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The prognosis of children with neuroblastoma (NBL) can be dismal with significant variations depending on the stage and biology of the tumor. We assessed the event-free (EFS) and overall (OS) survival using harmonized data from three Southern-Eastern European (SEE) countries. Data for 520 incident NBL cases (2009-2018) were collected from Greece, Slovenia and Russia. Kaplan-Meier curves were fitted, and EFS/OS were derived from Cox proportional models by study variables including the protocol-based risk-group (low/observation, intermediate, high). Over one-third of cases were coded in the high-risk group, of which 23 children (4.4%) received treatment with anti-ganglioside 2 (GD2) mAb. Survival rates were inferior in older (OS 5-year; 1.5-4.9 years: 61%; EFS 5-year; 1.5-4.9 years: 48%) compared to children younger than 1.5 years (OS 5-year

Wilms tumour (WT) management represents a success story in pediatric oncology. We aimed to assess, for the first time, the event-free survival (EFS) vs. overall survival (OS) in Southern and Eastern Europe (SEE) using harmonised clinical data collected by childhood cancer registries and to identify respective prognostic factors.From 1999 to 2017, data for incident WT cases aged 0-14 years from 3 nationwide (Greece, Belarus and Slovenia) and one regional (Greater Poland) SEE registries were collected following common coding. Kaplan-Meier curves were constructed, and EFS vs. OS values were derived from Cox proportional hazard models by study variables.A total of 338 WT cases (45.6% males; median age, 3.19 years; age5 years, 75%) were included in the analyses. Bilateral were 21 tumours (6.2%). Among the 317 unilateral cases, the majority (93.7%) received International Society of Pediatric Oncology-based protocols; EFSOur results delineate the potential of high-quality childhood cancer registration entailing clinical data to assess predictors of WT outcome over and beyond those derived from enrolment into clinical trials. Specifically, outcomes among children with WT residing in the four participating SEE countries were comparable with those reported by major cooperative international groups, albeit somehow inferior. Despite the excellent overall prognosis, however, subgroups of patients with advanced or bilateral disease and/or high-risk histology still suffer poor outcomes.

Background Despite overall striking advances in survival of childhood liver tumors, outcomes remain poor for specific patient segments. We aimed to assess overall survival (OS) of this rare disease and evaluate the generalizability of prognostic variables included in international collaborative systems using, for the first time, harmonized clinical data from two geographically different cohorts (Greece and Moscow). Methods Data for children (0-14 years) with liver tumors were retrieved from two Southern-Eastern European areas (Greece; 2001-2019 and Moscow; 2012-2019). Kaplan-Meier curves were constructed, and OS values were derived from Cox proportional models controlling for study variables. Results A total of 171 newly diagnosed cases (54.4% males) were included. The OS5-year exceeded 80% in patients Conclusions Outcomes of patients with liver tumors registered in two SEE areas were comparable to those reported by major collaborative trials. Ongoing clinical cancer registration could facilitate comparison of outcomes between different study groups in order to shape state of the art of treatment.

Purpose Undervirilization represents a serious pathological condition. Disturbances within the androgen receptor (AR) pathway frequently account for androgen insensitivity and undervirilization. The individual long-term gender-related outcome is often unsatisfactory. Herein we present a long-term AR-gene-mutation-associated follow-up in a group of patients diagnosed as undervirilized males. Material and methods 21 patients (46 XY) who underwent genitoplasty for ambiguous genitalia were retrospectively identified from the hospital's database. Mean follow-up after corrective surgery was 15.35 years (2-28). All children displayed severe undervirilization. 13 patients had female gender reassignment whereas 7 were raised as males. A genital skin biopsy was performed to harvest androgen-responsive tissue. After fibroblast cultures, the specific binding of dihydrotestosterone, the thermostability of the receptor hormone complex, and -reductase activity were measured. AR gene mutations were detected by directα5- sequencing and results were compared with previously described mutations. Furthermore, the individual outcome was correlated with specific AR mutations. Results AR point mutations were detected in 15 patients of which 7 were previously unknown. 6 did not display any structural alteration of the AR gene. There was no specific androgen binding in 3, severely reduced affinity in 9, and normal -reductase activity wasαbinding capacities in 8 patients, respectively. 5- normal in 16, reduced in 4 and completely absent in 1 patient, respectively. Conclusions Retrospective evaluation revealed several AR gene-mutations. Those mutations are associated with a distinct long-term outcome. Identification of the molecular mechanisms that cause undervirilization will improve both diagnosis and therapy. Exact characterization of AR activation and function may offer a possible treatment modality in affected patients. These data may allow us to give prognostic estimations on the individual outcome and therefore provide objective criteria for gender assignment of undervirilized males.

Purpose Gender assignment in children with ambiguous genitalia represents an extremely difficult task since there is still a lack of agreement about optimal management. Those born with a small phallus and perineoscrotal hypospadias are difficult to treat and to counsel correctly. Herein, we present a homogenous group of undervirilized males with their long-term surgical and clinical outcome as well as their gender identity. Material and methods 21 patients (all 46 XY) who underwent genitoplasty for ambiguous genitalia in infancy or early childhood were retrospectively identified from the hospital's database. Mean follow-up after corrective surgery was 15.35 years. Initially all children presented with ambiguous genitalia (perineoscrotal hypospadias and cryptorchidism). Either female gender reassignment including gonadectomy, genital reconstruction and secondary vaginoplasty or orchidopexy and hypospadias repair were performed. All patients exhibited disturbances within the androgen receptor pathway. Gender identity and subjective satisfaction with genital surgery were individually assessed. Results 13 patients had female gender reassignment whereas 8 were raised as males. Gender identity and phenotypic sex were identical in all but one patient (28 y) who had a male gender identity despite a female sex of rearing. Genito-sexual function and cosmetic outcome as well as gender acceptance were reported to be satisfactory in 20 patients (95.2%). Conclusions Retrospectively, initial gender assignment was considered appropriate by the overwhelming majority of our patients reflected by a consistently high gender acceptance. Corrective surgery for ambiguous genitalia yielded durable functional and cosmetic results. Regarding the relative success of this therapeutic strategy we suggest that the sex of rearing should be decided based upon thorough information about the child's medical and surgical options as well as about all available outcome data.