Tingting Chen

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.

Precision Diagnosis and Individualized Therapy of Non‐Gestational Choriocarcinoma Invading the Corpus Uteri and Cervix: A Case Report and Literature Review

ABSTRACT Background Non‐gestational choriocarcinoma (NGCC) is a rare type of malignant tumor. Primary lesions are typically detected in the ovary and rarely invade the corpus uteri and cervix. NGCC usually has a poor prognosis due to the difficulty in achieving early and accurate diagnoses because of its rarity. Case This case described a female who was initially diagnosed with gestational choriocarcinoma and treated with EMA‐CO chemotherapy. However, subsequent short tandem repeat (STR) analysis confirmed the diagnosis as NGCC, prompting surgical intervention. Given her favorable response and after thorough communication, three additional cycles of EMA‐CO chemotherapy were recommended. At her last follow‐up, her human chorionic gonadotropin level had normalized. Conclusion This case presents a rare instance of NGCC with simultaneous uterine and cervical involvement, confirmed by STR analysis and successfully managed with the EMA‐CO regime. It highlights the necessity of precise diagnosis and personalized treatment for effective management of this disease.

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.

Upregulation of CXCL1 and LY9 contributes to BRCAness in ovarian cancer and mediates response to PARPi and immune checkpoint blockade

Mutations in BRCA1 or BRCA2 (BRCA1/2) cause homologous recombination deficiency (HRD). Ovarian cancer (OvCa) patients harbouring HRD beyond BRCA1/2 mutation result in a state referred to as "BRCAness". OvCa with BRCAness could benefit from PARP inhibitors. This study aims to identify a signature to detect the BRCAness population at the transcriptome level. We used a rank-based algorithm to develop a qualitative BRCAness signature for OvCa. Upregulation of CXCL1 with downregulation of SV2A and upregulation of LY9 with downregulation of CHRNB3 were constructed as the BRCAness signature (2 gene pairs, 2-GPS) for OvCa. OvCa samples that were classified as BRCAness by 2-GPS showed improved overall survival, progression-free survival and exhibited increased multi-omics alterations in homologous recombination genes and enhanced sensitivity to immune checkpoint blockade. BRCAness cells were sensitive to PARP inhibitors. By biological experiments, we validated SKOV3 cells and patients with HRD exhibited higher expression of CXCL1 than SV2A and higher expression of LY9 than CHRNB3 at mRNA level. Both SKOV3 and A2780 with HRD were sensitive to mitomycin C, cisplatin and olaparib. In conclusion, 2-GPS could robustly predict BRCAness OvCa at the individual level and extend the population who may benefit from PARP inhibitors.

Cost-effectiveness of human papillomavirus vaccine in China: a systematic review of modelling studies

Objectives China suffers from high burdens of human papillomavirus (HPV) and cervical cancer, whereas the uptake of HPV vaccine remains low. The first Chinese domestic HPV vaccine was released in 2019. However, collective evidence on cost-effectiveness of HPV vaccination in China has yet to be established. We summarised evidence on the cost-effectiveness of HPV vaccine in China. Design Systematic review and narrative synthesis Data sources PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang Data were searched through 2 January 2021 Eligibility criteria for selecting studies Cost-effectiveness studies using a modelling approach focusing on HPV vaccination interventions in the setting of China were included for review. Data extraction and synthesis We extracted information from the selected studies focusing on cost-effectiveness results of various vaccination programmes, key contextual and methodological factors influencing cost-effectiveness estimates and an assessment of study quality. Results A total of 14 studies were included for review. Considerable heterogeneity was found in terms of the methodologies used, HPV vaccination strategies evaluated and study quality. The reviewed studies generally supported the cost-effectiveness of HPV vaccine in China, although some reached alternative conclusions, particularly when assessed incremental to cervical cancer screening. Cost of vaccination was consistently identified as a key determinant for the cost-effectiveness of HPV vaccination programmes. Conclusions Implementing HPV vaccination programmes should be complemented with expanded cervical cancer screening, while the release of lower-priced domestic vaccine offers more promising potential for initiating public HPV vaccination programmes. Findings of this study contributes important evidence for policies for cervical cancer prevention in China and methodological implications for future modelling efforts.

MRI Using Artificial Intelligence Algorithm to Evaluate Concurrent Chemoradiotherapy for Local Recurrence and Distant Metastasis of Cervical Squamous Cell Carcinoma

The aim of this study was to investigate the magnetic resonance imaging (MRI) features of patients with local recurrence and distant metastasis of cervical squamous cell carcinoma before and after concurrent chemoradiotherapy based on artificial intelligence algorithm. In this study, 100 patients with cervical squamous cell carcinoma with local recurrence and distant metastasis who underwent concurrent chemoradiotherapy were collected as the research subjects, and all underwent MRI multisequence imaging scans. At the same time, according to the evaluation criteria of solid tumor efficacy, patients with complete remission were classified into the effective group, and patients with partial remission, progressive disease, and stable disease were classified into the ineffective group. In addition, an image segmentation algorithm based on Balloon Snake model was proposed for MRI image processing, and simulation experiments were carried out. The results showed that the Dice coefficient of the proposed model segmentation of the reconstructed image was significantly higher than that of the level set model and the greedy algorithm, while the running time was the opposite ( P < 0.05 ). The lesion volume ( 38.76 ± 5.34  cm3) in the effective group after treatment was significantly smaller than that in the noneffective group ( 46.33 ± 4.64  cm3), and the rate of lesion volume shrinkage (28.71%) was significantly larger than that in the noneffective group (12.49%) ( P < 0.05 ). The relative apparent diffusion coefficient (rADC) value and rADC value change rate of the lesion after treatment in the effective group were significantly greater than those in the noneffective group ( P < 0.05 ). In summary, the image segmentation and reconstruction algorithm based on Balloon Snake model can not only improve the quality of MRI images but also shorten the processing time and improve the diagnostic efficiency. The volume regression rate and rADC value change rate of cervical squamous cell carcinoma lesion can reflect the early efficacy of concurrent chemoradiotherapy for cervical squamous cell carcinoma and have predictive value.

A Task Decomposing and Cell Comparing Method for Cervical Lesion Cell Detection

Automatic detection of cervical lesion cells or cell clumps using cervical cytology images is critical to computer-aided diagnosis (CAD) for accurate, objective, and efficient cervical cancer screening. Recently, many methods based on modern object detectors were proposed and showed great potential for automatic cervical lesion detection. Although effective, several issues still hinder further performance improvement of such known methods, such as large appearance variances between single-cell and multi-cell lesion regions, neglecting normal cells, and visual similarity among abnormal cells. To tackle these issues, we propose a new task decomposing and cell comparing network, called TDCC-Net, for cervical lesion cell detection. Specifically, our task decomposing scheme decomposes the original detection task into two subtasks and models them separately, which aims to learn more efficient and useful feature representations for specific cell structures and then improve the detection performance of the original task. Our cell comparing scheme imitates clinical diagnosis of experts and performs cell comparison with a dynamic comparing module (normal-abnormal cells comparing) and an instance contrastive loss (abnormal-abnormal cells comparing). Comprehensive experiments on a large cervical cytology image dataset confirm the superiority of our method over state-of-the-art methods.

Discriminative Cervical Lesion Detection in Colposcopic Images With Global Class Activation and Local Bin Excitation

Accurate cervical lesion detection (CLD) methods using colposcopic images are highly demanded in computer-aided diagnosis (CAD) for automatic diagnosis of High-grade Squamous Intraepithelial Lesions (HSIL). However, compared to natural scene images, the specific characteristics of colposcopic images, such as low contrast, visual similarity, and ambiguous lesion boundaries, pose difficulties to accurately locating HSIL regions and also significantly impede the performance improvement of existing CLD approaches. To tackle these difficulties and better capture cervical lesions, we develop novel feature enhancing mechanisms from both global and local perspectives, and propose a new discriminative CLD framework, called CervixNet, with a Global Class Activation (GCA) module and a Local Bin Excitation (LBE) module. Specifically, the GCA module learns discriminative features by introducing an auxiliary classifier, and guides our model to focus on HSIL regions while ignoring noisy regions. It globally facilitates the feature extraction process and helps boost feature discriminability. Further, our LBE module excites lesion features in a local manner, and allows the lesion regions to be more fine-grained enhanced by explicitly modelling the inter-dependencies among bins of proposal feature. Extensive experiments on a number of 9888 clinical colposcopic images verify the superiority of our method (AP

A Corresponding Region Fusion Framework for Multi-Modal Cervical Lesion Detection

Cervical lesion detection (CLD) using colposcopic images of multi-modality (acetic and iodine) is critical to computer-aided diagnosis (CAD) systems for accurate, objective, and comprehensive cervical cancer screening. To robustly capture lesion features and conform with clinical diagnosis practice, we propose a novel corresponding region fusion network (CRFNet) for multi-modal CLD. CRFNet first extracts feature maps and generates proposals for each modality, then performs proposal shifting to obtain corresponding regions under large position shifts between modalities, and finally fuses those region features with a new corresponding channel attention to detect lesion regions on both modalities. To evaluate CRFNet, we build a large multi-modal colposcopic image dataset collected from our collaborative hospital. We show that our proposed CRFNet surpasses known single-modal and multi-modal CLD methods and achieves state-of-the-art performance, especially in terms of Average Precision.

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.