Manabu Seino

Investigation of tumor mutation burden using the comprehensive genomic profiling data of vulvar and vaginal malignant tumors: an observational study using C-CAT database

This study aimed to reveal the gene alteration and tumor mutation burden (TMB) statuses of vulvar and vaginal malignant tumors in Japan. We investigated the cancer genomic profiling (CGP) data of 79 patients with vulvar and vaginal cancers. These data were obtained from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT). None of the patients had high microsatellite instability. Although 21.9% of the patients with vulvar and vaginal squamous cell carcinoma (SCC) had high TMB, those with other histological types did not. The top single-nucleotide variants (SNVs) in SCC were TERT, TP53, CDKN2A, KMT2D, and NOTCH1. The frequencies of ATRX and PBRM1 were significantly higher in TMB-high SCC than in non-TMB-high SCC. SCC of the vulva and vagina is expected to have high TMB, and gene alteration status differed between TMB-high and non-TMB-high groups.

Impact of adjuvant chemotherapy on the overall survival of patients with resectable bulky small cell neuroendocrine cervical cancer: a JSGO-JSOG joint study

The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment. The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology between 2004 and 2015. All cases were modified and unified by International Federation of Gynecology and Obstetrics 2008 (Union for International Cancer Control 7th edition). There were 822 registered patients diagnosed with SCNEC from 2004 to 2015 which comprised 1.1% (822/73,698) of all uterine cervical cancer cases. Rates of lymph-node and distant metastasis were significantly higher in T1b2 (38.9% and 13.7%, respectively) than T1b1 (14.2% and 4.4%, respectively) (p4 cm in size had greater rates of lymph-node and distant metastasis when compared with tumors ≤4 cm. Adjuvant chemotherapy, rather than radiotherapy, may improve prognosis after surgery in T1bN1M0 SCNEC.

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.

Revision of quality indicators for cervical cancer and trend analysis of existing indicators in Japan

Cervical cancer rates in Japan (16.0/100,000) exceed the global average rate (11.3/100,000, according to the High/Very-High Human Development Index in 2020). This necessitates the evaluation of care quality and the quality indicators (QIs) for cervical cancer that were developed in 2013 to serve this purpose. This study updated these indicators using current evidence and consensus while longitudinally examining trends in practice patterns. The revision involved reviewing existing QIs and patterns of care indicators and incorporating new indicators using the modified Delphi method. Adherence to these indicators was assessed using a linked hospital-based cancer registry-based diagnostic procedure combination database covering approximately 70% of patients with cancer in Japan. The longitudinal trends of the existing indicators were evaluated using the linear probability model. Seven new indicators were added to the existing twelve. Two of the new indicators mainly focused on early-stage surgical intervention, while one focused on advanced-stage bevacizumab combination therapy, with adherence rates of 81.7%, 0.8%, and 45.9%. Longitudinal analyses revealed significant improvements with the use of cisplatin in concurrent chemoradiotherapy for advanced-stage cervical cancer (+1%/year), oral anticancer agents as maintenance therapy after primary treatment for early-stage cervical cancer (-0.8%/year), and hysterectomy for adenocarcinoma in situ in patients above 44 years old (-2%/year). The QIs for cervical cancer in Japan have been revised based on 2022 evidence. The existing and new indicators should be continually evaluated to correspond to the latest knowledge. This will facilitate the standardization and promotion of bottom-up improvements in cervical cancer care.

Quality indicators for endometrial cancer care in Japan

The incidence and mortality rates of endometrial cancer are increasing globally, including in Japan. Quality of cancer care is promoted through guideline adherence. This study aimed to establish quality indicators (QIs) for endometrial cancer and explore the factors contributing to treatment nonadherence. QIs and pattern-of-care indicators (PCIs) were developed using the Research and Development/University of California Los Angeles modified Delphi method. QIs reflect desirable healthcare patterns, whereas PCIs address treatment areas with lacking evidence. Data from the Hospital-Based Cancer Registry and Diagnosis Procedure Combination Survey were used. Patients diagnosed or treated between January 1 and December 31, 2020 were included. The reasons for nonadherence were collected. Logistic regression was used to analyze the factors influencing adherence, including age, body mass index, comorbidities, facilities, and recurrence risk. Of the 35 proposed QI candidates, 8 QIs and 9 PCIs were selected, predominantly focusing on surgical aspects. Adherence rates varied, with peritoneal lavage cytology being the highest (93.1%), and postoperative hormone replacement therapy (HRT) for patients aged <45 years being the lowest (30.9%), when focusing on process indicators. Reasons for nonadherence included patient preference and medical comorbidities as significant factors. Multivariate analysis highlighted age, clinical stage, and Barthel index as significant contributors to nonadherence. We developed QIs to comprehensively assess endometrial cancer treatment. Adherence rates are favorable; however, HRT has a low adherence rate. Factors leading to nonadherence include advanced age and incomplete activities of daily living, particularly in advanced stages.