Niraparib as maintenance therapy in Japan: a retrospective observational study using a Japanese claims database.

OBJECTIVE: Epithelial ovarian cancer (EOC) is the leading cause of female mortality in gynecologic malignancies, with a rising incidence in Japan. This study aimed to validate the treatment patterns and safety of niraparib as maintenance therapy for EOC following initial chemotherapy in clinical practice in Japan. METHODS: Leveraging claims data between April 2008 and December 2022, this descriptive study comprised EOC-diagnosed patients receiving initial platinum-based chemotherapy, debulking surgery, and niraparib as maintenance therapy. Patient characteristics, prescription status, transfusion details, and laboratory data were assessed and reported as summary statistics and frequencies. RESULTS: Among 291 patients, the median age was 64.0 years and 94.5% received a 200-mg daily dose of niraparib. At week 12, 78.7% (229/291) continued niraparib treatment, 21.3% (62/291) discontinued, and 52.2% (152/291) required treatment interruptions. Of the 62 patients who discontinued treatment, 27 patients initiated subsequent EOC treatment within 12 weeks following niraparib discontinuation. Blood transfusions were needed in 10.3% (30/291), and of 55 patients with available laboratory data, 61.8% (34/55) had decreased platelet count <100,000/µL, 25.5% (14/55) had decreased hemoglobin level <8 g/dL, and 22.7% (5/22) had decreased neutrophil count <1,000/µL, meeting the criteria for treatment interruption. Among those with thrombocytopenia, 88.2% (30/34) were able to either resume or continue treatment. CONCLUSION: Niraparib demonstrated favorable tolerability in Japanese patients with advanced EOC, with effective management of thrombocytopenia through dose adjustments and supportive care, supporting its viability as post-chemotherapy maintenance therapy.

Detailed report on the clinicopathological factors of patients with endometrial cancer in Japan: a JSOG gynecologic tumor registry-based study.

OBJECTIVE: In this study, we collected data over 8 years (2012-2019) from the Japan Society of Obstetrics and Gynecology (JSOG) tumor registry to determine the status of endometrial cancer in Japan, and analyzed detailed clinicopathological factors. METHODS: The JSOG maintains a tumor registry that gathers information on endometrial cancer treated at the JSOG-registered institutions. Data from the patients whose endometrial cancer treatment was initiated from 2012 to 2019 were analyzed retrospectively. RESULTS: A total of 82,969 patients with endometrial cancer underwent treatment from 2012 to 2019. Chemotherapy alone or in combination with hormonal therapy is more common among endometrial cancer patients under 40 years compared with those over 40 years. The number of patients with endometrial cancer, treated with laparoscopic or robot-assisted surgery was observed to have increased yearly. Small cell carcinomas and undifferentiated carcinomas were more likely to be diagnosed at an advanced stage. Lymphadenectomy was most commonly performed for stage IIIC2 disease, whereas positive peritoneal washing cytology was most common for stage IVB and serous carcinoma. CONCLUSION: Multi-year summary reports provided detailed clinicopathological information regarding endometrial cancer that could not be obtained in a single year. These reports were useful in understanding treatment strategies and trends over time based on age, histology, and stage.

Quality of care measurement for patients with ovarian cancer in Japan.

AIM: Quality of care is important to reduce disease progression, and improve both survival and quality of life. The Japan Society of Gynecologic Oncology has published treatment guidelines to promote standardized high-quality care for ovarian cancer in Japan. We developed quality indicators based on the guideline recommendations and used them on large datasets of health service use to examine the quality of ovarian cancer care. METHODS: A panel of experts developed the indicators using a modified Delphi method. Adherence to each indicator was evaluated using data from a hospital-based cancer registry of patients diagnosed in 2018. All patients receiving first-line treatment at participating facilities were included. The adherence rates were returned to participating hospitals, and reasons for nonadherence were collected. A total of 580 hospitals participated, and the study examined the care received by 6611 patients with ovarian cancer and 1879 with borderline tumors using 11 measurable quality indicators. RESULTS: The adherence rate ranged from 22.6% for "Estrogen replacement within 6 months of operation" to 93.5% for "Bleomycin, etoposide, and cisplatin for germ cell tumor more than Stage II." Of 580 hospitals, 184 submitted the reasons for nonadherence. CONCLUSIONS: The quality of ovarian cancer care should be continuously assessed to encourage the use of best practices. These indicators may be a useful tool for this purpose.

A survey of carboplatin desensitization therapy in Japan: A multicenter retrospective study.

INTRODUCTION: Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. METHODS: Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. RESULTS: This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre-existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620-18,282) mg, and the mean number of doses was 14 (4-63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. CONCLUSION: Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

Long-Term and Short-Interval Assessment of Self-Reported Urinary and Sexual Functions after Nerve-Sparing Radical Hysterectomy: A Prospective Cohort Study.

The aim of this study was to determine the impact of nerve preservation confirmed by intraoperative electrical stimulation (IES) on subjective symptoms of urinary and sexual function in uterine cervical cancer patients who underwent radical hysterectomies. This study included 85 patients who underwent type C radical hysterectomy with IES. Pelvic splanchnic nerve preservation with IES after hysterectomy (nerve-stimulation positive group) was confirmed in 61 women and 24 women did not have nerve preservation (negative group). Urinary function was assessed with the Overactive Bladder Symptom Score (OABSS), International Prostate Symptom Score (IPSS), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaires. Sexual function was surveyed using the Female Sexual Function Index (FSFI). Longitudinal changes in those scores according to response to nerve-stimulation were evaluated using a generalized estimating equation. IPSS quality of life (QOL) scores were significantly better in the nerve-stimulation positive group compared with the scores in the negative group until 12 months after surgery, whereas OABSS, IPSS total, IPSS voiding, and ICIQ-SF scores evaluating urinary symptoms were not significantly different between the two groups. FSFI scores were better in the nerve-stimulation positive group 36 months after surgery compared with the scores in the negative group. In this study, we assessed self-reported urinary and sexual symptoms after nerve-sparing radical hysterectomy (NSRH) with IES in the long term. We demonstrated that nerve-sparing significantly reduced distress associated with QOL until 1 year, improved urinary storage symptoms at 2 years, and sexual symptoms 3 years after surgery.

Impact of COVID-19 on gynecological cancer incidence: a large cohort study in Japan.

BACKGROUND: The influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of newly diagnosed gynecological cancers has not been extensively investigated in Japan. This study determined the impact of COVID-19 on the incidence of gynecological cancer. METHODS: Using the Japanese Society of Obstetricians and Gynecologic Oncology registry database, the distribution of the number of patients based on clinical staging or tumor-node-metastasis classifications before and during the COVID-19 pandemic was analyzed to compare the trends. The clinical staging classification of cervical cancer in Japan was based on the International Federation of Gynecology and Obstetrics (FIGO) 2008 from 2018 to 2020 and on the FIGO 2018 from 2021. Since FIGO-2018 classified N1 cases as stage IIIC, we focused on T classification without referencing the clinical staging (FIGO staging) of patients with cervical cancer in 2021. RESULTS: The number of patients with endometrial cancer and malignant ovarian tumors of all clinical stages increased uniformly yearly, while that of those with stage III cervical cancer rapidly increased in 2021 owing to the adoption of the revised classification. On comparing cases of cervical cancer in 2020 and 2021, we found that T1 cases decreased and T2 and T3 cases increased in 2021 compared to those in 2020 (p = 0.006). Cervical intraepithelial neoplasia/adenocarcinoma in situ incidence decreased in 2020 compared to that in 2019 but increased again in 2021. The number of patients with cervical cancer decreased in most prefectures in 2020. CONCLUSION: The incidence of locally advanced cervical cancer increased during the COVID-19 pandemic.

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.

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.

Lenvatinib plus Pembrolizumab Combination Therapy for Advanced or Recurrent Endometrial Cancer: A Single-Center, Retrospective Analysis.

A multi-kinase inhibitor, lenvatinib, plus an immune checkpoint inhibitor, pembrolizumab, became a viable therapeutic option for advanced or recurrent endometrial cancer in Japan by the end of 2021. The Japanese population has a relatively unique genetic background. Hence, the safety profile and effectiveness of lenvatinib plus pembrolizumab may differ between the Japanese and other populations. This single-center, retrospective study aimed to evaluate the treatment efficacy of lenvatinib plus pembrolizumab and the safety profile of the associated adverse events. The clinical records of 15 patients, who received lenvatinib plus pembrolizumab for advanced or recurrent endometrial cancer at the Tohoku University Hospital, were reviewed. Best overall response and disease control rates were 40.0% and 73.3%, respectively. Treatment was discontinued owing to disease progression and adverse events in six patients, respectively. As of the end of July 2023, treatment was ongoing in the remaining three patients. The median treatment and progression-free survival durations were 118 and 258 days, respectively. Relative dose intensity of lenvatinib was not positively associated with progression-free survival, neither during the first 4 weeks after treatment initiation nor during the entire treatment period. All patients experienced one or more adverse events, the most common of which were hypothyroidism (90%) and hypertension (83.3%). Among the 15 patients, 13 required lenvatinib dose reduction owing to adverse events. One patient developed grade 4 interstitial pneumonia requiring intensive care. Our results validate the short-term efficacy of lenvatinib plus pembrolizumab, and indicate that dose optimization of lenvatinib could be individualized without impairing efficacy.

Japan Society of Gynecologic Oncology 2022 guidelines for uterine cervical neoplasm treatment.

The Japan Society of Gynecologic Oncology (JSGO) Guidelines 2022 for the Treatment of Uterine Cervical Cancer are revised from the 2017 guideline. This guideline aimed to provide standard care for cervical cancer, indicate appropriate current treatment methods for cervical cancer, minimize variances in treatment methods among institutions, improve disease prognosis and treatment safety, reduce the economic and psychosomatic burden of patients by promoting the performance of appropriate treatment, and enhance mutual understanding between patients and healthcare professionals. The guidelines were prepared through the consensus of the JSGO Guideline Committee, based on a careful review of evidence gathered through the literature searches and the medical health insurance system and actual clinical practice situations in Japan. The guidelines comprise seven chapters and 5 algorithms. The main features of the 2022 revision are as follows: 1) added discussed points at the final consensus meeting; 2) revised the treatment methods based on the International Federation of Gynecology and Obstetrics 2018 staging system; 3) examined minimally invasive surgery based on Laparoscopic Approach to Cervical Cancer trial; 4) added clinical question (CQ) for treatments of rare histological types, gastric type, and small-cell neuroendocrine carcinoma; 5) added CQ for intensity-modulated radiation therapy; 6) added CQ for cancer genomic profiling test; and 7) added CQ for cancer survivorship. Each recommendation is accompanied by a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSGO Guidelines 2022 for the Treatment of Uterine Cervical Cancer.

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

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

Intratumoral cortisol associated with aromatase in the endometrial cancer microenvironment.

Glucocorticoids bind to glucocorticoid receptors (GR). In the peripheral tissues, active cortisol is produced from inactive cortisone by 11ß-hydroxysteroid dehydrogenase (HSD)1. 11ß-HSD2 is responsible for this reverse catalysis. Although GR and 11ß-HSDs have been reported to be involved in the malignant behavior of various cancer types, the concentration of glucocorticoids in cancer tissues has not been investigated. In this study, we measured glucocorticoids in serum and cancer tissues using liquid chromatography-tandem mass spectrometry and clarified, for the first time, the intratumoral "intracrine" production of cortisol by 11ß-HSD1/2 in endometrial cancer. Intratumoral cortisol levels were high in the high-malignancy type and the cancer proliferation marker Ki-67-high group, suggesting that cortisol greatly contributes to the malignant behavior of endometrial cancer. A low expression level of the metabolizing enzyme 11ß-HSD2 is more important than a high expression level of the synthase 11ß-HSD1 for intratumoral cortisol action. Intratumoral cortisol was positively related to the expression/activity of estrogen synthase aromatase, which involved GR expressed in fibroblastic stromal cells but not in cancer cells. Blockade of GR signaling by hormone therapy is expected to benefit patients with endometrial cancer.

Identification of predictive biomarkers for endometrial cancer diagnosis and treatment response monitoring using plasma metabolome profiling.

BACKGROUND: Endometrial cancer (EMC) is the most common female genital tract malignancy with an increasing prevalence in many countries including Japan, a fact that renders early detection and treatment necessary to protect health and fertility. Although early detection and treatment are necessary to further improve the prognosis of women with endometrial cancer, biomarkers that accurately reflect the pathophysiology of EMC patients are still unclear. Therefore, it is clinically critical to identify biomarkers to assess diagnosis and treatment efficacy to facilitate appropriate treatment and development of new therapies for EMC. METHODS: In this study, wide-targeted plasma metabolome analysis was performed to identify biomarkers for EMC diagnosis and the prediction of treatment responses. The absolute quantification of 628 metabolites in plasma samples from 142 patients with EMC was performed using ultra-high-performance liquid chromatography with tandem mass spectrometry. RESULTS: The concentrations of 111 metabolites increased significantly, while the concentrations of 148 metabolites decreased significantly in patients with EMC compared to healthy controls. Specifically, LysoPC and TGs, including unsaturated fatty acids, were reduced in patients with stage IA EMC compared to healthy controls, indicating that these metabolic profiles could be used as early diagnostic markers of EMC. In contrast, blood levels of amino acids such as histidine and tryptophan decreased as the risk of recurrence increased and the stages of EMC advanced. Furthermore, a marked increase in total TG and a decrease in specific TGs and free fatty acids including polyunsaturated fatty acids levels were observed in patients with EMC. These results suggest that the polyunsaturated fatty acids in patients with EMC are crucial for disease progression. CONCLUSIONS: Our data identified specific metabolite profiles that reflect the pathogenesis of EMC and showed that these metabolites correlate with the risk of recurrence and disease stage. Analysis of changes in plasma metabolite profiles could be applied for the early diagnosis and monitoring of the course of treatment of EMC patients.

Diagnostic Performance of Preoperative Imaging in Endometrial Cancer.

BACKGROUND: Endometrial cancer is one of the most common gynecological malignancies. Because the findings mentioned in radiogram interpretation reports issued by diagnostic radiologists influence treatment strategies, we aimed to evaluate the diagnostic accuracy of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) interpretation results in clinically relevant settings. METHODS: The clinical records of patients diagnosed with endometrial cancer treated at Tohoku University Hospital from January 2012 to December 2021 were reviewed. The preoperative and pathologically estimated cancer stages were compared based on the results mentioned in the radiogram interpretation report. RESULTS: The preoperative and postoperative cancer stages were concordant in 70.0% of the patients. By contrast, the cancer stage was underdiagnosed and overdiagnosed in 21.7% and 8.2% of the patients, respectively. The sensitivities of MRI for deep myometrial invasion, cervical stromal invasion, vaginal invasion, and adnexal metastasis were 65.1%, 58.2%, 33.3%, and 18.4%, respectively. The sensitivity and specificity for pelvic lymph node metastasis using a combination of CT and MRI were 40.9% and 98.4%, respectively. Those for para-aortic lymph node metastases using CT were 37.0% and 99.5%, respectively. CONCLUSIONS: The low sensitivity observed in this study clarified the limitations of preoperative diagnostic performance in current clinical practice.

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

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

Assessing the Significance of Lymphadenectomy in Older Patients with Stage I Endometrial Cancer: A Single-Center, Retrospective Cohort Study.

Advantages of lymphadenectomy for early stage endometrial cancer remain controversial. Lymphadenectomy had been routinely omitted for patients aged ≥ 70 years at our institute if lymph node metastasis was unsuspected due to an increased risk of peri- and postsurgical complications. Since 2013, with the introduction of minimally invasive surgery and considering the heterogeneous medical conditions, we started performing lymphadenectomy in patients who were considered well-tolerated. We retrospectively investigated our clinical database to assess the effect of lymphadenectomy in older patients with early stage endometrial carcinoma. Patients aged ≥ 70 years, preoperatively diagnosed with stage I endometrial carcinoma, and who underwent lymphadenectomy between 2013 and 2021 at Tohoku University Hospital were included in the lymphadenectomy group (n = 33), whereas patients who underwent surgery without lymphadenectomy before the end of 2012 were included in the no-lymphadenectomy group (n = 49). Clinical parameters and patient outcomes, such as disease-free survival (DFS) and disease-specific survival (DSS), were compared. The median age was significantly higher and fewer patients received adjuvant chemotherapy in the no-lymphadenectomy group. Neither DSS nor DFS differed significantly between the two groups. Five-year-DFS rates were 77.2% and 82.5% and 5-year-DSS rates were 89.7% and 97.8% for the lymphadenectomy and no-lymphadenectomy groups, respectively. No significant differences were observed in the subsequent survival analysis by substage, histological subtype, or risk of recurrence. Our results suggest that the indications for lymphadenectomy in older patients should be individually optimized according to the risk of recurrence and postoperative complications.

Identification of predictive biomarkers for diagnosis and radiation sensitivity of uterine cervical cancer using wide-targeted metabolomics.

AIM: Uterine cervical cancer (UCC) is the fourth most common cancer in women, responsible for more than 300 000 deaths worldwide. Its early detection, by cervical cytology, and prevention, by vaccinating against human papilloma virus, greatly contribute to reducing cervical cancer mortality in women. However, penetration of the effective prevention of UCC in Japan remains low. Plasma metabolome analysis is widely used for biomarker discovery and the identification of cancer-specific metabolic pathways. Here, we aimed to identify predictive biomarkers for the diagnosis and radiation sensitivity of UCC using wide-targeted plasma metabolomics. METHODS: We analyzed 628 metabolites in plasma samples obtained from 45 patients with UCC using ultra-high-performance liquid chromatography with tandem mass spectrometry. RESULTS: The levels of 47 metabolites were significantly increased and those of 75 metabolites were significantly decreased in patients with UCC relative to healthy controls. Increased levels of arginine and ceramides, and decreased levels of tryptophan, ornithine, glycosylceramides, lysophosphatidylcholine, and phosphatidylcholine were characteristic of patients with UCC. Comparison of metabolite profiles in groups susceptible and non-susceptible to radiation therapy, a treatment for UCC, revealed marked variations in polyunsaturated fatty acid, nucleic acid, and arginine metabolism in the group not susceptible to treatment. CONCLUSIONS: Our findings suggest that the metabolite profile of patients with UCC may be an important indicator for distinguishing these patients from healthy cohorts, and may also be useful for predicting sensitivity to radiotherapy.

Retrospective analysis of local recurrence pattern by computed tomography image-guided intracavitary and interstitial brachytherapy for locally advanced cervical cancer in a single Japanese institution.

PURPOSE: The purpose of this study was to investigate the treatment results with focus on local control (LC) by computed tomography (CT)-guided intracavity brachytherapy and interstitial brachytherapy (ICBT/ISBT) for locally advanced cervical cancer (LACC). METHODS AND MATERIALS: Patients with LACC undergoing ICBT/ISBT at least once in our institution between January 2017 and June 2019 were analyzed retrospectively. The primary endpoint was local control (LC), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and late toxicities. Differences between patient subgroups for prognostic factors in LC, PFS, and OS were analyzed using the log-rank test. The recurrence patterns of LC were also investigated. RESULTS: Forty-four patients were included in the present study. The median high-risk clinical target volume (HR-CTV) at the initial brachytherapy was 48.2 cc. The median total dose of HR-CTV D90 (EQD2) was 70.7 Gy. The median followup period was 39.4 months. The 3-year LC, PFS and OS rates in all patients were 88.2%, 56.6%, and 65.4% (95% CI 50.3-78.0%), respectively. Corpus invasion and large HR-CTV (70 cc or more) were significant prognostic factors in LC, PFS, and OS. Marginal recurrences at the fundus of the uterus were detected in 3 of 5 patients in whom local recurrence was observed. Late toxicities of Grade 3 or higher were detected in 3 patients (6.8%). CONCLUSIONS: Favorable LC was achieved by performing CT-guided ICBT/ISBT for LACC. The brachytherapy strategy for patients with corpus invasion or large HR-CTV may need to be reconsidered.

Poor Treatment Outcomes of Locally Advanced Cervical Adenocarcinoma of Human Papilloma Virus Independent Type, Represented by Gastric Type Adenocarcinoma: A Multi-Center Retrospective Study (Sankai Gynecology Study Group).

The revised World Health Organization classification of cervical cancer divides adenocarcinomas into human papillomavirus-associated (HPVa) and -independent (HPVi) types; the HPVi type is represented by the gastric type. The treatment outcomes of locally advanced adenocarcinoma (LaAC), based on this classification, are understudied. We investigated the outcomes of patients with HPVa and HPVi LaACs. Data for all consecutive patients with stage IB3 to IIIC1 adenocarcinoma who received treatment at 12 institutions throughout Japan between 2004 and 2009 were retrieved to analyze progression-free and overall survival. Central pathological review classified 103 and 48 patients as having HPVa and HPVi tumors, respectively. Usual- (84%) and gastric- (90%) type adenocarcinomas were the most frequent subtypes. Surgery was the primary treatment strategy for most patients. Progression-free and overall survival of patients with HPVi were worse than those of patients with HPVa (p = 0.009 and 0.032, respectively). Subgroup analysis by stage showed that progression-free survival was significantly different for stage IIB. The current surgical treatment strategy for LaACs is less effective for HPVi tumors than for HPVa tumors, especially those in stage IIB.

Homologous recombination inquiry through ovarian malignancy investigations: JGOG3025 Study.

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

Precautions during Direct Oral Anticoagulant Introduction in Gynecologic Malignancies: A Single-Center Retrospective Cohort Study.

The risk factors for venous thromboembolism (VTE) recurrence/exacerbation or a change from a direct oral anticoagulant (DOAC) to another anticoagulant in patients with gynecologic cancer using DOACs have not been thoroughly elucidated. Here, we aimed to investigate the risk factors for a composite primary outcome, including VTE recurrence/exacerbation, or a change from a DOAC to another anticoagulant, in this population. A total of 63 patients were analyzed. Risk factors for a primary outcome within 2 years after DOAC initiation were investigated using multiple logistic regression analysis. Among the 63 patients, 10 developed a primary outcome. Clear cell carcinoma of the ovary (adjusted odds ratio (aOR), 18.9; 95% confidence interval (CI), 2.25-350.74), pulmonary embolism (PE) or proximal deep vein thrombosis without PE (aOR, 55.6; 95% CI, 3.29-11,774.66), and D-dimer levels in the third tertile (≥7.6 µg/dL) when VTE was first diagnosed (aOR, 6.37; 95% CI, 1.17-66.61) were associated with increased odds of a primary outcome in patients with gynecologic cancer using DOACs. Patients with one or more risk factors for a primary outcome require careful follow-up after DOAC initiation for the early recognition of treatment failure.