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The massive amount of human biological, imaging, and clinical data produced by multiple and diverse sources necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell-signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels, as well as their orchestration and links, are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof-of-concept study cases. Personalized simulations of the actual anatomy of a patient have been conducted. The hypermodel has also been applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin-based clinical decision support system and as the core of future in silico trial platforms, although additional retrospective adaptation and validation are necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: Wilms tumor (WT), as the most common renal tumor in childhood, is treated very successfully within prospective trials and studies. The association with various genetic alterations has been studied, but it is still unclear why a WT develops in a specific child and why some children suffer from relapse. Genetic risk and external, environmental factors need further attention. Parental age at birth plays a role in various childhood diseases, so it is reasonable to also investigate whether older parental age is a risk factor for the development of childhood renal tumors. We could demonstrate that parental age has no correlation with the incidence of renal tumors in childhood. Despite excellent outcomes, many open questions remain about Wilms tumor (WT). Influences and risk factors for tumorigenesis, as well as tumor aggressiveness and recurrence, are not fully understood. Parental age plays a role in various childhood diseases and is also discussed as a risk factor for childhood cancer. We analyzed both maternal and paternal age at birth as risk factors for the occurrence of Wilms and non-Wilms tumors in children and investigated whether older maternal or paternal age is associated with a higher tumor incidence. During 1990 and 2019 we collected data from 3991 patients from the multicenter studies SIOP9/GPO, SIOP 93-01/GPOH, and SIOP 2001/GPOH, of whom maternal and paternal age was available in 2277 cases. Data from the Federal Statistical Office containing live births in Germany from 1990–2019 served as a comparative database. For maternal age at birth, the control data yielded 22,451,412 cases and for paternal age yielded 19,046,314 cases. Comparing maternal and paternal ages of the study patients with those of the control data, we confirmed that higher parental age is not correlated with the incidence of renal tumors in childhood. Mean ages of fathers and mothers in patients and the control cohort increased between 1991 and 2019 (fathers: 30.28 vs. 34.04; mothers: 27.68 vs. 29.79 in the patient group and 31.29 vs. 34.23 and 28.88 vs. 32.67 in the control group, respectively) without higher numbers of patients with kidney cancer over time. No influence was found for the subtype of cancer nor for syndromes. In addition, overall survival of patients is independent of the year of diagnosis and the age of the parents but depends on histology type and stage in WT. [ABSTRACT FROM AUTHOR]

Digital learning plays an increasing role in medical education. Virtual Reality (VR) has a high potential for acquiring clinical competencies in a safe and immersive environment. With this survey, we assessed the level of acceptance and potential for VR in medical education among students. From January to April 2022, we provided an anonymous online survey at Saarland University. Besides demographic data, items covered previous VR experience, expectations of including VR in medical curricula, and estimated advantages and disadvantages. Additionally, ideas for VR scenarios could be submitted. Two hundred fifty-two medical students completed the survey. Of these, 54.4% were 21–25 years old, with 34.5% males, 50.4% being preclinical students, and 67.5% never had contact with VR. Males and preclinical students were more likely to be VR experienced. While almost all students approved the integration of VR into their curriculum, most use cases have been allocated to anatomy and surgery. Technical requirements and competencies were the main selected disadvantages. Most medical students can imagine VR being integrated into medical curricula. The implementation of immersive VR technology into medical curricula will allow students to train in practical, procedural, and soft skills repeatedly to acquire highly relevant clinical decision-making competencies with great benefit to public health. [ABSTRACT FROM AUTHOR]

Simple Summary: In SIOP, trials and studies for Wilms tumor (WT) start with chemotherapy before the surgical removal of the tumor. The aim of this study is to find out whether the time between the start of preoperative chemotherapy and surgery has an influence on the outcome of WT patients. Therefore, we analyzed a completely German, Austrian, and Swiss cohort of 2561 unilateral WT patients pretreated between 1989 and 2022. This retrospective analysis shows no such influence on the occurrence of relapses and survival in unilateral WTs. However, in bilateral tumors with prolonged pretreatment, to achieve as many nephron-sparing surgeries as possible, preoperative treatment should not exceed 120 days due to an increased risk of relapses. (1) Background: Wilms tumor (WT) treated preoperatively is cured in over 90% of cases. However, how long preoperative chemotherapy can be given is unknown. (2) Methods: 2561/3030 patients with WT (age < 18 years) treated between 1989 and 2022 according to SIOP-9/GPOH, SIOP-93-01/GPOH, and SIOP-2001/GPOH are retrospectively analyzed to assess the risk of time to surgery (TTS) for relapse-free survival (RFS) and overall survival (OS). (3) Results: TTS was calculated for all surgeries, with the mean being 39 days (38.5 ± 12.5) for unilateral tumors (UWT) and 70 days (69.9 ± 32.7) for bilateral disease (BWT). Relapse occurred in 347 patients, of which 63 (2.5%) were local, 199 (7.8%) were metastatic, and 85 (3.3%) were combined. Moreover, 184 patients (7.2%) died, 152 (5.9%) due to tumor progression. In UWT, recurrences and mortality are independent of TTS. For BWT without metastases at diagnosis, the incidence of recurrence is less than 18% up to 120 days and increases to 29% after 120 days, and to 60% after 150 days. The risk of relapse (Hazard Ratio) adjusted for age, local stage, and histological risk group increases to 2.87 after 120 days (CI 1.19–7.95, p = 0.022) and to 4.62 after 150 days (CI 1.17–18.26, p = 0.029). In metastatic BWT, no influence of TTS is detected. (4) Conclusions: The length of preoperative chemotherapy has no negative impact on RFS or OS in UWT. In BWT without metastatic disease, surgery should be performed before day 120, as the risk of recurrence increases significantly thereafter. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute leukemias in children have an excellent outcome. Therefore, reasons for long-term sequelae need to be discovered to avoid them. Our retrospective analysis in addition to a literature review focuses on neurotoxicity by investigating cerebral morphologic changes diagnosed in cranial MRIs in children with acute leukemias. Such changes occur in more than 50% of children. They were detected especially in patients below 6 years of age, in ALL and in patients receiving more than 12 intrathecal MTX applications. The ventricular width, as one of the cerebral abnormalities, has the potential to normalize again. It is important to prospectively investigate and correlate these changes with the neurocognitive outcome in children with acute leukemias to evaluate the impact of intrathecal MTX in this context. Due to high survival rates, long-term sequelae, especially neurotoxicity, need to be considered in childhood acute leukemias. In this retrospective analysis of morphologic changes of the brain in children treated for acute leukemias, we included 94 patients (77 ALL, 17 AML; 51 male, 43 female; median age: 5 years) from a single center. We analyzed 170 cranial MRI scans (T2, FLAIR axial) for morphologic alterations of the brain and variations of the ventricular width (GDAH). In addition, the corresponding literature was reviewed. More than 50% of all patients showed cerebral pathomorphologies (CP). They were seen more often in children with ALL (55.8%), ≤ 6 years of age (60.8%), in relapse (58.8%) or after CNS irradiation (75.0%) and included white matter changes, brain atrophy, sinus vein thrombosis and ischemic events. GDAH significantly enlarged mainly in children up to 6 years, with relapse, high-risk leukemias or ALL patients. However, GDAH can normalize again. The number of intrathecal Methotrexate applications (≤12 vs. >12) showed no correlation to morphologic alterations besides a significant increase in GDAH (−0.3 vs. 0.9 mm) between the first and last follow-up MRI in ALL patients receiving >12 ith. MTX applications. The role of ith. MTX on CP needs to be further investigated and correlated to the neurocognitive outcome of children with acute leukemias. [ABSTRACT FROM AUTHOR]

Simple Summary: Wilms tumor (WT) is the most common solid renal tumor in childhood. Today, more than 90% are alive 5 years after treatment. If the tumor extends into the major abdominal vessels, treatment still faces significant challenges. In these cases, tumor removal from the vessel is also required, sometimes requiring complex management. Knowledge of factors that positively or negatively affect treatment and survival is therefore of particular interest. We, therefore, compiled data on this small group of WT patients and evaluated them in terms of survival. This revealed that certain tumor-related features, as well as the presence or absence of metastases, significantly affect survival. This information helps us to further improve the treatment for this group of patients. (1) Background: Vena cava thrombus (VCT) is rare in Wilms tumor (WT) (4–10%). The aim of this study is to identify factors for an outcome to improve treatment for better survival. (2) Methods: 148/3015 patients with WT (aged < 18 years) and VCT, prospectively enrolled over a period of 32 years (1989–2020) by the German Society for Pediatric Oncology and Hematology (SIOP-9/GPOH, SIOP-93-01/GPOH and SIOP-2001/GPOH), are retrospectively analyzed to describe clinical features, response to preoperative chemotherapy (PC) (142 patients) and surgical interventions and to evaluate risk factors for overall survival (OS). (3) Results: 14 VCT regressed completely with PC and another 12 in parts. The thrombus was completely removed in 111 (85.4%), incompletely in 16 (12.3%), and not removed in 3 (2.3%). The type of removal is unknown in four patients. Patients without VCT have a significantly (p < 0.001) better OS (97.8%) than those with VCT (90.1%). OS after complete resection is (89.9%), after incomplete (93.8%) and with no resection (100%). Patients with anaplasia or stage IV without complete remission (CR) after PC had a significantly worse OS compared to the remaining patients with VCT (77.1% vs. 94.4%; p = 0.002). (4) Conclusions: As a result of our study, two risk factors for poor outcomes in WT patients with VCT emerge: diffuse anaplasia and metastatic disease, especially those with non-CR after PC. [ABSTRACT FROM AUTHOR]

Simple Summary: The individual's ability to conceive and regulate the broad spectrum of their human emotions is closely linked to their mental health. The implications of a serious disease such as cancer represent an extraordinary burden to these internal coping mechanisms, especially in the case of young patients. Regarding their well-being and support, it is therefore of particular interest for caregivers to be able to follow the dynamics of the patient's emotional world and perceptions. Technical progress enables new possibilities for data collection through tools for digital patient self-reports while simultaneously creating new challenges. Within the scope of this article, we provide an overview of the literature on this topic, outlining the current strengths and weaknesses and possible perspectives on digital aids, especially in terms of capturing the flexibility, fluctuations and early detection of symptom changes. Emotion dysregulation is regarded as a driving mechanism for the development of mental health problems and psychopathology. The role of emotion regulation (ER) in the management of cancer distress and quality of life (QoL) has recently been recognized in psycho-oncology. The latest technological advances afford ways to assess ER, affective experiences and QoL in child, adolescent and young adult (CAYA) cancer patients through electronic patient-reported outcomes (ePRO) in their daily environment in real-time. Such tools facilitate ways to study the dynamics of affect and the flexibility of ER. However, technological advancement is not risk-free. We critically review the literature on ePRO in cancer existing models of ER in pediatric psycho-oncology and analyze strength, weaknesses, opportunities and threats of ePRO with a focus on CAYA cancer research and care. Supported by personal study-based experiences, this narrative review serves as a foundation to propose a novel methodological and metatheoretical framework based on: (a) an extended notion of ER, which includes its dynamic, adaptive and flexible nature and focuses on processes and conditions rather than fixed categorical strategies; (b) ePRO as a means to measure emotion regulation flexibility and affect dynamics; (c) identifying early warning signals for symptom change via ePRO and building forecasting models using dynamical systems theory. [ABSTRACT FROM AUTHOR]

Wilms tumor (WT) is the most common childhood renal cancer. Recent findings of mutations in microRNA (miRNA) processing proteins suggest a pivotal role of miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of different subtypes and four normal kidney tissues using microarrays. Additionally, we determined the gene expression profile of 28 of these tumors to identify potentially correlated target genes and affected pathways. We identified 85 miRNAs and 2107 messenger RNAs (mRNA) differentially expressed in blastemal WT, and 266 miRNAs and 1267 mRNAs differentially expressed in regressive subtype. The hierarchical clustering of the samples, using either the miRNA or mRNA profile, showed the clear separation of WT from normal kidney samples, but the miRNA pattern yielded better separation of WT subtypes. A correlation analysis of the deregulated miRNA and mRNAs identified 13,026 miRNA/mRNA pairs with inversely correlated expression, of which 2844 are potential interactions of miRNA and their predicted mRNA targets. We found significant upregulation of miRNAs-183, -301a/b and -335 for the blastemal subtype, and miRNAs-181b, -223 and -630 for the regressive subtype. We found marked deregulation of miRNAs regulating epithelial to mesenchymal transition, especially in the blastemal subtype, and miRNAs influencing chemosensitivity, especially in regressive subtypes. Further research is needed to assess the influence of preoperative chemotherapy and tumor infiltrating lymphocytes on the miRNA and mRNA patterns in WT. [ABSTRACT FROM AUTHOR]

Simple Summary: It is well known that different cancer predisposition syndromes are associated with characteristic WT-features. The following findings from our retrospective analysis of patients with nephroblastoma treated according to the SIOP/GPOH trials between 1989 and 2017 are relevant: (1) The outcome of patients with a cancer predisposition syndrome is not always favorable despite early diagnosis, small tumors and less metastatic disease. This finding is partly depending on complications related to the underlying syndrome. (2) Predisposition syndromes seem to be underdiagnosed as several clinical and pathological features of Wilms tumor being clearly linked to a cancer predisposition syndrome did not lead to genetic counseling before and after WT diagnosis. As a conclusion, in children with a nephroblastoma and specific clinical and pathological features that are in line with a nephroblastoma cancer predisposition syndrome such a syndrome should always be considered and ruled out if unknown at the time of tumor diagnosis. (1) Background: about 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. (3) Results: Genitourinary malformations (GU, N = 66, 2.3%), Beckwith-Wiedemann spectrum (BWS, N = 32, 1.1%), isolated hemihypertrophy (IHH, N = 29, 1.0%), Denys-Drash syndrome (DDS, N = 24, 0.8%) and WAGR syndrome (N = 20, 0.7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24.5 months vs. 39.0 months), had smaller tumors (349.4 mL vs. 487.5 mL), less often metastasis (8.2% vs. 18%), but more often nephroblastomatosis (12.9% vs. 1.9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (0.4% increase) and favorable in BWS (86.9% reduction). The event-free survival (EFS) of patients with BWS was significantly (p = 0.002) worse than in others. (4) Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable. [ABSTRACT FROM AUTHOR]

Simple Summary: A Wilms tumor is a childhood kidney tumor. In high-income countries, 90% of patients with this tumor survive. However, the tumor recurs in 15% of patients. It is important to identify the patients at risk of recurrence in order to adjust treatment in such a way that recurrence may potentially be prevented. However, we are currently unable to determine precisely which patients are at risk of recurrence. Therefore, we present an overview of factors that influence the risk of recurrence, also known as prognostic factors. These factors range from patient-, tumor- and treatment-related characteristics to geographic and socioeconomic factors. In addition to these factors, biological markers, such as genetic alterations, should be studied more intensively as these markers may be able to better identify patients at risk of tumor recurrence. In high-income countries, the overall survival of children with Wilms tumors (WT) is ~90%. However, overall, 15% of patients experience tumor recurrence. The adverse prognostic factors currently used for risk stratification (advanced stage, high risk histology, and combined loss of heterozygosity at 1p and 16q in chemotherapy-naïve WTs) are present in only one third of these cases, and the significance of these factors is prone to change with advancing knowledge and improved treatment regimens. Therefore, we present a comprehensive, updated overview of the published prognostic variables for WT recurrence, ranging from patient-, tumor- and treatment-related characteristics to geographic and socioeconomic factors. Improved first-line treatment regimens based on clinicopathological characteristics and advancing knowledge on copy number variations unveil the importance of further investigating the significance of biological markers for WT recurrence in international collaborations. [ABSTRACT FROM AUTHOR]

We present a differential absorption lidar (DIAL) laser transmitter concept designed around a Nested Cavity Optical Parametric Oscillator (NesCOPO) based Master Oscillator Power Amplifier (MOPA). The spectral bands are located around 2051 nm for CO2 probing and 1982 nm for H216O and HD16O water vapor isotopes. This laser is aimed at being integrated into an airborne lidar, intended to demonstrate future spaceborne instrument characteristics: high-energy (several tens of mJ nanosecond pulses) and high optical frequency stability (less than a few hundreds of kHz long term drift). For integration and efficiency purposes, the proposed design is oriented toward the use of state-of-the-art high aperture periodically poled nonlinear materials. This approach is supported by numerical calculations and preliminary experimental validations, showing that it is possible to achieve energies in the 40–50 mJ range, reaching the requirement levels for spaceborne Integrated Path Differential Absorption (IPDA) measurements. We also propose a frequency referencing technique based on beat note measurement of the laser signal with a self-stabilized optical frequency comb, which is expected to enable frequency measurement precisions better than a few 100 kHz over tens of seconds integration time, and will then be used to feed the cavity locking of the NesCOPO. [ABSTRACT FROM AUTHOR]

Simple Summary: Although renal tumors in children are mostly solid masses, cystic renal tumors also occur. The most likely diagnoses for cystic renal tumors include cystic partially differentiated nephroblastoma and cystic nephroma. Since these tumors are rare, limited information on the treatment, clinical and molecular characteristics, and outcome is available. In this review, we aim to summarize all reported patients with cystic partially differentiated nephroblastoma and cystic nephroma. We identified 113 cystic partially differentiated nephroblastoma and 167 cystic nephroma patients. Surgery was the cornerstone of treatment for both tumor types and chemotherapy was generally not recommended. Cystic nephroma was often related to DICER1-mutations and second tumors, whereas cystic partially differentiated nephroblastoma was related to somatic hyperdiploidy, although testing was rare. The outcome for both tumors is favorable. This study provides information for treatment decisions and stresses the importance of a central review of radiology and pathology, as well as referral to a clinical geneticist. In children presenting with a predominantly cystic renal tumor, the most likely diagnoses include cystic partially differentiated nephroblastoma (CPDN) and cystic nephroma (CN). Both entities are rare and limited information on the clinical and molecular characteristics, treatment, and outcome is available since large cohort studies are lacking. We performed an extensive literature review, in which we identified 113 CPDN and 167 CN. The median age at presentation for CPDN and CN was 12 months (range: 3 weeks–4 years) and 16 months (prenatal diagnosis–16 years), respectively. No patients presented with metastatic disease. Bilateral disease occurred in both entities. Surgery was the main treatment for both. Two/113 CPDN patients and 26/167 CN patients had previous, concomitant, or subsequent other tumors. Unlike CPDN, CN was strongly associated with somatic (n = 27/29) and germline (n = 12/12) DICER1-mutations. Four CPDN patients and one CN patient relapsed. Death was reported in six/103 patients with CPDN and six/118 CN patients, none directly due to disease. In conclusion, children with CPDN and CN are young, do not present with metastases, and have an excellent outcome. Awareness of concomitant or subsequent tumors and genetic testing is important. International registration of cystic renal tumor cohorts is required to enable a better understanding of clinical and genetic characteristics. [ABSTRACT FROM AUTHOR]

Simple Summary: Around 15–20% of all Wilms tumour (WT) patients present with metastatic disease. Approximately 10% of these patients achieve complete necrosis after preoperative chemotherapy, which is associated with a favourable prognosis. The aim of this observational study is to describe the outcome of metastatic patients with completely necrotic (low-risk histology), local stage III WT treated according to the SIOP 2001 protocol, whether or not postoperative radiotherapy was applied. Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP– Renal Tumour Study Group (SIOP–RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%; 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1–151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP–RTSG 2016 UMBRELLA protocol. [ABSTRACT FROM AUTHOR]

Pediatric renal cell carcinoma (RCC) is a rare type of kidney cancer, most commonly occurring in teenagers and young adolescents. Few relatively large series of pediatric RCC have been reported. Knowledge of clinical characteristics, outcome and treatment strategies are often based on the more frequently occurring adult types of RCC. However, published pediatric data suggest that clinical, molecular and histological characteristics of pediatric RCC differ from adult RCC. This paper summarizes reported series consisting of ≥10 RCC pediatric patients in order to create an up-to-date overview of the clinical and histopathological characteristics, treatment and outcome of pediatric RCC patients. [ABSTRACT FROM AUTHOR]

Renal tumors comprise approximately 7% of all malignant pediatric tumors. This is a highly heterogeneous group of tumors, each with its own therapeutic management, outcome, and association with germline predispositions. Histopathology is the key in establishing the correct diagnosis, and therefore pathologists with expertise in pediatric oncology are needed for dealing with these rare tumors. While each tumor shows different histologic features, they do have considerable overlap in cell type and histologic pattern, making the diagnosis difficult to establish, if based on routine histology alone. To this end, ancillary techniques, such as immunohistochemistry and molecular analysis, can be of great importance for the correct diagnosis, resulting in appropriate treatment. To use ancillary techniques cost-effectively, we propose a pattern-based approach and provide recommendations to aid in deciding which panel of antibodies, supplemented by molecular characterization of a subset of genes, are required. [ABSTRACT FROM AUTHOR]