Norbert Graf

Norbert Graf
Universität des Saarlandes | UKS · Klinik für Pädiatrische Onkologie und Hämatologie

Prof. Dr.

About

757
Publications
82,861
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18,070
Citations
Citations since 2017
163 Research Items
8636 Citations
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201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500

Publications

Publications (757)
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
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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 analyze 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
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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...
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
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(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
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
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
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
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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...
Article
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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...
Preprint
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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
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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
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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
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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
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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
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...
Article
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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. (Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP...
Article
Full-text available
(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 t...
Preprint
Full-text available
Allogeneic hematopoietic cell transplantation (HCT) treats high-risk hematologic diseases effectively but can entail HCT-specific complications, which may be minimized by appropriate patient management and accurate, individual risk estimation. Existing clinical scores typically provide a single risk assessment before HCT and do not incorporate addi...
Article
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The increasing number of digital solutions developed for use in clinical health care settings is accompanied by new challenges to develop and conduct clinical studies that include eHealth technologies. Clinical study implementation plans often disregard or underestimate the necessity of additional administrative and logistic tasks required at clini...
Article
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INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up of 519 patients in whom molecular alterations were evaluated according to a predefined seven-scale target prioritization algorithm. Mean turnaround tim...
Preprint
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. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/...
Article
Full-text available
Since previous consensus-based Wilms tumour (WT) surveillance guidelines were published, novel genes and syndromes associated with WT risk have been identified, and diagnostic molecular tests for previously known syndromes have improved. In view of this, the International Society of Pediatric Oncology (SIOP)-Europe Host Genome Working Group and SIO...
Article
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Background: The SIOP-Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis-based treatment initiation, but only for a relatively small percentage of approximately 10% of non-Wilms tumors (non-WTs). MRI could be useful for reducing misdiagnosis, but ther...
Article
Background Meropenem is an important second- or third-line antibiotic in pediatric cancer patients with febrile neutropenia (FN). Concise utilization data of meropenem in this setting is limited. It remains unclear how drug dispensing data from the hospital pharmacy correlate with data derived from patients’ files. Methods Retrospective audit of me...
Article
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Purpose To assess the value of diffusion-weighted MRI (DW-MRI) in the non-invasive prediction of blastemal remnant after neoadjuvant chemotherapy in nephroblastoma. Methods This IRB-approved study included 32 pediatric patients with 35 tumors who underwent DW-MRI prior and after completion of neoadjuvant chemotherapy and subsequent surgical resect...
Article
CLINICAL/METHODOLOGICAL ISSUE Renal tumors in children are treated according to the guidelines of the Renal Tumor Study Group of the International Society of Pediatric Oncology (SIOP-RTSG). Nephroblastoma is the most frequent renal tumor in children. STANDARD RADIOLOGICAL METHODS After sonography, magnetic resonance imaging (MRI) is the preferred i...
Article
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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...
Article
Clinical/methodological issueRenal tumors in children are treated according to the guidelines of the Renal Tumor Study Group of the International Society of Pediatric Oncology (SIOP-RTSG). Nephroblastoma is the most frequent renal tumor in children.Standard radiological methodsAfter sonography, magnetic resonance imaging (MRI) is the preferred imag...
Article
Full-text available
In the SIOP Wilms tumor (WT) studies preoperative chemotherapy is used as primary treatment, and tumors are classified thereafter by pathologists. Completely necrotic WTs (CN-WTs) are classified as low-risk tumors. The aim of the study was to evaluate whether a subset of regressive type WTs (RT-WTs)(67-99% chemotherapy-induced changes - CIC) showin...
Article
We report on an 11-year old pediatric cancer patient with T-lymphoblastic lymphoma who acquired a severe SARS-CoV-2 pneumonia immediately after the start of oral maintenance treatment with mercaptopurine. He was admitted to our hospital on day 7 after onset of symptoms (day 5 after diagnosis). Due to respiratory failure, he was transferred to the p...
Article
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Introduction Electronic patient-reported outcomes (ePROs) have tremendous potential to optimise palliative and supportive care for children with cancer, their families and healthcare providers. Particularly, these children and their families are subjected to multiple strains caused by the disease and its treatment. The MyPal digital health platform...
Article
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Background and purpose Recently, the SIOP-RTSG developed a highly-conformal flank target volume definition for children with renal tumors. The aims of this study were to evaluate the inter-clinician delineation variation of this new target volume definition in an international multicenter setting and to explore the necessity of quality assurance....
Article
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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...
Article
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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...
Article
Zusammenfassung Hintergrund Gentamicin kommt in vielen pädiatrisch onkologischen Behandlungszentren in der Erstlinien-Kombinationstherapie bei Fieber und Granulozytopenie zum Einsatz. Seit 2011 verwenden wir hierzu eine Dosierung von 250 mg/m2 KOF (max. 10 mg/kg, max. 400 mg) als tgl. Einmalgabe nach der deutschen Leitlinie. Patienten und Methoden...
Article
Wilms tumour (WT) accounts for about 6% of all childhood cancers and overall survival of WT is about 90% in international protocols. However, for WT subgroups with much poorer prognoses, i.e. typically high-risk (unfavorable) histology and/or relapse, there is an unmet need to better understand the biology of WT and to translate biological findings...
Article
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In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology‐Renal Tumor Study Group (SIOP‐RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93‐01, 2001, and UK‐IMPORT databases, were included. Event‐free sur...
Article
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Introduction Clear cell sarcoma of the kidney (CCSK) is a rare malignant childhood renal tumour. Recently, the central nervous system (CNS) was found to be the most frequent site of relapse associated with a poor outcome. Optimal treatment strategies are scarce. Patients and Methods Retrospective data analysis of all Austrian children with CCSK. T...
Article
Introduction Extracranial rhabdoid tumours are rare, highly aggressive malignancies primarily affecting young children. The EU-RHAB registry was initiated in 2009 to prospectively collect data of rhabdoid tumour patients treated according to the EU-RHAB therapeutic framework. Methods We evaluated 100 patients recruited within EU-RHAB (2009–2018)....
Article
Purpose: The segmentation of brain tumors is one of the most active areas of medical image analysis. While current methods perform superhuman on benchmark data sets, their applicability in daily clinical practice has not been evaluated. In this work, we investigate the generalization behavior of deep neural networks in this scenario. Approach: We e...
Article
For decades, radiotherapy with two opposing photon beams has been the standard technique used to cover the flank target volume in paediatric patients with renal tumours. Nowadays, many institutes are implementing advanced radiotherapy techniques that spare healthy tissue. To decrease the radiotherapy dose to healthy structures while preserving onco...
Article
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Background: WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of developing Wilms tumor (WT). Currently, surveillance and treatment recommendations are based on limited evidence. Methods: Clinical characteristics, treatments, and ou...
Article
PURPOSE Rhabdoid tumor of the kidney (RTK) is one of the most aggressive childhood renal tumors. Overall survival ranges from 22% to 47%. The indication for radiation therapy (RT) in usually very young patients is an ongoing discussion. Recent protocols recommend RT independent of local stage, the latter being a good discriminator in other childhoo...
Article
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PurposeTo assess the value of diffusion-weighted MRI in the pre-therapeutic evaluation of pediatric renal cortical tumors.Methods This IRB-approved, retrospective multi-center study included 122 pediatric patients with 130 renal tumors, who underwent MRI including DWI before neoadjuvant chemotherapy and nephrectomy. Two radiologists independently a...
Article
Medulloblastoma is a malignant childhood brain tumor arising from the developing cerebellum. In Sonic Hedgehog (SHH) subgroup medulloblastoma, aberrant activation of SHH signaling causes increased proliferation of granule neuron progenitors (GNPs), and predisposes these cells to tumorigenesis. A second, cooperating genetic hit is often required to...
Conference Paper
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The practical goal of this work is to develop a “bottomup” multiscale (tri-scale) mathematical model of glioma growth, invasion and survival of cells following radiation that would serve as the core of the “Continuous Mathematics Based GBM Oncosimulator.”. It is an extension of the model for untreated glioma growth, described in previous papers to...
Article
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Background: In patients with neurosurgical interventions requiring dura reconstruction, the use of bovine graft material may be required. Patients and methods: Case report. Results: We present a 12-year-old girl with a profound graft reaction with severe neurologic symptoms mimicking post-neurosurgical bacterial meningitis after resection of a...
Article
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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, publi...
Article
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Background: Despite its cardiotoxicity doxorubicin is widely used for the treatment of paediatric malignancies. Current treatment regimens appear to be suboptimal as treatment strategies vary and do not follow a clear pharmacological rationale. Standardisation of dosing strategies in particular for infants and younger children is required but is h...
Article
In the context of the ‘Mobile Haemophilia Outpatient Care (MHOC)’ project we aimed to gather insights into the health-related quality of life (HRQoL), treatment satisfaction (TS) and adherence of persons with haemophilia (PWHs) who get treated at the Saarland University Hospital Haemophilia Treatment Centre (HTC). PWHs were visited at home at least...
Article
Background Rhabdoid tumor of the kidney (RTK) is one of the most aggressive childhood renal tumors. Overall survival ranges from 22 to 47%. Indication for radiotherapy (RTx) in usually very young patients is an ongoing discussion. Recent protocols recommend RTx independent of local stage, the latter being a good discriminator in other childhood kid...
Article
A retrospective analysis of the Children's Oncology Group AREN03B2 study has revealed that stage I epithelial‐predominant favorable‐histology Wilms tumors have excellent outcomes, and this suggests that primary treatment with surgery alone should be investigated in future protocols.
Article
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Aim Osteopontin (OPN) has been investigated as a biomarker for cancer and nonmalignant diseases during the last decades. Data about OPN as a potential biomarker in childhood diseases are still sparse, and reference values are not available in children. We aimed to establish reference values for children from birth to young adulthood and evaluate wh...
Article
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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 a...
Article
Introduction: High-risk (HR) metastatic (stage IV) Wilms tumours (WTs) have a particular poor outcome. Methods: Here, we report the results of HR (diffuse anaplastic [DA] or blastemal type [BT]) stage IV WT treated patients according to the HR arm in the SIOP2001 prospective study. Results: From January 2002 to August 2014, 3559 patients with...
Article
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Survival for subgroups of patients with Wilms tumor (WT), such as those who suffer from relapse, is disappointing. Some patients’ treatment plans include high-dose chemotherapy (HDT) with autologous hematopoietic cell transplantation (aHCT), although proof for its benefit is lacking. To increase the level of evidence regarding children with WT rece...