Defects in meiosis I contribute to the genesis of androgenetic hydatidiform moles.

To identify novel genes responsible for recurrent hydatidiform moles (HMs), we performed exome sequencing on 75 unrelated patients who were negative for mutations in the known genes. We identified biallelic deleterious variants in 6 genes, FOXL2, MAJIN, KASH5, SYCP2, MEIOB, and HFM1, in patients with androgenetic HMs, including a familial case of 3 affected members. Five of these genes are essential for meiosis I, and their deficiencies lead to premature ovarian insufficiency.

Future Directions for Gestational Trophoblastic Disease.

Gestational trophoblastic disease encompasses a spectrum of premalignant and malignant conditions. While centralized care models significantly improve survival rates, many countries still lack such specialized centers, leading to preventable deaths. Current research focuses on refining diagnostic and treatment methods, aiming to better predict the risk of malignancy and reduce the need for aggressive therapies.

Investigating the Regulation of Ribosomal Protein S6 Kinase 1 by CoAlation.

Ribosomal protein S6 kinases belong to a family of highly conserved enzymes in eukaryotes that regulate cell growth, proliferation, survival, and the stress response. It is well established that the activation and downstream signalling of p70S6Ks involve multiple phosphorylation events by key regulators of cell growth, survival, and energy metabolism. Here, we report for the first time the covalent modification of p70S6K1 by coenzyme A (CoA) in response to oxidative stress, which regulates its kinase activity.

Morphology combined with D-DISH ploidy analysis to diagnose partial hydatidiform mole: an evaluation audit using molecular genotyping.

Aims: A hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to confirm a morphologically suspected PHM diagnosis. This study sought to evaluate the clinical accuracy of PHM diagnosis using morphological assessment supported by dual-colour dual-hapten in situ hybridisation (D-DISH) ploidy determination.

Management of patients with rare adult solid cancers: objectives and evaluation of European reference networks (ERN) EURACAN.

About 500,000 patients with rare adult solid cancers (RASC) are diagnosed yearly in Europe. Delays and unequal quality of management impact negatively their survival. Since 2017, European reference networks (ERN) aim to improve the quality of care of patients with rare disease.

Chemotherapy is not needed when complete evacuation of gestational choriocarcinoma leads to hCG normalization.

Background: The standard treatment for gestational choriocarcinoma is chemotherapy.

Objective: To describe the risk of recurrence with expectant management of gestational choriocarcinoma that has reached a normal human chorionic gonadotropin level after tumor removal without adjuvant chemotherapy.

Methods: A retrospective multicenter international cohort study was conducted from 1981 to 2017 involving 11 gestational trophoblastic disease reference centers with patient's follow-up extended until 2023.

Effectiveness of adjuvant systemic therapy following complete cytoreductive surgery in patients with recurrent granulosa cell tumours of the ovary.

Aim of the present analysis is to compare the impact of antihormonal therapy versus cytotoxic chemotherapy versus a watch a wait approach on disease-free survival (DFS) in the adjuvant setting of patients who underwent complete cytoreductive surgery(CRS) for recurrent adult type granulosa cell tumours of the ovary (GCT). Moreover, we wished to identify prognostic risk factors for recurrence. We included recurrent GCT-patients who underwent CRS resulting in total macroscopic tumour clearance, treated in two gynaecological cancer centres over a 20-year period (2000-2020).

PREDICT-GTN 2: Two-factor streamlined models match FIGO performance in gestational trophoblastic neoplasia.

Objective: The International Federation of Gynecology and Obstetrics (FIGO) scoring system uses the sum of eight risk-factors to predict single-agent chemotherapy resistance in Gestational Trophoblastic Neoplasia (GTN). To improve ease of use, this study aimed to generate: (i) streamlined models that match FIGO performance and; (ii) visual-decision aids (nomograms) for guiding management.

Methods: Using training (n = 4191) and validation datasets (n = 144) of GTN patients from two UK specialist centres, logistic regression analysis generated two-factor models for cross-validation and exploration.

Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.

Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking.

Fertility outcomes following surgery and multiagent chemotherapy in malignant ovarian germ cell tumor survivors: a survey study.

Objective: To assess fertility outcomes in long-term survivors of malignant ovarian germ cell tumors treated with fertility-sparing surgery with or without additional chemotherapy.

Methods: Women diagnosed and treated for malignant ovarian germ cell tumors at Charing Cross Hospital or Mount Vernon Cancer Centre between 1977 and 2015 were included. Questionnaires assessing fertility issues were sent to patients treated with fertility-sparing surgery.

From National to International Collaboration in Gestational Trophoblastic Disease: Hurdles and Possibilities.

Background: Today, most women with gestational trophoblastic disease (GTD) can expect to be cured, particularly if they live in middle- to high-income countries with access to GTD centres. In contrast, countries lacking organized GTD care achieve lower survival rates.

Objectives: The aim of the study was to review and consider some of the successes and areas for improvement in GTD care that have been achieved through national and international collaborations.

Primary hepatic metastatic epitheloid trophoblastic tumor of the uterus treated with multimodal therapy including pembrolizumab and thermoablation. Case report of an extremely rare disease and review of the literature.

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor, first described by Shih and Kurman in 1998. ETT often present as abnormal vaginal bleeding in women of reproductive age, but unlike more common forms of GTN tend to produce much less human chorionic gonadotropin (hCG) for the volume of disease present. ETT can occur after any gestational event and can occur in both intrauterine and extrauterine sites.

European multidisciplinary tumor boards support cross-border networking and increase treatment options for patients with rare gynecological tumors.

Objective: To evaluate outcomes of European cross-border multidisciplinary tumor boards in terms of participation, adherence to treatment recommendations, and access to novel treatment strategies.

Methods: The European reference network for rare gynecological tumors (EURACAN G2 domain) aims to improve the diagnosis, management, and treatment of patients with these cancers. Cross-border multidisciplinary tumor boards were initiated to facilitate intercollegiate clinical discussions across Europe and increase patients' access to specialist treatment recommendations and clinical trials.

Combined chemotherapy and pembrolizumab salvages multi-chemotherapy agent and avelumab resistant choriocarcinoma: A case report.

Introduction: Gestational trophoblastic neoplasia (GTN) including choriocarcinoma (CC) frequently requires multi-agent chemotherapy to achieve cure. In chemotherapy-resistant GTN, immunotherapy with the checkpoint inhibitors pembrolizumab, avelumab and camrelizumab are potential new treatment options previously described in small case series, phase 2 trials and case reports.

Case Description: A 32-year-old woman was diagnosed with gestational choriocarcinoma (FIGO score 5).

Efficacy analysis of single-agent carboplatin AUC4 2-weekly as second-line therapy for methotrexate-resistant (MTX-R) low risk gestational trophoblastic neoplasia (GTN).

Background: Approximately one-third of patients with low-risk Gestational Trophoblastic Neoplasia (WHO 0-6) develop methotrexate-resistance (MTX-R). In the UK, subsequent treatment with either actinomycin-D (ActD) or multi-agent combination chemotherapy has depended on whether the hCG was above or below an hCG threshold. To reduce exposure to combination chemotherapy (CC), over the years the UK service has raised this threshold as well as using single-agent carboplatin AUC6 3-weekly at MTX-R instead of CC.

REFINE-Lung implements a novel multi-arm randomised trial design to address possible immunotherapy overtreatment.

Increasing evidence suggests that some immunotherapy dosing regimens for patients with advanced cancer could result in overtreatment. Given the high costs of these agents, and important implications for quality of life and toxicity, new approaches are needed to identify and reduce unnecessary treatment. Conventional two-arm non-inferiority designs are inefficient in this context because they require large numbers of patients to explore a single alternative to the standard of care.

Epithelioid trophoblastic tumor with antecedent molar pregnancy in an HIV-positive patient.

Epithelioid trophoblastic tumor (ETT) is a rare malignancy arising from neoplastic proliferation of chorionic-type intermediate trophoblasts. ETT poses significant challenges to clinicians in the diagnosis and treatment and can hence lead to a poor prognosis. We report a unique case of metastatic ETT in a HIV-positive patient.

Novel approaches to managing gestational trophoblastic tumors in the age of immunotherapy.

The discovery that anti-programmed death-1 antibody (anti-PD-1) immunotherapy can cure patients with multidrug-resistant gestational trophoblastic neoplasia provides a new powerful and low toxicity treatment. This heralds an era within which the majority of patients, including those with previously difficult to treat disease, can expect to achieve long-term remission. This development should prompt a rethink of how patients with this rare disease are managed, focusing on maximizing cure rate with minimal exposure to toxic chemotherapy.

Recurrence of primitive germ cell tumour 20 years on.

We present a case of a woman in her 20s, with a prior history of paediatric sacrococcygeal germ cell tumour, presenting with a 6-month history of perianal pain. An MRI pelvis revealed a heterogeneous soft tissue mass causing destruction of the sacrococcygeal bone. A staging CT demonstrated metastatic deposits in the lungs and hypodense foci in the liver suspicious of metastatic disease.

REFINE (REduced Frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers.

Background: Immune checkpoint inhibitors (ICI) have revolutionised treating advanced cancers. ICI are administered intravenously every 2-6 weeks for up to 2 years, until cancer progression/unacceptable toxicity. Physiological efficacy is observed at lower doses than those used as standard of care (SOC).