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Gynecologic Cancer

Relevant Articles About Research and Clinical Trials in Gynecologic Cancer

RELATED :Cervical Cancer:Ovarian Cancer:Uterine Cancer

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Other CancersOvarian CancerMirvetuximab SoravtansinePaclitaxelPegylated liposomal doxorubicinTopotecanCompletedBelgiumBosnia and HerzegovinaCanadaCzechiaFranceIrelandItalyRussian FederationSerbiaSpainSwitzerlandUnited KingdomUnited States 0NCT02631876Phase 3FORWARD I
A Study of Mirvetuximab Soravtansine vs. Investigator’s Choice of Chemotherapy in Women With Folate Receptor (FR) Alpha Positive Advanced Epithelial Ovarian Cancer (EOC), Primary Peritoneal or Fallopian Tube Cancer

A Study of Mirvetuximab Soravtansine vs. Investigator’s Choice of Chemotherapy in Women With Folate Receptor (FR) Alpha Positive Advanced Epithelial Ovarian Cancer (EOC), Primary Peritoneal or Fallopian Tube Cancer

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Cell-Free DNA & HE4 for Ovarian Cancer Diagnosis

KEY TAKEAWAYS

  • The study aimed to evaluate liquid biopsy biomarkers’ feasibility for pre-operative ovarian cancer risk assessment and compare them with the RMI.
  • The study indicated that cell-free DNA is effective for pre-operative ovarian malignancy risk assessment, yet further validation in larger clinical trials is needed.

Early detection of ovarian cancer remains challenging due to the lack of effective screening methods. Liquid biopsy, utilizing cell-free DNA and biomarkers like HE4 and CA125, offers a promising approach for pre-operative risk assessment. However, their feasibility and performance in diagnostically challenging cases remain to be determined.

Duco H K Gaillard and his team conducted the study that aimed to fill this gap by evaluating these biomarkers alongside the established Risk of Malignancy Index (RMI) in a clinically representative population.

About 100 patients presenting with an ovarian mass suspected to be early-stage ovarian cancer were included. Among these, 50 patients were diagnosed with a malignant mass (cases), while the remaining 50 had a benign mass (controls). Employing WisecondorX, an algorithm widely utilized in non-invasive prenatal testing, they computed the benign-calibrated copy number profile abnormality score. This score reflected the deviation of a sample from benign controls, based on copy number profiles. The study integrated this score with serum concentration of HE4 to distinguish between cases and controls.

This study showed the potential of utilizing cell-free DNA for pre-operative assessment of malignancy risk in ovarian masses; nevertheless, further validation in larger clinical trials is warranted.

Source: https://ijgc.bmj.com/content/early/2024/02/22/ijgc-2023-005073

Gaillard, D.H.K., Lof, P., Sistermans, E.A., et al. (2024) ‘’Evaluating the effectiveness of pre-operative diagnosis of ovarian cancer using minimally invasive liquid biopsies by combining serum human epididymis protein 4 and cell-free DNA in patients with an ovarian mass.’’ International Journal of Gynecologic Cancer Published Online First: 22 February 2024. doi: 10.1136/ijgc-2023-005073.

Necroptosis and Immune Interaction in Uterine Cancer

KEY TAKEAWAYS

  • The study aimed to create a novel miRNA profile linked to necroptosis for predicting UCEC patient prognosis.
  • The results demonstrated that necroptosis potentially contributes to UCEC development via its interplay with immune responses.

Necroptosis, a recently identified caspase-independent cell death mechanism, is implicated in uterine cancer initiation and progression. MicroRNAs (miRNAs), crucial in uterine corpus endometrial carcinoma (UCEC) development, serve as essential regulators within the necroptotic process.

Qi Zhang and the team conducted the study that aimed to formulate a novel miRNA profile associated with necroptosis for prognostic prediction in UCEC patients. 

The RNA sequencing data from the TCGA-UCEC cohort, comprising 534 tumor samples and 33 normal samples, was obtained. Ten miRNAs showing differential expression related to necroptosis were identified. A prediction model for necroptosis-associated miRNAs was then developed using COX regression and nomogram analysis. Clinical and pathological parameters were incorporated to construct a nomogram and assess the model. 

Prognosis-related miRNAs were utilized to predict target genes, followed by functional analysis to elucidate potential mechanisms of these targets. Subsequent immune infiltration analysis, using transcriptome data, was conducted to identify immune genes linked to prognosis, and the expression levels of target genes were validated using UCEC tissues.

The study identified 7 up-regulated miRNAs (hsa-miR-577, hsa-miR-7-5p, hsa-miR-210-3p, hsa-miR-210-5p, hsa-miR-200a-5p, hsa-miR-141-3p, hsa-miR-425-5p) and 3 down-regulated miRNAs (hsa-miR-7-2-3p, hsa-miR-383-5p, hsa-miR-29a-3p). The risk signature, derived from univariate and multivariate COX analyses, incorporated two independent prognostic factors and miRNAs (hsa-miR-425-5p, hsa-miR-7-5p) associated with necroptosis. 

Nomograms illustrated the prognostic significance of risk level, age, FIGO stage, and histological type. Kaplan-Meier analysis indicated significant differences in overall survival (OS) outcomes linked to hsa-miR-425-5p (P < 0.001) and hsa-miR-7-5p (P = 0.015) expression. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted the pivotal roles of these miRNAs in tumor development, metastasis, and prognosis. Immune infiltration analysis revealed reduced infiltration of CD8+ T cells, CD8+ T cells, NK cells, and M1 macrophages in normal tissues. 

Furthermore, a necroptosis-related immune gene significantly associated with prognosis (THRB) was identified, with western blot and immunohistochemical staining confirming differential expression of THRB in normal endometrial tissues and tumors. The findings underscored the intimate link between necroptosis and UCEC. 

The results showed that the two necroptosis-related miRNAs investigated in this study may serve as valuable prognostic markers for UCEC patients and are associated with immune cell infiltration.This implies that necroptosis might contribute to UCEC development by interacting with immune responses. No funding information was available.

Source: https://pubmed.ncbi.nlm.nih.gov/38383747/

Zhang, Q., Luo, Y., Zhang, S. et al. Development of a necroptosis-related prognostic model for uterine corpus endometrial carcinoma. Sci Rep 14, 4257 (2024). https://doi.org/10.1038/s41598-024-54651-3.

Agricultural Exposures & Ovarian Cancer Risk: AGRICAN Cohort

KEY TAKEAWAYS

  • The study aimed to investigate the association between endocrine disrupters, hormones, and reproductive factors in rare and poorly prognosis ovarian cancer patients.
  • Researchers noticed varied associations, puberty pesticide exposure linked, early-life exposure protective, and no confirmed impact from triazine herbicides on ovarian cancer.

Ovarian cancer is characterized by rarity, poor prognosis, and limited established risk factors. Marine Renier and her team aimed to assess a notable influence of hormones and reproductive factors on its development, indicating a potential association with endocrine disrupters.

Researchers performed an inclusive analysis within the AGRICAN cohort, encompassing 59,391 female farmers who provided comprehensive data on lifelong agricultural exposures and reproductive history. Cox models, utilizing attained age as the timescale, were employed to calculate HR and 95% CI. The study considered hormonal factors as potential confounders and investigated specific time windows for exposure, including childhood, puberty, and menopause. Female farmers served as the reference group in the principal analyses.

Between enrolment (2005-2007) and the end of follow-up (December 2017), 262 incidents of ovarian cancer were identified in the AGRICAN cohort. Increased ovarian cancer risk was observed for females involved in pig farming (HR=2.12, 95% CI 1.27 to 3.52), particularly during puberty (HR=1.83, 95% CI 1.13 to 2.94), as well as in fruit-growing (HR=2.17, 95% CI 1.09 to 4.30) and potato seed treatment (HR=2.81, 95% CI 1.29 to 6.09). Conversely, females born on farms growing grain cereals exhibited a reduced risk (HR=0.64, 95% CI 0.46 to 0.90), as did those in pig-breeding (HR=0.78, 95% CI 0.55 to 1.12). Triazine herbicide exposure showed no association with ovarian cancer. Notably, the effects of agricultural exposures remained unchanged in multivariate models, accounting for contraception, parity, puberty age, menopause age, and body mass index.

The study concluded that positive associations indicate potential roles of pesticide exposure, particularly during puberty, in ovarian cancer development. Conversely, early-life agricultural exposure appears protective, aligning with observations of lung cancer among farmers. Importantly, the study did not confirm the previously suggested effect of triazine herbicide exposure on ovarian cancer.

The study is sponsored by Ligue Contre le Cancer, The Mutualité Sociale Agricole, The Fondation de France, The Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES) with funding from l’Office national de l’eau et des milieux aquatiques, The Institut National du Cancer (Grant No. InCA 8422), The Association pour la Recherche sur le Cancer (Grant No. ARC 02-010), The Institut National de Médecine Agricole, the Centre François Baclesse, Ministère de l’Enseignement Supérieur et de la Recherche.

Source: https://pubmed.ncbi.nlm.nih.gov/38199811/

Renier M, Hippert J, Louis-Bastien W, et.al (2024). Agricultural exposure and risk of ovarian cancer in the AGRIculture and CANcer (AGRICAN) cohort. Occup Environ Med. 2024 Feb 2;81(2):75-83. doi: 10.1136/oemed-2023-109089. PMID: 38199811.

LBC vs. Cell Blocks in Cervical Pathology

LBC vs. Cell Blocks in Cervical Pathology

KEY TAKEAWAYS

  • The study aimed to investigate the enhanced detection of epithelial cell abnormalities in cervical smear samples through the incorporation of cell block analysis.
  • Researchers noticed that cell block analysis shows promise for superior diagnostic accuracy, particularly in detecting HSIL.

Cervical cancer, a global health concern with high mortality, necessitates advances in screening for its elimination. Elif Kuzucular and her team aimed to assess the impact of cell block analysis on detecting epithelial cell abnormalities in cervical smear samples.

Researchers performed an inclusive analysis involving 559 patients with suspected cervical pathology. Both liquid-based cytology (LBC) and cell blocks were employed for sample analysis. Biopsy results from 149 out of the 559 patients were subsequently obtained.

About 50 patients diagnosed with HSIL by biopsy showed significant disparities in LBC and cell block results. Only 12 were identified as HSIL by LBC, with 22 as LSIL, 12 as ASCUS, and 4 as ASC-H (p < 0.001). In contrast, cell block analysis identified 20 as HSIL, 17 as LSIL, 7 as NILM, 4 as ‘unsatisfactory,’ and 2 as ASC (p < 0.001). LBC detected only 1 of the 10 patients with biopsy-diagnosed tumors, where 7 were HSIL, 1 ASCUS, and 1 AGC. Cell block analysis results in patients with biopsy-diagnosed tumors were 7 HSIL, 1 tumor, 1 ASC, and 1 LSIL.

The study concluded that cell block analysis exhibits potential superiority over LBC in diagnosing cervical pathologies, especially in detecting HSIL. Despite both methods demonstrating limitations in tumor diagnosis, cell blocks emerge as a valuable complementary tool to LBC, offering enhanced diagnostic accuracy and the advantage of revealing histological architecture.

No Fundings were provided for this study.

Source: https://pubmed.ncbi.nlm.nih.gov/38266543/

Kuzucular E, Ozden F, Muezzinoglu B. Comparison of liquid-based cytology and cell blocks prepared from cell remnants for diagnosis of cervical pathology. Ann Diagn Pathol. 2024 Apr;69:152265. doi: 10.1016/j.anndiagpath.2024.152265. Epub 2024 Jan 12. PMID: 38266543.

Role of HE4 and CA125 Predicting EOC Surgery

KEY TAKEAWAYS

  • The study investigated the correlation between pre-operative HE4 and CA125 levels in non-mucinous EOC patients.
  • Researchers noticed an association between lower levels of HE4 and CA125 in non-mucinous EOC among OS compared to SS, suggesting predictive markers for optimal surgery.

Kanokwan Promchit and her team aimed to explore the connection between pre-operative HE4 and CA125 levels in non-mucinous epithelial ovarian cancer (EOC) cases and their impact on primary surgery outcomes, specifically focusing on predicting optimal surgery.

Researchers performed an inclusive analysis in a retrospective study involving non-mucinous EOC patients who underwent primary surgery. Demographic and clinical characteristics, histopathology, and pre-operative tumor markers (HE4 and CA125) were collected. Surgical outcomes were categorized as optimal (OS) or suboptimal surgery (SS).

About 170 patients participated in the study, with 130 undergoing OS and 40 experiencing SS. EOC patients’ average age and body mass index (BMI) were 54.2 years and 23.1 Kg/m2, respectively, showing comparable demographic characteristics between both groups. Among the participants, (103/170) two-thirds had early-stage disease, while (63/170) one-third exhibited clear cell histopathology.

The median HE4 levels were 118.60 pmol/L in OS and 603.45 pmol/L in SS, demonstrating notable differences. Similarly, OS and SS patients had average CA125 levels of 146.95 and 814.70 U/L, respectively. The optimal cut-off points for predicting OS were less than 170.95 pmol/L for HE4 and 316.4 U/mL for CA125. The corresponding area under the curve (AUC) values were 0.78 for HE4 and 0.75 for CA125.

In terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), the HE4 cut-off point exhibited percentages of 60.8/60.8, 87.5/82.5, 94.1/91.9, and 40.7/39.3, respectively.

The study concluded that HE4 and CA125 levels in non-mucinous EOC were significantly lower among patients with OS than SS. 

No funding was provided for the study.

Source: https://pubmed.ncbi.nlm.nih.gov/38285795/

Promchit K, Oranratanaphan S. et al (2024). “Human Epididymis Protein 4 (HE4) and Cancer Antigen 125 (CA125) for Prediction of Optimal Primary Surgery in Non-Mucinous Epithelial Ovarian Cancer.” Asian Pac J Cancer Prev. 2024 Jan 1;25(1):281-286. doi: 10.31557/APJCP.2024.25.1.281. PMID: 38285795.

PD-L1 in Cervical Cancer: Combining Immunotherapy With Lenvatin

KEY TAKEAWAYS

  • The study aimed to investigate the potential of targeted therapy against PD-1/PD-L1 and receptor tyrosine kinases in cervical cancer patients.
  • Researchers noticed a frequent expression of PD-1 in cervical cancer samples.

Cervical cancer stands as the fourth leading cause of cancer-related deaths among women globally.
Karen Bräutigam and her team aimed to delve into the exploration of targeted therapeutic approaches, specifically focusing on the immune checkpoint PD-1/PD-L1 and receptor tyrosine kinases. The investigation included both cervical cancer patients and cell lines to comprehend the potential of these targeted therapies in the context of cervical cancer.

Researchers performed an inclusive analysis by examining 123 cervical cancer samples through immunohistochemistry on tissue microarrays to assess PD-L1 expression. In parallel, the combination of lenvatinib with a PD-1/PD-L1 inhibitor was investigated in SiHa, HeLa, and CaSki cervical cancer cell lines. Cell viability assays were employed to evaluate the effects, while western blots were utilized to assess the activation of cell signaling pathway proteins. Additionally, gene expression was quantified using quantitative reverse transcriptase-PCR to comprehensively understand the combined treatment’s impact on cervical cancer cells.

Of about 113 evaluable samples, 90 (79.6%) exhibited more than 1% PD-L1 positive cells. The PD-1/PD-L1 inhibitor as a single treatment demonstrated the greatest reduction in growth for CaSki cells, while lenvatinib alone showed efficacy in inhibiting HeLa cell growth. In contrast, the combined treatment of lenvatinib with the PD-1/PD-L1 inhibitor exhibited significantly stronger inhibition of proliferation across all three cell lines. Specifically, this combined treatment resulted in notably less phosphorylation of signaling molecules, including ERK and S6 in SiHa and S6 and STAT3 in HeLa cells, although not in CaSki.

Moreover, all treatments decreased PD-L1, Il-8, and FGFR mRNA levels in SiHa cells. The comprehensive analysis of the results underscores the potential synergy of lenvatinib with PD-1/PD-L1 inhibitors in impeding cervical cancer cell proliferation, with distinct molecular effects observed in different cell lines.

The study concluded that frequent PD-1 expression in cervical cancer samples, coupled with the inhibitory impact on cell line proliferation through combining lenvatinib with a PD-1/PD-L1 inhibitor, suggested a promising treatment avenue for cervical cancer. Although the combined treatment effectively blocked signaling pathways related to tumor cell growth, the underlying mechanism remains elusive.

Source: https://pubmed.ncbi.nlm.nih.gov/38307554/

Bräutigam K, Schmidt T, Baur M, et al. (2024). “Prevalence of PD-L1 in Cervical Cancer Patients and the Potential for Combining an Immune Checkpoint Inhibitor With Lenvatinib.” Anticancer Res. 2024 Feb;44(2):503-510. doi: 10.21873/anticanres.16838. PMID: 38307554.

Ovarian Cancer Liver Metastases: Surgical Perspectives

KEY TAKEAWAYS

  • The study aimed to investigate the patterns and survival rates of ovarian-derived liver metastasis patients undergoing hepatic resections with or without HIPEC.
  • Researchers noticed that complete cytoreductive surgery offers potential survival benefits for ovarian cancer patients.

Miklos Acs and his team aimed to assess patterns, perioperative outcomes, and survival rates of patients undergoing hepatic resections for liver metastasis from ovarian cancer as part of cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Their additional objective was to examine two tumor pattern subgroups: hematogenous liver metastasis and infiltrative liver metastatic spread.

Researchers performed an inclusive analysis through a retrospective study involving patients with primary or recurrent ovarian cancer at a University Tertiary Hepatic and Peritoneal Surface Malignancy Center. The study focused on individuals who underwent liver resection during cytoreductive surgery from January 1992 to December 2022.

About 35 patients’ data underwent analysis, revealing a median overall survival (OS) and disease-specific survival (DSS) of 24.97 months. In a multivariate context, researchers tested the combined impact of age, peritoneal carcinomatosis index, body mass index, hematogenous liver metastasis vs. infiltrative spread types, and HIPEC (HR=0.2372; 95%CI=0.0719-0.7823; P=0.0181) over OS. Survival analysis indicated no significant differences between the two metastatic spread types (OS: P=0.9720; DSS: P=0.9610). Younger age (P=0.0301), splenectomy (P=0.0320), lesser omentectomy (P=0.0178), and right upper quadrant peritonectomy (P=0.0373) were more characteristic of patients with infiltrative liver metastatic spread.

The study concluded that complete cytoreductive surgery, encompassing hepatic resection with or without additional HIPEC, is a viable and beneficial approach for patients facing advanced and/or recurrent ovarian cancer. The study recommends using liver-specific imaging for improved diagnostic precision in cases where metastatic and infiltrative liver involvement is suspected.

Source: https://pubmed.ncbi.nlm.nih.gov/38307555/

Acs M, Herold Z, Neumann L, Slowik P, et al (2024). “Surgical Treatment and Outcome of Ovarian Cancer Patients With Liver Metastases: Experience of a Tertiary Hepatic and Peritoneal Surface Malignancy Center. Anticancer Res. 2024 Feb;44(2):731-741. doi: 10.21873/anticanres.16864. PMID: 38307555.

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