Role of MRI in Assessing the Feasibility of Fertility-Sparing Treatments for Early-Stage Endometrial and Cervical Cancers.

Fertility-sparing treatment (FST) has become a key aspect of managing gynecologic cancers in reproductive-age patients who wish to preserve fertility. Several leading clinical societies, including the European Society of Gynecological Oncology, the European Society for Radiotherapy and Oncology, the European Society of Pathology, and the European Society of Human Reproduction and Embryology, have recently published evidence-based guidelines on fertility-sparing strategies and posttreatment surveillance of patients with early-stage gynecologic cancers, in particular endometrial and cervical cancers. These guidelines highlight MRI as essential to initial patient selection and follow-up.

Optimizing Mainstreaming of Genetic Testing in Parallel With Ovarian and Endometrial Cancer Tumor Testing: How Do We Maximize Our Impact?

Purpose: Although germline genetic testing (GT) is recommended for all patients with ovarian cancer (OC) and some patients with endometrial cancer (EC), uptake remains low with multiple barriers. Our center performs GT in parallel with somatic testing via a targeted sequencing assay (MSK-IMPACT) and initiates testing in oncology clinics (mainstreaming). We sought to optimize our GT processes for OC/EC.

Gestational trophoblastic neoplasm: Patient outcomes and clinical pearls from a multidisciplinary referral center.

Objectives: To describe clinical outcomes and pearls for patients with gestational trophoblastic neoplasm (GTN).

Methods: Patients with GTN treated at a referral center from 1/2006 to 12/2022 were included. Clinical characteristics, World Health Organization risk score (low-risk 0-6, high-risk ≥7), and treatments/outcomes were evaluated using summary statistics, stratified by initial treatment at a referral center versus locally.

Evolutionary pathways in early-stage, non-myoinvasive endometrioid endometrial cancers of no specific molecular profile.

Objective: To characterize the genomic landscape of FIGO 2009 stage IA, non-myometrial invasive endometrioid endometrial cancers (ECs) of no specific molecular profile (NSMP) and define the earliest driver genetic alterations and subsequent tumor evolution.

Methods: Early-stage (FIGO 2009 stage IA), non-myoinvasive endometrioid NSMP ECs subjected to clinical tumor-normal targeted sequencing between 2014 and 2022 were identified. ECs were dichotomized into low- and high-volume disease based on gross and histologic measurement using a cutoff of 1.

Lymph node metastases in endometrial carcinoma: A modern assessment in the era of sentinel lymph node mapping and molecular subtyping.

Objective: To examine the risk of sentinel lymph node (SLN) metastases in apparent uterine-confined endometrial cancer (EC) using molecular classification with clinicopathologic features and assess oncologic outcomes by molecular subtypes with micro- or macro-metastases in SLN.

Methods: Patients undergoing surgical staging for presumed uterine-confined EC of any histology, with successful bilateral SLN mapping were included. Primary tumors were assigned molecular subtypes using a published algorithm.

Concurrent POLE hotspot mutations and mismatch repair deficiency/microsatellite instability in endometrial cancer: A challenge in molecular classification.

Objective: Endometrial carcinoma (EC) has different molecular subtypes associated with varied prognosis. We sought to characterize the molecular features of ECs with POLE hotspot mutations and concurrent mismatch repair (MMR) deficiency/high microsatellite instability (MSI).

Methods: We identified POLE-mutated (POLEmut), MMR-deficient (MMRd)/MSI-high (MSI-H), or combined POLEmut/MMRd ECs subjected to clinical tumor-normal panel sequencing between 2014 and 2023.

Survival associated with the use of sentinel lymph node in addition to lymphadenectomy in early-stage cervical cancer treated with surgery alone: A sub-analysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study.

Aim: The aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer.

Methods: International, multicenter, retrospective study.

Inclusion Criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach.

Impact of adjuvant therapy on oncologic outcomes in uterine-confined clear cell carcinoma of the endometrium.

Objectives: To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC).

Methods: We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000-12/31/2015 were included.

Tracking clonal evolution of drug resistance in ovarian cancer patients by exploiting structural variants in cfDNA.

Drug resistance is the major cause of therapeutic failure in high-grade serous ovarian cancer (HGSOC). Yet, the mechanisms by which tumors evolve to drug resistant states remains largely unknown. To address this, we aimed to exploit clone-specific genomic structural variations by combining scaled single-cell whole genome sequencing with longitudinally collected cell-free DNA (cfDNA), enabling clonal tracking before, during and after treatment.

Assessing minimally invasive simple hysterectomy in low risk cervical cancer: set up for the LASH trial.

After the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, open surgery has become the standard approach for radical hysterectomy in early stage cervical cancer. Recent studies assessed the role of a non-radical approach in low risk cervical cancer and showed no survival difference compared with radical hysterectomy. However, there is a gap in knowledge regarding the oncologic outcomes of minimally invasive simple hysterectomy in low risk cervical cancer.

Oncologic outcomes based on lymphovascular space invasion in node-negative FIGO 2009 stage I endometrioid endometrial adenocarcinoma: a multicenter retrospective cohort study.

Background: The 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system includes lymphovascular invasion quantification as a staging criterion for endometrioid endometrial carcinomas; no lymphovascular invasion and focal invasion (≤4 vessels involved) are grouped as one category, and substantial invasion as another.

Objective: To assess the association between lymphovascular invasion and oncologic outcomes.

Methods: We retrospectively identified patients with FIGO 2009 stage I endometrioid endometrial cancer treated surgically with total hysterectomy and lymph node assessment at two tertiary care centers between January 1, 2012, and December 31, 2019.

2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIIA endometrial cancer: oncologic outcomes based on involvement of adnexa, serosa, or both.

Objective: To assess clinicopathologic features and survival outcomes of patients with endometrial carcinoma involving adnexal, full-thickness serosal, or combined involvement.

Methods: This international, multi-institutional, retrospective study examined patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIIA endometrial cancer and tumors involving the uterine serosa and/or adnexa, who were surgically staged between 2000 and 2019. Patients with sarcoma histology, concurrent endometrial/ovarian malignancy, neoadjuvant treatment, positive lymph nodes, or peritoneal disease were excluded.

Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer.

Whole-genome doubling (WGD) is a critical driver of tumor development and is linked to drug resistance and metastasis in solid malignancies. Here, we demonstrate that WGD is an ongoing mutational process in tumor evolution. Using single-cell whole-genome sequencing, we measured and modeled how WGD events are distributed across cellular populations within tumors and associated WGD dynamics with properties of genome diversification and phenotypic consequences of innate immunity.

ERBB2 mutations define a subgroup of endometrial carcinomas associated with high tumor mutational burden and the microsatellite instability-high (MSI-H) molecular subtype.

Anti-HER2 therapy is indicated for erb-b2 receptor tyrosine kinase 2 (ERBB2)-amplified/overexpressing endometrial carcinoma (EC). Mutations constitute another mode of ERBB2 activation, but only rare ERBB2-mutated ECs have been reported. We sought to characterize the clinicopathologic and genetic features of ERBB2-mutated EC.

A pre-operative scoring model to estimate the risk of blood transfusion over an ovarian cancer debulking surgery (BLOODS score): a Memorial Sloan Kettering Cancer Center Team Ovary study.

Objectives: To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery.

Methods: We retrospectively reviewed an institutional database to identify patients who underwent primary debulking surgery for ovarian cancer at a single center between January 1, 2001 and May 31, 2019. Receiver operating characteristic curve and area under the receiver operating characteristic curve (AUC) were calculated.

Prognosis of isolated tumor cells and use of molecular classification in early stage endometrioid endometrial cancer.

Objective: We assessed the prognosis and molecular subtypes of early stage endometrioid endometrial cancer with isolated tumor cells within sentinel lymph nodes (SLNs) compared with node negative disease.

Methods: Patients diagnosed with stage IA, IB, or II endometrioid endometrial cancer and primary surgical management were identified from January 1, 2007 to December 31, 2019. All SLNs underwent ultrastaging according to the institutional protocol.

Molecular profiling of primary endometrioid endometrial cancer and matched lung metastases: mutation as a potential driver.

•Both primary endometrial cancers (ECs) and matched lung metastases shared a common ancestor with independent evolution at each site.•The two endometrioid ECs studied acquired additional mutations during the distant metastatic process.•Subclonal hotspot mutations in the two primary ECs studied became clonal in the distant metastases.

ARIA II: a randomized controlled trial of near-infrared Angiography during RectosIgmoid resection and Anastomosis in women with ovarian cancer.

Background: Ovarian cancer with extensive metastatic disease involving pelvic structures often requires rectosigmoid resection for complete gross resection; however, it is associated with increased surgical morbidity. There are limited data, and none in ovarian cancer, on near-infrared assessment of perfusion in rectosigmoid resections with anastomosis.

Primary Objective: To compare the rate of pelvic complications (pelvic abscesses, anastomotic leaks, and infections) within 30 days of surgery with and without near-infrared assessment of perfusion at time of rectosigmoid resection and re-anastomosis in patients undergoing cytoreductive surgery for ovarian cancer.

Molecular and pathologic data to guide selection of patients with endometrioid endometrial cancer for ovarian preservation.

Objectives: To investigate the association of molecular and pathologic factors with concurrent or recurrent ovarian disease to guide ovarian preservation in endometrioid endometrial cancer.

Methods: Patients with endometrial cancer ≤50 years of age at diagnosis were grouped by elective oophorectomy versus ovarian preservation at staging (January 2010 to June 2021). Tumors were stratified by molecular sub-type and mutational status with next generation sequencing and immunohistochemistry.