The impact of systematic retroperitoneal lymphadenectomy on long-term oncologic outcome of women with advanced ovarian clear-cell carcinoma

Hiroaki Kajiyama,Shiro Suzuki,Nobuhisa Yoshikawa,Satoshi Tamauchi,Kiyosumi Shibata,Fumitaka Kikkawa 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.4

Objective: The impact of systematic retroperitoneal lymphadenectomy (SRL) remainscontroversial in patients with advanced ovarian clear-cell carcinoma (CCC) who areoptimally debulked. Methods: Between 1986 and 2017, a total of 3,227 women with epithelial ovarian carcinomawere analyzed in a multi-institutional study. Among them, 166 optimally debulked womenwith stage IIB–IV CCC were collected (residual tumor of <1 cm). All patients were divided into2 groups: 1) Group I (n=112): underwent standard radical surgery with SRL, 2) Group II (n=54):underwent non-staging limited surgery. The pathological slides were assessed based on centralpathological review. Oncologic outcomes were compared between the two groups using apropensity score (PS)-matching technique to adjust for various clinicopathologic factors. Results: The median follow-up duration of all surviving women was 52.8 (1.6–184.2) months. Overall, 88 patients (53.0%) experienced recurrence and 68 patients (41.0%) died of thedisease. In the original cohort, the 5-year overall survival (OS) rates of groups I and II were57.9 and 64.9%, respectively (log-rank p=0.415). In the PS-adjusted cohort, the 5-year OSrates were 64.9 and 58.8% in women in groups I and II, respectively (p=0.453). Furthermore,in the PS-matched cohort after adjustment for multiple clinicopathologic factors, there wasno significant difference in OS between the 2 groups (group I vs. group II; hazard ratio=1.170;95% confidence interval=0.633–2.187; p=0.615). Conclusions: This study suggests that the performance of SRL including radical surgery maynot lead to a significant improvement in the oncologic outcome of advanced CCC patientswith optimal cytoreduction.

Fertility sparing surgery in patients with early stage epithelial ovarian cancer: implication of survival analysis and lymphadenectomy

Hiroaki Kajiyama 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.4

Survival benefit of taxane plus platinum in recurrent ovarian cancer with non-clear cell, non-mucinous histology

Hiroaki Kajiyama,Kiyosumi Shibata,Mika Mizuno,Tomokazu Umezu,Shiro Suzuki,Ryuichiro Sekiya,Kaoru Niimi,Hiroko Mitsui,Eiko Yamamoto,Michiyasu Kawai,Tetsuro Nagasaka,Fumitaka Kikkawa 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.1

Objective: This study was conducted to examine the effects of front-line chemotherapy on overall survival (OS) and postrecurrence survival (PRS) of patients with recurrent ovarian cancer, when stratifying the histologic type. Methods: Five hundred and seventy-four patients with recurrent ovarian cancer with sufficient clinical information, including front-line chemotherapy, were analyzed. The pathologic slides were evaluated by central pathologic review. The patients were divided into two groups: group A (n=261), who underwent taxane plus platinum, and group B (n=313), who underwent conventional platinum-based chemotherapy without taxanes. Results: The median age was 54 years (range, 14 to 89 years). Group A had significantly better median OS (45.0 months vs. 30.3 months, p<0.001) and PRS (23.0 months vs. 13.0 months, p<0.001) compared to group B. The OS and PRS were similar between the groups in patients with clear cell or mucinous histology. In contrast, among patients with non-clear cell, non-mucinous histologies, the OS and PRS of group A were significantly better than those of group B (OS, p<0.001; PRS, p<0.001). Multivariable analyses revealed that, among patients with non-clear cell, non-mucinous histologies, chemotherapy including taxane and platinum was an independent predictor of favorable survival outcomes. Conversely, in patients with clear cell or mucinous histology, taxane-including platinum-based combination chemotherapy did not improve the OS and PRS compared to a conventional platinum-based regimen which did not include taxanes. Conclusion: Since the emergence of taxane plus platinum, the prognosis of patients with recurrent ovarian cancer has improved. However, we here demonstrate that this improvement is limited to patients with non-clear cell, non-mucinous histologies.

Prognostic factors and effects of fertility-sparing surgery in women of reproductive age with ovarian clear-cell carcinoma: a propensity score analysis

Masato Yoshihara,Hiroaki Kajiyama,Satoshi Tamauchi,Shiro Suzuki,Kunihiko Takahashi,Shigeyuki Matsui,Fumitaka Kikkawa 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.6

Objective: The aim of this study was to investigate the clinical characteristics of youngpatients with stage I clear-cell carcinoma (CCC) and evaluate the prognostic factors andeffects of fertility-sparing surgery (FSS) using propensity score (PS) adjustment. Methods: We conducted a regional multi-institutional study between 1986 and 2017. Among4,277 patients with ovarian tumor, clinical and pathological data of 103 fertile women withstage I unilateral CCC were collected. We evaluated survival and reproductive outcomesin these patients. Additionally, to analyze the effects of FSS, baseline imbalance betweenpatients with and those without FSS was adjusted with an inverse probability of treatmentweighting using PSs involving independent clinical variables. Results: The mean patient age was 39.4 years, and the median follow-up period for survivingpatients was 55.6 months. In multivariate analysis, stage IC2/IC3 (vs. IA/IC1) was the onlyindependent prognostic factor for recurrence-free survival (RFS) and overall survival (OS). FSS was not associated with poorer prognosis when compared to the prognosis with nonpreservingsurgery with regard to both RFS and OS. No statistical difference in survivaloutcomes between FSS and other approaches was confirmed after PS adjustment. Amongpatients who underwent FSS, four deliveries with healthy neonates were noted without anygestational complications. Conclusion: FSS can be considered in stage I CCC, specifically in stage IA and IC1 patientswho strongly desire to have children in the future. Further clinical research is needed toclarify the optimal application of FSS for CCC.

Clinicopathologic features of epithelial ovarian carcinoma in younger vs. older patients: analysis in Japanese women

Nobuhisa Yoshikawa,Hiroaki Kajiyama,Mika Mizuno,Kiyosumi Shibata,Michiyasu Kawai,Tetsuro Nagasaka,Fumitaka Kikkawa 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.2

Objective: The purpose of this study was to clarify the clinical features of epithelial ovarian carcinoma (EOC) in younger vs. older patients in Japan. Methods: We collected data on 1,562 patients with EOC treated at multiple institutions in the Tokai Ovarian Tumor Study Group, and analyzed them retrospectively. All patients were divided into 2 groups: group A (≤40 years old) and group B (>40 years old). The data were analyzed to evaluate prognostic factors and the distribution of features in each group. Patients were subjected to univariate and multivariate analyses to evaluate overall survival (OS). Results: The median follow-up time was 45.1 months (range, 1 to 257 months). Patients in group A had a significantly higher rate of stage I disease (67.3% vs. 42.6%, respectively; p<0.001) and the mucinous type (36.7% vs. 13.5%, respectively; p<0.001) than those in group B. There was a significant difference of OS between the 2 groups (p=0.013). However, upon stratification according to the stage, there were no significant differences in the OS between the 2 groups (group A vs. B: stage I, p=0.533; stage II-IV, p=0.407). Multivariate analysis revealed that younger age was not an independent prognostic factor for OS. Conclusion: On the basis of our data, younger patients had a different clinical profile than older patients, particularly regarding the stage of the disease and pathological distribution; however, they showed a similar long-term prognosis, even upon stratification according to the stage.

Survival benefits of retroperitoneal lymphadenectomy for optimally- resected advanced ovarian high-grade serous carcinoma: a multi-institutional retrospective study

Yoshiki Ikeda,Masato Yoshihara,Satoshi Tamauchi,Akira Yokoi,Nobuhisa Yoshikawa,Hiroaki Kajiyama 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.4

Objective: The survival benefits of retroperitoneal lymphadenectomy (RLNA) for epithelial ovarian cancer (EOC) remain controversial because clinical behaviors differ among subtypes. The purpose of the present study was to clarify whether RLNA increases the survival rate of advanced high-grade serous carcinoma (HGSC). Methods: This was a retrospective cohort analysis of 3,227 patients with EOC treated between 1986 and 2017 at 14 institutions. Among them, 335 patients with stage IIB-IV HGSC who underwent optimal cytoreduction (residual tumor of <1 cm) were included. Patients were divided into the RLNA group (n=170) and non-RLNA group (n=165). All pathological slides were assessed based on a central pathological review. Oncologic outcomes were compared between the two groups in the original and weighted cohorts adjusted with the inverse probability of treatment weighting. Results: The median observation period was 49.8 (0.5–241.5) months. Overall, 219 (65%) out of 335 patients had recurrence or progression, while 146 (44%) died of the disease. In the original cohort, RLNA was a significant prognostic factor for longer progression-free survival (PFS) (hazard ratio [HR]=0.741; 95% confidence interval [CI]=0.558–0.985) and overall survival (OS) (HR=0.652; 95% CI=0.459–0.927). In the weighted cohort in which all variables were well balanced as standardized differences decreased, RLNA was also a significant prognostic factor for more favorable oncologic outcomes (PFS, adjusted HR=0.742; 95% CI=0.613–0.899) and OS, adjusted HR=0.620; 95% CI=0.488–0.787). Conclusion: The present study demonstrated that RLNA for stage III-IV HGSC with no residual tumor after primary debulking surgery contributed to better oncologic outcomes.

Impact of incomplete surgery and adjuvant chemotherapy for the intraoperative rupture of capsulated stage I epithelial ovarian cancer: a multi-institutional study with an in- depth subgroup analysis

Masato Yoshihara,Satoshi Tamauchi,Shohei Iyoshi,Kazuhisa Kitami,Kaname Uno,Kazumasa Mogi,Hiroaki Kajiyama 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.5

Objective: The aim of the present study was to examine the effects of incomplete surgery and adjuvant chemotherapy on the prognosis of patients with intraoperative rupture of capsulated stage I epithelial ovarian cancer (OvCa). Methods: A regional retrospective study was conducted between 1986 and 2019. Among 4,730 patients with malignant ovarian tumors, 534 women with International Federation of Gynecology and Obstetrics stage IA and IC1 epithelial OvCa were eligible. Differences in survival outcomes were examined between patients with stage IA and IC1 tumors and the effects of uterine preservation, complete-staging lymphadenectomy, and adjuvant chemotherapy were investigated by an in-depth subgroup analysis. To analyze therapeutic effects, baseline imbalances were adjusted using propensity score (PS). Results: The prognosis of patients with stage IC1 tumors was worse than those with stage IA. Surgical spill did not affect the site of recurrence. In the PS-adjusted subgroup analysis, uterine preservation (hazard ratio [HR]=1.669; 95% confidence interval [CI]=1.052–2.744), incomplete-staging lymphadenectomy (HR=1.689; 95% CI=1.211–2.355), and the omission of adjuvant chemotherapy (HR=3.729; 95% CI=2.090–6.653) significantly increased the HR of recurrence for patients with stage IC1 tumors compared to those with stage IA tumors. Adjuvant chemotherapy decreased the impact of rupture with uterine preservation (HR=0.159; 95% CI=0.230–1.168) or incomplete-staging lymphadenectomy (HR=0.987; 95% CI=0.638–1.527). Conclusion: The present results suggest intraoperative rupture of capsulated stage I epithelial OvCa is associated with a poor prognosis. When chemotherapy is given for patients receiving incomplete surgery, there is no longer an increased risk of recurrence observed with the rupture.

Prognostic value of neutrophil-to-lymphocyte ratio in early-stage ovarian clear-cell carcinoma

Kosuke Yoshida,Nobuhisa Yoshikawa,Akira Shirakawa,Kaoru Niimi,Shiro Suzuki,Hiroaki Kajiyama,Fumitaka Kikkawa 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.6

Objectives: There is increasing evidence that systemic inflammatory response (SIR) markersare prognostic factors for various types of cancers. This is the first study to evaluate theusefulness of SIR markers for the prognosis of early-stage ovarian clear-cell carcinoma (OCCC). Methods: We retrospectively investigated 83 patients diagnosed with stage I–II OCCC whounderwent surgery between 2005 and 2017. Initially, receiver operating characteristic curveanalysis for overall survival (OS) was used to determine optimal cut-off values for neutrophilto-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Patients were stratifiedinto 2 groups by the cut-off values (NLR=3.26, PLR=160). Univariate and multivariateanalyses were performed to elucidate the significance of SIR markers as prognostic factors. Results: In the median follow-up period of 64.1 months, 16 patients experienced recurrence,and nine patients died. The Kaplan-Meier curve showed that OS of the NLR-low group wassignificantly longer than the NLR-high group (p=0.021). There was no significant differencein progression-free survival between the 2 groups (p=0.668), but the post-recurrencesurvival of the NLR-low group was significantly longer than the NLR-high group (p=0.019). Furthermore, multivariate analysis showed that increase in NLR is a significant independentprognostic factor for poor prognosis (hazard ratio=7.437, p=0.017). There was no significantdifference between PLR-low and PLR-high group. Conclusion: Results suggest that NLR can be a significant independent prognostic factor forearly-stage OCCC.

Preoperative serum microRNAs as potential prognostic biomarkers in ovarian clear cell carcinoma

Kazuhiro Suzuki,Akira Yokoi,Kosuke Yoshida,Tomoyasu Kato,Takahiro Ochiya,Yusuke Yamamoto,Hiroaki Kajiyama 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.3

Objective: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian carcinoma with poor prognosis. However, no effective biomarkers have been established for predicting unfavorable events, including recurrence and poor prognoses. Serum microRNAs (miRNAs) have been increasingly reported to be useful in predicting a patient’s condition and have been recognized as a potentially less-invasive source for liquid biopsy in cancer. Therefore, this study aimed to evaluate serum miRNA profiles from patients with OCCC and to establish biomarker for predicting the prognoses. Methods: The GSE106817, which included preoperative serum miRNA profiles of patients with ovarian tumors, was used, and clinical information was investigated. In all, 66 patients with OCCC were included, excluding those with other histological subtypes or insufficient prognostic information. Moreover, miRNA profiles of OCCC tissues were also examined. Results: The median follow-up period was 64.3 (8.0–153.3) months. Based on multivariable Cox regression analyses and the expression of miRNAs in OCCC tissues, miR-150-3p, miR-3195, and miR-7704 were selected as miRNA candidates associated with both progression-free survival (PFS) and overall survival (OS). Then, the prognostic index was calculated based on expression values of 3 serum miRNAs. Kaplan-Meier survival analysis indicated that the prognostic index was significantly predictive of PFS and OS (p=0.004 and p=0.012, respectively). Conclusion: Preoperative serum miRNA profiles of miR-150-3p, miR-3195, and miR-7704 can be used to potentially predict the prognosis of patients with OCCC.

An attempt to establish real-world databases of poly(ADP-ribose) polymerase inhibitors for advanced or recurrent epithelial ovarian cancer: the Japanese Gynecologic Oncology Group

Muneaki Shimada,Kosuke Yoshihara,Terumi Tanigawa,Hiroyuki Nomura,Junzo Hamanishi,Satoe Fujiwara,Hiroshi Tanabe,Hiroaki Kajiyama,Masaki Mandai,Daisuke Aoki,Takayuki Enomoto,Aikou Okamoto 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.3

The development of new treatments for gynecological malignancies has been conducted mainly through collaborative international phase III trials led by the United States and Europe. The survival outcomes of many gynecological malignancies have greatly improved as a result. Recent large-scale genome-wide association studies have revealed that drug efficacy and adverse event profiles are not always uniform. Thus, it is important to validate new treatment options in each country to safely and efficiently provide newly developed treatment options to patients with gynecological malignancies. The Japanese Gynecologic Oncology Group (JGOG) is conducting 5 cohort studies (JGOG 3026, 3027, 3028, 3030, and 3031) to establish real-world data (RWD) of poly(ADP-ribose) polymerase (PARP) inhibitor use in patients with advanced or recurrent epithelial ovarian cancer. The RWD constructed will be used to provide newly developed PARP inhibitors for women with advanced or recurrent ovarian cancer in a safer and more efficient manner as well as to develop further treatment options. In 2022, The JGOG, Korean Gynecologic Oncology Group, Chinese Gynecologic Cancer Society, and Taiwanese Gynecologic Oncology Group established the East Asian Gynecologic Oncology Trial Group to collaborate with East Asian countries in clinical research on gynecologic malignancies and disseminate new knowledge on gynecologic malignancies from Asia. The JGOG will conduct a collaborative integrated analysis of the RWD generated from Asian countries and disseminate real-world clinical knowledge regarding new treatment options that have been clinically implemented.