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.

Rethinking the significance of surgery for uterine cervical cancer.

Background: Treatment strategies based on histological subtypes are unestablished.

Aims: Rethinking the significance of surgery for uterine cervical cancer.

Methods: Using the database of cervical cancer stages IB-IIB with extensive hysterectomy (Federation of Gynecology and Obstetrics [FIGO] 2008) established by the Japanese Gynecologic Oncology Group network, we conducted a clinicopathological study of cervical cancer cases reclassified according to the FIGO 2018 staging.

Is cytology/HPV co-testing for cervical cancer screening useful in Japan?

Objective: In Japan, no region has introduced primary HPV testing for cervical cancer screening. We assessed the diagnostic value and possible harm of HPV testing in Japan.

Methods: This cross-sectional study with historical controls used cytology-based screening and co-testing data in Japan.

Docetaxel and carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix: a phase II study.

Background: This phase II study evaluated the efficacy and safety of docetaxel/carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix.

Methods: A total of 50 patients with International Federation of Gynecology and Obstetrics stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix were enrolled and administered docetaxel at a dose of 60 mg/m, followed by carboplatin at a dose based on the area under the receiver operating characteristic curve of 6. The treatments were repeated every 21 days until disease progression or unacceptable adverse events.

Impact of Histopathological Risk Factors on the Treatment of Stage IB-IIB Uterine Cervical Cancer.

In the past decade, the incidence of adenocarcinoma of the uterine cervix gradually increased. Recent literature revealed that the molecular pathogenesis differs by histological subtype, and the histological subtype should be considered in deciding treatments for patients with uterine cervical cancer. However, no treatment based on histological type or genomic signature has been recommended in various treatment guidelines.

Phase II study of a new multidisciplinary therapy using once every 3 week carboplatin plus dose-dense weekly paclitaxel before and after radical hysterectomy for locally advanced cervical cancer.

Background: We proposed a novel treatment strategy, consisting of triweekly cisplatin plus dose-dense weekly paclitaxel before and after radical hysterectomy without adjuvant radiation therapy to treat locally advanced cervical cancer. However, cisplatin-related severe non-hematologic toxicities were frequent during this strategy. This study aimed to assess the applicability of replacing cisplatin with carboplatin in our proposed strategy.

Implementation of primary HPV testing in Japan.

Cervical cancer screening has been shifting from primary cytology to primary HPV testing worldwide as primary HPV testing is more sensitive than primary cytology. To the best of our knowledge, the current study is the first in Japan to examine the feasibility of primary HPV testing. One of the disadvantages of this shift is that hrHPV-/≥LSIL/CIN2+ (high-risk HPV negative cancers or pre-cancerous lesions with abnormal cytology results) can be missed.

Association of gBRCA1/2 mutation locations with ovarian cancer risk in Japanese patients from the CHARLOTTE study.

Whether germline (g) breast cancer susceptibility gene (BRCA) mutations are located within or outside the ovarian cancer cluster region (OCCR) (1380-4062 bp for gBRCA1, and between 3249-5681 bp and 6645-7471 bp for gBRCA2) may influence risk variations for ovarian cancers. This ad hoc analysis of the CHARLOTTE epidemiological study in Japan assessed the distribution of gBRCA1/2 mutations in patients with newly diagnosed ovarian cancer, and investigated an association between gBRCA1/2 mutation locations and ovarian cancer risk. Differences in patient background and clinical characteristics in subgroups stratified by gBRCA1/2 mutation locations were also evaluated.

The first Japanese nationwide multicenter study of mutation testing in ovarian cancer: CHARacterizing the cross-sectionaL approach to Ovarian cancer geneTic TEsting of (CHARLOTTE).

Introduction: gene mutations are associated with hereditary ovarian cancer. plays a key role in genome integrity, and mutations result in an increased risk for ovarian cancer. Although various guidelines recommend testing in patients with ovarian cancer, data on germline (g) mutation frequency in ovarian cancer in Japan are scarce.

A phase II randomized controlled study of pegylated liposomal doxorubicin and carboplatin vs. gemcitabine and carboplatin for platinum-sensitive recurrent ovarian cancer (GOTIC003/intergroup study).

Purpose: To compare the efficacy, safety, and tolerability profiles of pegylated liposomal doxorubicin and carboplatin (PLDC) with those of gemcitabine and carboplatin (GC) for the treatment of patients with platinum-sensitive recurrent ovarian cancer.

Methods: Ovarian cancer patients with recurrence > 6 months after first-line platinum and taxane-based therapies were randomly assigned to PLDC [pegylated liposomal doxorubicin 30 mg/m plus carboplatin area under the curve (AUC) 5 mg/mL/min on day 1] every 4 weeks or GC (gemcitabine 1000 mg/m on days 1 and 8 plus carboplatin AUC 4 mg/mL/min on day 1) every 3 weeks for at least 6 cycles. The primary endpoint was progression-free survival, and overall response rate, overall survival, toxicity, and dose administration were secondary endpoints.

Neoadjuvant Chemotherapy with Taxane and Platinum Followed by Radical Hysterectomy for Stage IB2-IIB Cervical Cancer: Impact of Histology Type on Survival.

The current study examined the histology-specific impact of neoadjuvant chemotherapy (NACT) with a taxane/platinum regimen on survival in women with locally-advanced cervical cancer who underwent radical hysterectomy. This nation-wide retrospective cohort study examined women with clinical stage IB2-IIB cervical cancer who received NACT prior to radical hysterectomy from 2004⁻2008 ( = 684). NACT type (taxane/platinum others) was correlated with survival based on histology: 511 squamous 173 non-squamous.

An open-label, randomized, phase II trial evaluating the efficacy and safety of standard of care with or without bevacizumab in platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer patients previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer: rationale, design, and methods of the Japanese Gynecologic Oncology Group study JGOG3023.

Background: We present the study rationale and design of the JGOG3023 study, an open-label, parallel-arm, randomized, phase II trial that aimed to assess the efficacy and safety of chemotherapy with or without bevacizumab in patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer. We hypothesize that patients treated with a combination of single-agent chemotherapy and bevacizumab will show improved progression-free survival (PFS) compared with those treated with single-agent chemotherapy alone, in the setting beyond disease progression following prior bevacizumab treatment.

Methods/design: A total of 106 patients who have recurrence or progression of ovarian cancer, while receiving chemotherapy or within 6 months after the final dose of platinum, after completing at least three cycles of bevacizumab plus platinum chemotherapy will be randomized in a 1:1 ratio to treatment with single-agent chemotherapy or single-agent chemotherapy combined with bevacizumab.

Impact of institutional accreditation by the Japan Society of Gynecologic Oncology on the treatment and survival of women with cervical cancer.

Objective: The Japan Society of Gynecologic Oncology (JSGO) initiated a nation-wide training system for the education and certification for gynecologic oncologists in 2005. To assess the impact of the quality of the JSGO-accredited institutions, JSGO undertook an analysis of the Uterine Cervical Cancer Registry of the Japan Society of Obstetrics and Gynecology (JSOG) to determine the effectiveness of the JSGO-accredited institutions on the treatment and survival of women with cervical cancer.

Methods: The effectiveness of 119 JSGO-accredited institutions and 125 non-JSGO-accredited institutions on the treatment and survival of women with cervical cancer were compared by analyzing the tumor characteristics, treatment patterns, and survival outcomes of women with stage T1B-T4 cervical cancer utilizing the data in the JSOG nation-wide registry for cervical cancer (2006-2009).

Chemoresistance of Gastric-Type Mucinous Carcinoma of the Uterine Cervix: A Study of the Sankai Gynecology Study Group.

Objective: Gastric-type mucinous carcinoma (GAS) is a novel variant of mucinous carcinoma of the uterine cervix, characterized by aggressive clinical behavior and absence of high-risk human papillomavirus. We conducted this study to evaluate the chemosensitivity of GAS compared with that of usual-type endocervical adenocarcinoma (UEA) in patients who had been enrolled in our previous study.

Methods: Of 52 patients from our previous phase 2 study (SGSG005) of neoadjuvant chemotherapy with docetaxel and carboplatin for stage IB2 to IIB nonsquamous cervical cancer, 47 (stage IB2, 12; stage IIA2, 7; stage IIB, 28) were enrolled in this study with written informed consent.

Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma.

Background: Ovarian clear cell carcinoma (OCCC) is mostly resistant to standard chemotherapy that results in poor patient survival. To understand the genetic background of these tumours, we performed whole-genome sequencing of OCCC tumours.

Methods: Tumour tissue samples and matched blood samples were obtained from 55 Japanese women diagnosed with OCCC.

Cisplatin with dose-dense paclitaxel before and after radical hysterectomy for locally advanced cervical cancer: a prospective multicenter phase II trial with a dose-finding study.

The aim of this study is to evaluate the outcome and safety of the multidisciplinary strategy using cisplatin plus dose-dense paclitaxel (dose-dense TP) before and after radical hysterectomy (RH) for stage IB2, IIA2, or IIB patients with cervical cancer. In the dose-finding phase, 12 patients received 3 cycles of cisplatin (75 mg/m, day 1) with paclitaxel (70 or 80 mg/m, days 1, 8, and 15) every 21 days as neoadjuvant chemotherapy (NAC). In the phase II study, 51 patients received 3 cycles of dose-dense TP at the recommended dose as NAC, and another 2 cycles of the same regimen after RH.

Neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy for stage IB2, IIA2, and IIB patients with non-squamous cell carcinoma of the uterine cervix.

Background: We conducted a phase II study to evaluate the efficacy of neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy for patients with non-squamous cell carcinoma of the uterine cervix.

Methods: Sixty-one patients with International Federation of Gynecology and Obstetrics stage IB2, IIA2, or IIB non-squamous cell carcinoma of the uterine cervix were enrolled. The patients were administered docetaxel at a dose of 60 mg/m, followed by carboplatin at a dose based on an area under the curve of 6.

Feasibility study on combination chemotherapy using nogitecan hydrochloride (topotecan) and cisplatin for patients with metastatic, persistent, or recurrent uterine cervical cancer.

Background: The standard chemotherapeutic regimen for stage IVB, persistent, or recurrent uterine cervical cancer is platinum-based combination chemotherapy such as cisplatin (CDDP)/paclitaxel and CDDP/nogitecan hydrochloride (NGT, topotecan). Because it is unclear whether the CDDP/NGT combination chemotherapy is tolerable for Japanese patients, we conducted the present study to assess the feasibility of CDDP/NGT combination chemotherapy.

Methods: Between June 2012 and April 2014, 15 patients with stage IVB, persistent, or recurrent uterine cervical cancer were enrolled in this study.

Feasibility Study of Adjuvant Chemotherapy Using Taxane Plus Carboplatin for High-Risk Patients With Uterine Cervical Non-Squamous Cell Carcinoma After Radical Hysterectomy.

Objective: We conducted this study to evaluate the efficacy and safety of adjuvant chemotherapy using taxane plus carboplatin (CBDCA) for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy.

Methods: Thirty-seven patients were eligible. Pelvic lymph node involvement and/or parametrial invasion were defined as high-risk factors.

Human papillomavirus type-specific persistence and reappearance after successful conization in patients with cervical intraepithelial neoplasia.

Objective: To assess the relationship between pre- and postoperative high-risk human papillomavirus (hrHPV) genotypes and hrHPV type-specific persistence and reappearance of abnormal cytology after successful conization.

Methods: A retrospective analysis was performed of 211 patients who were undergoing conization after hrHPV genotype testing at Tottori University Hospital between July 2009 and June 2013. Of the 211 women, 129 underwent pre- and postoperative hrHPV genotype testing and were diagnosed with cervical intraepithelial neoplasia (CIN) grades 1-3 with negative margins.

What is an appropriate second-line regimen for recurrent endometrial cancer? Ancillary analysis of the SGSG012/GOTIC004/Intergroup study.

Purpose: We previously reported that the concept of "platinum sensitivity" could be applied to recurrent endometrial cancer. We conducted an ancillary analysis to determine an appropriate second-line regimen for patients who received a platinum agent as first-line chemotherapy.

Methods: We extracted and reanalyzed data of patients treated with doxorubicin and cisplatin (AP), paclitaxel and carboplatin (TC), or docetaxel and carboplatin (DC) as first- and second-line chemotherapies from the SGSG012/GOTIC004/Intergroup study.

Loss of ARID1A expression is associated with poor prognosis in patients with stage I/II clear cell carcinoma of the ovary.

Background: Recent studies have shown that somatic mutations in the AT-rich interactive domain 1A (SWI-like) gene (ARID1A) are the most common genetic changes in clear cell carcinoma of the ovary (CCC). A gene mutation of ARID1A was found in approximately half of CCC cases, and led to absence of the encoded protein and inactivation of the putative tumor suppressor. Here, we investigated whether ARID1A could be a prognostic biomarker for this disease.

Somatic copy number alterations associated with Japanese or endometriosis in ovarian clear cell adenocarcinoma.

When compared with other epithelial ovarian cancers, the clinical characteristics of ovarian clear cell adenocarcinoma (CCC) include 1) a higher incidence among Japanese, 2) an association with endometriosis, 3) poor prognosis in advanced stages, and 4) a higher incidence of thrombosis as a complication. We used high resolution comparative genomic hybridization (CGH) to identify somatic copy number alterations (SCNAs) associated with each of these clinical characteristics of CCC. The Human Genome CGH 244A Oligo Microarray was used to examine 144 samples obtained from 120 Japanese, 15 Korean, and nine German patients with CCC.