Purpose: DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing- and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant. One of the goals of the Registry is to continue to refine these guidelines as additional data become available. Experimental Design: Individuals were enrolled in the International PPB/DICER1 Registry, the International Ovarian and Testicular Stromal Tumor Registry, and/or the NCI Natural History of DICER1 Syndrome study. Results: Review of participant records identified 713 participants with a germline DICER1 P/LP variant from 38 countries. To date, 5 cases of type I and 29 cases of type Ir PPB have been diagnosed by surveillance in enrolled individuals. One hundred and three individuals with a germline P/LP variant developed a primary ovarian Sertoli–Leydig cell tumor at a median age of 14 years (range: 11 months–66 years); 13% were diagnosed before 8 years of age, the current age of onset of pelvic surveillance. Additionally, 4% of Sertoli–Leydig cell tumors were diagnosed before 4 years of age. Conclusions: Ongoing data collection highlights the role of lung surveillance in the early detection of PPB and suggests that imaging-based detection and early resection may decrease the risk of advanced PPB. DICER1-related ovarian tumors were detected before 8 years of age, prompting the Registry to recommend earlier initiation of ovarian surveillance with pelvic ultrasound beginning at the time of detection of a germline DICER1 P/LP variant.

Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option.

Dmitry Akhaladze, Natalia Uskova, Gavriil Rabaev, Denis Kachanov, and Nikolay Grachev. Ann Hepatobiliary Pancreat Surg 2020;24:352-6. https://doi.org/10.14701/ahbps.2020.24.3.352

Background. The aim of the study was to assess the main epidemiologic characteristics of solid tumours in young children. Methods. The data were retrieved from the Childhood Cancer Registry of Moscow Region, Russian Federation. Children aged 0-4 years with solid tumours diagnosed in 2000-2006 were included in the analysis. Results. The data on total 142 children with solid tumours were analyzed. The average number of annually registered cases was 5.9 ± 1.1 in infants and 14 ± 1.8 in older children with male-to-female ratio 1.1:1 and 0.92:1, respectively. The average incidence rate (IR) of all solid tumours was 10.6 per 100.000 children/year in infants and 7.35 per 100.000 children/year in children 1-4 years old. The prevalent types of solid tumours in infants were hepatic (IR 2.46) and renal (IR 2.26) tumours. In children aged 1-4 years the following IRs for certain malignancies were found: CNS tumours 1.70, renal tumours 1.76, sympathetic nervous system tumours 1.73, retinoblastoma 0.87, soft tissue sarcomas 0.70, germ-cell tumours 0.19, hepatic tumours 0.14, and bone tumours 0.13. Conclusions. The lower IR of CNS tumours can be explained by under-reporting of this cancer type in Moscow region as a result of patient scattering through non-oncological hospitals. As compared to the data from cancer registries of the most European countries and US, lower IR of sympathetic nervous system tumours and retinoblastoma and higher IR of liver tumours and soft tissue sarcomas in infants were revealed in this study.

The aim of the study was to assess the incidence and survival rates of soft tissue sarcomas (STSs) in children 014 years of age in Moscow Region, Russian Federation. The database of childhood population-based cancer registry of Moscow Region was used as a data source. Tumors were stratified according to International Classification of Childhood Cancer, 3d ed. Sixty-eight cases of STS were registered from 2000 to 2009. Crude incidence rate was 0,78, and age-standardized incidence rate using World Standard Population was 0,81 per 100.000 children/year. The highest age-specific incidence was observed in infants: 1,76 per 100.000 children/year. Rhabdomyosarcoma (RMS) was the most common histological type comprising 54,4% of all STS. 5-year observed survival (OS) of all patients with STS was 64,1 (95%CI 55,073,2). There was no statistically significant difference in OS between RMS59,2 (95%CI47,071,4) and nonrhabdomyosarcoma STS69,3 (95%CI55,882,8) (𝑃=0.63). Incidence and survival rates of STS observed in the study were comparable to the other Eastern European countries.