| Autor(en) |
Titel |
Quelle |
Links |
| Faber J, Wingerter A, Neu MA, Henninger N, Eckerle S, Münzel T, Lackner KJ, Beutel ME, Blettner M, Rathmann W, Peters A, Meisinger C, Linkohr B, Neuhauser H, Kaatsch P, Spix C, Schneider A, Merzenich H, Panova-Noeva M, Prochaska JH, Wild PS |
Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study. |
European heart journal 2018 May 1; 39: 1555 |
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| Faivre L, Meerpohl J, Da Costa L, Marie I, Nouvel C, Gnekow A, Bender-Götze C, Bauters F, Coiffier B, Peaud PY, Rispal P, Berrebi A, Berger C, Flesch M, Sagot P, Varet B, Niemeyer C, Tchernia G, Leblanc T |
High-risk pregnancies in Diamond-Blackfan anemia: a survey of 64 pregnancies from the French and German registries. |
Haematologica 2006, 91: 530 |
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| We reviewed 64 pregnancies in 26 women with Diamond-Blackfan anemia (DBA) included in the French and German DBA registries. Complications were seen in 42 pregnancies (66%) and included abortion, pre-eclampsia, in utero fetal death, intrauterine growth retardation, retroplacental hematoma, pre-term delivery and fetal malformations. Of the 34 children (53%) born alive, 13 had DBA. No correlations were found between pregnancy outcome and features of either maternal or child DBA. Pregnancies in DBA-affected women are at high risk, especially for complications likely to be of vascular-placental origin. Careful monitoring with prevention of severe anemia and early introduction of aspirin is suggested. |
| Fajardo RD, van den Heuvel-Eibrink MM, van Tinteren H, Spreafico F, Acha T, Bergeron C, de Camargo B, Oldenburger F, Rübe C, Oue T, Vokuhl C, de Krijger RR, Vujanic G, Sebire N, Coulomb-L'Hermine A, Collini P, Gandola L, Pritchard-Jones K, Graf N, Janssens GO, van Grotel M |
Is radiotherapy required in first-line treatment of stage I diffuse anaplastic Wilms tumor? A report of SIOP-RTSG, AIEOP, JWiTS, and UKCCSG. |
Pediatric blood & cancer 2020, 67:e28039 |
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| As a significant proportion of relapses occurred in the tumor bed or abdomen on patients with the fifth National Wilms Tumor Study stage I anaplastic Wilms tumor (WT), flank radiotherapy was added for stage I anaplastic WT in the subsequent study of the Children's Oncology Group (AREN0321). Preliminary results revealed reduction of relapse rate and improved survival. In cases treated with preoperative chemotherapy, such as in International Society of Pediatric Oncology (SIOP), the value of radiotherapy has never been studied. The aim of this observational study is to describe the pattern of recurrence and survival of patients with stage I diffuse anaplastic WT (DAWT) after induction chemotherapy. |
| Falkenstein F, Gessi M, Kandels D, Ng HK, Schmidt R, Warmuth-Metz M, Bison B, Krauss J, Kortmann RD, Timmermann B, Thomale UW, Albert MH, Pekrun A, Maaà E, Gnekow AK, Pietsch T |
Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO-grade II-Report from the German/Swiss SIOP-LGG 2004 cohort. |
International journal of cancer 2020, Epup ahead of print |
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| Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.8-17.8âÂÂyears, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event-free survival dropped to 0.44, while 5âÂÂyears overall survival was 0.90 (median observation time 8.3âÂÂyears). Extensive genetic profiling of 65/100 DG2 identified Histone3-K27M-mutation in 4, IDH1-mutation in 11, BRAF-V600-mutation in 12, KIAA1549-BRAF-fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8âÂÂyears, except for tumors carrying KIAA1549-BRAF-fusions. Histone3-K27M-mutant tumors proved uniformly fatal within 0.6 to 2.4âÂÂyears. The current LGG treatment strategy seems appropriate for all DG2-entities, with the exemption of Histone3-K27M-mutant tumors that require a HGG-related treatment strategy. Our data confirm the importance to genetically define pediatric low-grade diffuse gliomas for proper treatment decisions and risk assessment. |
| Fanconi G |
Familiäre infantile perniziosaartige Anämie (perniziöses Blutbild und Konstitution). |
Jahrb Kinderheilk 1927,: 257 |
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| Fanconi G |
Familial constitutional panmyelocytopathy, Fanconi's anemia (F. A.). I. Clinical aspects. |
Semin Hematol 1967, 4: 233 |
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| Fangusaro J, Witt O, Hernáiz Driever P, Bag AK, de Blank P, Kadom N, Kilburn L, Lober RM, Robison NJ, Fisher MJ, Packer RJ, Young Poussaint T, Papusha L, Avula S, Brandes AA, Bouffet E, Bowers D, Artemov A, Chintagumpala M, Zurakowski D, van den Bent M, Bison B, Yeom KW, Taal W, Warren KE |
Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. |
The Lancet. Oncology 2020, 21:e305-e316 |
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| Paediatric low-grade gliomas (also known as pLGG) are the most common type of CNS tumours in children. In general, paediatric low-grade gliomas show clinical and biological features that are distinct from adult low-grade gliomas, and the developing paediatric brain is more susceptible to toxic late effects of the tumour and its treatment. Therefore, response assessment in children requires additional considerations compared with the adult Response Assessment in Neuro-Oncology criteria. There are no standardised response criteria in paediatric clinical trials, which makes it more difficult to compare responses across studies. The Response Assessment in Pediatric Neuro-Oncology working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop consensus recommendations for response assessment in paediatric low-grade gliomas. Final recommendations were based on literature review, current practice, and expert opinion of working group members. Consensus recommendations include imaging response assessments, with additional guidelines for visual functional outcomes in patients with optic pathway tumours. As with previous consensus recommendations, these recommendations will need to be validated in prospective clinical trials. |
| Farahati J, Bucsky P, Parlowsky T, Mader U, Reiners C |
Characteristics of differentiated thyroid carcinoma in children and adolescents with respect to age, gender, and histology. |
Cancer 1997, 80: 2156 |
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| Farahati J, Parlowsky T, Mader U, Reiners C, Bucsky P |
Differentiated thyroid cancer in children and adolescents. |
Langenbecks Arch Surg 1998, 383: 235 |
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| Farrar JE, Vlachos A, Atsidaftos E, Carlson-Donohoe H, Markello TC, Arceci RJ, Ellis SR, Lipton JM, Bodine DM |
Ribosomal protein gene deletions in Diamond-Blackfan anemia. |
Blood 2011, 118: 6943 |
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| Diamond-Blackfan anemia (DBA) is a congenital BM failure syndrome characterized by hypoproliferative anemia, associated physical abnormalities, and a predisposition to cancer. Perturbations of the ribosome appear to be critically important in DBA; alterations in 9 different ribosomal protein genes have been identified in multiple unrelated families, along with rarer abnormalities of additional ribosomal proteins. However, at present, only 50% to 60% of patients have an identifiable genetic lesion by ribosomal protein gene sequencing. Using genome-wide single-nucleotide polymorphism array to evaluate for regions of recurrent copy variation, we identified deletions at known DBA-related ribosomal protein gene loci in 17% (9 of 51) of patients without an identifiable mutation, including RPS19, RPS17, RPS26, and RPL35A. No recurrent regions of copy variation at novel loci were identified. Because RPS17 is a duplicated gene with 4 copies in a diploid genome, we demonstrate haploinsufficient RPS17 expression and a small subunit ribosomal RNA processing abnormality in patients harboring RPS17 deletions. Finally, we report the novel identification of variable mosaic loss involving known DBA gene regions in 3 patients from 2 kindreds. These data suggest that ribosomal protein gene deletion is more common than previously suspected and should be considered a component of the initial genetic evaluation in cases of suspected DBA. |
| Farruggia P, Fioredda F, Puccio G, Porretti L, Lanza T, Ramenghi U, Ferro F, Macaluso A, Barone A, Bonanomi S, Caruso S, Casazza G, Davitto M, Ghilardi R, Ladogana S, Mandaglio R, Marra N, Martire B, Mastrodicasa E, Dora Notarangelo L, Onofrillo D, Robustelli G, Russo G, Trizzino A, Tucci F, Pillon M, Dufour C |
Autoimmune neutropenia of infancy: Data from the Italian neutropenia registry. |
American journal of hematology 2015, 90:E221 |
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| Farashi S, Harteveld CL |
Molecular basis of α-thalassemia. |
Blood cells, molecules & diseases 2017 |
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| α-Thalassemia is an inherited, autosomal recessive, disorder characterized by a microcytic hypochromic anemia. It is one of the most common monogenic gene disorders in the world population. The clinical severity varies from almost asymptomatic, to mild microcytic hypochromic, and to a lethal hemolytic condition, called Hb Bart's Hydrops Foetalis Syndrome. The molecular basis are usually deletions and less frequently, point mutations affecting the expression of one or more of the duplicated α-genes. The clinical variation and increase in disease severity is directly related to the decreased expression of one, two, three or four copies of the α-globin genes. Deletions and point mutations in the α-globin genes and their regulatory elements have been studied extensively in carriers and patients and these studies have given insight into the α-globin genes are regulated. By looking at naturally occurring deletions and point mutations, our knowledge of globin-gene regulation and expression will continue to increase and will lead to new targets of therapy. |
| Fasano RM, Meier ER, Hulbert ML |
Cerebral vasculopathy in children with sickle cell anemia. |
Blood cells, molecules & diseases 2015, 54: 17 |
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| Sickle cell anemia (SCA)-associated cerebral vasculopathy and moyamoya is a unique entity reflecting the abnormal interactions between sickled red blood cells (RBCs) and the cerebral arterial endothelium. Endothelial injury, coagulation activation, and the inflammatory response generated by sickled RBCs are implicated in the development of cerebral vasculopathy, but the pathophysiology remains incompletely understood. SCA-specific screening and treatment guidelines have successfully reduced the incidence of overt strokes in this high-risk population. However, despite aggressive hematological management, many children with cerebral vasculopathy due to SCA have progressive vasculopathy and recurrent strokes; therefore, more effective therapies, such as revascularization surgery and curative hematopoietic stem cell transplant, are urgently needed. |
| Faure Conter C, Calaminus G, Nicholson J, Idbaih A, Hoang Xuan K, Vasiljevic A, Morana G, Szathmari A, Ajithkumar T, Frappaz D |
Central nervous system germ cell tumor, an archetypal AYA tumor and a model for pediatric and neuro-oncology collaboration, review from the EURACAN domain 10 group. |
Frontiers in oncology 2022, 12: 971697 |
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| Adolescents and young adults (AYA) with cancer often fall through gaps between children's and adults' cancer services. They are consequently under-represented in clinical trials, and their survival is often inferior to that of children or adults with the same tumor type; in this paper, we use the example of central nervous system germ cell tumors (CNS-GCT), as a model of AYA tumor to illustrate this challenge. We describe how we have built bridges between pediatric and adult oncology, how this can apply to other types of brain tumors, and discuss ways to promote cancer care in the AYA population. Adolescents and young adults (AYA) with cancer are under-represented in clinical trials and have thus not benefited from the same improvement in outcomes as either younger or older patients. Central nervous system germ cell tumors (CNS-GCT) represent an ideal model of AYA tumor as their incidence peaks during adolescence and young adulthood. Since the early 90's, SIOP (International Society of Pediatric Oncology) has launched two successive European trials: SIOP CNS-GCT96 (January 1996 to December 2005) and SIOP CNS-GCTII protocols (October 2011 to July 2018), for CNS-GCTs. With the removal of the upper age limit in the SIOP CNS-GCTII trial, and closer collaboration between pediatric and adult oncologists within AYA multidisciplinary tumor boards, the proportion of adults enrolled in France has dramatically increased over time. The current article will use the example of CNS-GCT to illustrate how to build a bridge between pediatric and adult oncology, how this can apply to other types of brain tumors, and how to promote cancer care in the AYA population. |
| Favrot M, Ambros P, Schilling F, Frappaz D, Combaret V, Berthold F, Dominici C, Erttmann R, Esteve J, Jenkner A, Kerbl R, Mann J, Mathieu P, Parker L, Powell J, Philip T |
Comparison of the diagnostic and prognostic value of biological markers in neuroblastoma. Proposal for a common methodology of analysis. SENSE group. |
Ann Oncol 1996, 7: 607 |
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| Favara B, Feller A, Pauli M, Jaffe E, Weiss L, Arico M, Bucsky P, Egeler R, Elinder G, Gadner H, Gresik M, Henter J, Imashuku S, Janka-Schaub G, Jaffe R, Ladisch S, Nezelof C, Pritchard J |
Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. |
Med Pediatr Oncol 1997, 29: 157 |
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| Favaloro EJ |
Clinical utility of closure times using the platelet function analyzer-100/200. |
American journal of hematology 2017, 92: 398 |
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| Fazekas T, Eickhoff P, Lawitschka A, Knotek B, Pötschger U, Peters C |
Exhaled nitric oxide and pulmonary complications after paediatric stem cell transplantation. |
European journal of pediatrics 2012 Feb 16; |
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| Pulmonary complications are major causes of morbidity and mortality after haematopoietic stem cell transplantation (HSCT). We hypothesise that elevated exhaled nitric oxide (FeNO) levels early after HSCT in children are predictive for pulmonary complications. The present prospective study included 30 children (age, 4-18 years) before HSCT. FeNO levels were evaluated 10 days before transplant, at day 0, day +28 and day +60 after HSCT. During the follow-up period until day +100, pulmonary complications and lung function were assessed. Before HSCT, the mean FeNO levels were comparable in children with or without post-transplant pulmonary complications. However, they differed at day 0 and day +28 with a mean of 7 (±1.95) and 13 (±3.44) ppb at day 0 and a mean of 13 (±3.44) and 14 (±3.57) ppb at day +28, respectively. Conclusion: Children with pulmonary complications after day +28 have higher mean FeNO levels 28 days after HSCT than children without later pulmonary complications. Therefore, FeNO could be an important diagnostic tool for hyperinflammatory response in bronchial epithelium after paediatric HSCT. |
| Fazekas T, Attarbaschi A, Lawitschka A, Seidel M, Pötschger U, Peters C, Mann G, Gadner H, Matthes-Martin S |
Lethal pulmonary complications after pediatric allogeneic hematopoietic stem cell transplantation. |
The Pediatric infectious disease journal 2012, 31: 115 |
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| Hematopoietic stem cell transplantation (HSCT) in children is accompanied by a transplant-related mortality of 10% to 30%, which is the result of lethal pulmonary complications (LPCs) in many cases. |
| Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK |
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. |
Nature genetics 1996, 13: 399 |
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| Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism. |
| Federico A, Thomas C, Miskiewicz K, Woltering N, Zin F, Nemes K, Bison B, Johann PD, Hawes D, Bens S, Kordes U, Albrecht S, Dohmen H, Hauser P, Keyvani K, van Landeghem FKH, Lund EL, Scheie D, Mawrin C, Monoranu CM, Parm Ulhøi B, Pietsch T, Reinhard H, Riemenschneider MJ, Sehested A, Sumerauer D, Siebert R, Paulus W, Frühwald MC, Kool M, Hasselblatt M |
ATRT-SHH comprises three molecular subgroups with characteristic clinical and histopathological features and prognostic significance. |
Acta neuropathologica 2022, 143: 697 |
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| Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT-TYR, ATRT-MYC and ATRT-SHH. ATRT-SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT-SHH might also have biological and clinical importance. Consensus clustering of DNA methylation profiles and confirmatory t-SNE analysis of 65 ATRT-SHH yielded three robust molecular subgroups, i.e., SHH-1A, SHH-1B and SHH-2. These subgroups differed by median age of onset (SHH-1A: 18 months, SHH-1B: 107 months, SHH-2: 13 months) and tumor location (SHH-1A: 88% supratentorial; SHH-1B: 85% supratentorial; SHH-2: 93% infratentorial, often extending to the pineal region). Subgroups showed comparable SMARCB1 mutational profiles, but pathogenic/likely pathogenic SMARCB1 germline variants were over-represented in SHH-2 (63%) as compared to SHH-1A (20%) and SHH-1B (0%). Protein expression of proneural marker ASCL1 (enriched in SHH-1B) and glial markers OLIG2 and GFAP (absent in SHH-2) as well as global mRNA expression patterns differed, but all subgroups were characterized by overexpression of SHH as well as Notch pathway members. In a Drosophila model, knockdown of Snr1 (the fly homologue of SMARCB1) in hedgehog activated cells not only altered hedgehog signaling, but also caused aberrant Notch signaling and formation of tumor-like structures. Finally, on survival analysis, molecular subgroup and age of onset (but not ASCL1 staining status) were independently associated with overall survival, older patients (> 3 years) harboring SHH-1B experiencing relatively favorable outcome. In conclusion, ATRT-SHH comprises three subgroups characterized by SHH and Notch pathway activation, but divergent molecular and clinical features. Our data suggest that molecular subgrouping of ATRT-SHH has prognostic relevance and might aid to stratify patients within future clinical trials. |
| Fengler R, Baumgarten E, Buchmann S, Creutzig U, Harbott J, Ludwig R, Henze G |
Biklonale Leukämie (O-ALL/AMoL) mit 11;19 Translokation und Trisomie X bei einem 8 Monate alten Mädchen. |
Klinische Pädiatrie 1986, 198: 178 |
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| Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L |
A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. |
Blood 1999 Aug 15; 94: 1192 |
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| All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA-->CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/microL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA -->CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P =.0002) and close to significance in the elderly group (P =.086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA-->CT group (P =.04, relative risk [RR] =.41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA-->CT group (P =.1, RR =.62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P =.0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P =.02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P =.01), and there was a trend for better survival in patients who received maintenance ATRA (P =.22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT. |
| Ferrari A, Casanova M, Bisogno G, Mattke A, Meazza C, Gronchi A, Cecchetto G, Fidani P, Kunz D, Treuner J, Carli M |
Hemangiopericytoma in pediatric ages. |
Cancer 2001, 92: 2692 |
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| Ferris Tortajada J, Garcia Castell J, Berbel Tornero O, Clar Gimeno S |
Risk factors for non-Hodgkin’s lymphomas. |
An Esp Pediatr 2001, 55: 230 |
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| Ferris Tortajada J, Garcia Castell J, Lopez Andreu JA, Clar Gimeno S, Berbel Tornero O |
Risk factors for Hodgkin's lymphomas. |
An Esp Pediatr 2001, 55: 239 |
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| Ferrari A, Bisogno G, Casanova M, Meazza C, Piva L, Cecchetto G, Zanetti I, Pilz T, Mattke A, Treuner J, Carli M |
Paratesticular rhabdomyosarcoma. |
J Clin Oncol 2002, 20: 449 |
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| Ferrari A, Casanova M, Bisogno G, Cecchetto G, Meazza C, Gandola L, Garaventa A, Mattke A, Treuner J, Carli M |
Malignant vascular tumors in children and adolescents. |
Med Pediatr Oncol 2002, 39: 109 |
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| Ferrari A, Casanova M, Bisogno G, Mattke A, Meazza C, Gandola L, Sotti G, Cecchetto G, Harms D, Koscielniak E, Treuner J, Carli M |
Clear cell sarcoma of tendons and aponeuroses in pediatric patients. |
Cancer 2002, 94: 3269 |
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| Ferrari A, Bisogno G, Casanova M, Brecht I, Alaggio R, Cecchetto G, Provenzi M, Koscielniak E, Treuner J, Carli M |
Is alveolar histotype a prognostic factor in paratesticular rhabdomyosarcoma? |
Pediatr Blood Cancer 2004, 42: 134 |
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| Ferrari A, Casanova M, Bisogno G, Carli M, Treuner J |
What chemotherapy should alveolar paratesticular rhabdomyosarcoma receive? |
Pediatr Blood Cancer 2004, 43: 295 |
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| Ferrari A, Brecht IB, Koscielniak E, Casanova M, Scagnellato A, Bisogno G, Alaggio R, Cecchetto G, Catania S, Meazza C, Int-Veen C, Kirsch S, Dantonello T, Carli M, Treuner J |
The role of adjuvant chemotherapy in children and adolescents with surgically resected, high-risk adult-type soft tissue sarcomas. |
Pediatric blood & cancer 2005, 45: 128 |
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| PURPOSE: This analysis evaluates whether adjuvant chemotherapy can be recommended for high-risk, surgically-resected, adult-type non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) within the new European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) protocol. The Italian and German Cooperative Groups reviewed their data-bases, analyzing patients classified as group I-II, with high-grade tumor (G3) larger than 5 cm in size. METHODS: The analysis included 36 patients, and compared the clinical features and outcome of the group of 21 patients who received chemotherapy versus the group of 15 patients treated with local therapies only. RESULTS: For the series as a whole, 5-year event-free survival (EFS), metastasis-free survival (MFS), and overall survival (OS) were 26.2%, 34.0%, and 37.5%, respectively. In patients treated with chemotherapy, MFS and OS were 49.5% and 41.5% (median time to relapse: 13 months). In patients who did not receive chemotherapy, MFS and OS were 0% and 23.8% (median time to relapse: 3 months). CONCLUSION: The role of adjuvant chemotherapy in NRSTS is still uncertain, however, the current retrospective analysis showed that: (1) despite the globally good prognosis of grossly-resected cases, patients with G3 and large-size have a high-risk of metastatic spread, and (2) MFS appears to be better in patients who had chemotherapy. Based in part on these results, and in accordance with recent suggestions coming from the literature on adult sarcomas, the EpSSG NRSTS protocol will recommend adjuvant chemotherapy in high-risk surgically-resected patients. |
| Ferrari A, Bisogno G, De Salvo GL, Indolfi P, Perilongo G, Cecchetto G, Italian Study on Rare Tumours in Paediatric Age (TREP),Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) |
The challenge of very rare tumours in childhood: the Italian TREP project. |
European journal of cancer 2007, 43: 654 |
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| A national cooperative project on rare paediatric tumours (the TREP project) was launched in 2000 in Italy, with a view to improving the clinical management and the basic research on these 'orphan' tumours, defined as those childhood solid malignancies characterised by an annual incidence <2/million and not considered in other clinical trials. This paper describes the process that the group developed and the problems it had to face, and aims to stimulate a debate on the rationale, scientific relevance and feasibility of running scientific research programs on rare childhood neoplasms. In the first phase of its activity, the project developed diagnostic and therapeutic recommendations for each rare tumour and established a collaborative network between 'experts' dedicated to each histotype and other specialists (i.e. adult oncologists, surgeons) involved in the management of these tumours. From 2000 to 2005, 297 patients have been registered from 35 Italian centres. This experience demonstrates the feasibility of a national multidisciplinary cooperation on rare paediatric malignancies and suggests that international studies could be realised. |
| Ferrari A, Schneider DT, Bisogno G, EXPeRT Board |
The founding of the European Cooperative Study Group on Pediatric Rare Tumors--EXPeRT. |
Expert review of anticancer therapy 2013, 13: 1 |
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| Lê PQ, Gulbis B, Dedeken L, Dupont S, Vanderfaeillie A, Heijmans C, Huybrechts S, Devalck C, Efira A, Dresse MF, Rozen L, Benghiat FS, Ferster A |
Survival among children and adults with sickle cell disease in Belgium: Benefit from hydroxyurea treatment. |
Pediatric blood & cancer 2015, 62: 1956 |
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| OBJECTIVE:
To evaluate the survival of patients with sickle cell disease (SCD) recorded in the Belgian SCD Registry and to assess the impact of disease-modifying treatments (DMT).
METHOD:
The Registry created in 2008 included patients of eight centers. All available data in 2008 were retrospectively encoded in the database. After 2008 and until 2012, all data were recorded prospectively for already registered patients as well as newly diagnosed subjects. Data were registered from neonatal screening or from diagnosis (first contact) until last follow-up or death. Data included diagnosis, demography, and outcome data.
RESULTS:
We collected data from 469 patients over a 5,110 patient years (PY) follow-up period. The global mortality rate was low (0.25/100 PY), although 13 patients died (2.8%) and was similar between children, adolescents (10-18 years), and young adults (P = 0.76). Out of the cohort, 185 patients received hydroxyurea at last follow-up (median duration of treatment: 10.3 years), 90 underwent hematopoietic stem cell transplantation (HSCT), 24 were chronically transfused, and 170 had never had any DMT. Hydroxyurea showed significant benefit on patients outcome as reflected by a lower mortality rate compared to transplanted individuals or people without DMT (0.14, 0.36, and 0.38 per 100 PY, respectively) and by higher Kaplan-Meier estimates of 15 year survival (99.4%) compared to HSCT (93.8%; P = 0.01) or no DMT groups (95.4%; P = 0.04).
CONCLUSION:
SCD mortality in Belgium is low with no increase observed in young adults. Patients treated with hydroxyurea demonstrate a significant benefit in survival when compared to those without DMT or transplanted. |
| Ferrua F, Marangoni F, Aiuti A, Roncarolo MG |
Gene therapy for Wiskott-Aldrich syndrome: History, new vectors, future directions. |
The Journal of allergy and clinical immunology 2020, 146: 262 |
|
| Ferrari A, Lopez Almaraz R, Reguerre Y, Cesen M, Bergamaschi L, Indini A, Schneider DT, Godzinski J, Bien E, Stachowicz-Stencel T, Eigentler TK, Chiaravalli S, Krawczyk MA, Pappo A, Orbach D, Bisogno G, Brecht IB |
Cutaneous melanoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations. |
Pediatric blood & cancer 2021, 68 Suppl 4:e28992 |
|
| Cutaneous melanoma is rare in children and, like other very rare pediatric tumors, it suffers from a shortage of knowledge and clinical expertise. The clinical management of pediatric melanoma is often challenging. Its clinical and pathological diagnosis may be difficult, and there is no standard treatment. In the absence of specific treatment guidelines, young patients are generally treated following the same principle as for adults, but concern remains about their access to clinical trials and new drugs, which have been shown to dramatically change the natural history of advanced melanoma. This paper presents the internationally recognized recommendations for the diagnosis and treatment of children and adolescents with cutaneous melanoma, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded project called PARTNER (Paediatric Rare Tumours Network - European Registry). Main recommendations for melanoma are to discuss pediatric patients in multidisciplinary teams that include both pediatric oncologists and specialists in adult melanoma; to enroll patients in prospective trials, if available; to collect data in national-international databases; and to develop an effective international collaboration between pediatric and adult melanoma groups in order to facilitate the transfer of potentially effective new agents from the adult to the pediatric setting. |
| Ferrari A, Brecht IB, Gatta G, Schneider DT, Orbach D, Cecchetto G, Godzinski J, Reguerre Y, Bien E, Stachowicz-Stencel T, Ost M, Magni C, Kearns P, Vassal G, Massimino M, Biondi A, Bisogno G, Trama A |
Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. |
European journal of cancer (Oxford, England : 1990) 2019, 110: 120 |
|
| Although all tumours are rare in childhood, there are some particularly rare paediatric cancers which have not benefited from advances made by the international paediatric oncology network. To establish a shared definition and produce a list of these entities, the European Union Joint Action on Rare Cancers (JARC) promoted a consensus effort. The definition was based on the incidence rates estimated using the information network on rare cancers (RARECAREnet) database, pooling data from 94 population-based cancer registries and 27 countries. The RARECAREnet list of cancers was used to estimate the incidence rates. This list groups cancers by combining the International Classification of Diseases for Oncology, third edition, morphology and topography codes. According to the consensus, very rare paediatric cancers were identified as those with an annual incidence <2/1000000 and corresponded to 11% of all cancers in patients aged 0-14 years. Two subgroups were identified: tumour types typical of childhood (i.e. hepatoblastoma, pleuropulmonary blastoma, pancreatoblastoma) and those typical of adult age (i.e. carcinomas, melanoma). The threshold of 2/1000000 could also be adopted in populations aged 0-19 years: in this case, three tumour types had an incidence rate which was >2/1000000 (i.e. thyroid and testicular cancers and skin melanoma), but the consensus experts considered them as 'very rare' according to their clinical needs (e.g. shortage of knowledge and clinical expertise as the other rare paediatric cancers). The JARC consensus produced a definition and a list of very rare paediatric cancers which may represent a starting point for prioritising research on these tumours, based on data and patients' clinical needs. |
| Ferrari A, Schneider DT, Bisogno G, Reguerre Y, Godzinski J, Bien E, Stachowicz-Stencel T, Cecchetto G, Brennan B, Roganovic J, Ben-Ami T, Virgone C, Farinha NR, Mancini S, Orbach D, Brecht IB |
Facing the challenges of very rare tumors of pediatric age: The European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) background, goals, and achievements. |
Pediatric blood & cancer 2021, 68 Suppl 4:e28993 |
|
| It has become increasingly clear in recent years that we need to develop ad hoc strategies to combat very rare tumors (VRT) of pediatric age. In 2008, several schemes being run in different countries were pooled together to create the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) project: a cooperative study group that aimed to promote research in the relatively uncharted territory of rare tumors of pediatric age. EXPeRT members were able to activate different levels of cooperation to achieve their goals, and to obtain dedicated funding by participating in EU-financed projects. Their experiences emphasize the merits of networking, seeking new partnerships, joining forces, and pooling resources to extend the reach of research efforts, and ultimately improve the quality of patient care. Between 2018 and 2021, the EXPeRT has been active in establishing the Pediatric Rare Tumors Network - European Registry (PARTNER). This project had the main purposes of building a European common registry of pediatric VRT, but also the major task of developing diagnostic and treatment guidelines for VRT (or at least part of them). These clinical recommendations are the subject of a series of papers on Pediatric Blood and Cancer. |
| Ferrari A, Orbach D, Sparber-Sauer M, Walterhouse DO, Pajtler KW, Meyer WH, Spunt SL, Weiss AR |
The treatment approach to pediatric non-rhabdomyosarcoma soft tissue sarcomas: a critical review from the INternational Soft Tissue SaRcoma ConsorTium. |
European journal of cancer 2022, 169: 10 |
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| The current article focuses on non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), the heterogeneous group of mesenchymal tumours different from rhabdomyosarcoma that may affect children and adolescents, with clinical behaviour varying from relatively benign to highly malignant. This review represents the effort of the international scientific paediatric community within the context of the INternational Soft Tissue SaRcoma ConsorTium (INSTRuCT), a project founded by the leadership of three large cooperative groups - Children's Oncology Group, Cooperative Weichteilsarkom Studiengruppe and European paediatric Soft tissue sarcoma Study Group - with the main goal to pool expertise and resources on a broader international level in order to improve knowledge of soft tissue sarcomas of children, adolescents and young adults. This article describes the current standard treatment approach in NRSTS, with a focus on the controversies and challenges in the management of these tumours. Developing research projects and clinical protocols for NRSTS has always been challenging, supporting the need to develop international integrated prospective dedicated programs, including paediatric NRSTS experts together with the adult sarcoma community. INSTRuCT provides a unique mechanism to increase international collaboration by agreeing on a common language, developing consensus standards to guide diagnosis and treatment, comparing clinical trial results across cooperative groups, and through a shared data dictionary providing answers to questions that can only be addressed by a larger data set. |
| Ferrari A, Spunt SL, Sparber-Sauer M, Walterhouse DO, Pajtler KW, Meyer WH, Orbach D, Weiss A |
Controversies and challenges in the management of paediatric non-rhabdomyosarcoma soft tissue sarcomas. |
The Lancet 2022, 6: 221 |
|
| Feuchtinger T |
Susceptibility to childhood leukemia. |
Blood 2011 118: 1189 |
|
| Fichtner I, Lemm M, Becker M, Berthold F |
Effects of amifostine (WR-2721, ethyol) on tumor growth and pharmacology of cytotoxic drugs in human xenotransplanted neuroblastomas. |
Anticancer Drugs 1997, 8: 174 |
|
| Fichtner I, Paal K, Borgmann A, Badiali L, Wurm R, Henze G |
Chemo- and radiation sensitivity of xenografted acute lymphoblastic leukemias--correlation to the expression of multidrug resistance proteins. |
Anticancer Res 2003, 23: 2657 |
|
| Filipovich AH, Mathur A, Kamat D, Shapiro RS |
Primary inmunodeficiencies: genetic risk factors for lymphoma. |
Cancer Res 1992, 52: 5465 |
|
| Filipovich AH |
Life-threatening hemophagocytic syndromes: current outcomes with hematopoietic stem cell transplantation. |
Pediatric transplantation 2005, 9 Suppl 7: 87 |
|
| Life-threatening hemophagocytic syndromes represent a subset of genetic disorders of inflammation. Many are rapidly lethal and can only be definitively treated at the present time with allogeneic hematopoietic stem cell transplantation (HSCT). In this report, current results with allogeneic transplantation for Hemophagocytic Lymphohistiocytosis (HLH) are described. HLH typically presents symptomatically during infancy and early childhood and can be identified by a constellation of numerous physical findings and laboratory tests indicative of overwhelming inflammation. The majority of patients with familial HLH lack natural killer (NK) cell function; in approximately 50% of cases the specific underlying genetic cause can now be discerned. Effective treatment consists of initial combination therapy with proapoptotic chemotherapy (typically etoposide) and anti-inflammatory therapies (principally steroids) in addition to aggressive supportive care, followed by allogeneic HSCT from the best available donor. Over the past 25 yr, through collaborative worldwide efforts, survival of children with HLH and related disorders has improved from 5% at 1 yr after diagnosis to greater than 50% 3-5 yr after diagnosis. |
| Finger PT, Czechonska G, Demirci H, Rausen A |
Chemotherapy for retinoblastoma: a current topic. |
Drugs 1999, 58: 983 |
|
| Retinoblastoma is the most common primary intraocular tumour in children, with an incidence of 1 in 15,000 live births. Treatment strategies for retinoblastoma have gradually evolved over the past few decades. There has been a trend away from enucleation (removal of the eye) and external beam radiation therapy toward focal 'conservative' treatments. Every effort has been made to save the child's life with preservation of eye and sight, if possible. Primary enucleation continues to be the commonly used method of treatment for retinoblastoma. It is employed in situations where eyes contain large tumours, long standing retinal detachments, neovascular glaucoma and suspicion of optic nerve invasion or extrascleral extension. Most of these eyes either have or are expected to have no useful vision. Radiation therapy continues to be an effective treatment option for retinoblastoma. However, external beam radiotherapy has unfortunately been associated with secondary non-ocular cancers in the field of radiation (primarily in children carrying the RB-1 germline mutation). Ophthalmic plaque brachytherapy has a more focal and shielded radiation field, and may carry less risk. Unfortunately, its applicability is limited to small to medium-sized retinoblastomas in accessible locations. Cryotherapy and transpupillary thermotherapy (TTT) have been used to provide control of selected small tumours. TTT is an advanced laser system adapted to the indirect ophthalmoscope which provides flexible nonsurgical treatment for small retinoblastomas. Recent research in the treatment of retinoblastoma has concentrated on methods of combining chemotherapy with other local treatment modalities (TTT, radiotherapy, cryotherapy). This approach combines the principle of chemotherapeutic debulking in paediatric oncology with conservative focal therapies in ophthalmology. Termed chemoreduction, intravenous or subconjunctival chemotherapy is used to debulk the initial tumour volume and allow for local treatment with TTT, cryotherapy and plaque radiotherapy. Cyclosporin has been added to the chemotherapy regimen in several centres. Other clinical settings where chemotherapy is considered are situations where the histopathology suggests a high risk for metastatic disease and where there is extraocular extension. There is no consensus that chemotherapy is needed when choroidal invasion is observed on histopathology. However, in patients where the retinoblastoma is noted beyond the cut end of the optic nerve or if there is disruption of the sclera with microscopic invasion of the orbital tissue, treatment has been helpful. Systemic and intrathecal chemotherapy with local and cranial radiotherapy has improved the survival of these patients. Most recently, the use of new chemotherapy modalities with haematopoietic stem cell rescue or local radiotherapy has increased the survival of patients with distant metastasis. Nevertheless, the prognosis of patients with central nervous system involvement is still poor. |
| Fine B, Stanulla M, Schrappe M, Ho M, Viehmann S, Harbott J, Boxer L |
Gene expression patterns associated with recurrent chromosomal translocations in acute lymphoblastic leukemia. |
Blood 2004, 103: 1043 |
|
| Fioredda F, Skokowa J, Tamary H, Spanoudakis M, Farruggia P, Almeida A, Guardo D, Höglund P, Newburger PE, Palmblad J, Touw IP, Zeidler C, Warren AJ, Dale DC, Welte K, Dufour C, Papadaki HA |
The European Guidelines on Diagnosis and Management of Neutropenia in Adults and Children: A Consensus Between the European Hematology Association and the EuNet-INNOCHRON COST Action. |
HemaSphere 2023, 7:e872 |
|
| Neutropenia, as an isolated blood cell deficiency, is a feature of a wide spectrum of acquired or congenital, benign or premalignant disorders with a predisposition to develop myelodysplastic neoplasms/acute myeloid leukemia that may arise at any age. In recent years, advances in diagnostic methodologies, particularly in the field of genomics, have revealed novel genes and mechanisms responsible for etiology and disease evolution and opened new perspectives for tailored treatment. Despite the research and diagnostic advances in the field, real world evidence, arising from international neutropenia patient registries and scientific networks, has shown that the diagnosis and management of neutropenic patients is mostly based on the physicians' experience and local practices. Therefore, experts participating in the European Network for the Innovative Diagnosis and Treatment of Chronic Neutropenias have collaborated under the auspices of the European Hematology Association to produce recommendations for the diagnosis and management of patients across the whole spectrum of chronic neutropenias. In the present article, we describe evidence- and consensus-based guidelines for the definition and classification, diagnosis, and follow-up of patients with chronic neutropenias including special entities such as pregnancy and the neonatal period. We particularly emphasize the importance of combining the clinical findings with classical and novel laboratory testing, and advanced germline and/or somatic mutational analyses, for the characterization, risk stratification, and monitoring of the entire spectrum of neutropenia patients. We believe that the wide clinical use of these practical recommendations will be particularly beneficial for patients, families, and treating physicians. |
| Fischer M, Berthold F |
Characterization of the gene expression profile of neuroblastoma cell line IMR-5 using serial analysis of gene expression. |
Cancer Lett 2003, 190: 79 |
|
| Fischer M, Skowron M, Berthold F |
Reliable transcript quantification by real-time reverse transcriptase-polymerase chain reaction in primary neuroblastoma using normalization to averaged expression levels of the control genes HPRT1 and SDHA. |
The Journal of molecular diagnostics 2005, 7: 89 |
|
| Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) represents a sensitive and efficient technique to determine expression levels of target genes in multiple samples and is increasingly used in clinical oncology to evaluate the patient's outcome or to detect minimal residual disease. Normalization of raw data are required to obtain comparable results between different specimens and is usually achieved by correlating transcript abundances of target genes with those of a single control gene with putatively stable expression levels. In this study, expression stability of six supposed control genes was evaluated in 64 samples of primary neuroblastoma and HPRT1 and SDHA mRNA levels were shown to exhibit the least expression variability among the samples. Because application of more than one control gene may enhance reliability of real-time RT-PCR results, various normalization factors consisting of the geometrical mean of multiple control gene expression values were calculated and evaluated by mRNA quantification of 14 target genes. Comparison with transcript levels determined by oligonucleotide-array expression analysis revealed that target gene mRNA quantification became most consistent after normalization to averaged expression levels of HPRT1 and SDHA. This normalization factor was in addition demonstrated to be not associated with stage of disease or MYCN amplification status of the tumor. Thus, these data indicate that the geometrical mean of HPRT1 and SDHA transcript levels represents a suitable internal control for biological and clinical studies investigating differential gene expression in primary neuroblastoma by real-time RT-PCR. |
| Fischer M, Oberthuer A, Brors B, Kahlert Y, Skowron M, Voth H, Warnat P, Ernestus K, Hero B, Berthold F |
Differential expression of neuronal genes defines subtypes of disseminated neuroblastoma with favorable and unfavorable outcome. |
Clinical cancer research : an official journal of the American Association for Cancer Research 2006, 12: 5118 |
|
| PURPOSE: Identification of molecular characteristics of spontaneously regressing stage IVS and progressing stage IV neuroblastoma to improve discrimination of patients with metastatic disease following favorable and unfavorable clinical courses. EXPERIMENTAL DESIGN: Serial analysis of gene expression profiles were generated from five stage IVS and three stage IV neuroblastoma. Differential expression of candidate genes was evaluated by real-time quantitative reverse transcription-PCR in 76 pretreatment tumor samples (stage IVS n=27 and stage IV n=49). Gene expression-based outcome prediction was determined by Prediction Analysis for Microarrays using 38 tumors as a training set and 38 tumors as a test set. RESULTS: Comparison of serial analysis of gene expression profiles from stage IV and IVS neuroblastoma revealed approximately 500 differentially expressed transcripts. Genes related to neuronal differentiation were observed more frequently in stage IVS tumors as determined by associating transcripts to Gene Ontology annotations. Forty-one candidate genes were evaluated by quantitative reverse transcription-PCR and 18 were confirmed to be differentially expressed (P |
| Fischer M, Spitz R, Oberthür A, Westermann F, Berthold F |
Risk estimation of neuroblastoma patients using molecular markers. |
Klinische Padiatrie 2008, 220: 137 |
|
| The pediatric tumor neuroblastoma is a heterogeneous disease: Patients' clinical courses can range from spontaneous regression to fatal progression of the disease. Accordingly, treatment protocols vary from |
| Fischer M, Bauer T, Oberthür A, Hero B, Theissen J, Ehrich M, Spitz R, Eils R, Westermann F, Brors B, König R, Berthold F |
Integrated genomic profiling identifies two distinct molecular subtypes with divergent outcome in neuroblastoma with loss of chromosome 11q. |
Oncogene 2010, 29: 865 |
|
| Imbalances in chromosome 11q occur in approximately 30% of primary neuroblastoma and are associated with poor outcome. It has been suggested that 11q loss constitutes a distinct clinico-genetic neuroblastoma subgroup by affecting expression levels of corresponding genes. This study analysed the relationship of 11q loss, clinical phenotype and global transcriptomic profiles in four clinico-genetic subgroups (11q alteration/favourable outcome, n=7; 11q alteration/unfavourable outcome, n=14; no 11q alteration/favourable outcome, n=81; no 11q alteration/unfavourable outcome, n=8; tumours with MYCN amplification and/or 1p loss were excluded). Unsupervised and supervised comparisons of gene expression profiles consistently showed significantly different mRNA patterns between favourable and unfavourable neuroblastomas, both in the subgroups with and without 11q loss. In contrast, favourable tumours with and without 11q loss showed highly similar transcriptomic profiles. Disproportionate downregulation of 11q genes was observed only in unfavourable tumours with 11q loss. The diverging molecular profiles were neither caused by considerable differences in the size of the deleted regions nor by differential methylation patterns of 11q genes. Together, this study shows that neuroblastoma with 11q loss comprises two biological subgroups that differ both in their clinical phenotype and gene expression patterns, indicating that 11q loss is not a primary determinant of neuroblastoma tumour behaviour. |
| Fischer M, Berthold F |
The role of complex genomic alterations in neuroblastoma risk estimation. |
Genome medicine 2010 May 19; 2: 31 |
|
| Specific genomic alterations, such as loss of the chromosomal region 11q or amplification of the oncogene MYCN, are well established markers of poor outcome in neuroblastoma. The advent of microarray-based comparative genomic hybridization (array-CGH) has enabled the analysis of pangenomic alteration profiles in the cancer genome, offering the possibility of identifying new prognostic markers from complex aberration patterns. Results from recent studies examining large primary neuroblastoma cohorts by array-CGH show that global genomic profiles may add significant prognostic information. Here, we discuss potential implications for risk estimation of neuroblastoma patients in clinical practice as well as for the understanding of neuroblastoma pathogenesis. |
| Fischer J, Pohl A, Volland R, Hero B, Dübbers M, Cernaianu G, Berthold F, von Schweinitz D, Simon T |
Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18Â months. |
BMC cancer 2017 Aug 4; 17: 520 |
|
| BACKGROUND: Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial.
METHODS: Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1-3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95-100%), gross total resection (90-95%), incomplete resection (50-90%), and biopsy (<50%) and correlated with local control rate and outcome. Patients were stratified according to the International Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test.
RESULTS: A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16.8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS.
CONCLUSIONS: In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification, extended surgery of the primary tumor site improved local control rate and survival with an acceptable risk of complications. |
| Fisher MJ, Jones DTW, Li Y, Guo X, Sonawane PS, Waanders AJ, Phillips JJ, Weiss WA, Resnick AC, Gosline S, Banerjee J, Guinney J, Gnekow A, Kandels D, Foreman NK, Korshunov A, Ryzhova M, Massimi L, Gururangan S, Kieran MW, Wang Z, Fouladi M, Sato M, Øra I, Holm S, Markham SJ, Beck P, Jäger N, Wittmann A, Sommerkamp AC, Sahm F, Pfister SM, Gutmann DH |
Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1). |
Acta neuropathologica 2021, 141: 605 |
|
| Low-grade gliomas (LGGs) are the most common childhood brain tumor in the general population and in individuals with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Surgical biopsy is rarely performed prior to treatment in the setting of NF1, resulting in a paucity of tumor genomic information. To define the molecular landscape of NF1-associated LGGs (NF1-LGG), we integrated clinical data, histological diagnoses, and multi-level genetic/genomic analyses on 70 individuals from 25 centers worldwide. Whereas, most tumors harbored bi-allelic NF1 inactivation as the only genetic abnormality, 11% had additional mutations. Moreover, tumors classified as non-pilocytic astrocytoma based on DNA methylation analysis were significantly more likely to harbor these additional mutations. The most common secondary alteration was FGFR1 mutation, which conferred an additional growth advantage in multiple complementary experimental murine Nf1 models. Taken together, this comprehensive characterization has important implications for the management of children with NF1-LGG, distinct from their sporadic counterparts. |
| Flaadt T, Ebinger M, Schreiber M, Ladenstein RL, Simon T, Lode HN, Hero B, Schuhmann MU, Schäfer J, Paulsen F, Timmermann B, Eggert A, Lang P |
Multimodal Therapy with Consolidating Haploidentical Stem Cell Transplantation and Dinutuximab Beta for Patients with High-Risk Neuroblastoma and Central Nervous System Relapse. |
Journal of clinical medicine 2023, 12 |
|
| Despite highly intensive multimodality treatment regimens, the prognosis of patients with high-risk neuroblastoma (HRNB) and central nervous system (CNS) relapse remains poor. We retrospectively reviewed data from 13 patients with HRNB and CNS relapse who received multimodal therapy with consolidating haploidentical stem cell transplantation (haplo-SCT) followed by dinutuximab beta ± subcutaneous interleukin-2 (scIL-2). Following individual relapse treatment, patients aged 1-21 years underwent haplo-SCT with T/B-cell-depleted grafts followed by dinutuximab beta 20 mg/m/day × 5 days for 5-6 cycles. If a response was demonstrated after cycle 5 or 6, patients received up to nine treatment cycles. After haplo-SCT, eight patients had a complete response, four had a partial response, and one had a stable disease. All 13 patients received ≥3 cycles of immunotherapy. At the end of the follow-up, 9/13 patients (66.7%) demonstrated complete response. As of July 2023, all nine patients remain disease-free, with a median follow-up time of 5.1 years since relapse. Estimated 5-year event-free and overall survival rates were 55.5% and 65.27%, respectively. Dinutuximab beta ± scIL-2 following haplo-SCT is a promising treatment option with a generally well-tolerated safety profile for patients with HRNB and CNS relapse. |
| Flentje M, Weirich A, Potter R, Ludwig R |
Hepatotoxicity in irradiated nephroblastoma patients during postoperative treatment according to SIOP9/GPOH. |
Radiother Oncol 1994, 31: 222 |
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| Flentje M, Weirich A, Graf N, Potter R, Zimmerman H, Ludwig R |
Abdominal irradiation in unilateral nephroblastoma and its impact on local control and survival. |
Int J Radiat Oncol Biol Phys 1998, 40: 163 |
|
| Fletcher O, Easton D, Anderson K, Gilham C, Jay M, Peto J |
Lifetime risks of common cancers among retinoblastoma survivors. |
Journal of the National Cancer Institute 2004, 96: 357 |
|
| BACKGROUND: Compared with the general population, carriers of germline mutations in RB1 who survive retinoblastoma (i.e., hereditary retinoblastoma survivors) are at increased risk of early-onset second cancers, particularly sarcomas, brain tumors, and melanoma. However, their risks for the epithelial cancers that commonly occur after age 50 years are not known. METHODS: We used hospital records to identify British retinoblastoma survivors born between 1873 and 1950, a period when few British retinoblastoma patients received high-dose radiotherapy. Cancers and deaths were identified by linkage with national registration records. All statistical tests were two-sided. RESULTS: We could trace the cancer histories of 144 survivors of hereditary retinoblastoma. From age 25 to age 84, there were 58 subsequent cancers, for a cumulative cancer incidence of 68.8% (95% confidence interval [CI] = 48.0% to 87.4%) and a cumulative cancer mortality of 56.3% (95% CI = 40.5% to 73.3%). Only eight of the 58 cancers were of bone or soft tissue, in marked contrast to findings from contemporary studies of American patients treated with external beam radiotherapy, among whom most second tumors are sarcomas. Compared with the general population, hereditary retinoblastoma survivors had higher mortality from lung cancer (standardized mortality ratio [SMR] = 7.01, 95% CI = 3.83 to 11.76), bladder cancer (SMR = 26.31, 95% CI = 8.54 to 61.41), and all other epithelial cancers combined (SMR = 3.29, 95% CI = 1.64 to 5.89). The overall standardized mortality ratio for epithelial cancer was inversely proportional to the approximate square of age (exponent of age = -2.1, 95% CI = -3.6 to -0.7), declining from 11.32 (95% CI = 4.15 to 24.64) at age 25-44 to 2.83 (95% CI = 1.04 to 6.16) at age 65-84. CONCLUSIONS: Survivors of hereditary retinoblastoma who are not exposed to high-dose radiotherapy have a high lifetime risk of developing a late-onset epithelial cancer. Most of the excess cancer risks in hereditary retinoblastoma survivors might be preventable by limiting exposures to DNA damaging agents (radiotherapy, tobacco, and UV light). |
| Fleischhack G, Rutkowski S, Pfister SM, Pietsch T, Tippelt S, Warmuth-Metz M, Bison B, van Velthoven-Wurster V, Messing-Jünger M, Kortmann RD, Timmermann B, Slavc I, Witt O, Gnekow A, Hernáiz Driever P, Kramm C, Benesch M, Frühwald MC, Hasselblatt M, Müller HL, Sörensen N, Kordes U, Calaminus G |
ZNS-Tumoren. |
in: Niemeyer C, Eggert A (Hrsg.): Pädiatrische Hämatologie und Onkologie. Springer-Verlag GmbH Deutschland, 2. vollständig überarbeitete Auflage 2018, 359 |
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| Fleischhack G, Massimino M, Warmuth-Metz M, Khuhlaeva E, Janssen G, Graf N, Rutkowski S, Beilken A, Schmid I, Biassoni V, Gorelishev SK, Kramm C, Reinhard H, Schlegel PG, Kortmann RD, Reuter D, Bach F, Iznaga-Escobar NE, Bode U |
Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG): a phase III clinical study. |
Journal of neuro-oncology 2019, 143: 107 |
|
| BACKGROUND:
Diffuse intrinsic pontine glioma (DIPG) is a devastating cancer of childhood and adolescence.
METHODS:
The study included patients between 3 and 20 years with clinically and radiologically confirmed DIPG. Primary endpoint was 6-month progression-free survival (PFS) following administration of nimotuzumab in combination with external beam radiotherapy (RT). Nimotuzumab was administered intravenously at 150 mg/m2 weekly for 12 weeks. Radiotherapy at total dose of 54 Gy was delivered between week 3 and week 9. Response was evaluated based on clinical features and MRI findings according to RECIST criteria at week 12. Thereafter, patients continued to receive nimotuzumab every alternate week until disease progression/unmanageable toxicity. Adverse events (AE) were evaluated according to Common Terminology Criteria for Adverse Events (CTC-AE) Version 3.0 (CTC-AE3).
RESULTS:
All 42 patients received at least one dose of nimotuzumab in outpatient settings. Two patients had partial response (4.8%), 27 had stable disease (64.3%), 10 had progressive disease (23.8%) and 3 patients (7.1%) could not be evaluated. The objective response rate (ORR) was 4.8%. Median PFS was 5.8 months and median overall survival (OS) was 9.4 months. Most common drug-related AEs were alopecia (14.3%), vomiting, headache and radiation skin injury (7.1% each). Therapy-related serious adverse events (SAEs) were intra-tumoral bleeding and acute respiratory failure, which were difficult to distinguish from effects of tumor progression.
CONCLUSIONS:
Concomitant treatment with RT and nimotuzumab was feasible in an outpatient setting. The PFS and OS were comparable to results achieved with RT and intensive chemotherapy in hospitalized setting. |
| Flotho C, Valcamonica S, Mach-Pascual S, Schmahl G, Corral L, Ritterbach J, Hasle H, Arico M, Biondi A, Niemeyer C |
RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). |
Leukemia 1999, 13: 32 |
|
| Flower KB, Hoppin JA, Lynch CF, Blair A, Knott C, Shore DL, Sandler DP |
Cancer risk and parental pesticide application in children of Agricultural Health Study participants. |
Environ Health Perspect 2004, 112: 631 |
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| Flohr T, Schrauder A, Cazzaniga G, Panzer-Grümayer R, van der Velden V, Fischer S, Stanulla M, Basso G, Niggli FK, Schäfer BW, Sutton R, Koehler R, Zimmermann M, Valsecchi MG, Gadner H, Masera G, Schrappe M, van Dongen JJ, Biondi A, Bartram CR, International BFM Study Group (I-BFM-SG) |
Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia. |
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 2008, 22: 771 |
|
| Detection of minimal residual disease (MRD) is the most sensitive method to evaluate treatment response and one of the strongest predictors of outcome in childhood acute lymphoblastic leukemia (ALL). The 10-year update on the I-BFM-SG MRD study 91 demonstrates stable results (event-free survival), that is, standard risk group (MRD-SR) 93%, intermediate risk group (MRD-IR) 74%, and high risk group (MRD-HR) 16%. In multicenter trial AIEOP-BFM ALL 2000, patients were stratified by MRD detection using quantitative PCR after induction (TP1) and consolidation treatment (TP2). From 1 July 2000 to 31 October 2004, PCR target identification was performed in 3341 patients: 2365 (71%) patients had two or more sensitive targets (< or =10(-4)), 671 (20%) patients revealed only one sensitive target, 217 (6%) patients had targets with lower sensitivity, and 88 (3%) patients had no targets. MRD-based risk group assignment was feasible in 2594 (78%) patients: 40% were classified as MRD-SR (two sensitive targets, MRD negativity at both time points), 8% as MRD-HR (MRD > or =10(-3) at TP2), and 52% as MRD-IR. The remaining 823 patients were stratified according to clinical risk features: HR (n=108) and IR (n=715). In conclusion, MRD-PCR-based stratification using stringent criteria is feasible in almost 80% of patients in an international multicenter trial. |
| Flotho C, Vraetz T, Lang P, Niemeyer CM, Strahm B |
Successful double umbilical cord blood transplantation for relapsed juvenile myelomonocytic leukemia. |
Leukemia 2013, 27: 988 |
|
| Fluss J, Dinomais M, Kossorotoff M, Vuillerot C, Darteyre S, Chabrier S |
Perspectives in neonatal and childhood arterial ischemic stroke. |
Expert review of neurotherapeutics 2017, 17: 135 |
|
| Foell JL, Max D, Giersberg C, Körholz D, Staege MS |
Sensitivity of Hodgkin's lymphoma cell lines to the cell cycle inhibitor roscovitine. |
Anticancer research 2008, 28: 887 |
|
| BACKGROUND: The prognosis of patients with Hodgkin's lymphoma (HL) has improved in recent decades. However, not all patients can be cured and the development of alternative treatment strategies is necessary. MATERIALS AND METHODS: Gene expression in HL cell lines was analyzed using DNA microarrays and both conventional and quantitative reverse transcriptase-polymerase chain reaction. Sensitivity of HL cell lines to the cell cycle inhibitor roscovitine was assessed in vitro. RESULTS: All HL cell lines express high levels of cyclin D2. Treatment of HL cells with roscovitine induced cell death in some cell lines whereas other cell lines were resistant to roscovitine. Roscovitine-sensitive cell lines were characterized by expression of T-cell markers and expressed high levels of the unusual cytokine interleukin-26. CONCLUSION: Roscovitine is a cytotoxic drug for a subpopulation of HL cells and might be an interesting agent for the treatment of patients with HL. |
| Foell J, Pfirstinger B, Rehe K, Wolff D, Holler E, Corbacioglu S |
Haploidentical stem cell transplantation with CD3+-/CD19+- depleted peripheral stem cells for patients with advanced stage sickle cell disease and no alternative donor: results of a pilot study. |
Bone marrow transplantation 2017, 52: 938 |
|
| Foulon S, Brennan B, Gaspar N, Dirksen U, Jeys L, Cassoni A, Claude L, Seddon B, Marec-Berard P, Whelan J, Paulussen M, Streitbuerger A, Oberlin O, Jürgens H, Grimer R, Le Deley MC |
Can postoperative radiotherapy be omitted in localised standard-risk Ewing sarcoma? An observational study of the Euro-E. W.I. N.G group. |
European journal of cancer 2016, 61: 128 |
|
| The role of postoperative radiotherapy (PORT) in Ewing sarcoma (ES) is unclear. We assessed the impact of PORTÂ on local control in patients with localised ES and good histological response to chemotherapy (<10% cells). |
| Franzius C, Bielack S, Sciuk J, Vollet B, Jürgens H, Schober O |
High-activity samarium-153-EDTMP therapy in unresectable osteosarcoma. |
Nuklearmedizin 1999, 38: 337 |
|
| Franzius C, Sciuk J, Brinkschmidt C, Jürgens H, Schober O |
Evaluation of chemotherapy response in primary bone tumors with F-18 FDG positron emission tomography compared with histologically assessed tumor necrosis. |
Clinical Nuclear Medicine 2000, 25: 874 |
|
| Franzius C, Sciuk J, Daldrup-Link H, Jürgens H, Schober O |
FDG-PET for detection of osseous metastases from malignant primary bone tumors. |
Eur J Nucl Med 2000, 27: 1305 |
|
| Franzius C, Daldrup-Link H, Sciuk J, Rummeny E, Bielack S, Jürgens H, Schober O |
FDG-PET for detection of pulmonary metastases from malignant primary bone tumors. |
Ann Oncol 2001, 12: 479 |
|
| Franzius C, Schulte M, Hillmann A, Winkelmann W, Jürgens H, Bockisch A, Schober O |
Klinische Wertigkeit der Positronenemissionstomographie (PET) in der Diagnostik der Knochen- und Weichteiltumore. |
Chirurg 2001, 72: 1071 |
|
| Franzius C, Bielack S, Flege S, Sciuk J, Jürgens H, Schober O |
Prognostic significance of (18)F-FDG and (99m)Tc-methylene diphosphonate uptake in primary osteosarcoma. |
J Nucl Med 2002, 43: 1012 |
|
| Franzius C, Daldrup-Link H, Wagner-Bohn A, Sciuk J, Heindel W, Jürgens H, Schober O |
FDG-PET for detection of recurrences from malignant primary bone tumors. |
Ann Oncol 2002, 13: 157 |
|
| Franzius C, Schuck A, Bielack S |
High-dose samarium-153 ethylene diamine tetramethylene phosphonate. |
J Clin Oncol 2002, 20: 1953 |
|
| Franzius C, Hotfilder M, Poremba C, Hermann S, Schafers K, Gabbert HE, Jürgens H, Schober O, Schafers M, Vormoor J |
Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model. |
European journal of nuclear medicine and molecular imaging 2006, 33: 1432 |
|
| PURPOSE: As primary osseous metastasis is the main adverse prognostic factor in patients with Ewing tumours, a NOD/scid mouse model for human Ewing tumour metastases has been established to examine the mechanisms of metastasis. The aim of this study was to evaluate the feasibility of diagnostic molecular imaging by small animal PET in this mouse model. METHODS: Human Ewing tumour cells were transplanted into immune-deficient NOD/scid mice via s.c injection (n=17) or i.v. injection (n=17). The animals (mean weight 23.2 g) were studied 2-7 weeks after transplantation using a submillimetre resolution animal PET scanner. To assess glucose utilisation and bone metabolism, mice were scanned after intravenous injection of 9.6 MBq (mean) 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) or 9.4 MBq (mean) [(18)F]fluoride. Whole-body PET images were analysed visually and semi-quantitatively [%ID/g, tumour to non-tumour ratio (T/NT)]. Foci of pathological uptake were identified with respect to the physiological organ uptake in corresponding regions. RESULTS: Subcutaneously transplanted Ewing tumours demonstrated a moderately increased glucose uptake (median %ID/g 2.5; median T/NT 2.2). After i.v. transplantation, the pattern of metastasis was similar to that in patients with metastases in lung, bone and soft tissue. These metastases showed an increased FDG uptake (median %ID/g 3.6; median T/NT 2.7). Osseous metastases were additionally visible on [(18)F]fluoride PET by virtue of decreased [(18)F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT 0.59). Metastases were confirmed immunohistologically. CONCLUSION: Diagnostic molecular imaging of Ewing tumours and their small metastases in an in vivo NOD/scid mouse model is feasible using a submillimetre resolution PET scanner. |
| Franzius C, Juergens KU, Vormoor J |
PET/CT with diagnostic CT in the evaluation of childhood sarcoma. |
AJR. American journal of roentgenology 2006, 186: 581; author reply 581 |
|
| Franke M, Hardes J, Helmke K, Jundt G, Jürgens H, Kempf-Bielack B, Kevric M, Tunn PU, Werner M, Bielack S |
Solitary skeletal osteosarcoma recurrence. Findings from the Cooperative Osteosarcoma Study Group. |
Pediatr Blood Cancer 2011, 56: 771 |
|
| BACKGROUND: Solitary skeletal osteosarcoma (OS) manifestations distant from the site of the primary tumor rarely arise as only sign of disease recurrence.
METHODS: This report reviews 38 patients with high-grade central OS of the limbs or axial skeleton and initial complete surgical remission (CR) who developed first recurrences as solitary osseous lesions distant from the primary tumor. The Cooperative Osteosarcoma Study Group (COSS) database was used to evaluate patient-, tumor-, and treatment-related variables and outcomes.
RESULTS: Thirty-eight patients (27 males and 11 females; 36 limb and 2 axial primaries) developed solitary osseous recurrences a median of 2.1 years (range: 0.5-14.3) from primary diagnosis. Relapses involved axial (24), extremity (10), or craniofacial bones (4). Treatment for recurrence included surgery (28), radiotherapy (10), and chemotherapy (27). After a median follow-up of 1.9 years (range: 0.1-21.2) from first recurrence for all 38 patients and 5.5 years (0.3-21.2) for 16 survivors (10 in continuous second CR), 2- and 5-year overall and event-free survival (EFS) probabilities were 55% and 34% and 34% and 27%, respectively. A long interval to recurrence (>1.5 years) predicted for better overall (P < 0.001) and EFS (P = 0.005). For 21 patients achieving a second CR, 2- and 5-year overall and EFS probabilities were 81% and 61% and 52% and 49%, respectively, while only 1/17 others survived beyond 5 years (P < 0.001). Survivors (14/16) had also received second-line chemotherapy.
CONCLUSION: First solitary skeletal recurrences of OS should be treated with curative intent. Some presumed bone metastases may represent second primary OSs. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc. |
| Franke M, Hardes J, Helmke K, Jundt G, Jürgens H, Kempf-Bielack B, Kevric M, Tunn PU, Werner M, Bielack S |
Solitary skeletal osteosarcoma recurrence. Findings from the Cooperative Osteosarcoma Study Group. |
Pediatric blood & cancer 2011, 56: 771 |
|
| Solitary skeletal osteosarcoma (OS) manifestations distant from the site of the primary tumor rarely arise as only sign of disease recurrence. |
| Frank JA, Ranft A, Paulussen M, Jürgens H, Kruseova J, Bauer S, Niggli F, Reichardt P, Dirksen U |
Results for patients with sarcoma not otherwise specified and other diagnoses than Ewing sarcoma treated according to the Euro-EWING 99 trial. |
Pediatric blood & cancer 2017, 64 |
|
| Euro-EWING 99 trial of the European Ewing tumor Working Initiative of National Groups (EE99) was an international phase III study in patients with Ewing sarcoma. The German Society of Pediatric Oncology and Hematology (GPOH) data center registered and followed patients with other diagnoses than Ewing sarcoma who were treated according to the EE99 protocol in an additional non-Ewing database. |
| Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, Foell J, de la Fuente J, Grupp S, Handgretinger R, Ho TW, Kattamis A, Kernytsky A, Lekstrom-Himes J, Li AM, Locatelli F, Mapara MY, de Montalembert M, Rondelli D, Sharma A, Sheth S, Soni S, Steinberg MH, Wall D, Yen A, Corbacioglu S |
CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. |
The New England journal of medicine 2021 Jan 21; 384: 252 |
|
| Freidank C |
Wegweiser für zu Hause. |
Leitung der bundesweiten Arbeitsgruppe pädiatrisch-onkologischer Kinderkrankenschwestern und Kinderkrankenpfleger (GPONG: German Pediatric Oncology Nurses Group) 2002 |
|
| Friedman JM, Birch PH |
Type 1 neurofibromatosis: a descriptive analysis of the disorder in 1,728 patients. |
Am J Med Genet 1997, 70: 138 |
|
| Friesen C, Fulda S, Debatin K |
Induction of CD95 ligand and apoptosis by doxorubicin is modulated by the redox state in chemosensitive- and drug-resistant tumor cells. |
Cell Death Differ 1999, 6: 471 |
|
| Friedrich C, von Bueren AO, von Hoff K, Gerber NU, Ottensmeier H, Deinlein F, Benesch M, Kwiecien R, Pietsch T, Warmuth-Metz M, Faldum A, Kuehl J, Kortmann RD, Rutkowski S |
Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy. |
Neuro-oncology 2013, 15: 224 |
|
| Especially in young children, primitive neuroectodermal tumors of the central nervous system (CNS-PNET) and pineoblastomas are associated with an unfavorable outcome, and only a few prospective trials have been conducted thus far. |
| Friedrich C, Warmuth-Metz M, von Bueren AO, Nowak J, Bison B, von Hoff K, Pietsch T, Kortmann RD, Rutkowski S |
Primitive neuroectodermal tumors of the brainstem in children treated according to the HIT trials: clinical findings of a rare disease. |
Journal of neurosurgery. Pediatrics 2015, 1 |
|
| OBJECT Primitive neuroectodermal tumors of the central nervous system (CNS-PNET) arising in the brainstem are extremely rare, and knowledge about them is limited. The few existing case series report fatal outcomes. The purpose of this study was to analyze clinical characteristics of and outcome for brainstem CNS-PNET patients treated according to the consecutive, population-based HIT studies covering a 19-year time period. METHODS Between September 1992 and November 2011, 6 eligible children with histologically proven brainstem CNS-PNET not otherwise specified and 2 children with brainstem ependymoblastomas (3, partial resection; 3, subtotal resection; 2, biopsy), median age 3.3 years (range 1.2-10.6 years), were treated according to consecutive multimodal HIT protocols for CNS-PNET/medulloblastoma. Postoperative treatment was according to maintenance chemotherapy protocols (3, craniospinal irradiation [CSI] followed by maintenance chemotherapy), sandwich chemotherapy protocols (2, neoadjuvant chemotherapy, CSI, maintenance chemotherapy), or a therapy protocol for children younger than 4 years (3, postoperative chemotherapy followed by CSI). RESULTS The median duration of prediagnostic symptoms, predominantly cranial nerve deficits (n = 7), pyramidal tract signs (n = 5), or ataxia (n = 5), was 5 weeks (range 1-13 weeks). The tumors were all located in the pons. Most involved more than half of the pontine axial diameter and were sharply marginated. All patients had postoperative residual disease, including metastasis in 1 case. With 1 exception all tumors progressed early during treatment within 3.9 months (range 2.5-10.4 months), leading to a 1-year event-free survival rate (± standard error) of 13% ± 12%. After progression, patients succumbed early to their disease resulting in a 1-year overall survival rate of 25% ± 15%. The only surviving patient had a partially resected CNS-PNET, received a sandwich chemotherapy protocol, and is without disease progression 14 months after diagnosis. CONCLUSIONS CNS-PNET is a rare but important differential diagnosis in childhood brainstem tumors. So far, efficient therapies are lacking. The sampling of tumor material for improved biological understanding and identification of new therapeutic targets is important. |
| Frisch S, Christiaens M, Guntrum F, Bauer S, Blase C, Fleischhack G, Bäumer C, Geismar D, Timmermann B |
EP-1404: Early results of proton beam therapy in sarcomas at the West German Proton Therapy Center Essen. |
Radiother Oncol 2016, 119: 654 |
|
| Friedrich C, Shalaby T, Oehler C, Pruschy M, Seifert B, Picard D, Remke M, Warmuth-Metz M, Kortmann RD, Rutkowski S, Grotzer MA, von Bueren AO |
Tropomyosin receptor kinase C (TrkC) expression in medulloblastoma: relation to the molecular subgroups and impact on treatment response. |
Child's nervous system 2017, 33: 1463 |
|
| Friesenbichler W, Lüftinger R, Kropshofer G, Henkel M, Amann G, Furtwängler R, Graf N, Kager L |
Clear cell sarcoma of the kidney in Austrian children: Long-term survival after relapse. |
Pediatric blood & cancer 2021, 68:e28860 |
|
| 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. |
| Frömmel C, Brose A, Klein J, Blankenstein O, Lobitz S |
Newborn screening for sickle cell disease: technical and legal aspects of a German pilot study with 38,220 participants. |
BioMed research international 2014, 2014, 695828 |
|
| Sickle cell disease (SCD) does not occur in the indigenous German population, but with the increasing number of immigrants from countries at high risk for hemoglobinopathies, the question emerges whether or not a newborn screening program (NBS) for SCD disease should be initiated in Germany anyhow. We have recently shown that in Berlin, a city with a very large immigrant population, the incidence of SCD is considerable, but our findings are insufficient to make a decision for the country as a whole. In this paper we will show that a large body of epidemiological data can be generated in a relatively short period of time, with a very high degree of precision and at relatively little expense--a result that might motivate other working groups to start such a pilot project locally. We examined previously collected dried blood cards that were up to six months old, using high performance liquid chromatography (HPLC) as first method and capillary electrophoresis (CE) as second method. A single, part-time laboratory technician processed 38,220 samples in a period of 162 working days. The total costs per sample including all incidentals (as well as labor costs) were EUR 1.44. |
| Frühwald MC, Graf N |
Rhabdoide Tumoren im Kindesalter - Einheitliches Konzept für die Behandlung von Tumoren des Gehirns, der Nieren und des Weichgewebes. |
WIR - Informationsschrift der Aktion für krebskranke Kinder e.V. des Dachverbandes Deutsche Leukämie-Forschungshilfe 4/2006 |
|
| Frühwald MC, Krefeld B, Benesch M, Büchner J, Boos J, Ebetsberger G, Graf N, Kortmann R, Nysom K, Rutkowski S, Schneppenheim R, Siebert R, Timmermann B, Warmuth-Matz M, Hasselblatt M |
The European Rhabdoid Registry (EU-RHAB) – A comprehensive approach towards biology and clinical management. |
Neurooncology 2010, 12:ii36 |
|
| Rhabdoid tumors mainly affect very young children; below 6 months of age they may be the most common intracranial malignancies. In 2007 we initiated the European Rhabdoid Registry (EU-RHAB) in cooperation with the SIOP subcommittee on brain tumors to increase our knowledge of rhabdoid tumors and to ultimately improve outcome. EU-RHAB has collected data on epidemiology, molecular genetics, pathology and treatment of
35 patients with atypical teratoid rhabdoid tumors (AT/RT). Median age at diagnosis was 22 months. All cases were confirmed by reference histopathology (in general by INI1 staining). Only one case showed no INI1-loss. Molecular genetic analyses of SMARCB1/hSNF5/INI1 were performed in 24 cases (germ line mutations n¼ 3). In only 11 of 29 patients initial pathology revealed the correct diagnosis. 2/35 received
no therapy, 32 were treated according to a consensus therapy. Follow-up is short (0 to 29 months). Patients treated according to the consensus demonstrate a 1-year-OS of 71.4%. 11 received some form of radiotherapy, all of these are alive. 10 patients are free of disease .12 months. The median age at diagnosis of the 9 patients who died within
0.5–12 months was 9 months. Patients with a germ line mutation and those who did not receive any therapy were among these. CONCLUSION: We present first data from the European Rhabdoid Registry (EU-RHAB). The prospective registration of children with rhabdoid tumors is a prerequisite for the development of innovative strategies
that will then be implemented into phase I/II clinical trials. Supported by
Horizont/Weseke and the Deutsche Kinderkrebsstiftung |
| Frühwald MC, Rutkowski S |
ZNS-Tumoren bei Kindern und Jugendlichen. |
Dtsch Arztebl Int 2011; 108: 390 |
|
| Frühwald MC, Biegel JA, Bourdeaut F, Roberts CW, Chi SN |
Atypical teratoid/rhabdoid tumors-current concepts, advances in biology, and potential future therapies. |
Neuro-oncology 2016, 18: 764 |
|
| Atypical teratoid/rhabdoid tumor (AT/RT) is the most common malignant CNS tumor of children below 6 months of age. The majority of AT/RTs demonstrate genomic alterations in SMARCB1 (INI1, SNF5, BAF47) or, to a lesser extent, SMARCA4 (BRG1) of the SWItch/sucrose nonfermentable chromatin remodeling complex. Recent transcription and methylation profiling studies suggest the existence of molecular subgroups. Thus, at the root of these seemingly enigmatic tumors lies a network of factors related to epigenetic regulation, which is not yet completely understood. While conventional-type chemotherapy may have significant survival benefit for certain patients, it remains to be determined which patients will eventually prove resistant to chemotherapy and thus need novel therapeutic strategies. Elucidation of the molecular consequences of a disturbed epigenome has led to the identification of a series of transduction cascades, which may be targeted for therapy. Among these are the pathways of cyclin D1/cyclin-dependent kinases 4 and 6, Hedgehog/GLI1, Wnt/ÃÂ-catenin, enhancer of zeste homolog 2, and aurora kinase A, among others. Compounds specifically targeting these pathways or agents that alter the epigenetic state of the cell are currently being evaluated in preclinical settings and in experimental clinical trials for AT/RT. |
| Frühwald MC, Hasselblatt M |
Rhabdoide Tumoren des ZNS, der Nieren und des Weichteilgewebes. |
in: Niemeyer C, Eggert A (Hrsg.): Pädiatrische Hämatologie und Onkologie, Springer-Verlag GmbH Deutschland 2. vollständig überarbeitete Auflage 2018, 402 |
|
| Frühwald MC, Furtwängler R |
Das Europäische Rhabdoidregister – Basis für klinischen Fortschritt in der Behandlung einer sehr seltenen Tumorerkrankung. |
WIR - die Zeitschrift der Deutschen Leukämie-Forschungshilfe e.V. und der Deutschen Kinderkrebsstiftung 2018, 2/18 |
|
| Frühwald MC, Hasselblatt M, Nemes K, Bens S, Steinbügl M, Johann PD, Kerl K, Hauser P, Quiroga E, Solano-Paez P, Biassoni V, Gil-da-Costa MJ, Perek-Polnik M, van de Wetering M, Sumerauer D, Pears J, Stabell N, Holm S, Hengartner H, Gerber NU, Grotzer M, Boos J, Ebinger M, Tippelt S, Paulus W, Furtwängler R, Hernáiz-Driever P, Reinhard H, Rutkowski S, Schlegel PG, Schmid I, Kortmann RD, Timmermann B, Warmuth-Metz M, Kordes U, Gerss J, Nysom K, Schneppenheim R, Siebert R, Kool M, Graf N |
Age and DNA-methylation subgroup as potential independent risk factors for treatment stratification in children with Atypical Teratoid/Rhabdoid Tumors (ATRT). |
Neuro-oncology 2020, |
|
| Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with Atypical Teratoid Rhabdoid Tumors (ATRT). The European Rhabdoid Registry, EU-RHAB, recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. |
| Frühwald MC, Nemes K, Boztug H, Cornips MCA, Evans DG, Farah R, Glentis S, Jorgensen M, Katsibardi K, Hirsch S, Jahnukainen K, Kventsel I, Kerl K, Kratz CP, Pajtler KW, Kordes U, Ridola V, Stutz E, Bourdeaut F |
Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group. |
Familial cancer 2021,online ahead of print |
|
| The rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future. |
| Frühwald MC et al. |
S1-Leitlinie „Atypische Teratoide / Rhabdoide Tumoren“ der Gesellschaft für Pädiatrische Onkologie und Hämatologie. |
Registernummer 025-037 AWMF online 2024 |
|
| Fröhlich B, Hotzinger H, Fritsch H |
Tomographical anatomy of the pelvis, pelvic floor, and related structures. |
Clin Anat 1997, 10: 223 |
|
| Fröhlich B, Ahrens S, Burdach S, Klingebiel T, Ladenstein R, Paulussen M, Zoubek A, Jürgens H |
High-dosage chemotherapy in primary metastasized and relapsed Ewing's sarcoma. (EI)CESS. |
Klin Pädiatr 1999, 211: 284 |
|
| Fuchs N, Winkler K |
Osteosarcoma. |
Curr Opin Oncol 1993, 5: 667 |
|
| Fuchs J, Wenderoth M, von Schweinitz D, Haindl J, Leuschner I |
Comparative activity of cisplatin, ifosfamide, doxorubicin, carboplatin, and etoposide in heterotransplanted hepatoblastoma. |
Cancer 1998, 83: 2400 |
|
| Fuchs N, Bielack S, Epler D, Bieling P, Delling G, Körholz D, Graf N, Heise U, Jürgens H, Kotz R, Salzer-Kuntschik M, Weinel P, Werner M, Winkler K |
Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group's protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. |
Ann Oncol 1998, 9: 893 |
|
| Fuchs J, Bode U, von Schweinitz D, Weinel P, Erttmann R, Harms D, Mildenberger H |
Analysis of treatment efficiency of carboplatin and etoposide in combination with radical surgery in advanced and recurrent childhood hepatoblastoma. |
Klin Pädiatr 1999, 211: 305 |
|
| Fuchs J, Rydzynski J, von Schweinitz D, Bode U, Hecker H, Weinel P, Burger D, Harms D, Erttmann R, Oldhafer K, Mildenberger H |
Pretreatment prognostic factors and treatment results in children with hepatoblastoma. |
Cancer 2002, 95: 172 |
|
| Fuchs S, Danßmann C, Klironomos F, Winkler A, Fallmann J, Kruetzfeldt LM, Szymansky A, Naderi J, Bernhart SH, Grunewald L, Helmsauer K, Rodriguez-Fos E, Kirchner M, Mertins P, Astrahantseff K, Suenkel C, Toedling J, Meggetto F, Remke M, Stadler PF, Hundsdoerfer P, Deubzer HE, Künkele A, Lang P, Fuchs J, Henssen AG, Eggert A, Rajewsky N, Hertwig F, Schulte JH |
Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN. |
Nature communications 2023, 14: 3936 |
|
| Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis. |
| de la Fuente J, Baruchel A, Biondi A, de Bont E, Dresse MF, Suttorp M, Millot F, International BFM Group (iBFM) Study Group Chronic Myeloid Leukaemia Committee |
Managing children with chronic myeloid leukaemia (CML): recommendations for the management of CML in children and young people up to the age of 18 years. |
British journal of haematology 2014, 167: 33 |
|
| Chronic myeloid leukaemia in children and young people is a relatively rare form of leukaemia that shows increased incidence with age and some evidence suggests that the molecular basis differs from that in adults. Significant advances in targeted therapy with the development and use in children of tyrosine kinase inhibitors and the ability to monitor and understand the prognostic significance of minimal residual disease by standardized molecular techniques has shifted the management of this condition from bone marrow transplantation as the main therapeutic modality to individualized treatment for each patient based on achieving specific milestones. The physiological changes occurring during childhood, particularly those affecting growth and development and the long-term use of treatment, pose specific challenges in this age group, which we are only beginning to understand. |
| Fulda S, Honer M, Menke-Moellers I, Berthold F |
Antiproliferative potential of cytostatic drugs on neuroblastoma cells in vitro. |
Eur J Cancer 1995, 31A: 616 |
|
| Fulda S, Susin S, Kroemer G, Debatin K |
Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells. |
Cancer Res 1998, 58: 4453 |
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| Fulda S, Jeremias I, Pietsch T, Debatin K |
Betulinic acid. |
Klin Pädiatr 1999, 211: 319 |
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| Fulda S, Jeremias I, Steiner H, Pietsch T, Debatin K |
Betulinic acid. |
Int J Cancer 1999, 82: 435 |
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| Fulda S, Lutz W, Schwab M, Debatin K |
MycN sensitizes neuroblastoma cells for drug-induced apoptosis. |
Oncogene 1999, 18: 1479 |
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| Fulda S, Meyer E, Debatin K |
Metabolic inhibitors sensitize for CD95 (APO-1/Fas)-induced apoptosis by down-regulating Fas-associated death domain-like interleukin 1-converting enzyme inhibitory protein expression. |
Cancer Res 2000, 60: 3947 |
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| Fulda S, Debatin KM |
Molekular zielgerichtete Therapien. |
In: Niemeyer C, Eggert A. ed. Pädiatrische Hämatologie und Onkologie Springer; 2018, 187 |
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| Furlan I, Batz C, Flotho C, Mohr B, Lübbert M, Suttorp M, Niemeyer CM |
Intriguing response to azacitidine in a patient with juvenile myelomonocytic leukemia and monosomy 7. |
Blood 2009, 113: 2867 |
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| Furtwängler R, Nourkami N, Alkassar M, von Schweinitz D, Schenk JP, Rübe C, Siemer S, Leuschner I, Graf N |
Update on relapses in unilateral nephroblastoma registered in 3 consecutive SIOP/GPOH studies - a report from the GPOH-nephroblastoma study group. |
Klin padiatr 2011, 223: 113 |
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| INTRODUCTION:
Treatment and stratification of progressive/relapsed unilateral nephroblastoma (PD) has significantly evolved over the last 20 years. Early PD (≤ 6 months), initial high risk histology, local stage III, multiple site PD and stage IV have been implemented as high risk classification factors and novel drugs have been introduced.
PATIENTS AND METHODS:
We analysed all 251 patients having had a unilateral nephroblastoma (Stage I-IV) and progressive disease who had been treated according to SIOP9/GPO (n = 77), SIOP93-1/GPOH (n = 93) and SIOP2001/GPOH (n = 81) initially.
RESULTS:
3y-overall survival (OS) increased from 43% to 61% and 59% respectively (both p<0.01). 3y-OS for localized stage I-III rose from 43% to 65% and 68% respectively while only little improvement can be seen for initial stage IV patients with 43%, 53% and 44% respectively. Multivariate analysis confirmed high risk histology, local stage III, shorter time to PD, combined relapse as independent risk factors. 26 patients had received high-dose chemotherapy showing 64% 3y-OS compared to 54% for all non-transplanted (p=0.11).
CONCLUSION:
Structuring the treatment of progressive nephroblastoma as well as introducing new drugs have improved the outcome significantly. However improvement is depending on the specific risk profile. Very high risk tumours are often resistant to conventional treatment, hence an international uniform treatment concept is needed to achieve conclusive results in this small group. |
| Furtwängler R, Gooskens SL, van Tinteren H, de Kraker J, Schleiermacher G, Bergeron C, de Camargo B, Acha T, Godzinski J, Sandstedt B, Leuschner I, Vujanic GM, Pieters R, Graf N, van den Heuvel-Eibrink MM |
Clear Cell Sarcomas of the Kidney registered on International Society of Pediatric Oncology (SIOP) 93-01 and SIOP 2001 protocols: A report of the SIOP Renal Tumour Study Group. |
European journal of cancer (Oxford, England : 1990) 2013, epub ahead of print |
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| Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood renal tumour. Only a few homogeneously treated CCSK cohorts have been reported. This study aims to describe clinical characteristics and survival of CCSK patients treated according to recent International Society of Pediatric Oncology (SIOP) protocols. |
| Furtwängler R, Schmolze M, Gräber S, Leuschner I, Amann G, Schenk JP, Niggli F, Kager L, von Schweinitz D, Graf N |
Pretreatment for bilateral nephroblastomatosis is an independent risk factor for progressive disease in patients with stage V nephroblastoma. |
Klinische Padiatrie 2014, 226: 175 |
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| Treatment of stage V nephroblastoma is less established and more complex than in unilateral nephroblastoma. |
| Fuhrmann S, Schabath R, Möricke A, Zimmermann M, Kunz JB, Kulozik AE, Ludwig WD, Schrappe M, Karawajew L, Ratei R |
Expression of CD56 defines a distinct subgroup in childhood T-ALL with inferior outcome. Results of the ALL-BFM 2000 trial. |
British journal of haematology 2018, 183: 96 |
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| This study reports the prognostic impact of the expression of the natural killer cell marker CD56 in a large series of risk-adapted paediatric patients with T cell acute lymphoblastic leukaemia (T-ALL; n = 493) treated within the ALL-Berlin-Frankfurt-Münster (BFM) 2000 protocol. The immunophenotype was analysed centrally at diagnosis using flow cytometry and correlated with clinical parameters and outcome. CD56 expression was detected in 7·1% and early T-cell precursor (ETP) phenotype in 6·7% of all T-ALL patients. The percentage of ETP in the CD56+ T-ALL cohort was 4-fold higher than in the whole cohort. CD56+ T-ALL frequently expressed the progenitor marker CD34 and myeloid antigens CD13 and CD33. The 5-year event-free survival (EFS) rates for the European Group for the Immunological classification of Leukaemias/World Health Organization subgroups and the ETP phenotype were not statistically different. By contrast, patients with CD56 expression had a significantly reduced EFS (60 ± 8%) and overall survival (60 ± 8%) at 5 years, with a hazard ratio of 2·46 (P = 0·002) and 2·99 (P < 0·001), respectively. Moreover, CD56 expression in combination with the minimal residual disease (MRD)-based high risk assignment defined a population with a 'very-high' risk probability of relapse in the ALL-BFM 2000 trial. The CD56 marker has the potential to augment MRD-based risk stratification and may serve as a molecular target for antibody-based treatment strategies in childhood T-ALL. |
| Furtwängler R, Graf N |
Nierentumoren, in: Niemeyer C, Eggert A (Hrsg.): Pädiatrische Hämatologie und Onkologie. |
Springer-Verlag GmbH GDeutschland 2006, 2018 2. vollständig überarbeitete Auflage 2018, 441 |
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| Futaki M, Yamashita T, Yagasaki H, Toda T, Yabe M, Kato S, Asano S, Nakahata T |
The IVS4 + 4 A to T mutation of the fanconi anemia gene FANCC is not associated with a severe phenotype in Japanese patients. |
Blood 2000, 95: 1493 |
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| Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and a susceptibility to leukemia. There are at least 8 complementation groups (A through H). Extensive analyses of the FA group C gene FANCC in Western countries revealed that 10% to 15% of FA patients have mutations of this gene. The most common mutation is IVS4 + 4 A to T (IVS4), a splice mutation in intron 4, which has been found only in patients of Ashkenazi Jewish ancestry. When we screened 29 Japanese patients (20 unrelated patients and 4 families) using polymerase chain reaction-single strand conformation polymorphism, we found 8 unrelated patients homozygous for IVS4. This is apparently the first non-Ashkenazi-Jewish population for whom this mutation has been detected. The Ashkenazi Jewish patients homozygous for IVS4 have a severe phenotype, in comparison with other FA patients. Our analyses of Japanese patients indicate no significant difference between IVS4 homozygotes and other patients with regard to severity of a clinical phenotype. Thus, ethnic background may have a significant effect on a clinical phenotype in FA patients carrying the same mutation. (Blood. 2000;95:1493-1498) |
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