Role of adipokines in ovarian cancer epidemiology and prognosis

Ovarian cancer is one of the most serious problems in modern oncological gynecology. The link between obesity (expressed in BMI, WHR, waist circumference, body weight) and ovarian cancer has been poorly studied. Obesity is defined as an excessive accumulation of bodily fat, exceeding its physiological needs and adaptability. Study results suggest a link between specific histological types of ovarian cancer with increased patients’ BMI. Adipose tissue is hormonally active and secretes biologically active proteins called adipokines. Resistin and leptin may show proliferative and anti-apoptotic effects. There is currently increasing attention to adipokine levels in ovarian cancer research. The influence of adiponectin on the secretion of angiogenic factors by ovarian cancer cells has been shown. It has been proven that leptin is associated with a worse prognosis for patients treated with platinum compounds combined with paclitaxel/docetaxel. The relation has been observed between the level of resistin and the growth of neoplastic cells, their spread and the resistance to chemotherapy. The level of AdipoR1 may be independent prognostic factor in the case of epithelial ovarian cancer. The role of adipokine in the neoplasm development requires further investigation, in the view of fact that results of current research are still inconclusive. Considering increasing number of people suffering from obesity as well as the current analysis results, it is necessary to extend experimentation on the influence of obesity on the development and prognosis of ovarian cancer

The Polish Society of Gynecological Oncology Guidelines for the Diagnosis and Treatment of Endometrial Carcinoma (2023)

Background: Due to the increasing amount of published data suggesting that endometrial carcinoma is a heterogenic entity with possible different treatment sequences and post-treatment follow-up, the Polish Society of Gynecological Oncology (PSGO) has developed new guidelines. Aim: to summarize the current evidence for diagnosis, treatment, and follow-up of endometrial carcinoma and to provide evidence-based recommendations for clinical practice. Methods: The guidelines have been developed according to standards set by the guideline evaluation tool AGREE II (Appraisal of Guidelines for Research and Evaluation). The strength of scientific evidence has been defined in agreement with The Agency for Health Technology Assessment and Tariff System (AOTMiT) guidelines for scientific evidence classification. The grades of recommendation have been based on the strength of evidence and the level of consensus of the PSGO development group. Conclusion: Based on current evidence, both the implementation of the molecular classification of endometrial cancer patients at the beginning of the treatment sequence and the extension of the final postoperative pathological report of additional biomarkers are needed to optimize and improve treatment results as well as to pave the route for future clinical trials on targeted therapies

A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45)

PURPOSEATHENA (ClinicalTrials.gov identifier: ) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo.METHODSPatients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population.RESULTSAs of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P &amp;lt; .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade &amp; GE; 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%).CONCLUSIONRucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.Funding Agencies|Clovis Oncology Inc.; NIHR Cambridge Biomedical Research Centre; [BRC-1215-20,014]</p

A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA–MONO/GOG-3020/ENGOT-ov45)

PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo. METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS: As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P =.0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P <.0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively). Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes