Lindsay Frazier

ObjectiveSertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT.MethodsIndividuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available.ResultsIn total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was …

Background An international expert panel recently recommended 15 ‘non‐stage prognostic indicators’ (NSPIs) across eight childhood cancers, classified as essential or additional, for collection in population‐based cancer registries. We aimed to describe the incidence distribution and survival of each of these NSPIs. Procedures Cases were extracted from the Australian Childhood Cancer Registry. The study cohort (n = 4187) comprised all children aged under 15 years diagnosed with an eligible cancer between 2010 and 2018, with follow‐up until 31 December 2020. NSPI data were collected directly from each patient's medical records. Differences in 5‐year relative survival were assessed using multivariable flexible parametric models, adjusted for sex and age group at diagnosis. Results The availability of data varied, exceeding 85% for all essential NSPIs apart from histologic subtype for Wilms tumours (69 …

Innovations in the care of adolescent and young adult (AYA) germ cell tumors (GCTs) are needed for one of the most common AYA cancers for which treatment has not significantly changed for several decades. Testicular GCTs (TGCTs) are the most common cancers in 15- to 39-year-old men, and ovarian GCTs (OvGCTs) are the leading gynecologic malignancies in women younger than 25 years. Excellent outcomes, even in widely metastatic disease using cisplatin-based chemotherapy, can be achieved since Einhorn and Donohue's landmark 1977 study in TGCT. However, as the severity of accompanying late effects (ototoxicity, neurotoxicity, cardiovascular disease, second malignant neoplasms, nephrotoxicity, and others) has emerged, efforts to deintensity treatment and find alternatives to cisplatin have taken on new urgency. Current innovations include the collaborative design of clinical trials that accrue …

Ovarian immature teratoma (IT) is a rare neoplasm comprising ∼3% of ovarian cancers, occurring primarily in young females. Management presents several challenges, including those with elevated serum alpha-fetoprotein, potential confusion regarding pathology interpretation, and paucity of data to support decision-making. MaGIC (https://magicconsortium.com/) is an interdisciplinary international consortium of GCT experts from multiple subspecialties, with members receiving frequent queries regarding IT patient management. With evidence from published literature where available, we summarise consensus management of such patients. Given lack of published data, controversy in certain areas remains. The most obvious variance in practice is between paediatric and adult teams, despite very similar outcomes. Paediatric teams typically employ a surgery-only approach, whereas in adult practice, all patients …

Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0–24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes …

BackgroundLymphovascular invasion (LVI) has been identified as a poor prognostic factor for a variety of tumors; however, its significance in malignant ovarian germ cell tumors (MOGCT) in pediatric and adolescent patients is not well described. We aim to clarify the significance of LVI in the subset of patients with nongerminomatous MOGCT.MethodsRecords of patients 0–20 years of age with MOGCT enrolled on Children's Oncology Group study AGCT0132 were reviewed. Patients with documented presence or absence of LVI in either institutional or central review pathology reports were included.ResultsOf 130 patients with MOGCTs, 83 patients had of the presence or absence of LVI documented in their pathology report. 42/83 patients (50.6%) were found to have LVI present. The estimated odds of having LVI was higher in patients with stage II and III disease, 11 years and older and with the presence of …

Introduction and objective Conventional serum tumor markers (STMs) for testicular germ cell tumors (GCTs) offer limited performance with particularly poor sensitivity in cases of minimal residual disease and pure seminoma. While growing evidence has indicated miR‐371a‐3p to be a superior biomarker, its utility in detecting pure seminoma at recurrence has not been extensively explored. This study's objective was to explore miR‐371a‐3p's utility in detecting metastatic pure seminoma at retroperitoneal lymph node dissection (RPLND). Methods RNA was isolated from patient serum samples collected pre‐RPLND. Fifteen patients were assigned to our ‘benign’ (n = 6) or ‘seminoma’ (n = 9) group based on pathological confirmation of viable seminoma. Five of the patients received chemotherapy before RPLND (PC‐RPLND), and 10 were chemotherapy naïve. MiR‐371a‐3p expression was quantified via RT …

BackgroundThe Toronto Paediatric Cancer Stage Guidelines are a compendium of staging systems developed to facilitate collection of consistent and comparable data on stage at diagnosis for childhood cancers by cancer registries.Material and MethodsThis retrospective, observational cohort study investigated changes in stage-specific incidence and survival for children diagnosed between 2000-2008 compared to 2009-2017 using the population-based Australian Childhood Cancer Registry. Information on mortality for each patient was available to 31st December 2020. Shifts in incidence by stage were evaluated using chi-square tests, and differences in stage-specific five-year observed survival for all causes of death over time were assessed using flexible parametric models.ResultsStage was assigned according to the Toronto Guidelines for 96% (n = 7944) of the total study cohort (n = 8292). Changes in …