Hua Yang

The Prognostic Significance of Adjuvant Chemotherapy in Adult Ovarian Granulosa Cell Tumors: A Systematic Review and Meta-analysis

Introduction This study aimed to evaluate the oncological and prognostic significance of adjuvant chemotherapy (CT) in patients with adult granulosa cell tumors of the ovary (AOGCT). Methods We searched the Chinese National Knowledge Infrastructure, Clinical Trials, Wanfang Database, Web of Science, Cochrane Library, and MEDLINE electronic databases for articles published up to May 2023. Reference lists of the enrolled studies, Google Scholar, and scientific meeting reports were also manually searched. Results We enrolled 5641 patients with AOGCT from 33 eligible studies, including 1674 (29.7%) and 3967 (70.3%) patients in the CT and non-CT groups, respectively. Based on the cumulative results, adjuvant CT did not affect the risk of recurrence or progression (R/P) (odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.01–2.78, I2 = 63%, P = .05) and 5-year overall survival (OR: .86, 95% CI: .70–1.04, I2 = 0%, P = .12) of patients with AOGCT. However, adjuvant CT might reduce the 5-year disease-free survival (OR: 2.90, 95% CI: 1.19–7.08, I2 = 55%, P = .02). Sub-group analysis revealed that adjuvant CT did not affect the risk of R/P in patients with early-stage AOGCT (OR: .78, 95% CI: .43–1.43, I2 = 2%, P = .43) and advanced or recurrent AOGCT (OR: .78, 95% CI: .43–1.43, I2 = 2%, P = .43). Conclusion This meta-analysis suggests that patients with AOGCT might not benefit from adjuvant CT, even those with advanced or recurrent disease. The results should be interpreted with caution because of the inherent limitations of retrospective studies.

The prognostic significance and role of adjuvant therapy for low-volume nodal metastasis in apparent early stage endometrial cancer: an updated systematic review and meta-analysis

Sentinel lymph node biopsy (SLNB) has improved detection of low-volume node metastasis (LVNM) in endometrial cancer (EC), but its prognostic significance and the need for adjuvant therapy (AT) remain unclear. A comprehensive search was performed until August 31, 2024 in multiple databases and sources. From 21 studies, 65,228 apparent early-stage EC patients were identified: 370 with macrometastases (MAC), 526 with micrometastases (MM), 2,138 with isolated tumor cells (ITCs), and 62,194 with negative nodes. Findings indicated: 1) The MM group had a lower risk of recurrence or progression (R/P) than the MAC group (risk ratio [RR]=0.49; 95% confidence interval [CI]=0.31-0.78; p=0.002), higher risk than the negative nodes group (RR=2.07; 95% CI=1.59-2.68; p<0.001), and similar risk to the ITC group (RR=0.67; 95% CI=0.44-1.02; p=0.060). 2) The MM group had higher 3-year progression-free survival (PFS) (RR=1.36; 95% CI=1.21-1.52; p<0.001) and overall survival (OS) (RR=1.22; 95% CI=1.09-1.37; p<0.001) than the MAC group, similar to the ITC and negative nodes groups. 3) The ITC group had a lower R/P risk and higher 3-year PFS/OS than the MAC group, similar to the negative nodes group. 4) AT reduced the R/P risk in the MM group (RR=0.41; 95% CI=0.22-0.76; p=0.005) and increased 3-year OS in the ITC group (RR=1.06; 95% CI=1.04-1.08; p<0.001). Early-stage EC with LVNM had better prognostic outcomes than MAC, and AT may improve outcomes of LVNM patients. More evidence from prospective randomized controlled trials is needed to confirm these findings due to the inherent biases of retrospective studies. PROSPERO Identifier: CRD42022364536.

MVT-Net: A novel cervical tumour segmentation using multi-view feature transfer learning

Cervical cancer is one of the most aggressive malignant tumours of the reproductive system, posing a significant global threat to women’s health. Accurately segmenting cervical tumours in MR images remains a challenging task due to the complex characteristics of tumours and the limitations of traditional methods. To address these challenges, this study proposes a novel cervical tumour segmentation model based on multi-view feature transfer learning, named MVT-Net. The model integrates a 2D global axial plane encoder-decoder network and a 3D multi-scale segmentation network as source and target domains, respectively. A transfer learning strategy is employed to extract diverse tumour-related information from multiple perspectives. In addition, a multi-scale residual blocks and a multi-scale residual attention blocks are embedded in the 3D network to effectively capture feature correlations across channels and spatial positions. Experiments on a cervical MR dataset of 160 images show that our proposed MVT-Net outperforms state-of-the-art methods, achieving a DICE score of 75.9±7.43%, an ASD of 2.69±0.58 mm and superior performance in tumour localisation, shape delineation and edge segmentation. Ablation studies further validate the effectiveness of the proposed multi-view feature transfer strategy. These results demonstrate that our proposed MVT-Net represents a significant advance in cervical tumour segmentation, offering improved accuracy and reliability in clinical applications.

The Significance of Radiotherapy in Ovarian Clear Cell Carcinoma: A Systematic Review and Meta-Analysis

Objective To assess the response rate and survival effect of adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) during ovarian clear cell carcinoma (OCCC). Methods We searched Web of Science, PubMed, Cochrane library electronic databases, Clinical Trials, WanFang Data and Chinese National Knowledge Infrastructure (CNKI) up to October 2022. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Results We identified a total of 4259 patients from 14 studies met the inclusion criteria. The pooled response rate of residual tumors for RT/CRT was 80.0%, the pooled 5-year progression-free survival (PFS) ratio during RT/CRT group was 61.0%, and the pooled 5-year overall survival (OS) ratio during RT/CRT group was 68.0%; heterogeneity tests demonstrated significant difference between studies (I 2 &gt;50%). Cumulative results suggested adjuvant RT/CRT improved 5-year PFS ratio of OCCC patients (OR: 0.51 (95% CI: 0.42–.88), I 2 = 22%, P = .009), had no impact on 5-year OS ratio (OR: 0.52 (95% CI: 0.19–1.44), I 2 = 87%, P = .21); meta-regression of studies before and after 2000 found consistent results. Sub-analysis observed that adjuvant RT/CRT had no impact on 5-year OS ratio of early-stage (stage I + II) OCCC patients (OR: 0.67 (95% CI: 0.25–1.83), I 2 = 85%, P = .44), but might improve 5-year OS ratio of advanced and recurrent OCCC patients (OR: 0.13(95% CI: 0.04–.44), P = .001). Conclusion This analysis suggested that adjuvant RT/CRT might improve oncologic outcomes of OCCC, especially for advanced and recurrent cases. Due to the inherent selective biases of retrospective studies enrolled in the meta-analysis, more convincing evidences based on prospective randomized controlled trials (RCTs) are urgently needed.

GnRHa as a treatment for letrozole-resistant recurrent adult granulosa cell tumors

Abstract Introduction: The optimal management of recurrent ovarian granulosa cell tumors is still unknown, and hormone therapy may be an alternative for chemotherapy-resistant cases. Patient concerns: A 46-year-old woman presented with a third recurrence after primary treatment of granulosa cell tumors. She developed tumor progression and drug-induced nephritis after 6 cycles of combined treatment with cisplatin and paclitaxel for the second recurrence and failed to benefit from chemotherapy, after the third optimal cytoreduction and tumor progression after 6 months of letrozole treatment. Diagnosis: Letrozole-resistant recurrent ovarian granulosa cell tumors Interventions: Intramuscular Diphereline 3.75 mg q28d. Outcomes: Computed tomography showed the metastatic neoplasm resolved. Progression-free survival is 20 months. Conclusion: Hormone therapy may be an alternative to treat recurrent granulosa cell tumors, and gonadotropin-releasing hormone agonists may be a rescue treatment for aromatase inhibitor-resistant cases.

Can adjuvant chemotherapy improve the prognosis of adult ovarian granulosa cell tumors?

Abstract Adult granulosa cell tumors (aGCTs) are rare ovarian neoplasms with a relatively favorable prognosis. They follow an indolent course, characterized by a prolonged natural history and a tendency to late recurrences, Around a quarter of patients develop recurrence and More than 70% of women with recurrence die from their disease, The percentage of patients received chemotherapy increases over time, whether adjuvant chemotherapy improve the prognosis of aGCTs is equivocal? The purpose of this review is to summarize the previously published evidence to evaluate whether adjuvant chemotherapy improve the prognosis of aGCTs to provide guidance for clinical practice. EMBASE, PubMed, Web of Science, WanFang Data and Chinese National Knowledge Infrastructure are searched up to December 2020, used the search strategy of ovar* and granulosa cell* and (tumor* or tumour* or malignan* or cancer* or carcinom* or neoplasm*) and chemotherapy. The screening process was conducted strictly based on inclusion and exclusion criteria. Clinical studies based on human including randomized controlled trial, quasi-randomised controlled trials, nonrandomised trials cohort study and case control study were included without restriction of time. The percentage of patients received chemotherapy increases over time, but the benefit of adjuvant chemotherapy is lack of high-grade evidence of prospective study, based on the current retrospective studies, we still do not have the evidence to confirm the survival benefit of adjuvant chemotherapy in early stage, advanced stage or recurrent aGCT with no residual tumor, but for inoperable disseminated disease or disease with suboptimal cytoreduction, adjuvant chemotherapy maybe an Optable options. Multinational prospective randomised controlled trials are urgently needed to validate the role of adjuvant chemotherapy. Further research on molecular mechanisms and developing novel targeted medicines may improve the survival of aGCTs.

Upregulation of lncRNA DARS‐AS1 accelerates tumor malignancy in cervical cancer by activating cGMP‐PKG pathway

AbstractThis paper investigates the function of lncRNA DARS‐AS1 in cervical cancer (CC) as well as its in‐depth mechanism. The differential expression of DARS‐AS1 and ATP1B2 were analyzed based on The Cancer Genome Atlas and the Genotype‐Tissue Expression databases, and the survival rate was measured using Kaplan–Meier survival analysis. Biological function experiments were performed to detect cell proliferation, invasion, and migration. Quantitative real‐time polymerase chain reaction was carried out to detect the expression of DARS‐AS1 and ATP1B2. Western blot analysis was utilized to assess the protein levels of ATP1B2 and cGMP‐PKG pathway‐related proteins. DARS‐AS1 was expressed at high levels in CC tissues and cell lines, and high expression of DARS‐AS1 indicated a lower survival rate. CCK‐8 and colony formation assays revealed that the overexpression of DARS‐AS1 promoted the proliferation of CC cells. Furthermore, bioinformatics analysis suggested that the cGMP‐PKG pathway ranks as the first pathway enriched by the differential genes that correlated with DARS‐AS1 (|r| &gt; 0.4). ATP1B2, as a cGMP‐PKG pathway‐related gene, was significantly correlated with the overall survival of CC patients. We further confirmed that ATP1B2 was lowly expressed in CC and negatively correlated with the DARS‐AS1 expression. Then, biological function experiments exhibited that the promotion of cell proliferation, invasion, and migration resulted due to the upregulation of DARS‐AS1 could be canceled by ATP1B2 overexpression. Finally, Western blot revealed that upregulation of DARS‐AS1 could activate the cGMP‐PKG pathway, while overexpression of ATP1B2 reversed this activation. Our study revealed that DARS‐AS1/ATP1B2 contributes to regulating the progression of CC at least partially by modulating the cGMP‐PKG pathway.

The significance of nonsurgical therapies for cervical infection of high‐risk human papilloma virus: A systematic review and meta‐analysis

AbstractObjectiveTo assess whether nonsurgical therapies were related with clearance of cervical infection of high‐risk human papilloma virus (hr‐HPV) or regression of mild abnormal cytology related with hr‐HPV.MethodsUntil March 2023, we identified a total of 10 424 women with cervical infection of hr‐HPV and 1966 women with mild abnormal cytology related with hr‐HPV from 44 studies that met the inclusion criteria.ResultsAfter systematically retrieving literature, we identified 2317 citations and 44 randomized controlled studies (RCT) were enrolled. Cumulative results suggested women with cervical infection of hr‐HPV might benefit from nonsurgical therapies. Both the clearance of hr‐HPV (OR: 3.83, I2 = 99%, p &lt; 0.00001) and regression of mild abnormal cytology related with hr‐HPV (OR: 3.12, I2 = 63%, p &lt; 0.00001) were significantly higher than control group. Subgroup analysis stratified by systematic therapy, topical therapy, traditional Chinese medicines (TCMs), and presistent hr‐HPV got consistent results. There was substantial heterogeneity between trials (I2 = 87% for clearance of hr‐HPV and 63% for regression of cytology), sensitivity analysis was performed by excluding single study one by one, and found the cumulative results were stable and dependable. Both the funnel plots for clearance of hr‐HPV and regression of abnormal cytology were asymmetrical, significant publication bias might exist.ConclusionNonsurgical therapies might benefit women who had a cervical infection of hr‐HPV with/without mild abnormal cytology related with hr‐HPV. Both the clearance of hr‐HPV and regression of abnormal cytology were significantly higher than control group. More studies with less heterogeneity were needed urgently to draw concrete conclusion.