Norbert Graf

Norbert Graf
Saarland University | UKS · Klinik für Pädiatrische Onkologie und Hämatologie

Prof. Dr.

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813
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Publications

Publications (813)
Article
Background Recent research elucidated the prognostic significance of molecular biology in Wilms tumor (WT) by linking somatic genomic variants (such as gain of chromosome 1q) to unfavorable patient outcomes. This analysis describes the clinical impact of copy number variations (CNV) in tumor samples of WT patients with stage IV disease. Methods Tu...
Article
Wilms tumors (WT) are characterized by variable contributions of blastemal, epithelial and stromal elements, reflecting their diverse cellular origins and genetic drivers. In vitro models remain rare, despite a growing need to better characterize tumor biology and evaluate new treatments. Using three approaches, we have now established a large coll...
Article
Approximately 10% of children with cancer harbor a mutation in a predisposition gene. In children with the kidney cancer Wilms tumor, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumorigenesis. To investigate this, we assembled a cohort of 137 chi...
Article
Introduction: Palliative care is a critical component of care for patients with chronic hematological malignancies. Leveraging eHealth approaches can potentially facilitate the delivery of palliative care, leading to improved quality of life (QoL). Methods: The MyPal study (NCT04370457) is a randomized controlled clinical trial assessing an eHealth...
Article
Full-text available
Cancer exhibits substantial heterogeneity, manifesting as distinct morphological and molecular variations across tumors, which frequently undermines the efficacy of conventional oncological treatments. Developments in multiomics and sequencing technologies have paved the way for unraveling this heterogeneity. Nevertheless, the complexity of the dat...
Article
Full-text available
Despite growing interest in the inclusion of virtual reality (VR) in medical education, its full potential for immersive and interactive training remains underutilized, particularly in dermatology. As part of a multidisciplinary project, we tested the feasibility of integrating a VR training scenario for a complete skin cancer screening into the cu...
Presentation
Ten percent of children with cancer harbor a predisposition mutation, and in children with the kidney cancer, Wilms tumor, the prevalence may be as high as 30%. Whilst clinical management of children with a known predisposition differs from that of children with sporadic Wilms tumors, it is not dependent on the type of predisposition. Some Wilms pr...
Preprint
Ten percent of children with cancer harbour a predisposition mutation. In children with the kidney cancer, Wilms tumour, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumour genetic development. To investigate this, we assembled a cohort of 137 chi...
Article
Background: Among patients with nephroblastoma, those with bilateral disease are a unique population where maximising tumour control must be balanced with preserving renal parenchyma. Methods: The SIOP 2001 protocol recommended surgery after neoadjuvant cycle(s) of Dactinomycin and Vincristine (AV) with response-adapted intensification, if neede...
Article
Full-text available
Background In medical education, new technologies like Virtual Reality (VR) are increasingly integrated to enhance digital learning. Originally used to train surgical procedures, now use cases also cover emergency scenarios and non-technical skills like clinical decision-making. This scoping review aims to provide an overview of VR in medical educa...
Article
Background Outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not been described systematically. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study aims at giving a comprehensive overview about clinical and molec...
Article
BACKGROUND Outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not systematically been described. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study provides a comprehensive overview about clinical and molecular c...
Article
BACKGROUND Throughout the past decade, molecular tools have revolutionised ependymoma classification, yet their application has been limited in clinical trial cohorts. METHODS We present the molecular analysis of paediatric ependymoma patients from the E-HIT2000 trial (n = 165), or subsequent HIT2000-interim and I-HIT-MED registries (n = 79) based...
Article
Objective This study aimed to identify parameters that allow the estimation of tumor-infiltrated lymph nodes (LN) after pretreatment for unilateral Wilms tumor (WT). Summary Background Data Complete tumor resection with removal of regional LN is always necessary. Positive LNs require local irradiation influencing benefits in case of NSS in long-te...
Article
Full-text available
Introduction Wilms tumor (WT) is the most common childhood kidney cancer. It is a rapid growing embryonal tumor in young children and can be diagnosed with and without tumor related symptoms. Methods We retrospectively analyzed the route to diagnosis of WT treated prospectively according to the SIOP 93‐01/GPOH and 2001/GPOH in Germany between 1993...
Article
Background The term Gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features have not been established yet. Methods We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characteri...
Article
Full-text available
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 t...
Article
Full-text available
Background Congenital mesoblastic nephroma is the most common solid renal tumor in neonates. Therefore, patients <3 months of age are advised to undergo upfront nephrectomy, whereas invasive procedures at diagnosis in patients ≥3 months of age are discouraged by the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG). Ne...
Preprint
Full-text available
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 t...
Article
Full-text available
Non‐invasive differentiation of paediatric kidney tumours is particularly important in the SIOP‐RTSG protocols, which recommend pre‐operative chemotherapy without histological confirmation. The identification of clinical and tumour‐related parameters may enhance diagnostic accuracy. Age, metastases, and tumour volume (TV) were retrospectively analy...
Technical Report
Full-text available
This document outlines the user and ecosystem requirements identified from related research projects and literature research. Some key aspects of the ecosystem user requirements were collected through a stakeholder survey. The ethical and medical considerations for the ecosystem described and the key legal requirements, form the framework for a fut...
Article
Background Completely necrotic Wilms tumor (CN‐WT) following preoperative chemotherapy has been regarded as low‐risk WT since the International Society of Paediatric Oncology (SIOP) 93‐01 study, and patients have been treated with reduced postoperative therapy. The aim of the study was to evaluate whether the omission of adjuvant chemotherapy in pa...
Article
Full-text available
Background Acute graft‐versus‐host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification. Methods In thi...
Article
Full-text available
Introduction Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology–Renal Tumor Study Group (SIOP‐RTSG) 2016 UMBRELLA protocol recomm...
Article
Full-text available
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, envir...
Article
The modern study of Wilms tumour was prompted nearly 50 years ago, when Alfred Knudson proposed the 'two-hit' model of tumour development. Since then, the efforts of researchers worldwide have substantially expanded our knowledge of Wilms tumour biology, including major advances in genetics - from cloning the first Wilms tumour gene to high-through...
Presentation
Presenting the results of an analysis of about 3000 patients with nephroblastoma with regard to the correlation of route to diagnosis and outcome.
Poster
https://cslide.ctimeetingtech.com/siop23/attendee/eposter/poster/1334?q=Politis
Article
Wilms tumors (WTs) are histologically diverse childhood cancers with variable contributions of blastema, stroma, and epithelia. A variety of cancer genes operate in WTs, including the tripartite‐motif‐containing‐28 gene ( TRIM28 ). Case reports and small case series suggest that TRIM28 mutations are associated with epithelial morphology and WT pred...
Article
Full-text available
Background: The COVID-19 pandemic had global catastrophic effects on the management of non-communicable diseases including paediatric cancers. Restrictions during the start of 2020 complicated timely referrals of patients to specialized centres. We aimed to evaluate the pandemic's impact on the number of new diagnoses, disease characteristics and...
Article
Full-text available
Background: Due to an increasing focus of medical curricula on clinical decision-making skills, new learning tools are constantly developed. Virtual reality (VR) is one of the emerging technologies with the potential to improve health professionals’ education. Highly realistic learning experiences with repeatable training scenarios can be created w...
Article
Full-text available
The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology cen...
Article
Full-text available
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...
Article
Full-text available
Background: Medical students need to be prepared for various situations in clinical decision-making that cannot be systematically trained with real patients without risking their health or integrity. To target system-related limitations of actor-based training, digital learning methods are increasingly used in medical education, with vir- tual real...
Article
Full-text available
Background Patients treated with preoperative chemotherapy with stage I intermediate‐risk Wilms tumor (IR‐WT) represent the largest group of patients with Wilms tumor (WT), and they have excellent outcomes. Methods The authors performed a retrospective analysis of patients with stage I epithelial (ET‐WT) or stromal type WT (ST‐WT) treated pre‐ and...
Article
Full-text available
Background: Due to the high risk of severe infection among pediatric hematology and oncology patients, antimicrobial use is particularly high. With our study, we quantitatively and qualitatively evaluated, based on institutional standards and national guidelines, antimicrobial usage by employing a point-prevalence survey with a multi-step, expert...
Article
Full-text available
(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 ri...
Article
Full-text available
The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology cen...
Article
Full-text available
Stage III Wilms' tumour (WT) represents a heterogeneous group which includes different criteria, but all stage III patients are treated according to the same study regiment. The aim of the study was to retrospectively analyse outcomes in patients with stage III due to positive resection margins (RM) only, sub‐grouped in RM with viable (RM‐v) and no...
Chapter
Das Nephroblastom stellt den häufigsten kindlichen Nierentumor dar. Nur 11 Prozent der Nierentumoren im Kindesalter weisen eine andere Histologie auf (Mesoblastisches Nephrom, Klarzellensarkom, Rhabdoidtumor, Nierenzellkarzinom oder sehr selten: Onkozytome, Sarkome, Angiomyolipome). Häufig sind die Patienten beschwerdefrei oder fallen durch eine sc...
Article
Full-text available
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...
Conference Paper
Full-text available
1. Introduction The Nephroblastoma Oncosimulator (NO) is a digital twin for Wilms tumour that is based on a mechanistic multiscale simulation model of tumour growth and response to treatment. It exploits the patient’s imaging, cellular, molecular and clinical data [1,2]. The NO maps the patient’s imaging and other data into a 3D discretization mesh...
Article
Objective: This study aims to identify factors associated with the occurrence of local relapse (LR) after treatment for unilateral nephroblastoma. Summary of background data: Despite the fact that LR is rare (~5%) its adverse impact on the need for relapse treatment and outcome (40-80% OS) cannot be neglected. Identifying the causative factors m...
Article
Clinical/methodical issue: The Beckwith-Wiedemann spectrum (BWSp) as well as the WT1-related syndromes, Denys-Drash syndrome (DDS) and WAGR spectrum (Wilms tumor, Aniridia, genitourinary anomalies and a range of developmental delays) are tumor predisposition syndromes (TPS) of Wilms tumor (WT). Patients with associated TPS are at higher risk of de...
Article
Full-text available
Allogeneic hematopoietic cell transplantation (HCT) effectively treats high‐risk hematologic diseases but can entail HCT‐specific complications, which may be minimized by appropriate patient management, supported by accurate, individual risk estimation. However, almost all HCT risk scores are limited to a single risk assessment before HCT without i...
Article
Full-text available
(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 Oncolog...
Article
Full-text available
Background Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence stu...
Article
Full-text available
BACKGROUND: Gliomatosis cerebri (GC), a radiologically defined diffusely infiltrating glioma, is no longer considered a distinct entity since the 2016 WHO classification for tumors of the CNS. Due to its rarity and dismal prognosis treatment recommendations in children remain ambiguous. Using central neuroradiological review, we performed a multi-i...
Chapter
Hodentumoren im Kindesalter umfassen vor allem Keimzell-, seltener die Stromatumoren und paratestikuläre Weichteilsarkome. Selten kommt es zu einer Beteiligung des Hodens im Rahmen einer Infiltration durch ein Lymphom oder als Beteiligung bei einer Leukämie. Die Basisdiagnostik umfasst die Bildgebung des Lokalbefundes, der lymphatischen Abflusswege...
Article
Full-text available
We report the case of a Jehovah's Witness adolescent patient with immune‐mediated thrombotic thrombocytopenic purpura after SARS‐Cov2 infection successfully treated without therapeutic plasma exchange (TPE) using caplacizumab, corticosteroids, rituximab, and extracorporeal immunoadsorption (EIA). Further patients for whom TPE is not an option might...
Article
The International Society of Paediatric Oncology Renal Tumour Study Group (SIOP‐RTSG) advocate treating children with Wilms tumour (WT) with preoperative chemotherapy, whereas the Renal Tumor Committee of the Children's Oncology Group (COG) advocates primary nephrectomy (without biopsy) when feasible. Successive SIOP‐RTSG trial protocols recommende...
Article
Full-text available
The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of tr...
Article
Background Anaplasia is an unfavourable prognostic histological feature in Wilms tumour (WT). Patients with stage I anaplastic WT (AWT) typically achieve good outcomes, albeit with more treatment than for stage I non-AWT. Since the SIOP-WT-2001 study, patients with focal AWT (FAWT) have been classified as intermediate risk and received less intense...
Article
Full-text available
PURPOSE International comparisons of patient demographics, tumor characteristics, and survival can shed light on areas for health care system improvement. The International Society of Pediatric Oncology Wilms Tumor 2001 trial/study registered patients through national clinical study groups in Western Europe and Brazil. This retrospective post hoc a...
Preprint
Full-text available
Background: Histologically nephroblastomatosis consists of ≥2 microscopic foci of nephrogenic rests. In contrast, clinically apparent nephroblastomatosis consists of single, multiple or diffuse hyperplastic nephrogenic rests (HNR) that can be mistaken for nephroblastoma on imaging. Their treatment and outcome are as variable as published results. M...
Preprint
Full-text available
Background: Nephroblastomatosis is defined histologically as ≥2 microscopic foci of nephrogenic rests. In contrast, clinicans’ nephroblastomatosis consists of single, multiple or diffuse hyperplastic nephrogenic rests (HNR) apparent on imaging as a renal tumor. Methods: Analysis of 78 patients having clinically apparent uni- or bilateral nephroblas...
Article
Full-text available
Purpose Society of International Pediatric Oncology – Renal Tumor Study Group (SIOP-RTSG) treatment recommendations for relapsed Wilms tumour (WT) are stratified by the intensity of first-line treatment. To explore the evidence for the treatment of patients relapsing after vincristine and actinomycin-D (VA) treatment for primary WT, we retrospectiv...
Article
Full-text available
Pediatric renal cell carcinomas (RCC) differ from their adult counterparts not only in histologic subtypes, but also in clinical characteristics and outcome. However, the underlying biology is still largely unclear. For this reason, we performed whole-exome and transcriptome sequencing analyses on a cohort of 25 pediatric RCC patients with various...
Preprint
Full-text available
BACKGROUND Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence stu...
Article
Full-text available
MyPal is a European initiative focusing on the use of the electronic patient reported outcome (ePRO) measures to enhance patient engagement in palliative cancer care via digital self-reporting palliative care for patients with cancer. As a part of its approach, MyPal also focuses on pediatric patients, implementing a specific digital health platfor...