Investigator
University Of Tsukuba
Current Status of Fertility‐Sparing Treatment for Gynecological Cancers in Japan: A Nationwide Survey
ABSTRACT Aim There is an increasing demand for fertility‐sparing treatment (FST) among young women with gynecological cancer. This study aimed to clarify the current status of FST implementation across Japan by focusing on institutional practice patterns and clinical protocols for cervical, endometrial, and ovarian cancers. Methods A nationwide cross‐sectional survey was conducted between August and September 2024. An online questionnaire was distributed to 481 gynecologic tumor registry institutions through the Japan Society of Obstetrics and Gynecology mailing list. Data on institutional characteristics, specific FST eligibility criteria, treatment methods, and post‐treatment management were collected. Results Responses were received from 226 institutions (response rate: 47.0%), and all respondent institutions (100%) performed FST for at least one gynecological cancer. Although FST is widely available, significant heterogeneity in clinical protocols was observed across all three cancers. Key variations among respondent institutions included a low implementation rate of radical trachelectomy for cervical cancer (20.8%), a high rate of post‐FST hysterectomy for endometrial cancer (63.6%) compared to cervical cancer and ovarian cancer, and exclusion criteria for patients with hereditary cancer syndromes. Conclusion FST is an established practice in Japan; however, there is a lack of consensus regarding its clinical application. These findings provide a critical benchmark for future efforts to standardize care and develop collaborative networks to optimize this essential treatment modality for young patients with gynecological cancer.
Comparison of MR Imaging of High-grade Serous Carcinomas with and without Homologous Recombination-deficiency
MRI findings of high-grade serous carcinoma (HGSC) with and without homologous recombination deficiency (HRD) were compared to explore the feasibility of using MRI as a genetic predictor. We retrospectively reviewed MRI data from HRD-positive and HRD-negative HGSC and evaluated tumor size, appearance, apparent diffusion coefficient (ADC), time-intensity curve, and several dynamic contrast-enhanced curve descriptors. Age, primary site, tumor stage, bilaterality, presence of lymph node metastasis, presence of peritoneal metastasis, and tumor marker levels were also compared. Forty-eight patients with HRD-positive HGSC (17 patients with BRCA1 variant, 9 patients with BRCA2 variant, and 22 without BRCA variants) and 18 patients with HRD-negative HGSC were included. The HRD-negative patients' mean age was 67 years, which was significantly higher than that of the HRDpositive patients (60 years, P = 0.011). High-risk time-intensity curve (TIC) patterns were more common in HRD-negative tumors (94%) than in HRD-positive tumors (63%; P = 0.047). Tumors without HRD exhibited significantly higher wash-in rates (P = 0.023). Additionally, unresectable lymph node metastases were significantly more frequent in HRD-negative patients (P = 0.013). No significant differences were observed in the other evaluated factors. The comparison between HGSC with and without HRD revealed that HGSC without HRD was significantly associated with older age, a higher likelihood of exhibiting a high-risk TIC pattern, a higher wash-in rate, and a higher frequency of unresectable lymph node metastasis.
Cervical cancer in the modern era: cutting-edge strategies for diagnosis and treatment
Abstract Cervical cancer remains a major cause of mortality among women worldwide, highlighting the need for advances in diagnostic and therapeutic strategies. This review provides a comprehensive overview of recent developments in histopathological classification based on human papillomavirus association, as well as progress in imaging and treatment approaches supported by current research. Emerging technologies, such as artificial intelligence-assisted imaging, targeted molecular therapies, and personalized radiotherapy, hold substantial promise for improving patient outcomes. These innovations offer new possibilities for precision medicine in cervical cancer care, and their current applications are discussed in this review.
Population-adjusted indirect treatment comparison of the SOLO1 and PAOLA-1/ENGOT-ov25 trials evaluating maintenance olaparib or bevacizumab or the combination of both in newly diagnosed, advanced BRCA-mutated ovarian cancer
In the absence of randomised head-to-head trials, we conducted a population-adjusted indirect treatment comparison (PA-ITC) of phase III trial data to evaluate the relative efficacy and safety of maintenance olaparib and bevacizumab alone and in combination in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation (BRCAm). An unanchored PA-ITC was performed on investigator-assessed progression-free survival (PFS) data. Individual patient data from SOLO1 (olaparib versus placebo) and from BRCA-mutated patients in PAOLA-1/ENGOT-ov25 (olaparib plus bevacizumab versus placebo plus bevacizumab) were pooled. Each arm of PAOLA-1 was weighted so that key baseline patient characteristics were similar to the SOLO1 cohort. Analyses were performed in patients with complete baseline data. Weighted Cox regression analysis was used to estimate the comparative efficacy of different maintenance therapy strategies, supplemented by weighted Kaplan-Meier analyses. Data from SOLO1 patients (olaparib, n = 254; placebo, n = 126) were compared with data from BRCA-mutated PAOLA-1 patients (olaparib plus bevacizumab, n = 151; placebo plus bevacizumab, n = 71). Adding bevacizumab to olaparib was associated with a numerical improvement in PFS compared with olaparib alone (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.45-1.09). Statistically significant improvements in PFS were seen with olaparib alone versus placebo plus bevacizumab (HR 0.48; 95% CI 0.30-0.75), olaparib plus bevacizumab versus placebo (0.23; 0.14-0.34), and placebo plus bevacizumab versus placebo (0.65; 0.43-0.95). Results of this hypothesis-generating PA-ITC analysis support the use of maintenance olaparib alone or with bevacizumab in patients with newly diagnosed, advanced ovarian cancer and a BRCAm.
Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician’s choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer
In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1-43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49-1.10) and 0.64 (0.44-0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45-1.02) and 0.61 (0.41-0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3-5, 74% and 72%), respectively. Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC. ClinicalTrials.gov Identifier: NCT03517449.
