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.

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.

Progress to international harmonisation of care and future developments.

Considerable differences exist in the management of gestational trophoblastic disease (GTD) both nationally and internationally despite numerous efforts to harmonise patient care. This partly reflects differences in healthcare systems and availability of resources. However, even in first world equivalent economies with similar healthcare systems differences remain, which appear to impact survival.

Treatment of metastatic placental site trophoblastic tumor with surgery, chemotherapy, immunotherapy and coil embolization of multiple pulmonary arteriovenous fistulate.

Placental Site Trophoblastic Tumor (PSTT) is a rare malignancy that often presents with extensive disease and can be resistant to traditional treatments. We present the case of a woman with stage IV PSTT who was initially managed with neoadjuvant chemotherapy followed by tumor debulking. Adjuvant therapy was guided by further pathologic analysis that revealed high levels of staining for PD-L1 as well as the presence of tumor infiltrating lymphocytes (TILs).

Treatment of gestational trophoblastic disease in the 2020s.

Purpose Of Review: This review demonstrates the evidence for new systemic anticancer treatments and how they integrate within conventional management for gestational trophoblastic neoplasia (GTN). We present the evidence on atypical placental site nodules, and how they incorporate within the GTN spectrum, as well as updates regarding GTN staging and follow-up.

Recent Findings: First-line treatment for GTN still lies in conventional chemotherapy, although the introduction of anti-PD1/PD-L1 immune checkpoint inhibitors has shown significant promise in management of relapsed disease, with responses reported in multiple relapsed choriocarcinomas as well as epithelioid trophoblastic tumours and placental site trophoblastic tumours (ETT/PSTT).

Can we replace adjuvant chemotherapy with surveillance for stage IA-C immature ovarian teratomas of any grade? an international multicenter analysis.

Background: The role of surveillance after surgery for stage IA-C grade 2 (G2) or grade 3 (G3) immature teratomas (ITs) is controversial with many guidelines advocating adjuvant chemotherapy. Here, we investigate the safety of surveillance in stage IA-C G1-3 ITs.

Methods: Clinicopathological data were analysed on postpubertal patients with stage I pure ITs in Multicenter Italian Trials in Ovarian Cancer centres and at Charing Cross Hospital, UK, between January 1985 and January 2018.

Validation of an online tool for early prediction of the failure-risk in gestational trophoblastic neoplasia patients treated with methotrexate.

Purpose: In a low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX), the modeled hCG (human chorionic gonadotropin) residual concentration (hCGres), calculated with NONMEM program® (NM) during the first 50 treatment days, is a predictor of MTX-resistance risk. This model was implemented with another algorithm on https://www.biomarker-kinetics.

A case of intraplacental gestational choriocarcinoma; characterised by the methylation pattern of the early placenta and an absence of driver mutations.

Background: Gestational choriocarcinoma is a rare malignancy believed to arise from the trophoblast cells of the placenta. Despite the frequently aggressive clinical nature, choriocarcinoma has been routinely curable with cytotoxic chemotherapy for over 50 years. To date little is known regarding the route to oncogenesis in this malignancy.

The results of treatment with high-dose chemotherapy and peripheral blood stem cell support for gestational trophoblastic neoplasia.

Objective: The objective of the study was to evaluate the effect of high-dose chemotherapy (HDC) with peripheral blood stem cell support (PBSCS) on survival of patients with gestational trophoblastic neoplasia (GTN) with either refractory choriocarcinomas or a poor-prognosis placental site/epithelioid trophoblastic tumours (PSTT/ETTs).

Methods: Databases of two referral centres for gestational trophoblastic disease were searched, and 32 patients treated with HDC between 1994 and 2015 were identified. Tissue samples were retrieved for genetic evaluation.

Is there uniformity in definitions and treatment of gestational trophoblastic disease in Europe?

Objectives: Because gestational trophoblastic disease is rare, little evidence is available from randomized controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centers within countries. One of the goals of the European Organization for Treatment of Trophoblastic Diseases (EOTTD) is to harmonize treatment in Europe.

What is the optimal duration of human chorionic gonadotrophin surveillance following evacuation of a molar pregnancy? A retrospective analysis on over 20,000 consecutive patients.

Objective: To quantify the risk of developing post-molar gestational trophoblastic neoplasia (pGTN) beyond the first normal human chorionic gonadotrophin (hCG) in women who have had a complete (CHM) or partial molar pregnancy (PHM) and to re-evaluate the current UK Hydatidiform mole hCG surveillance guidelines.

Methods: The Charing Cross Hospital Trophoblast Disease Centre database was screened to identify all registered cases of hydatidiform mole (HM) between 1980 and 2009.

Results: We identified 20,144 cases of HM, comprising 8400 CHM, 9586 PHM, and 2158 cases of unclassified hydatidiform mole (UHM).

The extent of B-cell activation and dysfunction preceding lymphoma development in HIV-positive people.

Objectives: B-cell dysfunction and activation are thought to contribute to lymphoma development in HIV-positive people; however, the mechanisms are not well understood. We investigated levels of several markers of B-cell dysfunction [free light chain (FLC)-κ, FLC-λ, immunoglobulin G (IgG), IgA, IgM and IgD] prior to lymphoma diagnosis in HIV-positive people.

Methods: A nested matched case-control study was carried out within the EuroSIDA cohort, including 73 HIV-positive people with lymphoma and 143 HIV-positive lymphoma-free controls.

Intraplacental choriocarcinoma: Systematic review and management guidance.

Background: Intraplacental choriocarcinoma (IC) is a rare form of malignant gestational trophoblastic disease (GTD). We present a review of 62 cases, including four previously unreported, and a suggested management algorithm.

Patients And Methods: IC cases and clinical data were identified within the Charing Cross Hospital (CXH) national GTD database (1986-2014) and by systematic literature search (1949-2014).

Predictive value of prostate specific antigen in a European HIV-positive cohort: does one size fit all?

Background: It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men.

Late spontaneous resolution of persistent molar pregnancy.

Objective: To determine the outcome of women with persistently raised but falling human chorionic gonadotrophin (hCG) levels 6 months after surgical evacuation of a molar pregnancy.

Design: An 11-year retrospective review.

Setting: The United Kingdom supra-regional trophoblastic disease treatment centres at Weston Park Hospital (Sheffield) and Charing Cross Hospital (London).

Predictive value of prostate-specific antigen for prostate cancer: a nested case-control study in EuroSIDA.

Introduction: Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV- men. We aimed to describe the kinetics and predictive value of PSA in HIV+ men.

Methods: Men with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected.

Extracranial-intracranial bypass of the bilateral anterior cerebral circulation using a thoracodorsal axis artery-graft.

Bilateral extracranial-intracranial (EC-IC) bypass-grafting of the cerebral circulation is uncommon. We report a case of anterior cerebral artery EC-IC bypass using the thoracodorsal axis artery-graft. The bifurcation of the thoracodorsal axis allows bypass of both anterior hemispheres, while matching appropriate small-vessel dimensions.

Genetics of gestational trophoblastic neoplasia: an update for the clinician.

Gestational trophoblastic disease is a spectrum of disorders ranging from premalignant hydatidiform moles through to malignant invasive moles, choriocarcinoma and rare placental site trophoblastic tumor. The latter are often collectively referred to as gestational trophoblastic tumors or neoplasia (GTN). Although most women can expect to be cured of their disease, many interesting questions arise in the management of gestational trophoblastic disease.