International Journal of Gynecological Cancer最新文献

Objective: The aim of this study was to describe real-world use of immune checkpoint inhibitors for women with advanced or recurrent endometrial cancer.

Methods: Adult women with advanced or recurrent endometrial cancer who received at least one line of systemic treatment between January 1, 2014 and November 1, 2020, then followed to May 31, 2021 in a nationwide electronic health record-derived de-identified database. Chi-Squared test or Welch's 2-sample t-tests were used to compare patient and clinical factors associated with immune checkpoint inhibitor treatment. Time to next treatment analyses were performed based on the treatment line of the immune checkpoint inhibitor. Sankey plots depicted patient-level temporal systemic treatment.

Results: During our study period, 326 women received their first immune checkpoint inhibitor treatment, increasing from 12 patients in 2016 to 148 in 2020. Factors associated with ever receiving immune checkpoint inhibitors included disease stage (p=0.002), mismatch repair (MMR)/microsatellite instability (MSI) status (p<0.001), performance status (p=0.001), and prior radiation receipt (p<0.001) and modality (p=0.003). The most common immune checkpoint inhibitor regimen was pembrolizumab (47.9%) followed by pembrolizumab and lenvatinib (34.7%). Immune checkpoint inhibitors were given as first, second, and third or greater lines of therapy in 24.5%, 41.7%, and 46.1% of evaluable patients. The median time to next treatment was significantly longer if given as an earlier line of treatment (p=0.008). There were significant differences in treatment line of immune checkpoint inhibitor by region (p=0.004), stage (p<0.001), and prior radiation receipt (p=0.014) and modality (p=0.009). Among 326 patients who received immune checkpoint inhibitors, 114 (34.9%) received subsequent treatment including chemotherapy (43.9%), additional immune checkpoint inhibitors (29.8%), and other (26.3%) with no differences in demographic or clinical characteristics based on the type of post-immune checkpoint inhibitor treatment.

Conclusion: In an observational retrospective real-world database study, immune checkpoint inhibitors were used in 14.7% of patients with advanced or recurrent endometrial cancer across multiple lines of treatment, including after initial immune checkpoint inhibitor treatment.

There is a lack of biomarkers to predict outcome following initial treatment in patients with high-grade ovarian cancer. We hypothesized that monitoring TP53 mutation (TP53m) in circulating tumor DNA (ctDNA) could be a tumor-specific biomarker. Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples through the disease course. ctDNA was extracted and analyzed to detect the presence of TP53m Next-generation sequencing was performed on tumor tissue to detect TP53m and on whole blood to detect clonal hematopoiesis of indeterminate potential (CHIP).A total of 102 samples were sequentially collected from 26 patients. ctDNA was detected in all patients at diagnosis. The same TP53m was found in ctDNA and tumor tissue in 77% of patients. TP53m in ctDNA was not CHIP related. During neoadjuvant chemotherapy, increasing ctDNA was associated with failure to achieve complete interval cytoreductive surgery in 60% of patients. Rising ctDNA or de novo TP53m seemed to be associated with a trend for worst survival compared with decrease or complete clearance: progression-free survival 10 versus 26.5 months, HR 3.2. Despite macroscopically complete surgery, 30% of patients had detectable ctDNA post-operatively and had worse survival than those with undetectable ctDNA. Monitoring TP53m in ctDNA during chemotherapy or after surgery could help guide the best adjuvant therapy.

Introduction: Assessment of retroperitoneal nodes is an important part of the surgical staging of gynecologic cancers. Although pelvic and paraaortic lymphadenectomy have been widely described by different authors, there is little consensus on the description of the different surgical steps for each procedure. An Intergroup Committee on Onco-Gyn Minimally Invasive Surgery has been established with members of the European Society for Gynecological Endoscopy (ESGE), European Society of Gynaecological Oncology (ESGO) and the Society of European Robotic Gynaecological Surgery (SERGS). The Intergroup Committee has various objectives: writing down a surgical description of the technique, which will be assessed by a group of experts following a formal consensus method and developing a specific Objective Structured Assessment of Technical Skills (OSATS) scale for each procedure.

Methods: A hierarchical task analysis was conducted by a working group of eight experts from the three societies in order to identify the surgical steps of transperitoneal and extraperitoneal approach in paraaortic lymphadenectomy. The selection of the definitive surgical steps was confirmed by a group of 19 experts from the different societies, following a formal consensus method. Two rounds of Delphi panel rating were considered necessary for achieving an agreement. The consensus agreement identified 29 surgical steps in transperitoneal and 17 surgical steps in extraperitoneal approach to complete a paraaortic lymphadenectomy. Once the description of the procedure and the consensus were established, an Objective specific Scale for the Assessment of Technical Skills for Paraaortic lymphadenectomy (PA-OSATS) in the transperitoneal and extraperitoneal approach was developed.

Results: In the first round of rating we found that 28 steps out of 29 in the transperitoneal approach and 13 out of 17 in the extraperitoneal approach did not reach a strong degree of agreement. They were reformulated based on comments made by the experts, and submitted to a second round of rating and this finally achieved an agreement.

Conclusion: We defined a list of surgical steps in transperitoneal and extraperitoneal approach in paraaortic lymphadenectomy and a specific PA-OSATS scale for these procedures. This tool will be useful for teaching, assessing and standardizing this surgical procedure.

Background: Most women who are high-risk human papilloma virus (hrHPV) positive in a cervical cancer screening test will spontaneously heal from their infection. Visual inspection with acetic acid (VIA) is recommended by the World Health Organization as a triage test for cervical screening, however its accuracy as a triage test has been questioned. In this study, we aimed to examine the sensitivity and specificity of VIA with and without Lugol's iodine as a triage test to detect cervical intraepithelial neoplasia (CIN2+) among women who tested positive for hrHPV after self-sampling.

Method: This two-armed randomized controlled trial (RCT) took place in Adama, Ethiopia. The women who tested positive for vaginal hrHPV (Anyplex ΙΙ, Seegene) after self-sampling were randomized to VIA with or without iodine and appointed to a midwife-led clinic. The result of the triage test was categorized as positive, negative, suspicion of cancer or inconclusive, and treated accordingly. Cervical biopsies were collected from women who were hrHPV positive to serve as a gold standard.

Results: 22.4% (197/878) of women tested hrHPV positive. Sensitivity and specificity for VIA to detect CIN2+was 25.0% (95% CI 0.6 to 80.0) and 82.7% (95% CI 69.7 to 91.8), respectively. For VIA with iodine, the sensitivity was 50.0% (95% CI 0.7 to 93.2) and the specificity 86.3% (95% CI 71.4 to 93.0). The difference between the two methods was not statistically significant, p=0.5. The odds of detecting CIN2+ was 5.4 times higher if positive for VIA with iodine compared with a negative result. For VIA without iodine, the odds of detecting CIN2+ was 1.6 compared with a negative result. The odds of detecting CIN2+ was 6.4 times higher if the women were HIV positive than for those who were HIV negative.

Conclusion: VIA with iodine improved detection of CIN2+ in women who were hrHPV DNA positive but was not significantly better than VIA alone.

Trial registration number: NCT05125380.

Objective: Immune checkpoint inhibitors have recently demonstrated benefit in patients with advanced and recurrent endometrial carcinoma. This retrospective study investigated immune checkpoint molecules in endometrial carcinoma as they pertain to the molecular subtypes, clinical outcomes, and predictive value.

Methods: Tumoral RNA expression of genes controlling the immune checkpoint, programmed cell death 1 (PD1, encoded by PDCD1), its ligand (PDL1, encoded by CD274), and interferon gamma (IFNG) was determined in 239 endometrial carcinoma tissues by quantitative polymerase chain reaction (qPCR) and compared with endometrial tissue from 25 controls. A total of 81 endometrial carcinoma tissues were analyzed using the ProMiSe molecular classification, and patient trajectories were analyzed for the entire cohort. Findings were validated in an independent cohort from The Cancer Genome Atlas (TCGA; n=548).

Results: PD1, PDL1, and IFNG expression was significantly higher in endometrial carcinoma when compared with non-malignant control tissue with a mean expression of 0.12, 0.05, and 0.05 in control tissue and 0.44, 0.31, and 0.35 in endometrial carcinoma, respectively. POLE-mutated and mismatch repair-deficient (MMRd) (immunologically hot) tumors showed the highest expression of PD1 and IFNG. Increased expression of PD1, PDL1, and IFNG was associated with improved recurrence-free (HR 0.32, p<0.001; HR 0.30, p<0.001; HR 0.47, p=0.012, respectively), disease-specific (HR 0.38, p<0.001; HR 0.29, p<0.001; HR 0.45, p=0.017, respectively), and overall survival (HR 0.56, p=0.003; HR 0.38, p<0.001; HR 0.58, p=0.006, respectively). Cox regression confirmed the prognostic significance of PD1 for recurrence-free survival (HR 0.39, p=0.009) and PDL1 for overall survival (HR 0.55, p=0.037). The prognostic value of tumoral PD1 on recurrence-free survival, disease-specific survival, and overall survival was confirmed in the TCGA cohort.

Conclusions: Tumoral gene expression controlling the PD1 immune checkpoint, particularly expressed in "hot tumors", predicted recurrence-free, disease-specific, and overall survival in patients with endometrial carcinoma in two independent cohorts. Evaluation of these genes could be used to stratify patients who qualify for immune checkpoint inhibitors, which warrants prospective clinical trials.

Clinical outcomes remain challenging in advanced or recurrent endometrial cancer due to tumor heterogeneity and therapy resistance. Antibody-drug conjugates are a novel class of cancer therapeutics, representing a promising treatment option for endometrial cancer. Antibody-drug conjugates consist of a high-affinity antibody linked to a cytotoxic payload through a stable linker. After binding to specific antigens on tumor cells, the drug is internalized, and the payload is released. In addition, the free intracellular drug may be released outside the target cell through a 'bystander effect' and kill neighboring cells, which is crucial in treating malignancies characterized by heterogeneous biomarker expression like endometrial cancer.This article aims to provide a comprehensive overview of the current clinical landscape of antibody-drug conjugates in the treatment of endometrial cancer. We conducted a thorough analysis of recent clinical trials focusing on efficacy, safety profiles, and the mechanisms by which antibody-drug conjugates target endometrial cancer. We focused particularly on the most promising antibody-drug conjugate targets in endometrial cancer under clinical investigation, such as human epidermal growth factor receptor 2 (HER2), folate receptor alpha (FRα), trophoblast cell-surface antigen-2 (TROP2), and B7-H4. We also briefly comment on the challenges, including the emergence of resistance mechanisms, and future development directions (especially agents targeting multiple antigens, combinatorial strategies, and sequential use of agents targeting the same antigen but using different payloads) in antibody-drug conjugate therapy for endometrial cancer.