Junfen Xu

A Retrospective Study on the Clinicopathological Characteristics and Prognostic Analysis of Gynecologic Neuroendocrine Carcinoma

ABSTRACT Background Gynecologic neuroendocrine carcinomas (NECs) are rare, highly aggressive malignancies with early metastatic potential and limited evidence to guide optimal management across different primary sites. Aims To characterize the clinicopathological features, treatment patterns, survival outcomes, and prognostic factors of gynecologic NECs (cervix, endometrium, and ovary) treated at a single tertiary center over a 10‐year period. Materials and Methods This observational, single‐center retrospective cohort study included patients diagnosed with gynecologic NEC at Women's Hospital, Zhejiang University School of Medicine, between January 2013 and August 2023. Clinicopathological data, treatment modalities, recurrence, and follow‐up outcomes were collected. Progression‐free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods. Prognostic factors were assessed using log‐rank tests and multivariable Cox proportional hazards models. Results A total of 52 patients were identified, of whom 78.8% had cervical NEC. Primary surgery was performed in 90.4% of patients; adjuvant chemotherapy and radiotherapy were administered in 65.4% and 51.9%, respectively. Among cervical NEC cases with HPV testing, 69.7% were HPV16/18‐positive. Immunohistochemical (IHC) showed high positivity for synaptophysin (95.3%) and chromogranin A (72.7%); Ki‐67 exceeded 50% in 89.1% of evaluated cases. Median PFS for cervical NEC was 29 months; stage I cervical NEC showed a 5‐year PFS of 51.6% and 5‐year OS of 68.4%. Poorer prognosis was associated with FIGO stage ≥ IB3, mixed neuroendocrine‐non‐neuroendocrine neoplasm (MiNEN) with squamous cell carcinoma, tumor size > 4 cm, and lymph node metastasis. On multivariable analysis of cervical NEC, MiNEN with squamous cell carcinoma remained an independent predictor of reduced PFS (HR = 6.97, 95% CI: 1.60–30.31; p  = 0.010). Discussion Despite multimodal treatment, gynecologic NECs showed poor outcomes. The identification of MiNEN with squamous cell carcinoma as an independent adverse factor for PFS suggests histologic composition may meaningfully affect prognosis and warrants validation in larger, multicenter cohorts. Conclusion Cervical NEC was the predominant subtype, most patients underwent surgery with adjuvant therapy, and survival was strongly stage‐dependent. MiNEN with squamous cell carcinoma independently predicted worse PFS, highlighting a potential high‐risk subgroup and reinforcing the need for multicenter prospective studies and more effective, potentially targeted treatment approaches for gynecologic NECs.

Single‐cell landscape of the tumour immune microenvironment in human gynaecologic malignancies

Abstract Background The immune microenvironment of the three most common gynaecological malignancies—tubo‐ovarian cancer, endometrial cancer and cervical cancer—has not been systematically studied, limiting clinical application. Methods This study analyses 272 389 CD45 + immune cells by integrating publicly available single‐cell RNA sequencing (scRNA‐seq) data from 111 tumour and non‐malignant tissue samples. We identified distinct subsets within immune cells: 11 for monocytes/macrophages, six for CD4 T cells, eight for CD8 T cells and five for B cells, detailing their distribution, prevalence and distinct functions. Results A pro‐angiogenic macrophage subset linked to NF‐κB signalling was associated with worse clinical outcomes and an interferon‐primed macrophage subset correlated with improved survival by recruiting T cells through CXCL9/10/11 secretion, as confirmed by multi‐colour immunohistochemistry. T cells exhibited dynamic roles in tubo‐ovarian cancer, with CD8 Tex cells contributing to immune dysfunction and poor prognosis, while CD8 Trm cells in early‐stage tumours supported immune surveillance. Additionally, we identified co‐stimulatory and co‐inhibitory receptor interactions and classified distinct B cell subsets with varying prognostic implications. Conclusions This comprehensive analysis of the tumour immune microenvironment in gynaecological malignancies provides new insights into immune cell composition and function offering potential for optimising immunotherapies and improving clinical outcomes in these cancers.

RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B

Abstract Long non-coding RNAs (lncRNAs) play an indispensable role in the occurrence and development of ovarian cancer (OC). However, the potential involvement of lncRNAs in the progression of OC is largely unknown. To investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1 ( RAD51B-AS1 ), a novel lncRNA in OC, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to verify the expression of RAD51B-AS1 . Cellular proliferation, metastasis, and apoptosis were detected using the cell counting kit-8 (CCK-8), colony-formation, transwell, and flow cytometry assays. Mouse xenograft models were established for the detection of tumorigenesis. The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues. RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis. Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B . Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1 . Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo. Thus, RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B (Akt)/B cell lymphoma protein-2 (Bcl-2) signaling pathway, and these effects may be associated with the positive regulation of RAD51B expression. RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC, and as a potential therapeutic target for disease management.

Impact of PARP inhibitors on progression-free survival in platinum-sensitive recurrent epithelial ovarian cancer: a retrospective analysis

Poly (ADP-ribose) polymerase (PARP) inhibitors such as olaparib and niraparib have shown promise in extending progression-free survival (PFS) in patients with platinum-sensitive recurrent (PSR) epithelial ovarian cancer. In this retrospective study, we aimed to present our own data on the effect of PARP inhibitors on PFS in recurrent epithelial ovarian cancer. 82 patients diagnosed with PSR epithelial ovarian, tubal, or primary peritoneal cancer between May 2017 and September 2023 were initially enrolled from our hospital. However, 16 patients had prior exposure to PARP inhibitors during primary treatment, and 11 were lost to follow-up. Consequently, the study focused on 55 eligible patients. PFS was compared between patients receiving PARP inhibitor maintenance therapy and those who did not. Among the 55 patients with PSR epithelial ovarian cancer, 18 received olaparib as maintenance therapy, 19 received niraparib, and 18 opted for observation. PARP inhibitor therapy significantly extended PFS (mean 24.0 months) compared to observation (mean 9.0 months, p = 0.0005), regardless of BRCA mutation status (HR = 0.20, 95% CI: 0.08-0.50). Subgroup analysis showed no statistical difference between olaparib and niraparib. Additionally, there was no PFS difference based on BRCA mutation status within both PARP inhibitor groups. Our retrospective study demonstrates that PARP inhibitor maintenance therapy, including olaparib and niraparib, significantly prolongs PFS in patients with PSR epithelial ovarian, tubal, or primary peritoneal cancer, These findings support the broad utilization of PARP inhibitors as a standard maintenance therapy for PSR epithelial ovarian cancer irrespective of BRCA mutation status.

Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma

The present study used single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition of ovarian carcinosarcoma (OCS) and identify its molecular characteristics. scRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor microenvironment. Immunohistochemistry staining was used for validation. The scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma (HGSOC) tumors and other OCS tumors. Both malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this study. We identified four epithelial cell subclusters with different biological roles. Among them, epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog ( This study provides the single-cell transcriptomics signature of human OCS, which constitutes a new resource for elucidating OCS diversity.

Secondary cytoreduction surgery for recurrent epithelial ovarian cancer patients after PARPi maintenance: A multicenter, randomized, controlled clinical trial

Poly ADP-ribose polymerase inhibitors (PARPi) treatment has radically changed the treatment strategy for epithelial ovarian cancer. Cancer progression with PARPi maintenance is a new problem that has arisen in clinical practice, and the value of secondary cytoreduction surgery remains unknown. To evaluate the benefits of secondary cytoreductive surgery and to clarify the sensitivity to platinum in patients with firstline or secondline recurrent epithelial ovarian cancer who have completed ≥6 months of PARPi maintenance. Carefully selected patients who progress on PARPi maintenance will benefit from secondary cytoreductive surgery. This is a multicenter phase III trial. Eligible patients will be randomly assigned at a ratio of 1:1 to either the experimental or standard arm. Patients in the experimental arm will receive secondary cytoreductive surgery followed by platinum based chemotherapy, while patients in the standard arm will be provided with chemotherapy alone. Patients diagnosed with firstline or secondline recurrent epithelial ovarian cancer who had previously received ≥4 cycles of platinum based chemotherapy in initial treatment followed by PARPi maintenance therapy for ≥6 months prior to recurrence. Progression free survival. 400 patients. Accrual completion is expected in December 2024 with results mature after 2 years of follow-up in 2026. ClinicalTrials.gov NCT05607329.

Topoisomerase IIα orchestrates secretion of IL-6 and IL-8 with human papillomavirus replication

High-risk human papillomavirus (HPV) replication requires deregulation of host DNA damage response (DDR) and inflammatory pathways. DNA topoisomerase 2β (Top2β) was previously shown to promote HPV replication. We investigated whether its paralog Top2α protein acts similarly to the virus. Elevated levels of Top2α are consistently observed in cervical intraepithelial lesions and the related carcinomas, as well as in HPV-positive cell lines. Silencing Top2α with shRNA severely suppresses HPV genome maintenance and amplification, but in a DDR-independent manner. Instead, Top2α facilitates secretion of interleukin (IL)-6 and IL-8, which are necessary for HPV replication. Mechanistically, this manipulation is regulated by toll-like receptor 4 (TLR4). Top2α binds to the TLR4 promoter to transcriptionally induce TLR4 expression. Blockade of TLR4 signaling by the specific inhibitor TAK-242 significantly reduces the secreted IL-6/IL-8 levels and HPV replication. Overall, our results reveal a novel role of Top2α to shape the inflammatory microenvironment that benefits HPV replication, making it a promising therapeutic target for HPV-associated diseases.

An immunosuppressive tertiary lymphoid structure is associated with adverse prognosis in gastric-type endocervical adenocarcinoma

Abstract Background Gastric-type adenocarcinoma (GAC) is the predominant subtype of HPV-independent endocervical adenocarcinoma, characterized by aggressive clinical behavior and poor prognosis. However, its tumor immune microenvironment (TIME) remains largely unexplored. Methods We systematically profiled the immune landscape using bulk RNA sequencing and multiplex immunofluorescence staining and comprehensively analyzed the associations between immune features, clinicopathological parameters, and patient outcomes in a multi-institutional cohort of 153 GAC cases. Results GAC tumors exhibited sparse T cell but abundant macrophage infiltration, predominantly with M2-polarized macrophages in advanced stage. Tumors with tertiary lymphoid structure (TLS) demonstrated an immunosuppressive milieu characterized by enrichment of B cells, PD1-CD8+ T cells, and regulatory T cells. While TLS-positive patients were associated with poorer prognosis, 2 patients showed improved survival with chemoradiotherapy. Moreover, the TLS and FIGO stage-based prognostic model was robust in the risk stratification for tumor recurrence. Conclusions We reveal a distinct immunosuppressive TIME and TLS in GAC. TLS might confer an adverse prognosis. Our findings provide valuable clues for individualized therapy for this aggressive cancer in future.

Alveolar rhabdomyosarcoma of cervix: A case report

Rationale: Alveolar rhabdomyosarcoma (ARMS) is a rare and highly aggressive malignant soft tissue tumor. ARMS is associated with a poor prognosis, especially in adults, occurring in the uterine cervix infrequently. To date, only 6 cases have been reported in the literature. We discuss the challenges in diagnosing and managing cervical ARMS and highlights the need for ongoing research into optimal treatment strategies for this malignancy. Patient concerns: A 51-year-old female was diagnosed with advanced-stage ARMS. Positron emission tomography and computed tomography scans indicated a high metabolism mass in the uterus region, along with multiple lymph nodes enlargement in the pelvic, para-aorta and mediastinal regions. Cervical biopsy and segmental curettage revealed a small cell malignant tumor with poor differentiation. Histological and immunohistochemical examination confirmed ARMS. Diagnoses: The final diagnosis was cervical ARMS, staged IV according to the Intergroup Rhabdomyosarcoma Studies Group based on the imaging and histology results. Interventions: The patient underwent radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy. Postoperatively, the patient received a series of chemotherapy regimens including VAC† (vincristine, epirubicin, cyclophosphamide), EP (etoposide and cisplatin), VIP (etoposide, ifosfamide, cisplatin), gemcitabine and bevacizumab, gemcitabine and docetaxel, pertuzumab and lenvatinib and radiotherapy. Conclusion: ARMS has low incidence with unique clinical pathological characteristics. The biological behavior is more aggressive and the prognosis is worse in ARMS. Further research is necessary to refine treatment protocols and improve survival rates for this aggressive tumor.

A novel non-invasive mRNA-lncRNA biomarker panel for accurate prediction of cervical squamous cell carcinoma and adenocarcinoma

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) represent predominant histological subtypes of cervical cancer. To improve screening efficacy, we leveraged RNA sequencing data from 4 cervical SCC samples, 4 cervical ADC samples, and 8 normal cervix samples and conducted a comprehensive mRNA and long noncoding RNA (lncRNA) profiling analysis followed with a multi-phase study comprising 556 samples. Validating the RNA sequencing data in a clinical sample set comprising 45 normal cervix tissues, 45 SCC tissues, and 45 ADC tissues, we identified 9 mRNAs (SMC1B, OTX1, GRP, CELSR3, HOXC6, ITGB6, WDR62, SEPT3, and KLHL34) and 4 lncRNAs (FEZF1-AS1, LINC01305, LINC00857, and LINC00673) differentially expressed in both SCC and ADC samples. Utilizing quantitative reverse transcription polymerase chain reaction analysis and receiver operating characteristic (ROC) curve analysis in a training set (45 normal, 126 SCC, and 82 ADC tissues), we refined a novel mRNA-lncRNA-based panel (SMC1B/CELSR3/FEZF1-AS1/LINC01305). Employing logistic regression model and ROC analysis, this panel exhibited significant distinctions and promising area under the curve (AUC) values in both SCC (AUC=0.9520, p<0.0001) and ADC (AUC=0.9748, p<0.0001) tissues. Subsequent validation in an independent set (11 normal, 32 SCC, and 20 ADC tissues) demonstrated its diagnostic accuracy in both SCC (AUC=0.9659, p<0.0001) and ADC (AUC=0.9636, p<0.0001) patients. Notably, this tissue-based biomarker panel robustly discriminated precancerous lesion and cervical cancer patients from non-disease controls in a blood-based validation set (30 normal, 25 HSIL and 50 cervical cancer) with an AUC value of 0.9320. This study presents a non-invasive, efficient diagnostic panel for cervical cancer screening.

Evaluation of secondary cytoreduction surgery in platinum-resistant ovarian cancer patients within three-line recurrent: a multicenter, randomized controlled study

Epithelial ovarian cancer is the leading cause of death among gynecological malignancies. Platinum resistance remains a dilemma and bottleneck in treatment, and salvage chemotherapy has limited effectiveness. Recently, the role of secondary cytoreductive surgery (SCS) in patients with platinum-resistant recurrent ovarian cancer (ROC) has caused attention especially in patients with oligometastases. However, there is neither high-quality evidence-based evidence nor standardized criteria for selecting SCS for patients with platinum-resistant ROC until now. This multicenter, randomized, controlled clinical trial is to evaluate the value of SCS and to clarify reliable criteria of utilizing SCS in women with ROC, which is led by Gynecologic Oncology Group, Women's Hospital, Zhejiang University School of Medicine. Recruitment has started on January 1st, 2023, and is scheduled to end in December 2026. One hundred and forty participants with platinum-resistant ROC who meet the "RSCS criteria" will be randomized assigned at a ratio of 1:1 to either the experimental arm or the standard arm. Patients in the experimental arm will receive SCS followed by non-platinum single agent chemotherapy (paclitaxel, gemcitabine or liposomal adriamycin) for at least 4 cycles while patients in the standard arm will be provided with only non-platinum single agent chemotherapy. The primary outcome is progression-free survival. The secondary outcomes are overall survival, adverse events and health-related cancer-specific quality of life. ClinicalTrials.gov Identifier: NCT05633199.

CircMAN1A2_009 facilitates YBX1 nuclear localization to induce GLO1 activation for cervical adenocarcinoma cell growth

AbstractThe molecular mechanisms driving the development of cervical adenocarcinoma (CADC) and optimal patient management strategies remain elusive. In this study, we have identified circMAN1A2_009 as an oncogenic circular RNA (circRNA) in CADC. Clinically, circMAN1A2_009 showed significant upregulation in CADC tissues, with an impressive area under the curve value of 0.8075 for detecting CADC. Functional studies, involving both gain‐of‐function and loss‐of‐function experiments, revealed that circMAN1A2_009 suppressed reactive oxygen species accumulation and apoptosis, and boosted cell viability in CADC cells. Conversely, silencing circMAN1A2_009 reversed these effects. Further mechanistic investigations indicated that circMAN1A2_009 interacted with YBX1, facilitating the phosphorylation levels of YBX1 at serine 102 (p‐YBX1S102) and facilitating YBX1 nuclear localization through sequence 245–251. This interaction subsequently increased the activity of the glyoxalase 1 (GLO1) promoter, leading to the activation of GLO1 expression. Consistently, inhibition of either YBX1 or GLO1 mirrored the biological effects of circMAN1A2_009 in CADC cells. Additionally, knockdown of YBX1 or GLO1 partially reversed the oncogenic behaviors induced by circMAN1A2_009. In conclusion, our findings propose circMAN1A2_009 as a potential oncogene and a promising indicator for diagnosing and guiding therapy in CADC patients.

Olaparib synergizes with arsenic trioxide by promoting apoptosis and ferroptosis in platinum-resistant ovarian cancer

AbstractPoly (ADP-ribose) polymerase (PARP) inhibitors are efficacious in treating platinum-sensitive ovarian cancer (OC), but demonstrate limited efficiency in patients with platinum-resistant OC. Thus, further investigations into combined strategies that enhance the response to PARP inhibitors (PARPi) in platinum-resistant OC are required. The present study aimed to investigate the combined therapy of arsenic trioxide (ATO) with olaparib, a common PARPi, and determine how this synergistic cytotoxicity works in platinum-resistant OC cells. Functional assays demonstrated that the combined treatment of olaparib with ATO significantly suppressed cell proliferation and colony formation, and enhanced DNA damage as well as cell apoptosis in A2780-CIS and SKOV3-CIS cell lines. Results of the present study also demonstrated that a combination of olaparib with ATO increased lipid peroxidation and eventually triggered ferroptosis. Consistently, the combined treatment synergistically suppressed tumor growth in mice xenograft models. Mechanistically, ATO in combination with olaparib activated the AMPK α pathway and suppressed the expression levels of stearoyl-CoA desaturase 1 (SCD1). Collectively, results of the present study demonstrated that treatment with ATO enhanced the effects of olaparib in platinum-resistant OC.

Single-Cell RNA Sequencing Reveals the Tissue Architecture in Human High-Grade Serous Ovarian Cancer

Abstract Purpose: The heterogeneity of high-grade serous ovarian cancer (HGSOC) is not well studied, which severely hinders clinical treatment of HGSOC. Thus, it is necessary to characterize the heterogeneity of HGSOC within its tumor microenvironment (TME). Experimental Design: The tumors of 7 treatment-naïve patients with HGSOC at early or late stages and five age-matched nonmalignant ovarian samples were analyzed by deep single-cell RNA sequencing (scRNA-seq). Results: A total of 59,324 single cells obtained from HGSOC and nonmalignant ovarian tissues were sequenced by scRNA-seq. Among those cells, tumor cells were characterized by a set of epithelial-to-mesenchymal transition (EMT)-associated gene signatures, in which a combination of NOTCH1, SNAI2, TGFBR1, and WNT11 was further selected as a genetic panel to predict the poor outcomes of patients with HGSOC. Matrix cancer-associated fibroblasts (mCAF) expressing α-SMA, vimentin, COL3A, COL10A, and MMP11 were the dominant CAFs in HGSOC tumors and could induce EMT properties of ovarian cancer cells in the coculture system. Specific immune cell subsets such as C7-APOBEC3A M1 macrophages, CD8+ TRM, and TEX cells were preferentially enriched in early-stage tumors. In addition, an immune coinhibitory receptor TIGIT was highly expressed on CD8+ TEX cells and TIGIT blockade could significantly reduce ovarian cancer tumor growth in mouse models. Conclusions: Our transcriptomic results analyzed by scRNA-seq delineate an ecosystemic landscape of HGSOC at early or late stages with a focus on its heterogeneity with TME. The major applications of our findings are a four–EMT gene model for prediction of HGSOC patient outcomes, mCAFs’ capability of enhancing ovarian cancer cell invasion and potential therapeutic value of anti-TIGIT treatment.

Global characterization of extrachromosomal circular DNAs in advanced high grade serous ovarian cancer

AbstractHigh grade serous ovarian cancer (HGSOC) is the most aggressive subtype of ovarian cancer and HGSOC patients often appear with metastasis, leading to the poor prognosis. Up to date, the extrachromosomal circular DNAs (eccDNAs) have been shown to be involved in cancer genome remodeling but the roles of eccDNAs in metastatic HGSOC are still not clear. Here we explored eccDNA profiles in HGSOC by Circle-Sequencing analysis using four pairs of primary and metastatic tissues of HGSOC patients. Within the differentially expressed eccDNAs screened out by our analysis, eight candidates were validated by outward PCR and qRT-PCR analysis. Among them, DNMT1circle10302690-10302961 was further confirmed by FISH assay and BaseScope assay, as the most significantly down-regulated eccDNA in metastatic tumors of HGSOC. Lower expression of DNMT1circle10302690-10302961 in both primary and metastatic tumors was associated with worse prognosis of HGSOC. Taken together, our finding firstly demonstrated the eccDNAs landscape of primary and metastatic tissues of HGSOC. The eccDNA DNMT1circle10302690-10302961 can be considered as a potential biomarker or a therapeutically clinical target of HGSOC metastasis and prognosis.

Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1

Significance Persistent infections of oncogenic HPVs can lead to cervical, anogenital, and head-and-neck cancers. We report that HPV-infected cervical lesions display aberrant expression of 194 long-noncoding RNAs, including lnc-FANCI-2 . We show that, in cell and tissue cultures, lnc-FANCI-2 is induced primarily by the oncogenic HPV E7 protein via interacting with a cellular transcription factor YY1. HPV infection also increases YY1 protein expression by reducing miR-29a, which targets the 3′ UTR of YY1 RNA. In vivo and in vitro, the nearby DNA repair gene FANCI is co-upregulated. These findings highlight an aspect on how oncogenic HPV E7 contributes to pathogenesis.

Cytoreductive Surgery in Platinum-resistant Recurrent Ovarian Cancer

This novel study was specifically designed for platinum-resistant recurrent ovarian cancers with PFI\<6 months and aimed to compare prognosis of patients who received cytoreductive surgery followed by chemotherapy versus chemotherapy alone.

Secondary Cytoreduction Followed by Chemotherapy Versus Chemotherapy Alone in Relapsed Ovarian Cancer After PARPi Maintenance Treatment: a Multicentre, Open-label, Randomised, Phase 3 Trial

This study aims to carry out a multi-center, randomized controlled study on patients with recurrent ovarian cancer after PARPi maintenance, to explore the clinicopathological and molecular characteristics of patients with recurrent ovarian cancer after PARPi maintenance, and to clarify whether patients with recurrent ovarian cancer after PARPi maintenance for more than 6 months are sensitive to platinum drugs, and the value of secondary tumor cell reduction in such treatment, In order to provide evidence-based medicine basis for the standardized treatment mode of recurrent ovarian cancer after PARPi maintenance treatment.