Jie Yang

Role of adjuvant chemotherapy in stage IC ovarian granulosa cell tumors: a systematic review and meta-analysis

This systematic review and meta-analysis aimed to assess the impact of postoperative adjuvant chemotherapy on recurrence and mortality in stage IC granulosa cell tumors (GCTs). We searched the PubMed, Embase, and Cochrane Library for studies published up to December 1, 2024, comparing the oncological outcomes of adjuvant chemotherapy with observation in stage IC GCTs. Seventy studies were identified, with 12 included in the meta-analysis. Among 695 patients, 255 (36.7%) received postoperative adjuvant chemotherapy and 440 (63.3%) received observation. The overall recurrence and mortality rates were 18.7% and 7.6%, respectively. No significant differences were observed in survival outcomes between the adjuvant chemotherapy and observation groups, including recurrence rate (odds ratio [OR]=1.32; 95% confidence interval [CI]=0.67-2.58; p=0.424; I²=33%), mortality rate (OR=0.83; 95% CI=0.44-1.57; p=0.560; I²=0%), 5-year disease free survival (OR=0.88; 95% CI=0.18-4.18; p=0.868; I²=54%) and 5-year overall survival (OR=1.28; 95% CI=0.60-2.74; p=0.519; I²=0%). Subgroup analysis revealed no significant difference in recurrence rate between adjuvant chemotherapy and observation for both adult and juvenile GCTs, or between patients who underwent fertility-sparing surgery and those who did not. Additionally, no difference was found in recurrence rate between 'bleomycin, etoposide, and cisplatin' or 'etoposide and cisplatin' and 'paclitaxel combined with carboplatin or cisplatin' regimens. Postoperative adjuvant chemotherapy did not provide additional benefits in disease recurrence or survival outcomes compared to observation in stage IC GCTs. PROSPERO Identifier: CRD42024559478.

Comparison of carboplatin-based chemotherapy versus cisplatin-based chemotherapy in the treatment of malignant gonadal germ cell tumor: a systematic review and meta-analysis

To evaluate the role of carboplatin-based chemotherapy in patients diagnosed with malignant gonadal germ cell tumors (GCTs), we conducted a systematic review and meta-analysis. We searched PubMed, MEDLINE, Embase, Cochrane library, and Web of Science. Randomized controlled trials or cohort studies on gonadal GCTs between January 1, 1970 and April 26, 2023 were enrolled. The treatment failure rate and mortality rate were the primary outcomes. Subgroup analysis based on the primary tumor site and dose of carboplatin was also conducted. In total, 8 studies with 1,409 patients were included. Compared to cisplatin-based chemotherapy, carboplatin-based chemotherapy had an increased treatment failure rate (odds ratio [OR]=2.23; 95% confidence interval [CI]=1.61-3.08; p<0.001), but similar overall survival outcomes (OR=1.68; 95% CI=0.61-4.61; p=0.315). Subgroup analysis revealed that carboplatin-based chemotherapy did not increase the risk of treatment failure and death in ovarian GCT, while a higher risk of treatment failure and a similar risk of death were observed in testicular GCT. Patients treated with high-dose carboplatin calculated 400 or 600 mg/m² (area under the curve=7.9) obtained similar failure-free survival to the cisplatin group (OR=0.84; 95% CI=0.40-1.73; p=0.629). Compared to the cisplatin group, milder nausea and vomiting, nephrotoxicity, ototoxicity, and more severe myelosuppression were observed in the carboplatin group. In conclusion, carboplatin-based chemotherapy achieves a comparable overall survival outcome to cisplatin-based chemotherapy in gonadal GCT patients, suggesting that carboplatin is a candidate substitute for cisplatin. The efficacy of carboplatin is dose-dependent. High-dose carboplatin can obtain better therapeutic effects with more tolerable toxicities than cisplatin.

Ovarian squamous cell carcinoma: clinicopathological features, prognosis and immunotherapy outcomes

To explore the characteristics and survival outcomes of ovarian squamous cell carcinoma (SCC) and the treatment effectiveness of immune checkpoint inhibitors (ICIs). Patients diagnosed with ovarian SCC at Peking Union Medical College Hospital between January 2000 and September 2023 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analysis of OS were performed using the Cox proportional hazards model. A total of 42 patients were included, with a median age of 51.5 years (range, 23-74). The majority had SCC arising from teratomas (54.8%), followed by endometriosis (14.3%) and Brenner's tumor (2.4%). Patients undergoing molecular testing exhibited a median tumor mutation burden (TMB) of 10.00 mutations/Mb (range, 7.28-46.86), predominantly featuring The prognosis for ovarian SCC remains unfavorable. The stage and age were prognostic predictors for survival. ICIs may be beneficial for patients with ovarian SCC, particularly those with a high TMB.

Predicting outcomes in malignant ovarian germ cell tumors using the modified International Germ Cell Cancer Collaborative Group classification system

The aim of our study was to evaluate the feasibility of the modified International Germ Cell Cancer Collaborative Group risk classification system in Chinese female patients with malignant ovarian germ cell tumors and to identify predictive factors to enhance the risk classification system. In this retrospective cohort analysis, patients with malignant ovarian germ cell tumors who received surgery with/without chemotherapy were included. These patients had been followed-up by Peking Union Medical College Hospital between 2011 to 2020. Patients without complete medical records or no follow-up information were excluded. The study enrolled a total of 271 patients. The risk model classified 106 (39.1%) patients as good-, 84 (31%) as intermediate-, and 81 (29.9%) as poor-risk. With a median follow-up time of 34 months (range 2-147), 48 (17.7%) recurrence and 16 (5.9%) deaths were observed. The risk classification significantly correlated with 3 year disease-free survival and overall survival (log rank p<0.001 and p=0.003, respectively). The survival outcomes of disease-free survival and overall survival were not statistically different among risk groups in patients who received neoadjuvant chemotherapy (log rank p=0.77 and 0.41, respectively). Univariate and multivariable analysis showed that tumor stage (p=0.033, hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.06 to 3.96) was significantly associated with relapse or progression of disease. Patients over age 40 years exhibited a poor prognosis. The modified International Germ Cell Cancer Collaborative Group risk classification system was efficacious in patients with malignant ovarian germ cell tumors and was significantly associated with disease-free survival and overall survival. Risk assessment after neoadjuvant chemotherapy may be more predictive than stratification at initial diagnosis. Age and tumor stage were definitive prognostic factors for germ cell tumors, which may need to be incorporated in the stratification system.

Advanced ovarian yolk sac tumor: upfront surgery or neoadjuvant chemotherapy followed by interval debulking?

To compare surgery and survival outcomes between neoadjuvant chemotherapy and primary debulking surgery in patients with advanced ovarian yolk sac tumor. In this retrospective cohort analysis, patients with stage III to IV ovarian yolk sac tumor or mixed germ cell tumors containing yolk sac tumor elements, and who underwent surgery at Peking Union Medical College Hospital between January 2011 and December 2021, were identified. Patient characteristics, treatment, and survival data were analyzed between the two groups. A total of 40 patients were enrolled: 19 patients received neoadjuvant chemotherapy followed by interval surgery, and 21 patients were treated with primary debulking surgery. After neoadjuvant chemotherapy, the surgical conditions of patients were improved. All patients achieved cytoreduction to R0 or R1 at interval surgery. No statistical difference was found in 3-year disease-free survival and overall survival between the neoadjuvant chemotherapy group and the primary debulking surgery group (log rank p=0.4 and 0.94). Patients had less blood loss (328.4 vs 1285.7 mL, p=0.029), lower transfusion volume (1044.4 vs 3066.7 mL, p=0.011), and fewer peri-operative complications (15.8% vs 47.6%, p=0.032) at the interval debulking surgery after neoadjuvant chemotherapy compared with patients who underwent primary debulking surgery. For patients with advanced-stage ovarian yolk sac tumor, neoadjuvant chemotherapy followed by interval surgery is an alternative option, especially for those who cannot tolerate the primary debulking surgery because of high tumor burden and vulnerable status.

Bioinformatic analysis of key pathways and genes shared between endometriosis and ovarian cancer

The purpose of the study is to identify potential key genes and pathways, using bioinformatics, underlying the potentially common molecular mechanisms between endometriosis (EMS) and ovarian cancer (OC). Two datasets were collected from the Gene Expression Omnibus database, and the limma package identified common differentially expressed genes (DEGs) in the EMS and OC groups compared to controls. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene interaction network, and module analyses identified the enriched pathways associated with DEGs. A protein-protein interaction (PPI) network was then constructed, and the CytoHubba plugin of Cytoscape was used to calculate the degree of connectivity for proteins in the PPI network. A total of 571 overlapping DEGs were identified between EMS and OC (vs. controls). Enriched DEGs were associated with 36 gene ontology terms and 7 Kyoto Encyclopedia of Genes and Genomes pathways, which were mainly associated with deactivation of the p53 signaling pathway. The Kaplan-Meier plotter platform confirmed the expression of the identified hub genes, and survival analysis suggested that CCNB1, CCNB2, BUB1B, CCNA2, KIF2C, and TOP2A are associated with decreased survival and disease-free survival rates of OC. The key pathways identified herein elucidate the possible mechanism by which EMS evolves into OC; further, the identified hub genes may serve as potential biomarkers to predict OC occurrence and prognosis.

Surgical or imaging lymph node assessment in locally advanced cervical cancer: a systematic review and meta-analysis

To evaluate the survival impact of imaging vs surgical nodal assessment in patients with cervical cancer stage IB2-IVA prior to definitive chemoradiotherapy (CRT). PubMed, MEDLINE, Cochrane Library, and ClinicalTrials.gov were used to search for publications in English and Chinese over a 50-year period. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols was used to conduct this review. Inclusion criteria were studies that compared survival outcomes in International Federation of Gynecology and Obstetrics 2009 stage IB2-IVA cervical cancer patients with pre-therapy pelvic and/or aortic lymphadenectomy (LND) or imaging. One or more of the following modalities were used for nodal assessment: computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT. The National Institutes of Health Quality Assessment Tool was utilized to assess study quality. The initial search identified 65 studies, and five met the inclusion criteria. There were a total of 1,112 patients. Seven hundred and fifty-four underwent pelvic and/or aortic LND and 358 had imaging. When compared to LND, imaging had a sensitivity and specificity of 88.9% and 22.2% for pelvic lymph node (LN), and 33%-62.5% and 92%-95.5% for para-aortic LN. There were no differences in progression-free survival (PFS) (hazard ratio [HR]=1.13; 95% confidence interval [CI]=0.73-1.74; I²=75%; p<0.01) and overall survival (OS) (HR=1.06; 95% CI=0.66-1.69; I²=75%; p<0.01) between surgical and imaging nodal assessment. Imaging and surgical nodal assessment has comparable PFS and OS in patients with cervical cancer stage IB2-IVA. PROSPERO Identifier: CRD42020155486.

The Abnormal Expression of miR‐205‐5p, miR‐195‐5p, and VEGF‐A in Human Cervical Cancer Is Related to the Treatment of Venous Thromboembolism

Background. Low molecular heparin (LWMH) therapy can prevent the occurrence of VTE in tumor patients and may have a direct antitumor effect. However, the expression pattern of VEGF‐A and microRNAs was less reported in cervical cancer subjects who received concurrent chemoradiotherapy (CCRT) or received anticoagulant treatment with low molecular weight heparin (LWMH) after CCRT (CCRT+LWMH). Methods. In this study, 30 cervical cancer subjects treated with CCRT and 30 cervical cancer patients treated with CCRT+LWMH were enrolled. We screened five miRNAs (miR‐15a‐5p, miR‐16‐5p, miR‐29a‐3p, miR‐195‐5p, and miR‐205‐5p), which have multiple binding sites with VEGF‐A and are highly expressed in serum of patients with cervical cancer, by RT‐qPCR. The expression level of VEGF‐A was also detected by RT‐qPCR and ELISA. Statistical methods were used for difference and correlation analyses. Results. We observed the curative effect in the two treatment methods. In the CCRT group, the total effective rate was 60.00%, and in the CCRT+LWMT group, the total effective rate was 83.33% (P = 0.013, χ2 = 6.129). Additionally, the serum levels of VEGF‐A in the CCRT+LWMH group were downregulated, relative to the CCRT group (P &lt; 0.05), and VEGF‐A in serum was significantly positively correlated with venous thromboembolism (VTE) (r = 2.134, P = 0.035). Only miR‐205‐5p and miR‐195‐5p were upregulated in CCRT+LWMH, relative to CCRT (P &lt; 0.05). In serum of patients with cervical cancer after CCRT+LWMH treatment, there was no significant correlation between VEGF‐A and miR‐15a‐5p (r = −0.132, P = 0.209), miR‐16‐5p (r = −0.205, P = 0.311), or miR‐29a‐3p (r = −0.029, P = 0.662), but VEGF‐A was significantly negatively correlated with miR‐195‐5p (r = −0.396, P = 0.040) and miR‐205‐5p (r = −0.315, P = 0.032). Furthermore, VTE was also significantly negatively correlated with miR‐195‐5p (r = −0.412, P = 0.031) and miR‐205‐5p (r = −0.123, P = 0.044). Conclusion. These data revealed roles for VEGF‐A and these miRNAs as potential biomarkers in cervical cancer patients with VTE, which exhibited usage potential in the treatment of venous thromboembolism.

Completion hysterectomy after chemoradiotherapy for locally advanced adeno-type cervical carcinoma: updated survival outcomes and experience in post radiation surgery

To compare patient survival outcomes between completion hysterectomy and conventional surveillance in locally advanced adenocarcinoma of the cervix after concurrent chemoradiotherapy (CCRT). Patients with adenocarcinoma of the cervix after CCRT were identified in a tertiary academic center database from 2004 to 2018. Patients received completion hysterectomy or surveillance after CCRT. We compared the progression-free survival (PFS) and overall survival (OS) between the patients with or without adjuvant hysterectomy. Surgery features, operative complications, and pathologic characteristics were documented. Patient outcomes were also analyzed according to clinicopathologic factors. A total of 78 patients were assigned to completion surgery and 97 to surveillance after CCRT. The PFS was better in the surgery group compared to the CCRT only group, at 3 years the PFS rates were 68.1% and 45.2%, respectively (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.282-0.749; p=0.002). Adjuvant surgery was also associated with a higher rate of OS (HR=0.361; 95% CI=0.189-0.689; p=0.002), at 3 years, 87.9% and 67%, respectively. Tumor stage, size, lymph-vascular space invasion (LVSI), lymphadenopathy were associated with PFS but not with OS. Hysterectomy specimens revealed 64.1% (50/78) of the patients had pathologic residual tumor. Patients age less than 60, tumor size over 4 cm, stage IIB and persistent residual disease after CCRT were most likely to benefit from hysterectomy. Hysterectomy was associated with a lower rate of locoregional recurrence but did not reach statistical significance (5.13% vs. 13.5%, p=0.067). Completion hysterectomy after CCRT was associated with better survival outcome compared with the current standard of care.

Long-term survival outcomes of female genital tract rhabdomyosarcoma in children, adolescents and young adults at a national rare disease diagnosis and treatment center in China

Rhabdomyosarcoma (RMS) is a rare soft-tissue sarcoma mainly affecting children and adolescents. The genitourinary tract is the second common site involved by RMS. We report the therapeutic effects and long-term survival outcomes of female genital tract RMS. Patients diagnosed with female genital RMS and younger than 25 years old from Peking Union Medical College Hospital between January 1996 and December 2023 were identified. Clinical features, treatment modalities, and survival outcomes were documented. Patient prognosis evaluation was re-evaluated according to the Children's Oncology Group (COG) risk stratification system. A total of 26 patients were included, with a mean age of 8.1 years. The median follow-up duration was 59.3 months. Primary tumor sites were distributed as follows: vagina (n=12), cervix (n=8), vulva (n=2), pelvic region (n=2), uterus (n=1), and subcutaneous perineum (n=1). The COG Risk Stratification System classified 15 patients as low-risk subset 1, 8 as low-risk subset 2, 2 as intermediate-risk, and 1 as high-risk. Nine patients (34.62%) experienced disease recurrence with a median progression free survival of 15.3 months. The disease-specific mortality rate was 26.92% (7/26). Six patients (66.7% of recurrent cases) succumbed to the disease following recurrence, while one stage 4 patient died during initial treatment. Patients diagnosed as RMS in female genital tract in early stage can have relatively good prognosis. Advanced stage and nonstandard primary treatment were related with increased risk of recurrence. Patients with disease recurrence tend to have poor prognoses and higher mortality rates.

Current status and challenges in training the next generation of gynecologic cancer care providers in Asia

Gynecologic oncology is undergoing rapid development with continuous advances in treatment strategies, surgical techniques, and clinical research. Training programs must keep pace by providing future specialists with the necessary surgical skills and a solid understanding of evolving practices. This study aimed to examine the current state of gynecologic oncology training in Asia and to identify key challenges and opportunities for improvement. A descriptive survey was conducted in October 2023 under the leadership of the Education Committee of the Asian Society of Gynecologic Oncology (ASGO). Key stakeholders involved in clinical training and policy-making from eight countries and regions (China, Hong Kong SAR, India, Japan, the Philippines, South Korea, Taiwan, and Thailand) responded to an online questionnaire assessing the structure and quality of their national training programs. Six of the eight countries/regions have official gynecologic oncology societies. Training duration was three years or more in five regions and two years in the remaining three. Seven reported conducting formal assessments of surgical skills. While five programs offered adequate exposure to minimally invasive surgery, three noted limitations. Satisfaction with research opportunities and overall training quality also varied. The most frequently cited concern was the lack of standardized curricula. This regional overview reveals notable differences in training approaches across Asia. Standardizing educational frameworks and expanding collaborative initiatives - such as virtual tumor boards, elective rotations, and skills-based workshops - may help address current gaps and strengthen gynecologic oncology training in the region.