trials are needed to improve oncologic outcomes and the quality of life in patients with OCCC.

Quality of life but not cachexia definitions are associated with overall survival in women with cervical cancer: a STROBE-compliant cohort study

Abstract Background Cancer-related cachexia (CRC) has a profound impact on health-related quality of life (HRQL), and both were reported to be associated with overall survival (OS). We hypothesize that HRQL and CRC are associated with OS. This study analyzed the impact of CRC on HRQL and its prognostic value in women with cervical cancer (CC). Methods A cohort study including consecutive women with CC treated from October 2020 to October 2021 in a cancer center. Cox’s model defined the associations of immune, biochemical and nutritional parameters, clinical cachexia classifications and HRQL with OS. Results Two hundred forty-four consecutive women with CC were included. Cachexia classifications and several scales of the QLQ-C30 were associated with OS by bivariate but not by multivariate analysis. QLQ-CX24 scales were not associated with OS. The prognostic nutritional index (PNI) (hazard ratio (HR) 0.828; 95% confidence interval (CI) 0.766–0.896), Food aversion (HR 0.95; 95% CI 0.924–0.976), Eating difficulties (HR 1.041; 95% CI 1.013–1.071), Loss of control (HR 4.131; 95% CI 1.317–12.963), Forced self to eat (1.024; 95% CI 1.004–1.044) and Indigestion (HR 0.348; 95% CI 0.131–0.928) scales of the QLQ-CAX24 were independently associated with OS by multivariate analysis (p = 1.9×10−11). Conclusion This model permitted a clear stratification of prognostic subgroups. The PNI and several QLQ-CAX24 scales were associated with OS in women with CC. CRC, defined by several cachexia classifications, was not an independent prognostic factor. These findings require confirmation because of their possible diagnostic, therapeutic and prognostic implications. The prognostic nutritional index and several QLQ-CAX24 scales were associated with overall survival in women with cervical cancer. Cancer-related cachexia, defined by several cachexia classifications, was not an independent prognostic factor, neither The International Federation of Gynecology and Obstetrics (FIGO) stage classifications.

Clinical relevance of addition of conventional treatment to concurrent chemoradiotherapy in patients with FIGO stage III–IV cervical cancer: a retrospective analysis of a Japanese cohort

Abstract Background Concurrent chemoradiotherapy has limited therapeutic efficacy for stage III–IV cervical cancer. We aimed to identify a subgroup of patients with stage III–IV cervical cancer who benefit from concurrent chemoradiotherapy with additional treatment. Methods We retrospectively reviewed 120 patients with stage III–IV cervical cancer who were treated with concurrent chemoradiotherapy from 2002 to 2018. We compared overall survival between patients treated with concurrent chemoradiotherapy alone and those who received concurrent chemoradiotherapy with additional conventional treatments (systemic chemotherapy before and/or after concurrent chemoradiotherapy and/or extended-field radiation). Prognostic factors were statistically analysed. Results Overall, 44 (36.7%) and 21 (17.5%) patients were radiologically diagnosed with pelvic and para-aortic lymph node enlargement, respectively. The median tumour diameter was 5.7 cm. A total of 69 (57.5%) patients received no additional treatment, and 51 (42.5%) received additional treatment. Cox regression analysis identified the following prognostic factors: histological non-squamous cell carcinoma (hazard ratio, 3.9; 95% confidence interval, 1.8–8.2), tumour diameter of ≥6 cm (hazard ratio, 2.1; 95% confidence interval, 1.2–3.7), radiological pelvic lymph node enlargement (hazard ratio, 2.1; 95% confidence interval, 1.1–4.0) and radiological para-aortic lymph node enlargement (hazard ratio, 2.1; 95% confidence interval, 1.1–4.1). Even in the lowest risk group (no risk factors), the 5-year overall survival rate was lower in the additional treatment group than in the concurrent chemoradiotherapy alone group (78.7% vs. 80.9%, respectively; log-rank test, P = 0.79). Conclusions Addition of conventional treatments to concurrent chemoradiotherapy might not improve survival in patients with advanced cervical cancer. Novel treatment strategies including immune checkpoint inhibitors should be considered for such patients.

Trends in endometrial carcinoma: experience of a single institute for four decades

Abstract Objective To determine the current prognosis of endometrial carcinoma in Japan by analyzing long-term trends in endometrial carcinoma at our hospital. Methods We divided 1463 patients with endometrial carcinoma who visited our hospital between 1984 and 2022 into group 1984–1991, group 1992–1999, group 2000–2006, group 2007–2014 and group 2015–2022. Trends were determined using the Jonckheere–Terpstra and Cochran–Armitage tests. Data were analyzed using Cox regression analysis. Results When group 2015–2022 was used as a reference in the univariate analysis, the hazard ratios for the other groups were <1. In particular, the hazard ratio for group 2007–2014 was 0.65 (95% confidence interval, 0.47–0.90, P = 0.009), suggesting that the prognosis of group 2015–2022 was worse than that of group 2007–2014 and seemed to be the worst among all prognoses. In multivariate analysis, the hazard ratios for each group were 1.38, 1.42, 1.88, 1.16 and 1, respectively; the group with the worst prognosis changed from group 2015–2022 to group 2000–2006 (hazard ratio, 1.88; 95% confidence interval, 1.27–2.78, P = 0.001). Age and the rate of non-endometrioid carcinoma exhibited significantly increasing trends (P < 0.001 and P < 0.001, respectively), as did the rates of serous and mixed carcinomas (P = 0.001 and 0.024, respectively). The rates of non-endometrioid carcinoma, serous carcinoma and mixed carcinoma were 19.0%, 5.5% and 3.1% in group 2007–2014 and 28.2%, 10.8% and 4.6% in group 2015–2022, respectively. Conclusions The increasing rates of non-endometrioid carcinoma—especially serous and mixed carcinoma—may be associated with the worsening prognosis of endometrial carcinoma at our institution. Careful monitoring is needed to confirm whether this phenomenon is observed throughout Japan.

Risk stratification of invasive cervical cancer diagnosed after cervical conization

Abstract Background Cervical intraepithelial neoplasia (CIN) diagnosis is based on colposcopy-aided histological examination. However, its accuracy in CIN diagnosis is limited. Some invasive cervical cancers (ICCs) are diagnosed after cervical conization. Therefore, risk stratification of undetected ICC is particularly important for the management of patients with CIN. This study aimed to identify the risk factors for undetected ICC. We especially focused on the association of human papillomavirus (HPV) genotypes. Methods We retrospectively reviewed the clinicopathological characteristics (including age, parity, and preoperative diagnosis) and HPV genotypes of 348 patients diagnosed with CIN or adenocarcinoma in situ (AIS) who underwent cervical conization at our hospital between 2008 and 2016. The relationship between preoperative factors, including HPV genotypes and post-conization ICC, was evaluated. Results Among the 348 patients, 322, 7, and 19 had preoperative CIN3, CIN2, and AIS, respectively; 181 were nulliparous. The median patient age was 41 (23–83) years. HPV genotyping was performed on 237 patients. Overall, post-conization ICC was detected in 16 patients (4.6%). Multivariate analysis showed that nulliparity and HPV16 positivity were the independent risk factors for post-conization ICC (OR: 6.01, P = 0.0302; OR: 5.26, P = 0.0347, respectively). The combination of HPV16 status and parity improved diagnostic accuracy. Seven of 53 HPV16-positive cases (13%) without childbirth history were diagnosed with post-conization ICC. In contrast, none of the HPV16-negative cases with childbirth history was diagnosed with post-conization ICC. Conclusion HPV16 positivity and nulliparity were identified as risk factors for undetected ICC. Careful treatment selection and preoperative scrupulous examination are especially important in these cases.

Construction and validation of a prognostic nomogram for primary vulvar melanoma: a SEER population-based study

Abstract Background Primary vulvar melanoma was an aggressive and poorly understood gynecological tumor. Unlike cutaneous melanoma, the incidence of vulvar melanoma was low but the survival was poor. There were no standard staging system and no census on treatment strategies of vulvar melanoma. Therefore, we aimed to conduct and validate a comprehensive prognostic model for predicting overall survival of vulvar melanoma and provide guidance for clinical management. Methods Patients diagnosed with vulvar melanoma between year 2004 and 2015 from Surveillance, Epidemiology, and End Result (SEER) database were randomized to training cohort and validation cohort. Multivariate survival analysis was performed to screen for independent factors of survival. A nomogram was established to predict overall survival of vulvar melanoma. Receiver operating characteristic curve and calibration plot were performed to verify the discrimination and accuracy of the model. The decision curve analysis was performed to verify the clinical applicability of the model. Results Total 737 patients with vulvar melanoma were randomized to the training cohort (n = 517) and the validation cohort (n = 220). Nomogram including age, race, tumor site, depth of tumor invasion, lymph node status, distant metastasis, tumor size, surgery, chemotherapy and radiotherapy was established and validated. The c-indexes for SEER stage, American Joint Committee on Cancer stage and this model were 0.561, 0.635 and 0.826, respectively. The high-risk group scored by this model had worse survival than the low-risk group (P < 0.001). Decision curve analysis revealed this model was superior in predicting survival. Conclusions Our model was deemed to be a useful tool for predicting overall survival of vulvar melanoma with good discrimination and clinical applicability. We hoped this model would assist gynecologists in clinical decision and management of patients diagnosed with vulvar melanoma.

EML4-ALK, a potential therapeutic target that responds to alectinib in ovarian cancer

Abstract Ovarian cancer is prone to recurrence and chemotherapy resistance. Ovarian tumours of some patients have been positive for anaplastic lymphoma kinase fusion gene expression (ALK+). Preclinical studies indicate that anaplastic lymphoma kinase inhibitor can suppress the growth of ovarian cancer cells and transplantation tumours. Here, we present a patient with metastatic ALK+ high-grade serous ovarian cancer that testing positive for EML4-ALK (microtubule-associated protein-like 4 gene, fused to the anaplastic lymphoma kinase gene), experienced dramatic benefit after administration of the anaplastic lymphoma kinase inhibitor alectinib. This is the first clinical evidence that treatment with alectinib may provide a personalized maximum benefit for patients with high-grade serous ovarian cancer who are positive for EML4-ALK.

Risk-reducing mastectomy for women with hereditary breast and ovarian cancer (HBOC): analytical results of data from the Japanese Organization of HBOC

AbstractBackgroundRisk-reducing mastectomy is one option for women with hereditary breast and ovarian cancer to reduce the risk of breast cancer.Patients and methodsWe analyzed data of the Japanese Organization of Hereditary Breast and Ovarian Cancer on women who were diagnosed as hereditary breast and ovarian cancer by BRCA germline genetic testing between 2010 and 2019 to reveal the rate and likelihood of risk-reducing mastectomy.ResultsThere were 412 women with BRCA1, 271 with BRCA2 and 4 with both female pathogenic variants. Ninety (13.1%) received risk-reducing mastectomy. The rates of risk-reducing mastectomy were statistically significantly higher in women with BRCA1 pathogenic variants than BRCA2, in women who had breast cancer than those who did not, in women with a breast cancer family history than in those without, in mothers than in those without children, in women who were receiving surveillance with MRI than those who were not and in women who received risk-reducing salpingo-oophorectomy than in those who did not on univariate analyses. The ages when they received the genetic testing were statistically significantly younger in the women receiving risk-reducing mastectomy than those who did not receive it. The women with BRCA1 pathogenic variants, personal history of breast cancer, mothers, those receiving MRI surveillance and younger women were independently significantly more likely to receive risk-reducing mastectomy based on multivariate analysis.ConclusionsThe rate of risk-reducing mastectomy was not high in Japan; however, risk-reducing surgery was approved by the Japanese National Medical Insurance for hereditary breast and ovarian cancer patients with breast and/or ovarian cancer in 2020, so this rate will increase.

Significance of para-aortic lymph node evaluation in patients with FIGO IIIC1 cervical cancer

Abstract Objective This study investigated the effect of para-aortic lymph node sampling or dissection in recently revised International Federation of Gynecology and Obstetrics IIIC1p cervical cancer treated with primary surgery and adjuvant radiation therapy with concurrent chemotherapy. Methods We retrospectively reviewed the records of 343 patients with early-stage cervical cancer and pathologically proven pelvic lymph node metastasis following curative surgery from 2001 to 2014. No patient had imaging evidence of para-aortic lymph node involvement, and all patients received adjuvant concurrent chemotherapy with or without concurrent chemotherapy. We investigated the significance of para-aortic lymph node sampling or dissection on disease-free survival and overall survival. Results After median follow-up of 58.3 months, 5-year disease-free survival and overall survival in all patients were 69.9 and 80.2%, respectively. Disease-free survival and overall survival did not differ between the para-aortic lymph node dissection group and the No para-aortic lymph node dissection group (P = 0.700 and P = 0.605). However, patients with para-aortic lymph node-positive disease had poorer disease-free survival and overall survival compared with those with para-aortic lymph node-negative disease (P < 0.001 and P < 0.001). Conclusions This study found no survival benefit of para-aortic lymph node evaluation among patients with International Federation of Gynecology and Obstetrics IIIC1p cervical cancer who were clinically para-aortic lymph node-negative. Although para-aortic lymph node metastasis is a poor prognosticator, the benefit of para-aortic lymph node dissection in terms of survival needs further investigation.

Construction and validation of a nomogram model for predicting CINV in patients with gynecological malignancies

Abstract Background To establish a nomogram model for predicting chemotherapy-induced nausea and vomiting (CINV) in patients with gynecological malignancies based on relevant risk factors. Methods This retrospective study included patients with gynecological malignancies hospitalized in the oncology department of Affiliated People’s Hospital of Jiangsu University between February 2020 and October 2021. Patients were divided into a training set (between February 2020 and December 2020) and a validation set (between January 2021 and October 2021). Basic and clinical characteristics were collected and analyzed by univariate and multivariate logistic regression. A nomogram was constructed and assessed with the receiver operating characteristic curve (ROC). We have also conducted an external validation using data from 297 patients with gynecological malignancies admitted to two oncology wards at our hospital (140 patients from Ward 1 and 157 patients from Ward 2). Results This study comprised 148 patients in the training set and 148 in the validation set. Multivariate analysis revealed age <60 years (OR (Odds Ratio) = 4.001, 95% CI (Confidence interval) 1.349–11.872, P = 0.012), presence of motion sickness (OR = 3.841, 95% CI 1.200–12.296, P = 0.023), history of pregnancy-related vomiting (OR = 4.067, 95% CI 1.203–13.751, P = 0.024), and the use of moderate/high emetogenic chemotherapy drugs (OR = 10.299, 95% CI 2.858–37.115, P < 0.001) as independent risk factors for CINV. These factors were incorporated into a nomogram, which exhibited an area under the ROC (AUC) of 0.844, with a sensitivity of 81.4% and specificity of 80.0% at the optimal cut-off point of 159.48. The AUC for validation was 0.945, with sensitivity and specificity of 91.5% and 87.1% at the optimal cut-off point of 159.48, respectively. The external validation results showed an AUC of 0.704 (95% CI: 0.648–0.755), with a sensitivity of 93.33% and specificity of 48.15% (P = 0.001). Conclusion The developed nomogram, incorporating age, moderate/high emetogenic chemotherapy drugs, motion sickness, and pregnancy vomiting history, showed good discrimination for CINV.

Comparison of lymphatic complications between sentinel node navigation surgery and pelvic lymphadenectomy in patients with cervical cancer

Abstract Background Sentinel node navigation surgery (SNNS) has been frequently used in early cervical cancer. However, the incidence and potential reduction of lymphatic complications following the removal of the sentinel lymph node remain unknown. Thus, this study aimed to evaluate the occurrence of lymphatic complications post sentinel node navigation surgery in patients with early cervical cancer. Methods A total of 167 patients, including 70 and 97 patients who had undergone SNNS and pelvic lymphadenectomy (PLA), respectively, were enrolled in this study. We compared the lymphatic complications (lower extremity lymphedema and pelvic lymphocele) between the SNNS and PLA groups. Results The median number of sentinel lymph nodes removed was 2 (range: 1–14). Among the 70 patients in the SNNS group, there were 0 (0%) and 3 (4.3%) occurrences of lower extremity lymphedema and pelvic lymphocele, respectively. The occurrences of lower extremity lymphedema and pelvic lymphocele were significantly lower in the SNNS group than in the PLA group, despite circumflex iliac node removal. Conclusions The occurrence of lymphatic complications (lower extremity lymphedema and pelvic lymphocele) was significantly lower in the SNNS group than in the PLA group. We found that SNNS, and not PLA, was the best treatment option for preventing the development of lower extremity lymphedema and pelvic lymphocele, despite circumflex iliac node preservation.

Perioperative treatments for stage IB–IIB uterine cervical cancer

Abstract Japan Society of Gynecologic Oncology guidelines recommended either radical hysterectomy-based approach or the definitive radiotherapy including concurrent chemoradiotherapy as primary treatment for patients with not only stage IB1/IIA1, but also stages IB2, IIA2 and IIB. Based on pathological findings of surgical specimens, patients who underwent radical hysterectomy are divided into three recurrent-risk groups, low-risk, intermediate, and high-risk groups. Although some authors reported the usefulness of adjuvant chemotherapy for intermediate/high-risk patients, radiotherapy was standard adjuvant treatment for pathological-risk patients after radical hysterectomy. It has been uncertain whether neoadjuvant chemotherapy followed by radical hysterectomy is beneficial for stage IB2–IIB patients. Recently, the randomized phase III study revealed that neoadjuvant chemotherapy followed by radical hysterectomy failed to improve survival of stage IB2–IIB patients compared to concurrent chemoradiotherapy. Majority of stage IB2–IIB patients are required adjuvant radiotherapy after radical hysterectomy. The multimodality strategy consisting of radical hysterectomy followed by adjuvant radiotherapy is associated with not only impaired quality of life, but also conflicting of cost-effectiveness. Thereby, some authors investigated the significance of multimodality strategy consisting of chemotherapy before/after radical hysterectomy for stage IB2–IIB cervical cancer. Multimodality strategy consisting of radical hysterectomy/perioperative chemotherapy needs higher curability of radical hysterectomy, higher response to perioperative chemotherapy and less perioperative complications. Consequently, gynecologic oncologists have to examine the patients strictly before treatment and judge whether radical hysterectomy-based approach or definitive irradiation is appropriate for the patient with stage IB–IIB cervical cancer.

Post-operative small pelvic intensity-modulated radiation therapy for early-stage cervical cancer with intermediate-risk factors: efficacy and toxicity

Abstract Objective The aim of the present study was to retrospectively evaluate the toxicity and efficacy of post-operative small pelvic intensity-modulated radiotherapy in early-stage cervical cancer patients with intermediate-risk factors. Methods Between 2012 and 2016, 151 patients who had cervical cancer (International Federation of Gynecology and Obstetrics stage I–IIA) with intermediate-risk factors were treated with post-operative small pelvic intensity-modulated radiotherapy. The median dose of 50.4 Gy in 28 fractions with small pelvic intensity-modulated radiotherapy was prescribed to the planning target volume. The intensity-modulated radiotherapy technique used was conventional fixed-field intensity-modulated radiotherapy or helical tomotherapy. Results The median follow-up was 37 months. The 3-year disease-free survival and overall survival rates were 89 and 96%, respectively. A total of 144 patients (95.3%) were alive at the last follow-up. In total, 6 patients (3.9%) had recurrence: locoregional recurrence in 3 patients (2%), distant metastasis in 2 (1.3%), and both in 1 (0.6%). Diarrhoea was the most common acute toxicity. There were no patients suffering from acute or late grade ≥ 3 toxicity. Only 4 patients (2.6%) had late grade 2 toxicities. Conclusions For early-stage cervical cancer patients with intermediate-risk factors, post-operative small pelvic intensity-modulated radiotherapy was safe and well tolerated. The rates of acute and late toxicities were quite satisfactory.

Interstitial lung disease caused by niraparib in ovarian cancer patient: a case report and literature review

Abstract Drug-induced interstitial lung disease (DIILD) is one of the most common and important adverse drug reactions. Still, the details of the clinical presentation of DIILD caused by poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors are unknown. A 73-year-old Japanese woman was started on niraparib maintenance therapy after radical surgery and adjuvant chemotherapy for high-grade serous carcinoma originating from the fallopian tube. Forty-seven days after starting niraparib, she presented to the hospital with dyspnea and was diagnosed with DIILD caused by niraparib. The drug was discontinued, and the patient was treated with steroid pulse therapy, and her condition improved. In clinical trials of PARP inhibitors, DIILD was reported in 0.13% of patients with olaparib, but no DIILDs, including pneumonia or pneumonitis, were reported in any patient with niraparib. This is the first report of DIILD caused by niraparib worldwide. In the future, the frequency of DIILD caused by niraparib should be clarified in real-world data.

A qualitative systematic review of the significance of adjuvant therapy in patients with low-risk endometrial cancer presenting positive peritoneal cytology: a relevant study to the guideline update for endometrial cancer by the Japan society of gynecologic oncology guideline committee

Abstract In association with an update of the Japan Society of Gynecologic Oncology clinical practice guidelines for endometrial cancer in 2023, a systematic review was conducted about the therapeutic benefit of adjuvant therapy on patients with early-stage endometrial carcinoma, who presented positive peritoneal cytology (PPC) without the risk factors for recurrence. The systematic review only included two eligible retrospective studies. Both studies included patients with risk factors for recurrence. A nationwide study in the United States reported that adjuvant chemotherapy was associated with the reduced risk of death among patients with stages I–II endometrial cancer with PPC by multivariate, propensity score-adjusted analysis. Another single-center study in Japan reported no association between adjuvant chemotherapy and relapse-free survival among patients with stage IA endometrial cancer by univariate analysis. This systematic review identified that evidence was limited with conflicting results. Continuous evaluation is warranted to address this clinical question.

Comparison of radio-isotope method with 99m technetium and near-infrared fluorescent imaging with indocyanine green for sentinel lymph node detection in endometrial cancer

Abstract Background We aimed to compare the detection rate of pelvic sentinel lymph node between the radio-isotope with 99m technetium (99mTc)-labeled phytate and near-infrared fluorescent imaging with indocyanine green in patients with endometrial cancer. Methods This study included 122 patients who had undergone sentinel lymph node mapping using 99mTc and indocyanine green. In the radio-isotope method, sentinel lymph nodes were detected using uterine cervix 99mTc injections the day before surgery. Following injection, the number and locations of the sentinel lymph nodes were evaluated by lymphoscintigraphy. In addition, indocyanine green was injected into the cervix immediately before surgery. Results The overall pelvic sentinel lymph node detection rate (at least one pelvic sentinel lymph node detected) was not significantly different between 99mTc (95.9% [117/122]) and indocyanine green (94.3% [115/122]). Similarly, the bilateral sentinel lymph node detection rate was not significantly different between 99mTc (87.7% [107/122]) and indocyanine green (79.5% [97/122]). More than two sentinel lymph nodes per unilateral pelvic lymph node were found in 12.3% (15/122) and 27% (33/122) of cases with 99mTc and indocyanine green, respectively, in the right pelvic side, and 11.5% (14/122) and 32.8% (40/122) of cases with 99mTc and indocyanine green, respectively, in the left pelvic side. indocyanine green showed that there were significantly more than two sentinel lymph nodes in either the left or right pelvic sentinel lymph nodes (P < 0.0001). There was a significant difference in the mean number of total pelvic sentinel lymph nodes between 99mTc (2.2) and indocyanine green (2.5) (P = 0.028) methods. Conclusion Although indocyanine green is useful for sentinel lymph node identification, we believe it is better to use it in combination with 99mTc until the surgeon is accustomed to it.