Jiaxin 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.

Human malignant ovarian germ cell tumor cell lines derived from peritoneal cytology retrieving from circulating tumor cell system

Malignant ovarian germ cell tumor (MOGCT) is a rare neoplasm predominantly affecting adolescent and young adult females. Establishing personalized permanent tumor cell lines is crucial for understanding tumor behavior and optimizing precision treatment for these patients. We developed a novel procedure for isolating and culturing human MOGCT cells from peritoneal wash cytology using the circulating cell extraction technique (Labyrinthbiotech Co. LLC, LABYRINTHCE01, China). Peripheral blood and peritoneal washings were collected from 15 patients, including those with yolk sac tumor (n = 6), dysgerminoma (n = 2), immature teratoma (n = 5), and mixed germ cell tumor (n = 2). After washing and centrifugation, samples were processed using the labyrinth technique to achieve high-purity cell cultures. The isolated tumor cells were characterized by immunofluorescence microscopy and flow cytometry. Immunohistochemical analysis enabled specific discrimination from primary peritoneal human fibroblasts. Cultures were established from peritoneal cytology with cell densities ranging from 10² to 10⁵ cells per well, with 5 samples showing over 10⁵ cell growth, 3 samples over 10⁴ cell growth, and others at 10³ cell growth. The longest cell culture has been maintained for 18 generations. Short tandem repeat (STR) analysis of cultured cells confirmed their germ cell tumor origin. Preliminary assessments of chemosensitivity in cultured cells have been found to reflect similar clinical responses in the corresponding patients. The MOGCT cell lines derived from peritoneal washings using the circulating tumor cell chip represent the tumor characteristics. This method holds promise for functional studies on rare ovarian tumors and for evaluating chemo-sensitivity for potential therapeutic applications.

Humanized patient-derived xenograft mouse model bearing ovarian clear cell carcinoma

The study aimed to establish humanized patient-derived xenograft (PDX) mouse models of ovarian clear cell carcinoma (OCCC) and evaluate their therapeutic responses. PDX models and their humanized counterparts (CD34+ humanized PDX models) derived from the same tumor source were developed, and the therapeutic responses were compared between the models. Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor significantly reduced tumor size in traditional OCCC PDX models (p=0.021). Although differences in tumor growth between traditional PDX models and humanized PDX models were observed, they were not statistically significant (p=0.438). However, treatment effects of PI3K inhibitor differed significantly between conventional and humanized mice (p=0.006). In the Humanized PDX cohort, both programmed cell death protein-1 antibody monotherapy and PI3K inhibitor treatment slowed tumor growth relative to controls, with a synergistic effect noted during the latter part of the study, though these effects were not statistically significant. This pioneering study successfully develop a humanized PDX model for OCCC, highlighting differential responses to treatments compared to conventional PDX models.

Efficacy and safety of an oral combination therapy of niraparib and etoposide in platinum resistant/refractory ovarian cancer: a single arm, prospective, phase II study

Non-platinum chemotherapy is used in platinum resistant/refractory ovarian cancer patients but offers limited efficacy, especially in those who develop platinum resistance after ≤2 lines of platinum based chemotherapy. This phase II study aimed to evaluate the efficacy and safety of oral niraparib plus etoposide in platinum resistant/refractory ovarian cancer. Platinum resistant/refractory ovarian cancer patients after ≤2 lines of platinum based chemotherapy, histologically confirmed as non-mucinous epithelial ovarian cancer, regardless of biomarker status, were eligible. Patients received niraparib with a starting dose of 200 mg/100 mg alternate once a day, and oral etoposide of 50 mg once a day, on days 1-20 of 30 days per cycle for a maximum of 6-8 cycles, followed by niraparib until disease progression or intolerable toxicity. The primary endpoint was investigator assessed progression free survival. 29 patients were enrolled from 22 May 2020 to 3 February 2023; 26 patients were included in the efficacy analysis set as per protocol. Median progression free survival was 4.2 months (95% confidence interval (CI) 3.9 to 4.4). Overall response rate was 26.9% (95% CI 8.7 to 45.2). Disease control rate was 57.7% (95% CI 37.3 to 78.0). Overall response rate in patients with a BRCA mutation and homologous recombination deficiency was 50% and 41.7%, respectively. Median progression free survival in patients with primary platinum resistance was 4.5 months (95% CI 3.6 to 5.3). 29 patients were included in the safety analysis set, and 8 (28%) patients experienced treatment related adverse events of grade ≥3. There was no treatment related discontinuation. Niraparib combined with etoposide showed evidence of antitumor activity in platinum resistant/refractory ovarian cancer after ≤2 lines of platinum based chemotherapy, particularly in patients with a BRCA mutation, homologous recombination deficiency, or primary platinum resistance. This once-a-day oral combination was a convenient option. NCT04217798.

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.

An Exploratory Application of a Central Nervous System (CNS) Tumor Methylation Classifier in Ovarian Neuroectodermal Tumors

Ovarian neuroectodermal tumors (NETs) are rare malignancies with unclear diagnostic criteria and challenging treatment. We aimed to assess the utility of DNA methylation in the diagnostic classification and prognostic stratification of ovarian NETs. This retrospective study included 15 patients diagnosed with ovarian NETs at Peking Union Medical College Hospital between 2010 and 2024. Paraffin-embedded tumor tissues from all patients underwent clinicopathologic review, DNA methylation microarray assay, EWSR1 fluorescence in situ hybridization, and immunohistochemistry. The median age at diagnosis of ovarian NETs was 19 years (range, 9-73 years). These tumors often displayed nonspecific clinical manifestations and were frequently diagnosed at an advanced stage. Morphologic diagnosis included 3 medulloblastoma, 1 neuroblastoma, 3 embryonal tumors with multilayered rosettes (ETMRs), 3 ependymomas, 1 high-grade glioma, 1 gliosarcoma, 1 low-grade neuronal-glial tumor, and 2 tumors that cannot be specified. A teratoma background was present in 73.3% (11/15) of the cases. None of the tumors exhibited EWSR1 gene rearrangement. Methylation classification was consistent with morphologic diagnosis in 30% of patients (5/15). A novel ETMR, non-C19MC-altered type ovarian tumor was identified in 3 patients. The median follow-up period of all patients was 14.9 months (range, 2.1-216.4 months), during which 60.0% of patients experienced recurrence or disease progression, and the mortality rate was 33.3%. Patients with ETMR non-C19MC-altered subtype and unmatched tumors exhibited extremely poor outcomes, with 80% (4/5) mortality within 12 months. DNA methylation profiling classified a subset of ovarian NETs into molecular subtypes resembling those of central nervous system (CNS) tumor counterparts, with corresponding prognostic similarities. Leveraging the CNS tumor methylation classifier to diagnose peripheral neuroectodermal tumors may offer critical clinical insights for these rare malignancies, enabling molecular subtyping, prognostication, and alignment with CNS-targeted therapeutic strategies.

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.

Toripalimab combined with bevacizumab plus chemotherapy as first-line treatment for refractory recurrent or metastatic cervical cancer: a single-arm, open-label, phase II study (JS001-ISS-CO214)

To evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3-28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6-95.3) and the DCR was 95.8% (95% CI=78.9-99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4-34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative first-line treatment option for patients with R/M CC. ClinicalTrials.gov Identifier: NCT04973904.

Struma ovarii with synchronous ascites and elevated CA125 level: a retrospective cohort study

Benign struma ovarii (SO) with synchronous ascites and elevated CA125 level is extremely rare that the incidence, clinical characteristics, and risk factors remain unclear. We conducted a retrospective study of patients with SO treated in our hospital between 1980 and 2022. Logistic regression was used to identify potential risk factors for SO patients presenting with ascites and elevated CA125 levels. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the identified risk factors. A total of 21 patients with synchronous ascites and elevated CA125 levels were identified in 229 patients with SO, the crude incidence rate was 9.17%, and four patients (1.75%) had pseudo-Meigs' syndrome. Ascites were completely involuted within 1 month postoperatively and the serum CA125 level decreased to normal between 3 d and 6 weeks after surgery. Multivariate logistic regression showed that age ≥49 years (OR 3.71, 95% CI 1.29 - 10.64, Less than one-tenth of patients with SO would present ascites and elevated CA125 levels, while age ≥49 years, tumor sizes ≥10 cm, and the presence of proliferative SO were the risk factors.

&lt;p&gt;Importance of Standard Treatment in Prognosis of Patients with Ovarian Cancer and Associated Cerebral Infarction&lt;/p&gt;

Data on the treatment of patients with ovarian cancer (OC) and associated cerebral infarction (CI) are extremely limited. The objectives were to investigate the risk factors for prognosis in patients with OC and associated CI. We retrospectively reviewed the electronic medical records of patients with OC from January 2013 to November 2018 in Peking Union Medical Hospital. In total, 2632 inpatients were diagnosed with malignant ovarian cancer in our institution, and 30 patients (1.1%) were diagnosed with OC-associated CI. The median age was 60 years (range, 37-83). The standard treatment, according to National Comprehensive Cancer Network (NCCN) guidelines, was administered to 19 patients. The median follow-up time was 19.5 months (range, 1-59 months). In total, 17 patients experienced tumor progression, and 16 of them died. In univariate analysis, overall survival was significantly associated with the D-dimer level (P=0.017), FIGO stage (P=0.014), complete cytoreduction (P<0.000) and standard treatment (P<0.000). In multivariate analysis, the standard treatment remained an independent protective factor for death (hazard ratio=0.061, 95% confidence interval=0.007-0.537, P=0.012). Although the prognosis of patients with OC and associated CI was poor, those who underwent the standard treatment still benefited.

Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance

AbstractYolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. We show that microsatellite instability status and mutational signatures are informative of chemoresistance. We identify somatic driver candidates, including significantly mutated genesKRASandKITand copy-number alteration drivers, including deletedARID1AandPARK2, and amplifiedZNF217,CDKN1B, andKRAS. YSTs have very infrequentTP53mutations, whereas the tumors from patients with abnormal gonadal development contain bothKRASandTP53mutations. We further reveal a role ofOVOL2overexpression in YST resistance to cisplatin. This study lays a critical foundation for understanding key molecular aberrations in YSTs and developing related therapeutic strategies.

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.

Early prediction and risk stratification of ovarian cancer based on clinical data using machine learning approaches

Our study was aimed to construct a predictive model to advance ovarian cancer diagnosis by machine learning. A retrospective analysis of patients with pelvic/adnexal/ovarian mass was performed. Potential features related to ovarian cancer were obtained as many as possible. The optimal machine learning algorithm was selected among six candidates through 5-fold cross validation. Top 20 features having the most powerful predictive significance were ranked by Shapley Additive Interpretation (Shap) method. Clinical validation was further performed to confirm whether our model could advance diagnosis of ovarian cancer. A total of 9,799 patients were collected. The inclusion criteria included age >18 years old, the first diagnosis being pelvic/adnexal/ovarian mass of undetermined significance, and pathological report indispensable. Four hundred and thirty-eight dimensional features were obtained after filtration. LightGBM showed the best performance with accuracy 88%. Among the top 20 features, 55% belonged to laboratory test report, 35% came from imaging examination report, and 10% were attributed to basic demographics and main symptom. Age, CA125, and risk of ovarian malignancy algorithm were the top three. Our predictive model performed stably in testing and clinical validation datasets, and was found to advance the diagnosis of ovarian cancer about 17 days before clinical pathological examination. LightGBM was the optimal algorithm for our predictive model with accuracy of 88%. Laboratory test and imaging examination played essential roles in diagnosing ovarian cancer. Our model could advance the diagnosis of ovarian cancer before clinical pathological examination.

Toripalimab Combined With Chemotherapy and Bevacizumab as First-Line Treatment in Patients With Advanced Cervical Cancer

This is a single-arm, multicenter, phase II study to investigate efficacy and safety of Toripalimab combined with chemotherapy (paclitaxel and cisplatin) and Bevacizumab as first-line treatment in patients with recurrent, refractory and metastatic cervical cancer

Efficacy and Safety of Niraparib Combined With Oral Etoposide in Platinum Resistant/Refractory Recurrent Ovarian Cancer

To evaluate the efficacy and safety of niraparib combined with oral etoposide in platinum resistant or platinum refractory recurrent ovarian cancer.