| Autor(en) |
Titel |
Quelle |
Links |
| Gadner H, Heitger A, Grois N, Gatterer-Menz I, Ladisch S |
Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group. |
Med Pediatr Oncol 1994, 23: 72 |
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| Gadner H, Ladisch S, Arico M, Broadbent V, Jakobson A, Komp D, Nicholson S |
VP-16 and the treatment of histiocytosis. |
Eur J Pediatr 1994, 153: 389 |
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| Gadner H |
Etoposide in Langerhans cell histiocytosis. |
Pediatr Hematol Oncol 1996, 13: 309 |
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| Gadner H |
Therapie von Leukämien, Lymphomen, Soliden Tumoren, Spezielle Therapiemodalitäten, Regionale Chemotherapie, Notfälle. |
Langerhans-Zell-Histiozytose in Kompendium Internistische Onkologie 1999, 2294 |
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| Gadner H |
Langerhans' cell histiocytosis - still an unsolved problem editorial. |
Pediatr Hematol Oncol 1999, 16: 489 |
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| Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Potschger U, Pritchard J, Ladisch S |
A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. |
J Pediatr 2001, 138: 728 |
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| Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S, Histiocyte Society |
A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. [+] |
The Journal of pediatrics 2001, 138: 728 |
|
| OBJECTIVE: To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. STUDY DESIGN: One hundred forty-three untreated patients were randomly assigned to receive 24 weeks of vinblastine (6 mg/m(2), given intravenously every week) or etoposide (150 mg/m(2)/d, given intravenously for 3 days every 3 weeks), and a single initial dose of corticosteroids. RESULTS: Vinblastine and etoposide were equivalent (P > or = .2) in all respects: response at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity (47% and 58%); and probability of survival (76% and 83%) [corrected], of disease reactivation (61% and 55%), and of developing permanent consequences (39% and 51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually mild, as was toxicity. All children > or = 2 years old without risk organ involvement (liver, lungs, hematopoietic system, or spleen) survived. With such involvement, lack of rapid (within 6 weeks) response was identified as a new prognostic indicator, predicting a high (66%) mortality rate. CONCLUSIONS: Vinblastine and etoposide, with one dose of corticosteroids, are equally effective treatments for multisystem LCH, but patients who do not respond within 6 weeks are at increased risk for treatment failure and may require different therapy. |
| Gadner H, Haas O, Masera G, Pui C, Schrappe M |
'Ponte di Legno' Working Group--report on the Fifth International Childhood Acute Lymphoblastic Leukemia Workshop. |
Leukemia 2003, 17: 798 |
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| Gadner H, Gaedicke G, Niemeyer CH, Ritter J (Hrsg) |
Pädiatrische Hämatologie und Onkologie. |
Springer-Verlag 2006 |
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| Gajjar A, Sanford RA, Heideman R, Jenkins JJ, Walter A, Li Y, Langston JW, Muhlbauer M, Boyett JM, Kun LE |
Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1997, 15: 2792 |
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| To evaluate the impact of primary tumor site, age at diagnosis, extent of resection, and histology on progression-free survival (PFS) in pediatric low-grade astrocytoma. |
| Gajjar A, Kühl J, Epelman S, Bailey C, Allen J |
Chemotherapy of medulloblastoma. |
Childs Nerv Syst 1999, 15: 554 |
|
| Gallie BL, Dunn JM, Chan HS, Hamel PA, Phillips RA |
The genetics of retinoblastoma. Relevance to the patient. [+] |
Pediatric clinics of North America 1991, 38: 299 |
|
| The understanding of the molecular biology of human cancer has advanced rapidly in the last decade, in part due to discoveries in the rare, pediatric ocular tumor, retinoblastoma. RB studies have led to recognition of a class of human genes, the tumor suppressor genes, that are critical in the initiation and progression of the malignant process. Mutations in the RB1 gene initiate RB and other specific tumors. They may also contribute to progressive stages of many other malignancies. The protein product of RB1 (p110RB1) is a basic regulator of the cell cycle. In the absence of normal protein, the cell proceeds to the next cell division without the potential to become quiescent. Understanding the genetics of RB has benefited the patients, as the precise identification of the RB1 mutations in families has led to accurate prediction of individuals at risk for RB tumors. It seems unlikely, in the foreseeable future, that direct genetic manipulation of mutant RB1 genes will play a role in therapy, but complete understanding of the function of p110RB1 may eventually allow exploitation of its powerful antiproliferative effect. Other molecular genetic events in addition to RB1 mutations are documented in RB tumors, and may play a critical role in the full malignant phenotype. The oncogene, N-myc, is amplified in some RB tumors and is expressed in normal fetal retina. The cytogenetic abnormality, i(6p), is almost unique to RB tumors. The molecular and tissue-specific roles of these abnormalities are not yet known. Many RB tumors also acquire excessive expression of the cell surface membrane glycoprotein, p170, linked to multidrug resistance, whether or not the RB tumor has been exposed to chemotherapy. We anticipate that ways to avoid or counteract the drug resistance of excessive p170 expression will be developed for other pediatric tumors and eventually will be applied to chemotherapy for RB patients. |
| Galimi F, Noll M, Kanazawa Y, Lax T, Chen C, Grompe M, Verma IM |
Gene therapy of Fanconi anemia: preclinical efficacy using lentiviral vectors. [+] |
Blood 2002, 100: 2732 |
|
| Fanconi anemia (FA) is an inherited cancer susceptibility syndrome caused by mutations in a DNA repair pathway including at least 6 genes (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG). The clinical course of the disease is dominated by progressive, life-threatening bone marrow failure and high incidence of acute myelogenous leukemia and solid tumors. Allogeneic bone marrow transplantation (BMT) is a therapeutic option but requires HLA-matched donors. Gene therapy holds great promise for FA, but previous attempts to use retroviral vectors in humans have proven ineffective given the impaired proliferation potential of human FA hematopoietic progenitors (HPCs). In this work, we show that using lentiviral vectors efficient genetic correction can be achieved in quiescent hematopoietic progenitors from Fanca(-/-) and Fancc(-/-) mice. Long-term repopulating HPCs were transduced by a single exposure of unfractionated bone marrow mononuclear cells to lentivectors carrying the normal gene. Notably, no cell purification or cytokine prestimulation was necessary. Resistance to DNA- damaging agents was fully restored by lentiviral transduction, allowing for in vivo selection of the corrected cells with nonablative doses of cyclophosphamide. This study strongly supports the use of lentiviral vectors for FA gene therapy in humans. |
| Garre M, El-Hossainy M, Fondelli P, Göbel U, Brisigotti M, Donati P, Nantron M, Ravegnani M, Garaventa A, De Bernardi B |
Is chemotherapy effective therapy for intracranial immature teratoma? |
Cancer 1996, 77: 977 |
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| Garde S, Knaup P, Herold R |
Remodeling of Legacy Systems in Health Care using UML. |
Stud Health Technol Inform 2002, 90: 478 |
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| Garde S, Baumgarten B, Basu O, Graf N, Haux R, Herold R, Kutscha U, Schilling F, Selle B, Spiess C, Wetter T, Knaup P |
A Meta-Model of Chemotherapy Planning in the Multi-Hospital / Multi-Trial-Center-Environment of Pediatric Oncology. |
Methods of Information in Medicine 2004, 43: 171 |
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| Garbe E, Andersohn F, Bronder E, Klimpel A, Thomae M, Schrezenmeier H, Hildebrandt M, Späth-Schwalbe E, Grüneisen A, Mayer B, Salama A, Kurtal H |
Drug induced immune haemolytic anaemia in the Berlin Case-Control Surveillance Study. [+] |
British journal of haematology 2011, 154: 644 |
|
| Drug-induced immune haemolytic anaemia is a rare but serious condition. This study investigated the possibility of drug aetiology of immune haemolytic anaemia (IHA) in 134 patients with new onset of IHA who were identified in the Berlin Case-Control Surveillance Study between 2000 and 2009. Single drugs related to IHA in three or more patients and assessed more than once as a certain or probable cause of IHA in a standardized causality assessment included diclofenac, fludarabine, oxaliplatin, ceftriaxone and piperacillin. In a case-control study including all 124 IHA cases developed in outpatient care and 731 controls, significantly increased odds ratios (OR) were observed for beta-lactam antibiotics (OR=8·8; 95% confidence interval [CI] 3·2-25·2), cotrimoxazole (OR=6·5; CI 1·1-37·9), ciprofloxacin (OR=6·9, CI 1·3-38·5), fludarabine (OR=22·2; CI: 2·8-454·5) and lorazepam (OR=5·3; CI: 1·2-21·2). Excluding new onset cases with a chronic IHA disease course, an increased risk became also apparent for diclofenac with an OR of 3·1 (CI 1·3-7·0). This is the first case-control study investigating drugs as risk factors for IHA. It corroborates an increased risk for several drugs that have been implicated as a cause of IHA in the standardized causality assessment of individual cases. |
| Gatta G, Capocaccia R, Stiller C, Kaatsch P, Berrino F, Terenziani M, EUROCARE Working Group |
Childhood cancer survival trends in Europe: a EUROCARE Working Group study. [+] |
Journal of clinical oncology 2005, 23: 3742 |
|
| PURPOSE: EUROCARE collected data from population-based cancer registries in 20 European countries. We used this data to compare childhood cancer survival time trends in Europe. PATIENTS AND METHODS: Survival in 44,129 children diagnosed under the age of 15 years during 1983 to 1994 was analyzed. Sex- and age-adjusted 5-year survival trends for 10 common cancers and for all cancers combined were estimated for five regions (West Germany, the United Kingdom, Eastern Europe, Nordic countries, and West and South Europe) and Europe as a whole. Europe-wide trends for 14 rare cancers were estimated. RESULTS: For all cancers combined, 5-year survival increased from 65% for diagnoses in 1983 to 1985 to 75% in 1992 to 1994. Survival improved for all individual cancers except melanoma, osteosarcoma, and thyroid carcinoma; although for retinoblastoma, chondrosarcoma, and fibrosarcoma, improvements were not significant. The most marked improvements (50% to 66%) occurred in Eastern Europe. For common cancers, the greatest improvements were for leukemia and lymphomas, with risk of dying reducing significantly by 5% to 6% per year. Survival for CNS tumors improved significantly from 57% to 65%, with risk reducing by 3% per year. Risk reduced by 4% per year for neuroblastoma and 3% per year for Wilms' tumor and rhabdomyosarcoma. The survival gap between regions reduced over the period, particularly for acute nonlymphocytic leukemia, CNS tumors, and rhabdomyosarcoma. For rare Burkitt's lymphoma, hepatoblastoma, gonadal germ cell tumors, and nasopharyngeal carcinoma, risk reductions were at least 10% per year. CONCLUSION: These gratifying improvements in survival can often be plausibly related to advances in treatment. The prevalence of European adults with a history of childhood cancer will inevitably increase. |
| Gazda, HT, Zhong R, Long L, Niewiadomska E, Lipton, JM, Ploszynska A, Zaucha, JM, Vlachos A, Atsidaftos E, Viskochil, DH, Niemeyer, CM, Meerpohl, JJ, Rokicka-Milewska R, Pospisilova D, Wiktor-Jedrzejczak W, Nathan, DG, Beggs, AH, Sieff, CA |
RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutations. [+] |
Br J Haematol 2004, 127: 105 |
|
| The genetic basis of Diamond-Blackfan anaemia (DBA), a congenital erythroid hypoplasia that shows marked clinical heterogeneity, remains obscure. However, the fact that nearly one-quarter of patients harbour a variety of mutations in RPS19, a ribosomal protein gene, provides an opportunity to examine whether haplo-insufficiency of RPS19 protein can be demonstrated in certain cases. To that end, we identified 19 of 81 DBA index cases, both familial and sporadic, with RPS19 mutations. We found 14 distinct insertions, deletions, missense, nonsense and splice site mutations in the 19 probands, and studied mutations in 10 patients at the RNA level and in three patients at the protein level. Characterization of the mutations in 10 probands, including six with novel insertions, nonsense and splice site mutations, showed that the abnormal transcript was detectable in nine cases. The RPS19 mRNA and protein in CD34+ bone marrow cells identified haplo-insufficiency in three cases predicted to have one functional allele. Our data support the notion that, in addition to rare DBA patients with the deletion of one allele, the disease in certain other RPS19 mutant patients is because of RPS19 protein haplo-insufficiency. |
| Gazda, HT, Grabowska A, Merida-Long, LB, Latawiec E, Schneider, HE, Lipton, JM, Vlachos A, Atsidaftos E, Ball, SE, Orfali, KA, Niewiadomska E, Da Costa L, Tchernia G, Niemeyer C, Meerpohl, JJ, Stahl J, Schratt G, Glader B, Backer K, Wong C, Nathan, DG, Beggs, AH, Sieff, CA |
Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. [+] |
Am.J Hum.Genet 2006, 79: 1110-8. Epub 2006 Nov 2. |
|
| Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands. We report identification of de novo nonsense and splice-site mutations in another RP, RPS24 (encoded by RPS24 [10q22-q23]) in approximately 2% of RPS19 mutation-negative probands. This finding strongly suggests that DBA is a disorder of ribosome synthesis and that mutations in other RP or associated genes that lead to disrupted ribosomal biogenesis and/or function may also cause DBA. |
| Gebert C, Brinkschmidt C, Bielack S, Bernhardt T, Jürgens H, Böcker W, Winkelmann W, Bürger H, Gosheger, G |
The potential of comparative genomic hybridization as a tool in the differential diagnosis of matrix-producing bone lesions. [+] |
Int J Surg Pathol 2006, 14: 187 |
|
| Matrix-producing bone lesions consist of a wide variety of benign and malignant conditions. With respect to morphology, an overlap exists between benign and malignant bone tumors that causes difficulties in the final determination of the tumor. This study was conducted to show the potential of comparative genomic hybridization as a tool in the differential diagnosis of matrix-producing bone lesions. Thirty benign bone tumors were evaluated by conventional comparative genomic hybridization. To test its diagnostic reliability, 5 additional cases were analyzed, all with differential diagnostic difficulties related to morphology and radiology. All were ultimately diagnosed as malignant sarcomas, and unbalanced alterations were detected. In contrast benign tumors or tumor-like lesions did not reveal any chromosomal alterations. Comparative genomic hybridization is a useful adjunct in the complicated differential diagnostic algorithms of matrix-producing bone tumors. |
| Gehring M, Berthold F, Schwab M, Amler L |
Genetic stability of microsatellites in human neuroblastomas. |
J Clin Oncol 1994, 4: 1043 |
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| Gehring M, Berthold F, Edler L, Schwab M, Amler L |
The 1p deletion is not a reliable marker for the prognosis of patients with neuroblastoma. |
Cancer Res 1995, 55: 5366 |
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| Geoerger B, Hero B, Harms D, Grebe J, Scheidhauer K, Berthold F |
Metabolic activity and clinical features of primary ganglioneuromas. |
Cancer 2001, 91: 1905 |
|
| George JN, Vesely SK |
Immune thrombocytopenic purpura--let the treatment fit the patient. |
The New England journal of medicine 2003, 349: 903 |
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| George JN |
Children with ITP: Looking beyond the platelet count. |
Pediatric blood & cancer 2012, 58: 323 |
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| Gerhardt T, Schmahl G, Flotho C, Rath A, Niemeyer C |
Expression of the Evi-1 gene in haemopoietic cells of children with juvenile myelomonocytic leukaemia and normal donors. |
Br J Haematol 1997, 99: 882 |
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| Gerres L, Brämswig J, Schlegel W, Jürgens H, Schellong G |
The effects of etoposide on testicular function in boys treated for Hodgkin's disease. |
Cancer 1998, 83: 2217 |
|
| Gerth HU, Rompel A, Krebs B, Boos J, Lanvers-Kaminsky C |
Cytotoxic effects of novel polyoxotungstates and a platinum compound on human cancer cell lines. [+] |
Anti-cancer drugs 2005, 16: 101 |
|
| The cytotoxicity of a new platinum compound Pt1 [2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedichloroplatin(II)] and six polyoxometalates (POM1-6) on two neuroblastoma cell lines (SHEP-SF and KCN) and an Ewing's Sarcoma cell line (CADO-ES-1) was studied. Cisplatin [cis-diamminedichloroplatinum(II)] and carboplatin [cis-diammine(cyclobutanedicarboxylato)platinum(II)] were used as reference agents. Using MTT tests, the cytotoxicity (LD50: lethal doses 50%) of the compounds were measured at different concentrations. After 72 h exposure, the LD50 data for the platinum-containing substances ranged between 4.47 x 10(-6) and 1.91 x 10(-4) M. The SHEP-SF cell line displayed the highest sensitivity to cisplatin. The novel platinum agent Pt1 had a similar cytotoxic effect to the reference agent cisplatin. Both cisplatin and Pt1 were more cytotoxic than carboplatin. The POMs reduced cell viability compared to untreated cells at concentrations between 8.4 x 10(-7) and 3.47 x 10(-5) M. POM1 ([(CH3)4N]2Na6.5(NH4)2[SnII1.5(WO2(OH))0.5(WO2)2(SbW9O33)2] x 32H2O) was the most effective polyoxoanion with a mean LD50 value of 8.83 x 10(-6) M in the three cell lines tested. With CADO-ES-1 and KCN cells, POM1 was found to be more effective than the platinum compounds cisplatin, carboplatin and Pt1. |
| Germeshausen M, Skokowa J, Ballmaier M, Zeidler C, Welte K |
G-CSF receptor mutations in patients with congenital neutropenia. [+] |
Current opinion in hematology 2008, 15: 332 |
|
| In this review, we summarize our current knowledge on the acquisition of granulocyte-colony stimulating factor receptor (G-CSFR) gene (CSF3R) mutations in patients with congenital neutropenia and their role in leukemogenesis. Congenital neutropenia is a heterogeneous disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10/l. |
| Gerth HU, Juergens KU, Dirksen U, Gerss J, Schober O, Franzius C |
Significant benefit of multimodal imaging: PET/CT compared with PET alone in staging and follow-up of patients with Ewing tumors. |
Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2007, 48: 1932 |
|
| Gerrard M, Cairo MS, Weston C, Auperin A, Pinkerton R, Lambilliote A, Sposto R, McCarthy K, Lacombe MJ, Perkins SL, Patte C, FAB LMB96 International Study Committee |
Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study. [+] |
British journal of haematology 2008, 141: 840 |
|
| High cure rates are possible in children with localized mature B-cell lymphoma (B NHL) using a variety of chemotherapeutic strategies. To reduce late sequelae, the duration and intensity of chemotherapy has been progressively reduced. The Lymphome Malins de Burkitt (LMB) 89 study reported long-term survival in almost all children with localized resected disease treated with two courses of COPAD (cyclophosphamide, vincristine, prednisolone and doxorubicin). This study was designed to confirm the effectiveness of this approach in a larger number of patients in a multinational co-operative study. The patient cohort was part of an international study (French-American-British LMB 96), which included all disease stages and involved three national groups. Patients in this part of the study had resected stage I or completely resected abdominal stage II disease. Following surgery, two courses of COPAD were given, without intrathecal (IT) chemotherapy. One hundred and thirty-two children were evaluable. Two of 264 (0.9%) courses were associated with grade IV toxicity (one stomatitis and one infection). With a median follow up of 50.5 months, the 4 year event-free survival is 98.3% and overall survival is 99.2%. Children with resected localized B-NHL can be cured with minimal toxicity following two courses of low intensity treatment without IT chemotherapy. |
| Germing U, Aul C, Niemeyer CM, Haas R, Bennett JM |
Epidemiology, classification and prognosis of adults and children with myelodysplastic syndromes. [+] |
Annals of hematology 2008, 87: 691 |
|
| Myelodysplastic syndromes (MDS) belong to the most frequent bone marrow diseases with a crude incidence of about 4 in 100,000 per year. The diagnosis of MDS still is mainly based on morphologic findings in blood and marrow. The new WHO classification system takes into account the medullary and peripheral blast count as well as the degree of dysplasia in the different cell lines. To correctly identify MDS types, cytogenetic evaluation is of importance, as the WHO classification introduced the entity MDS with del(5q), which is characterized by special morphologic and hematologic features. The separation of MDS from acute leukemias has been redefined using a cutoff value of 20% peripheral and/or medullary blasts. The International Prognostic Scoring System still is the gold standard in prognostication, but new items like transfusion need will be used more and more and have been incorporated into the WHO adapted Prognostic Scoring System. In childhood, MDS is uncommon, accounting for less than 5% of all hematopoietic neoplasms in patients less than 14 years of age. To accommodate for the characteristics of pediatric MDS, a simple classification scheme based on morphological features and conforming with the WHO suggestions was proposed. The dysplastic prodrome of acute myeloid leukemia in Down syndrome is classified within myeloid leukemia in Down syndrome and excluded from the population-based studies of MDS. |
| Gerr H, Zimmermann M, Schrappe M, Dworzak M, Ludwig WD, Bradtke J, Moericke A, Schabath R, Creutzig U, Reinhardt D |
Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations. [+] |
British journal of haematology 2010, 149: 84 |
|
| Summary Acute leukaemias of ambiguous lineage (ALAL) represent a rare type of leukaemia, expressing both myeloid and lymphoid markers. This study retrospectively analyzed data from 92 children (biphenotypic n = 78, bilineal n = 6, lineage switch n = 8) with ALAL registered in the Berlin-Frankfürt-Münster (BFM) acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) studies between 1998 and 2006 (2.4% of all cases with acute leukaemia). Our cohort of ALAL patients was characterized by comparatively high median age (8.9 years), high median white blood cell count (14.9 x 10(9)/l), as well as frequent hyperleucocytosis (18.5%) and central nervous system involvement (24.1%). The most frequent cytogenetic abnormalities were ETV6/RUNX1 fusion (16%) and trisomy 8 (14.6%). Complete remission rate was significantly lower than in ALL-BFM patients (91.8% vs. 99.1%, P < 0.001), but comparable to AML-BFM patients (87.9%). Event-free survival (EFS) and overall survival (OS) of ALAL patients were low, at 62 +/- 5%. 5-year probability of EFS was significantly worse than in ALL patients (80 +/- 1%, P < 0.001), but better than for AML patients (49 +/- 2%, P = 0.027). Our data suggest that an intensive therapy regimen including stem cell transplantation may be favourable for bilineal or lineage switch cases, whereas patients with ETV6/RUNX1 fusion, lymphoid morphology and patients with expression of cyCD22 and cyCD79a should be treated with an ALL-directed therapy. |
| Gerber A, Rossi R |
Neonatologische Versorgung – Fallzahlregelung Einfluss auf Qualität und Finanzierung pädiatrischer Einrichtungen. |
Monatsschr Kinderheilkd 2010 158: 356–363 |
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| Gerber NU, von Hoff K, von Bueren AO, Treulieb W, Warmuth-Metz M, Pietsch T, Soerensen N, Faldum A, Emser A, Schlegel PG, Deinlein F, Kortmann RD, Rutkowski S |
Outcome of 11 children with ependymoblastoma treated within the prospective HIT-trials between 1991 and 2006. [+] |
J Neurooncol 2011, 102: 459 |
|
| Ependymoblastoma is a rare malignant brain tumor of early childhood. Data on clinical behavior and optimal treatment strategies are scarce. We report on 11 consecutively treated children with centrally confirmed diagnosis of CNS ependymoblastoma, registered between February 1994 and October 2006 to the prospective GPOH-HIT multicenter brain tumor trials, and treated by multimodal regimens. Median age at diagnosis was 3.5 years (range, 1.8-5.6 years), and the median follow-up of survivors was 5.9 years (range, 2.2-12.7 years). Initial stage was M0 in 9, and M0/1 (no cerebrospinal fluid examination done) in 2 patients. Gross-total tumor resection was achieved in 7 patients, incomplete resection in 4 patients. Further primary therapy included chemotherapy in all patients, craniospinal radiotherapy in 5 patients and high-dose chemotherapy in 2 patients. Tumor response to chemotherapy was observed in 1 of 4 evaluable patients. Tumor progression occurred in 7 patients after a median time of 5.0 months (range, 2.5-19.2 months). Five-year progression-free survival was 36.4% (±14.5%), 5-year overall survival 30.3% (±15.9%). Of 4 survivors, 3 had gross-total tumor resection, and all were treated by either craniospinal radiotherapy and/or high-dose chemotherapy with autologous blood stem cell rescue. Prognosis of children with ependymoblastoma is poor, but sustained remissions have been achieved after multimodal treatment. Considerable diagnostic discrepancies between local and central pathologists underscore the importance of central review. Further studies are needed to improve survival of children with this rare malignant central nervous system tumor. |
| Gerber NU, von Hoff K, von Bueren AO, Treulieb W, Deinlein F, Benesch M, Zwiener I, Soerensen N, Warmuth-Metz M, Pietsch T, Mittler U, Kuehl J, Kortmann RD, Grotzer MA, Rutkowski S |
A long duration of the prediagnostic symptomatic interval is not associated with an unfavourable prognosis in childhood medulloblastoma. [+] |
European journal of cancer 2011, [Epub ahead of print] |
|
| BACKGROUND: Due to the lacking specificity of symptoms making a correct diagnosis can be a challenge in children with medulloblastoma. This can lead to prediagnostic symptomatic intervals (PSIs) of several weeks to months. It is unknown whether the length of the PSI is associated with an inferior survival outcome in this population. METHODS: To study the association of PSI with disease stage at diagnosis, tumour control and survival in children with medulloblastoma, prospectively collected data on PSI, clinical, and biological features were analysed in 224 patients diagnosed at the age of 3-18years and treated within the prospective randomised multicentre trial HIT'91. RESULTS: Patients with lower-stage disease tended towards a longer median PSI than those with higher-stage disease (M0 stage, 2.0months; M1 stage, 2.0months; M2/M3 stage, 1month; p=0.094. M0/1 stage versus M2/3 stage; p=0.025). The patient group with the longest PSI had the best survival outcome (PSI ⩾4.0months: 10-year overall survival rate (OS), 71%; PSI <4.0months, 10-year OS, 61%; p=0.056). Age at diagnosis was positively correlated with PSI (p=0.027). No associations were found between PSI and sex histological subtype, presence of postoperative residual tumour, or c-myc and TrkC mRNA expression. CONCLUSION: Contrary to a common belief that a longer PSI may adversely affect prognosis, a longer PSI was associated with a trend towards lower metastatic stage and better survival probabilities. Nevertheless these findings do not obviate the importance of a timely diagnosis in paediatric patients with medulloblastoma. |
| Geyer JR, Finlay JL, Boyett JM, Wisoff J, Yates A, Mao L, Packer RJ |
Survival of infants with malignant astrocytomas. A Report from the Childrens Cancer Group. |
Cancer 1995, 75: 1045 |
|
| Giampietro PF, Adler-Brecher B, Verlander PC, Pavlakis SG, Davis JG, Auerbach AD |
The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry. [+] |
Pediatrics 1993, 91: 1116 |
|
| The objective of this study was to address the need for early diagnosis of Fanconi anemia (FA), an autosomal recessive chromosomal instability syndrome characterized by a unique cellular hypersensitivity to DNA cross-linking agents, such as diepoxybutane, and by a high risk of malignancies. |
| Gieseke F, Schütt B, Viebahn S, Koscielniak E, Friedrich W, Handgretinger R, Müller I |
Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression. [+] |
Blood 2007, 110: 2197 |
|
| Multipotent mesenchymal stromal cells (MSCs) inhibit proliferation, helper, and effector functions in most if not all peripheral blood mononuclear cell (PBMC) subpopulations in vitro. The molecular mechanism is widely thought to imply tryptophan degradation by the interferon-gamma (IFNgamma)-induced expression of indoleamine 2,3-dioxygenase (IDO). However, IDO inhibitors were not able to restore proliferation of PBMCs in each case. Moreover, human MSCs with an IFNgamma receptor 1 (R1) defect inhibited proliferation of HLA-mismatched PBMCs to a similar extent as control MSCs. In contrast to healthy MSCs, IFNgammaR1-deficient MSCs showed no detectable mRNA for IDO-neither in the absence nor in the presence of recombinant human IFNgamma, nor in coculture with HLA-mismatched PBMCs. Based on gene expression profiling, we were able to show that insulin-like growth factor (IGF)-binding proteins contribute to the inhibitory mechanism of MSCs. Taken together, human MSCs exert important immunomodulatory functions in the absence of IFNgammaR1 signaling and IDO, partially accounted for by IGF-binding proteins. |
| Ginsberg J, de Alava E, Ladanyi M, Wexler L, Kovar H, Paulussen M, Zoubek A, Jürgens H, Wunder J, Andrulis I, Malik R, Sorensen P, Womer R, Barr F |
EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing's sarcoma. |
J Clin Oncol 1999, 17: 1809 |
|
| Ginzburg Y, Rivella S |
{beta}-thalassemia: a model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism. [+] |
Blood 2011, 118: 4321 |
|
| β-thalassemia is a disease characterized by anemia and is associated with ineffective erythropoiesis and iron dysregulation resulting in iron overload. The peptide hormone hepcidin regulates iron metabolism, and insufficient hepcidin synthesis is responsible for iron overload in minimally transfused patients with this disease. Understanding the crosstalk between erythropoiesis and iron metabolism is an area of active investigation in which patients with and models of β-thalassemia have provided significant insight. The dependence of erythropoiesis on iron presupposes that iron demand for hemoglobin synthesis is involved in the regulation of iron metabolism. Major advances have been made in understanding iron availability for erythropoiesis and its dysregulation in β-thalassemia. In this review, we describe the clinical characteristics and current therapeutic standard in β-thalassemia, explore the definition of ineffective erythropoiesis, and discuss its role in hepcidin regulation. In preclinical experiments using interventions such as transferrin, hepcidin agonists, and JAK2 inhibitors, we provide evidence of potential new treatment alternatives that elucidate mechanisms by which expanded or ineffective erythropoiesis may regulate iron supply, distribution, and utilization in diseases such as β-thalassemia. |
| Giona F, Teofili L, Moleti ML, Martini M, Palumbo G, Amendola A, Mazzucconi MG, Testi AM, Pignoloni P, Orlando SM, Capodimonti S, Nanni M, Leone G, Larocca LM, Foà R |
Thrombocythemia and polycythemia in patients younger than 20 years at diagnosis: clinical and biologic features, treatment, and long-term outcome. [+] |
Blood 2012; 119: 2219 |
|
| Sixty-four patients < 20 years of age, investigated for a suspicion of Philadelphia-negative myeloproliferative disease (MPD), were retrospectively evaluated to characterize the different forms and to examine the treatments used and long-term outcome. JAK2 mutations, endogenous erythroid colony growth, and clonality were investigated in 51 children. Mutations of thrombopoietin, the thrombopoietin receptor (MPL), and the erythropoietin receptor and mutations of other genes involved in the pathogenesis of MPD were investigated in JAK2 wild-type patients. Based on our criteria for childhood MPD, we identified 34 patients with sporadic thrombocythemia (ST), 16 with hereditary thrombocytosis (HT), 11 with sporadic polycythemia (SP), and 3 with hereditary polycythemia (HP). JAK2(V617F) mutations were present in 47.5% of ST and in no HT. The MPL(S505A) mutation was detected in 15/16 HT patients and in no ST (P < .00001). The JAK2(V617F) mutation occurred in 27% of SP patients diagnosed according to the Polycythemia Vera Study Group or World Health Organization 2001 criteria. Children with ST received more cytoreductive drugs than those with HT (P = .0006). After a median follow-up of 124 months, no patient had developed leukemia or myelofibrosis and 5% had thrombosis; the miscarriage rate in thrombocythemic patients was 14%. The low complication rate in our population suggests that children with MPD may be managed by tailored approaches. |
| Giri N, Batista DL, Alter BP, Stratakis CA |
Endocrine abnormalities in patients with Fanconi anemia. [+] |
J Clin Endocrinol Metab 2007, 92: 2624 |
|
| Fanconi anemia (FA) is an inherited disorder with chromosomal instability, bone marrow failure, developmental defects, and a predisposition to cancer. Systematic and comprehensive endocrine function data in FA are limited. |
| Glaser SL, Lin RJ, Stewart SL, Ambinder RF, Jarrett RF, Brousset P, Pallesen G, Gulley ML, Khan G, O'Grady J, Hummel M, Preciado MV, Knecht H, Chan JK, Claviez A |
Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data. |
Int J Cancer 1997, 70: 375 |
|
| Gnekow A, Kaatsch P, Kortmann R, Wiestler OD |
HIT-LGG: Effektivität von Carboplatin-Vincristin bei progredienten Gliomen niedrigen Malignitätsgrades im Kindesalter - Zwischenbericht. |
Klin Pädiatr 2000, 212: 177 |
|
| Gnekow A |
Behandlung von Kindern und Jugendlichen mit Gliomen niedrigen Malignitätsgrades. |
Klinische Onkologie 2001, 372 |
|
| Gnekow A |
HIT-LGG. |
Aktuelle Neuropädiatrie 2001, 377 |
|
| Gnekow AK |
Therapie von Gliomen niedriger Malignität im Kindes- und Jugendalter. |
WIR Informationsschrift der Aktion für krebskranke Kinder e.V. (Bonn) 2003, 2: 8 |
|
| Gnekow AK, Packer RJ, Kortmann RD |
Astrocytic tumors, low-grade: general considerations, treatment considerations by primary site and tumor dissemination. |
In: Walker DA, Perilongo G, Punt JAG, Taylor RE (Eds) Brain and Spinal Tumors of Childhood Arnold publisher, London, 2004, V: 245 - 276 |
|
| Gnekow AK, Kortmann RD, Pietsch T, Emser A |
Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy -- report from the multicenter treatment study for children and adolescents with a low grade glioma -- HIT-LGG 1996 -- of the Society of Pediatric Oncology and Hematology (GPOH). [+] |
Klinische Padiatrie 2004, 216: 331 |
|
| BACKGROUND: Low grade gliomas arise in all CNS-locations and age groups, chiasmatic-hypothalamic tumors occur especially in young children. Early radiotherapy (RT) shall be deferred by chemotherapy (CT) within the concept of the HIT-LGG 1996 study, offering a comprehensive treatment strategy for all age groups. PATIENTS: 198 of 905 protocol patients (21.9 %) had a chiasmatic (34), chiasmatic-hypothalamic (144) or hypothalamic (20) primary tumor, median age at diagnosis 3.6 years (0.2-16.3 y.), 54 had neurofibromatosis (27.3 %), 108 female (54.5 %). 98 children had severe visual impairment as their first symptom. The initial neurosurgical intervention resulted in 5 complete, 26 subtotal, 45 partial resections, 67 biopsies; 55 children had a diagnosis on the basis of neuroradiologic findings. Histology showed 132 pilocytic astrocytoma I degrees , 6 astrocytoma II degrees /nos and 2 DIGG/DIA I degrees (3 not known). RESULTS: 82 children were treated at diagnosis, 68 upon clinical or radiological progression following observation times of 3.0 to 115.0 months. RT: 27 children received conventional (18) or interstitial (8) RT (1 not documented) at a median age of 7.3 years; 7 tumors went into further progression. At a median observation time of 50.1 months 21 tumors are stable, 3 regressive (2 not evaluable, 1 death). CT: 123 children received vincristin/carboplatin at a median age of 3.7 years. 105/123 achieved CR/PR/SD. 44/123 tumors were progressive after median 22.5 months, 37 with a chiasmatic-hypothalamic primary, 16/44 were irradiated. At a median observation time of 44.7 months 2 children are in complete remission, 92 tumors are stable, 8 regressive, 9 progressive. 4 children died, 8 are not evaluable. At 60 months overall survival of the cohort is 0.93; PFS of the CT-group is 0.61, the RT-free survival 0.83. Within the CT-group children with an age at diagnosis < 1 year and non-pilocytic histology are at increased risk for early progression. Causative factors cannot be defined, yet. CONCLUSION: Within the comprehensive treatment strategy for low grade glioma HIT-LGG 1996 chemotherapy is effective to delay the need for early radiotherapy in chiasmatic-hypothalamic glioma. More effective reduction of the risk for progression has to be sought for young children < 1 year. |
| Gnekow AK |
Gliome mit niedriger Malignität |
In: Gadner H, Gaedicke G, Niemeyer C, Ritter J (Hrsg.) Paediatrische Hämatologie und Onkologie Springer Verlag, Heidelberg, 2005, IV: 791 - 796 |
|
| Gnekow AK, Scheiderbauer J, Pietsch T, Soerensen N, Faldum A, Emser A, von Hornstein S, Warmuth-Metz M, Kuehl J |
HIT-LGG 1996-Success of a countrywide, comprehensive treatment strategy for children and adolescents with low grade glioma of all histologies and locations. |
Pedriatric Blood and Cancer 2005, 45: 465 |
|
| Gnekow A |
Gliome mit niedriger Malignität, in: Gadner H, Gaedicke G, Niemeyer CH, Ritter J (Hrsg.): Pädiatrische Hämatologie und Onkologie. |
Springer Verlag 2006 |
|
| Gnekow AK |
Gliome niedrigen Malignitätsgrades im Kindes- und Jugendalter. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Gesellschaft für Pädiatrische Onkologie und Hämatologie 2008 |
|
| Gnekow AK, Falkenstein F, von Hornstein S, Zwiener I, Berkefeld S, Bison B, Warmuth-Metz M, Driever PH, Soerensen N, Kortmann RD, Pietsch T, Faldum A |
Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low-grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology. [+] |
Neuro-oncology 2012, 14: 1265 |
|
| The Hirntumorstudien (HIT)-LGG-1996 protocol offered a comprehensive treatment strategy for pediatric patients with low-grade glioma (LGG), ie, observation, surgery, adjuvant radiotherapy, and chemotherapy to defer the start of irradiation in young children. In this current study, we sought to determine clinical factors for progression and survival. Between October 1, 1996 and March 31, 2004, 1031 patients were prospectively recruited into an observation arm (n = 668) and a nonsurgical arm stratifying 12 months of vincristine-carboplatin chemotherapy (n = 216) and conventional radiotherapy/brachytherapy (n = 147) in an age-dependent manner. Median patient age was 6.9 years; 28 patients had diencephalic syndrome, 44 had dissemination, and 108 had neurofibromatosis type 1(NF-1). Main tumor location was the supratentorial midline (40.4%), and the main histology was pilocytic astrocytoma (67.9%). Following a median observation of 9.3 years, 10-year overall survival (OS) was 0.94 and 10-year event-free survival (EFS) was 0.47. Ten-year progression-free survival was 0.62 following radiotherapy and 0.44 following chemotherapy. Sixty-one of 216 chemotherapy patients received radiotherapy 0.3-8.7 years after initial diagnosis. By multivariate analysis, diencephalic syndrome and incomplete resection were found to be unfavorable factors for OS and EFS, age ≥11 years for OS, and supratentorial midline location for EFS. Dissemination, age <1 year, and nonpilocytic histology were unfavorable factors for progression following radiotherapy (138 patients); and diencephalic syndrome, dissemination, and age ≥11 years were unfavorable factors following chemotherapy (210 patients). NF-1 patients and boys experienced prolonged tumor stabilization with chemotherapy. A nationwide multimodal treatment strategy is feasible for pediatric LGG. Extended follow-up yielded results comparable to single-institution series for the treatment groups. Three-quarters of surviving chemotherapy patients have not yet received radiation therapy. Infants with or without diencephalic syndrome and dissemination bear the highest risk for death and progression following diagnosis or treatment. |
| Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl G |
Definition and prevalence of subfertility and infertility. [+] |
Human reproduction (Oxford, England) 2005, 20: 1144 |
|
| A common definition of sub- and infertility is very important for the appropriate management of infertility. Subfertility generally describes any form of reduced fertility with prolonged time of unwanted non-conception. Infertility may be used synonymously with sterility with only sporadically occurring spontaneous pregnancies. The major factor affecting the individual spontaneous pregnancy prospect is the time of unwanted non-conception which determines the grading of subfertility. Most of the pregnancies occur in the first six cycles with intercourse in the fertile phase (80%). After that, serious subfertility must be assumed in every second couple (10%) although--after 12 unsuccessful cycles--untreated live birth rates among them will reach nearly 55% in the next 36 months. Thereafter (48 months), approximately 5% of the couples are definitive infertile with a nearly zero chance of becoming spontaneously pregnant in the future. With age, cumulative probabilities of conception decline because heterogeneity in fecundity increases due to a higher proportion of infertile couples. In truly fertile couples cumulative probabilities of conception are probably age independent. Under appropriate circumstances a basic infertility work-up after six unsuccessful cycles with fertility-focused intercourse will identify couples with significant infertility problems to avoid both infertility under- and over-treatment, regardless of age: Couples with a reasonably good prognosis (e.g. unexplained infertility) may be encouraged to wait because even with treatment they do not have a better chance of conceiving. The others may benefit from an early resort to assisted reproduction treatment. |
| Gobrecht O, Göbel U, Graubner U, Gutjahr P, Schock V, Spaar H, Janka-Schaub G |
Effect of dose intensity and therapy-induced leukocytopenia in intensive therapy on the prognosis of acute lymphatic leukemia in childhood. Results in 213 patients of the COALL-85 study. |
Klin Pädiatr 1992, 204: 230 |
|
| Godzinski J, Moorman-Voestermans C, Sawicz-Birkowska K, Tournade M, Voute P, de Kraker J, Weirich A, Ludwig R, Gauthier F |
Paediatric surgical oncology. 5--Nephroblastoma. International Society of Paediatric Oncology (SIOP) Nephroblastoma Trial & Study Committee. |
Eur J Surg Oncol 1995, 21: 414 |
|
| Goddard AG, Kingston JE, Hungerford JL |
Delay in diagnosis of retinoblastoma: risk factors and treatment outcome. [+] |
The British journal of ophthalmology 1999, 83: 1320 |
|
| BACKGROUND: Delay in diagnosis of retinoblastoma causes considerable parental distress; however, the primary healthcare professional (PHP) may have difficulty detecting the most common presenting symptom-leucocoria. Alternatively, the PHP may not appreciate that retinoblastoma is the pathology underlying more common ocular symptoms in infants and young children. METHOD: The parents of 100 recently diagnosed patients with retinoblastoma were interviewed to establish the extent of diagnostic delay, ascertain any associated risk factors, and to determine whether or not delay influenced treatment outcome. RESULTS: Although nearly 50% of patients were referred to an ophthalmologist within 1 week of first consulting a PHP, one quarter waited more than 8 weeks. There was a significantly increased risk of diagnostic delay in younger patients, those presenting with squint rather than leucocoria, and those first presenting to a health visitor rather than to a general practitioner. The risk of local tumour invasion was significantly increased by diagnostic delay. Treatment with primary enucleation was not increased by diagnostic delay. There were no deaths during the study period. CONCLUSION: Primary healthcare professionals require education about the importance of ocular symptoms, especially squint, in paediatric patients. |
| Godzinski J, Weirich A, Tournade M, Gauthier F, Buerger D, Moorman-Voestermans C, de Kraker J, Voute P, Ludwig R, Sawicz-Birkowska K, Vujanic G, Ducourtieux M |
Primary nephrectomy for emergency. |
Eur J Pediatr Surg 2001, 11: 36 |
|
| Göbel U, Schneider DT, Calaminus G, Haas RJ, Schmidt P, Harms D |
Germ-cell tumors in childhood and adolescence. GPOH MAKEI and the MAHO study groups. [+] |
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2000, 11: 263 |
|
| In mature and immature teratoma the treatment is surgical. The risk of recurrence can be estimated from the parameters primary site (with the coccygeal tumors being most at risk), histological grade of immaturity and completeness of the primary resection including the adjacent organ of origin (coccyx, ovary, testis etc.). In case of a microscopically complete tumor resection there is no role for adjuvant chemo- or radiotherapy irrespective of the histological grade of immaturity. Malignant germ-cell tumors (GCT) account for 2.9% of all malignant tumors of children younger than 15 years of age. More than half of the tumors occur at extragonadal sites such as the ovaries (26%), the coccygeal region (24%), the testes (18%) and the brain (18%) represent then primary sites. In patients with extensive tumor growth, metastatic disease or secreting intracranial tumors a delayed tumor resection after preoperative chemotherapy is preferable. In these patients malignant non-seminomatous GCT may be diagnosed clinically due to the increased serum or cerebrospinal fluid levels of the tumor markers AFP and/or beta-HCG. Current risk adapted treatment protocols containing cisplatinum allow long-term remissions in about 80% including patients with bulky or metastatic tumors. In the cisplatinum era the prognostic factors like histology, primary site of the tumor and initial tumor stage have partly lost their former impressive significance in infants and children. On the other hand the completeness of the primary tumor resection according to oncological standards has been established as the most powerful prognostic parameter superior to tumor marker levels or primary site of the tumor. |
| Göbel U, Schneider DT, Calaminus G, Jürgens H, Spaar HJ, Sternschulte W, Waag K, Harms D |
Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2001, 19: 1943 |
|
| PURPOSE: To evaluate a multimodal approach including surgery and cisplatinum chemotherapy for treatment of children with malignant sacrococcygeal germ cell tumors (GCT) and to compare adjuvant and neoadjuvant strategies in advanced tumors. PATIENTS AND METHODS: Between 1983 and 1995, 71 patients with malignant sacrococcygeal GCT were prospectively enrolled onto the German protocols for nontesticular GCT Maligne Keimzelltumoren 83/86 and 89. Five patients who received no chemotherapy (n = 2) or nonplatinum chemotherapy (n = 2) or who did not undergo tumor resection (n = 1) were excluded from this analysis. Among the 66 patients analyzed were 14 boys and 52 girls. The median age was 17.4 months (range, 7 months to 119 months). Median follow-up was 79 months (range, 4 months to 145 months). RESULTS: Fifty-two patients presented with locally advanced stage T2 tumors, and 30 patients had distant metastases at diagnosis. Patients received a median of eight cycles (range, four to nine cycles) of cisplatinum-based chemotherapy. Thirty-five patients underwent tumor resection at diagnosis and received adjuvant cisplatinum-based chemotherapy (group A). Thirty-one patients received up-front chemotherapy followed by delayed tumor resection (group B). Group B included more metastatic tumors than group A (group B, 19 of 31 patients; group A, 11 of 35 patients, P =.01). Preoperative chemotherapy facilitated complete tumor resections (group B, 20 of 31 patients; group A, five of 35 patients, P <.001) and avoided second-look surgery. Metastases at diagnosis and completeness of the first attempt of tumor resection were significant prognostic predictors; however, metastases were not predictive for patients treated with up-front chemotherapy. At 5 years follow-up, event-free survival was 0.76 +/- 0.05 (50 of 66 patients), and overall survival was 0.81 +/- 0.05 (54 of 66 patients). Four patients died as a result of therapy-related complications, and eight patients died of their tumors. Patients with locally advanced and metastatic tumors (T2b M1) fared better with neoadjuvant treatment [overall survival: 0.83 +/- 0.09 (16 of 19 patients) versus 0.45 +/- 0.15 (five of 11 patients), P =.01]. CONCLUSION: Even locally advanced and metastatic sacrococcygeal GCT can be successfully treated with up-front cisplatinum-based chemotherapy followed by delayed but complete tumor resection. |
| Goemans BF, Zwaan CM, Martinelli S, Harrell P, de Lange D, Carta C, Reinhardt D, Hahlen K, Creutzig U, Tartaglia M, Heinrich MC, Kaspers GJ |
Differences in the prevalence of PTPN11 mutations in FAB M5 paediatric acute myeloid leukaemia. |
British journal of haematology 2005, 130: 801 |
|
| Goemans BF, Zwaan CM, Miller M, Zimmermann M, Harlow A, Meshinchi S, Loonen AH, Hahlen K, Reinhardt D, Creutzig U, Kaspers GJ, Heinrich MC |
Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. [+] |
Leukemia 2005, 19: 1536 |
|
| Activating mutations in RAS and receptor tyrosine kinases such as KIT and FLT3 are hypothesized to cooperate with chimeric transcription factors in the pathogenesis of acute myeloid leukemia (AML). To test this hypothesis, we genotyped 150 pediatric AML samples for mutations in KIT (exons 8, 17), NRAS and KRAS (exons 1, 2) and FLT3/ITD. This is the largest cohort of pediatric AML patients reported thus far screened for all four mutations. Of the children with AML, 40% had a mutation in KIT (11.3%), RAS (18%) or FLT3/ITD (11.1%), and 70% of cases of core-binding factor (CBF) leukemia were associated with a mutation of KIT or RAS. Mutations in RAS or FLT3/ITD were frequently found in association with a normal karyotype. Patients with a FLT3/ITD mutation had a significantly worse clinical outcome. However, the presence of a KIT or RAS mutation did not significantly influence clinical outcome. We demonstrate that KIT exon 8 mutations result in constitutive ligand-independent kinase activation that can be inhibited by clinically relevant concentrations of imatinib. Our results demonstrate that abnormalities of signal transduction pathways are frequent in pediatric AML. Future clinical studies are needed to determine whether selective targeting of these abnormalities will improve treatment results. |
| Goemans BF, Zwaan CM, Harlow A, Loonen AH, Gibson BE, Hahlen K, Reinhardt D, Creutzig U, Heinrich MC, Kaspers GJ |
In vitro profiling of the sensitivity of pediatric leukemia cells to tipifarnib: identification of T-cell ALL and FAB M5 AML as the most sensitive subsets. [+] |
Blood 2005, 106: 3532 |
|
| Although the prognosis of pediatric leukemias has improved considerably, many patients still have relapses. Tipifarnib, a farnesyl transferase inhibitor (FTI), was developed to target malignancies with activated RAS, including leukemia. We tested 52 pediatric acute myeloid leukemia (AML) and 36 pediatric acute lymphoblastic leukemia (ALL) samples for in vitro sensitivity to tipifarnib using a total cell-kill assay and compared these results to those obtained with normal bone marrow (N BM) samples (n = 25). AML samples were significantly more sensitive to tipifarnib compared to B-cell precursor ALL (BCP ALL) or N BM samples. Within AML, French-American-British (FAB) M5 samples were most sensitive to tipifarnib. T-cell ALL samples were significantly more sensitive than BCP ALL and N BM samples. In AML there was a marked correlation between tipifarnib resistance and daunorubicin or etoposide resistance, but not to cytarabine or 6-thioguanine. RAS mutations were present in 32% of AML and 18% of ALL samples, but there was no correlation between RAS mutational status and sensitivity to tipifarnib. Future studies are needed to identify biomarkers predictive of tipifarnib sensitivity. In addition, clinical studies, especially in T-cell ALL, seem warranted. |
| Göbel U, Calaminus G, Schneider DT, Koch S, Teske C, Harms D |
The malignant potential of teratomas in infancy and childhood: the MAKEI experiences in non-testicular teratoma and implications for a new protocol. [+] |
Klinische Padiatrie 2006, 218: 309 |
|
| Since 1982, mature and immature teratomas have been recruited into the MAHO and MAKEI protocols of the German Society for Pediatric Oncology and Hematology (GPOH) for testicular and non-testicular germ cell tumors in order to study the epidemiology and clinical behaviour of teratomas. Patients were registered in the epidemiologic German Childrens Cancer Registry and the GPOH Childrens Tumor Registry for pathological review. Patients with immaturity grade 2 and 3 according to Gonzales-Crussi were eligible for adjuvant chemotherapy. The consecutive protocols MAKEI 83/86/89 have been published previously in detail (Klin Paediatr 1997; 209: 228-234, Med Pediat Oncol 1998; 31: 8-15) and will be compared to the data of MAKEI 96. For this comparison, 274 patients from MAKEI 83/86/89 and 261 patients from MAKEI 96 are evaluable. RESULTS: 1) EFS after complete tumor resection has been estimated to 0.96 +/- 0.01 in both observation periods. 2) Incomplete tumor resection remains the main risk factor for relapse (EFS 0.55 +/- 0.09). 3) The relapse rate declined from 13.9 % in MAKEI 83/86/89 to 9.5 % in MAKEI 96. 4) In MAKEI 83/86/89 four newborns with teratoma died due to perioperative complications and nine children as a result of tumor progression, whereas in MAKEI 96 no newborn died, only one child died from tumor progression, and another child died during long time observation for another reason (meningitis). 5) In accordance to the experience of the MAKEI 83/86/89 studies, no child of the MAKEI 96 study presented with yolk sac tumor at recurrence if adjuvant chemotherapy was administered during first-line treatment because of immaturity. In contrast, more than half of the children with tumor recurrence after watch and wait strategy had yolk sac tumor in addition to teratoma. |
| Goemans BF, Zwaan CM, Cloos J, de Lange D, Loonen AH, Reinhardt D, Hählen K, Gibson BE, Creutzig U, Kaspers GJ |
FLT3 and KIT mutated pediatric acute myeloid leukemia (AML) samples are sensitive in vitro to the tyrosine kinase inhibitor SU11657. [+] |
Leukemia research 2010, |
|
| New treatment strategies to improve the outcome of pediatric acute myeloid leukemia (AML) are required as 40% of children diagnosed with AML do not survive. Around 30% of pediatric AML patients harbour a mutation in the tyrosine kinases FLT3 (+/-20%) or KIT (+/-10%). In this study we investigated whether pediatric AML samples (N=61) were sensitive to the tyrosine kinase inhibitor SU11657 (similar to the clinically available drug sunitinib) in vitro, and whether sensitivity was related to expression of, and mutations in, FLT3 and KIT. Overall, SU11657 showed only moderate cytotoxicity. A FLT3 mutation was detected in 35% and a KIT mutation in 8% of the samples. FLT3 and KIT mutated samples were significantly more sensitive to SU11657 than WT KIT and FLT3 samples. Samples without KIT or FLT3 mutations, but with a high wild-type (WT) KIT expression were significantly more sensitive to SU11657 than samples with low KIT expression. Further clinical evaluation of SU11657 and sunitinib combined with chemotherapy would be of interest. Inclusion in clinical trials should not be restricted to patients with FLT3 or KIT mutations. |
| Göbel U, Schneider DT, Teske C, Schönberger S, Calaminus G |
Brain metastases in children and adolescents with extracranial germ cell tumor - data of the MAHO/MAKEI-registry. [+] |
Klinische Padiatrie 2010, 222: 140 |
|
| BACKGROUND: We analyzed 15 children and adolescents with extracranial germ cell tumor (GCT) and brain metastases reported to the MAHO/MAKEI registry. PATIENTS AND METHODS: Between 1982 and 2009, 2 077 patients were prospectively enrolled onto the MAHO/MAKEI studies (overall survival: 0.88+/-0.03). All patients with advanced malignant GCTs received cisplatin-based chemotherapy (overall survival: 0.81+/-0.04 (734/823). RESULTS: 15 patients with brain metastases were reported; in 6 of them at diagnosis and 9 respectively during follow-up (6 weeks-28 months after end of therapy, mean=10 months). Most patients were male (13/15) and adolescent (10/15). 8 patients suffered from mediastinal GCTs. Pure Choriocarcinoma (CC) or CC in combination with other histologies was diagnosed in 12 patients. Clinical symptoms were reported in most patients. In all patients with secondary brain metastases the previously normalised tumor markers AFP and/ or HCG increased again prior to the onset of neurological symptoms. Only 1 of the patients with primary brain metastases survived, whereas 4 of 9 with secondary metastases are in remission after additional treatment. CONCLUSION: The risk for intracranial metastases increases with age, male gender and mediastinal or testicular primary site and choriocarcinoma histology. Development of neurological symptoms at initial diagnosis or during follow-up should lead to rapid clinical re-evaluation including CNS imaging and assessment of tumor markers. Treatment of brain metastases includes intensified chemotherapy and surgical resection, irradiation has to be considered in special clinical situations. |
| Goedeke J, Haeberle B, Schmid I, von Schweinitz D |
30. AFP Negative Cystic Liver Lesion in a Child Should Let One Think of Hepatoblastoma. [+] |
J Pediatr Hematol Oncol 2011, 33:e245 |
|
| AFP is still the most important serologic marker for the hepatoblastoma as the most common liver tumor in children. An AFP negative hepatoblastoma is rare. We present the first documented case of an infant with an AFP negative and cystic liver lesion later diagnosed as a fetal hepatoblastoma. |
| Göbel U, von Kries R, Teske C, Schneider DT, Beyerlein A, Bernbeck B, Calaminus G |
Brain metastases during follow-up of children and adolescents with extracranial malignant germ cell tumors: Risk adapted management decision tree analysis based on data of the MAHO/MAKEI-registry. [+] |
Pediatric blood & cancer 2012, Epub ahead of print |
|
| BACKGROUND: The overall risk for brain metastases among children and adolescents with extracranial malignant germ cell tumors (mGCT) is low but may vary between subgroups. Early identification of subgroups with an increased risk for brain metastasis is therefore important. PROCEDURE: We analyzed 900/2,160 patients from the German MAHO/MAKEI registry on children and adolescents with malignant extracranial GCT (pure teratomas (grade 0-3) were not included). For follow-up evaluation, patients with brain metastases at diagnosis and those with a follow-up shorter than 32 months after diagnosis (longest interval to brain metastases in our cohort) were excluded. Patients were censored at detection of brain metastases or death due to other causes. A decision tree analysis considering age, gender, site of primary tumor, and presence of other metastases at diagnosis as risk factors for brain metastases was performed. RESULTS: Among 838 eligible patients, 9 acquired brain metastases during follow-up, accounting for death in 5. There were no brain metastases in absence of extracranial metastases at diagnosis. If extracranial metastases were detected in absence of mediastinal mGCT the risk for brain metastases was 1.2% (95% CI: 0.2-3.5.%). In contrast, risk was increased to 37.5 (95% CI 15.2-64.6%) in patients with mediastinal GCTs and extracranial metastases. CONCLUSION: A high-risk subgroup is detected with a decision tree analysis approach. These patients may benefit from an intensified chemotherapy. Close surveillance for CNS-metastases is warranted in this high-risk group while less close monitoring in low-risk patients is justified. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. |
| Goldwein JW, Leahy JM, Packer RJ, Sutton LN, Curran WJ, Rorke LB, Schut L, Littman PS, D'Angio GJ |
Intracranial ependymomas in children. [+] |
Int J Radiat Oncol Biol Phys 1990, 19: 1497 |
|
| Between 1970 and 1988, 51 children with intracranial ependymal tumors (33-infratentorial, 18-supratentorial received initial treatment at the University of Pennsylvania. Therapy consisted of total or near total tumor resection in 15 patients and partial resection or biopsy in 36. Postoperative irradiation alone was given to 18, chemotherapy to 4, and a combination of these two modalities to 26. Patients have been followed for a median period of 7.75 years. The 5-year actuarial survival and progression-free survival (PFS) rates are 46% and 30%, respectively. Of the 30 patients who have progressed, 29 did so locally and one died before the site of failure could be determined. Six patients also had disease outside the primary site at relapse; three of them had received craniospinal irradiation. Local control was significantly better for patients whose tumor dose exceeded 4500 cGy (32% vs. 0%, p = .01) and for Caucasian patients (34% vs. 15%, p =.05). Survival was better for patients who were over 4 years of age at diagnosis (55% vs. 30%, p = .04), for patients who received local radiation doses above 4500 cGy (51% vs. 18%, p = .01), and for Caucasian patients (43% vs. 14%, p = .01). Extent of resection, histology, location, the use of cranial or craniospinal irradiation, and the use of chemotherapy did not significantly impact on survival. We conclude that the inability to control local disease remains the single most important factor leading to treatment failure. Older age, higher local radiation dose, and Caucasian race appear to be the only favorable prognostic factors. |
| Goldstein-Jackson SY, Gosheger G, Delling G, Berdel WE, Exner GU, Jundt G, Machatschek JN, Zoubek A, Jürgens H, Bielack SS, Cooperative Osteosarcoma Study Group COSS |
Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma. [+] |
Journal of cancer research and clinical oncology 2005, 131: 520 |
|
| PURPOSE: The aims of this analysis were to investigate the clinical features of extraskeletal osteosarcoma (ESOS) and examine the outcome after multi-modal therapy. METHODS: The co-operative osteosarcoma study-group database was searched for patients with extraskeletal osteosarcoma. Eligible patients were included in a retrospective analysis of patient, tumour and treatment related variables and outcome. As for conventional osteosarcoma, scheduled treatment included surgery and multi-agent chemotherapy. RESULTS: Seventeen eligible patients were identified with a median age of 44 years (range, 3-65 years). The thigh was the commonest tumour site. Two patients had a history of previous malignancies and two had primary metastases. Median follow-up was 3.2 years (range: 0.6-7.4 years) and at last follow-up, 11 patients were alive in complete remission, 3 patients were alive with disease and 3 patients had died of their disease. Three-year overall actuarial and event-free survival rates were 77% and 56%, respectively. Patients with macroscopically complete surgical remission had an improved overall survival (P = 0.0004). CONCLUSIONS: The patients in this retrospective study had a surprisingly good survival rate. This may be due to the combination of multi-agent chemotherapy with surgery, and we recommend this approach in the treatment of ESOS. |
| Golan DE |
Hemolytic Anemias: redcell membrane and metabolic disorders. |
In: Goldman, L, Ausiele, D, eds,. Cecil medicine. 23rd. edt., Chap. 165 2007 |
|
| González-Murillo A, Lozano ML, Alvarez L, Jacome A, Almarza E, Navarro S, Segovia JC, Hanenberg H, Guenechea G, Bueren JA, Río P |
Development of lentiviral vectors with optimized transcriptional activity for the gene therapy of patients with fanconi anemia. [+] |
Human gene therapy 2010, 21: 623 |
|
| Fanconi anemia (FA) is an inherited genetic disease characterized mainly by bone marrow failure and cancer predisposition. Although gene therapy may constitute a good therapeutic option for many patients with FA, none of the clinical trials so far developed has improved the clinical status of these patients. We have proposed strategies for the genetic correction of bone marrow grafts from patients with FA, using lentiviral vectors (LVs). Here we investigate the relevance of the expression of FANCA to confer a therapeutic effect in cells from patients with FA-A, the most frequent complementation group in FA. Our data show that relatively weak promoters such as the vav or phosphoglycerate kinase (PGK) promoter confer, per copy of FANCA, physiological levels of FANCA mRNA in lymphoblastoid cell lines, whereas the cytomegalovirus and, more significantly, spleen focus-forming virus (SFFV) promoters mediated the expression of supraphysiological levels of FANCA mRNA. Insertion of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) or a mutated WPRE into the 3' region of PGK-FANCA LVs significantly increased FANCA mRNA levels. At the protein level, however, all tested vectors conferred, per copy of FANCA, similar and physiological levels of the protein, except SFFV LVs, which again conferred supraphysiological levels of FANCA. In spite of their different activity, all tested vectors mediated a similar phenotypic correction in FA-A lymphoblastoid cell lines and also in hematopoietic progenitors from patients with FA-A. On the basis of the efficacy and safety properties of PGK LVs, a PGK LV carrying FANCA and a mutant WPRE is proposed as an optimized vector for the gene therapy of patients with FA-A. |
| Gottstein C, Schon G, Tawadros S, Kube D, Wargalla-Plate U, Hansmann M, Wacker H, Berthold F, Diehl V, Engert A |
Antidisialoganglioside ricin A-chain immunotoxins show potent antitumor effects in vitro and in a disseminated human neuroblastoma severe combined immunodeficiency mouse model. |
Cancer Res 1994, 54: 6186 |
|
| Gottschling S, Längler A, Tautz C, Graf N |
Complementary and alternative medicine in pediatric oncology. [+] |
Klinische Pädiatrie 2006, 218: 157 |
|
| For many families of pediatric cancer patients the use of complementary and alternative medicine (CAM) is an accepted adjunct to conventional therapy, even if data regarding effects and risks are scarse. This report provides information about the prevalence of CAM use and reasons for CAM use among pediatric cancer patients. Frequently used CAM like nutrition (incl. diets and vitamins), homeopathy, anthroposophic medicine, phytotherapy, and acupuncture are highlighted, as were CAM bearing a special risk for their users. Physicians need to be more aware that a substantial percentage of their patients may use CAM without telling them for different reasons. Physicians need to be open-minded and should discuss CAM with parents. A differentiation between potentially useful and potentially dangerous CAM is necessary aiming at minimising the risks for CAM users. |
| Goumnerova L |
Results of stereotactic radiosurgery in the management of recurrent ependymoma. |
Proceedings VIIth Annual Symposium Pediatric Neurooncology, Abstract 30 Washington 1996 |
|
| Graf N, Winkler K, Betlemovic M, Fuchs N, Bode U |
Methotrexate pharmacokinetics and prognosis in osteosarcoma. |
J Clin Oncol 1994, 12: 1443 |
|
| Graf N |
Wilms' tumor. |
Schweiz Rundsch Med Prax 1996, 85: 753 |
|
| Graf N, Weirich A |
Wilms' tumor - the State of the Art. |
Onkologie 1996, 19: 36 |
|
| Graf N, Weirich A, de Kraker J |
Staging problems in the pre-operative chemotherapy of Wilms' tumour. |
Br J Urol 1996, 78: 479 |
|
| Graf N |
Nephroblastom (Wilmstumor). |
Qualitätssicherung in der Onkologie: Diagnostische und therapeutische Standards in der Pädiatrischen Onkologie 1997 |
|
| Graf N |
Der Wilstumor - State of the art. |
Monatsschr Kinderheilkd 1999 |
|
| Graf N, Zoubek A, Niggli F, Weirich A, Aliani S, Bürger D, Harms D, Flentje M, Pötter R, Zieger B, Ludwig R |
Tumor volume and prognosis in patients with localized unilateral nephroblastoma treated preoperatively. |
Med Pediatr Oncol 1999, 33 |
|
| Graf N, Zoubek A, Weirich A, Ludwig R |
Erste Ergebnisse der Nephroblastomstudie SIOP 93-01/GPOH und Darstellung einer Nachfolgestudie. |
Monatsschr Kinderheilkd 1999 |
|
| Graubner U, Boos J, Creutzig U, Dörffel W, Lakomek M, Niemeyer C, Schrappe M, Spaar H, Belohradsky B |
Die antiinfektiöse Prophylaxe in der Pädiatrischen Onkologie. |
Klinische Pädiatrie 1999, 211 |
|
| Graf N, Tournade M, de Kraker J |
The role of preoperative chemotherapy in the management of Wilms' tumor. The SIOP studies. International Society of Pediatric Oncology. |
Urol Clin North Am 2000, 27: 443 |
|
| Gray S, Eriksson T, Ekstrom C, Holm S, von Schweinitz D, Kogner P, Sandstedt B, Pietsch T, Ekstrom T |
Altered expression of members of the IGF-axis in hepatoblastomas. |
Br J Cancer 2000, 82: 1561 |
|
| Gray S, Eriksson T, Ekström C, Holm S, Schweinitz D, Kogner P, Sandstedt B, Pietsch T, Ekström T |
Decreased expression of insulin-like growth factor binding proteins 1 and 2 in hepatoblastomas; role of the IGF-axis components. |
British Journal of Cancer 2000, 82: 1561 |
|
| Grabenbauer GG, Schuchardt U, Buchfelder M, Rodel CM, Gusek G, Marx M, Doerr HG, Fahlbusch R, Huk WJ, Wenzel D, Sauer R |
Radiation therapy of optico-hypothalamic gliomas (OHG)--radiographic response, vision and late toxicity. |
Radiother Oncol 2000, 54: 239-45. |
|
| Graubner UB |
Antiviral prophylaxis. |
Klin Pädiatr 2001, 213 Suppl 1:A69 |
|
| Graubner UB, Liese J, Belohradsky BH |
Vaccination. |
Klin Pädiatr 2001 213 Suppl 1:A77 |
|
| Graf Einsiedel H, Taube T, Hartmann R, Wellmann S, Seifert G, Henze G, Seeger K |
Deletion analysis of p16(INKa) and p15(INKb) in relapsed childhood acute lymphoblastic leukemia. |
Blood 2002, 99: 4629 |
|
| Graf N, Reinhard H |
Wilms tumors. Diagnosis and therapy. |
Urologe A 2003, 42:W391-W407 |
|
| Graf N, Semler O, Reinhard H |
Prognosis of Wilm's tumor in the course of the SIOP trials and studies. |
Urologe A 2004, 43: 421 |
|
| Graf N |
Osteosarkome. |
in: Gutjahr P (Hrsg.): Krebs bei Kindern und Jugendlichen Deutscher Ärzte-Verlag, 5. Aufl. 2004, 473 |
|
| Graf N, Rübe C, Gessler M |
Nierentumoren, in: Gadner H, Gaedicke G, Niemeyer CH, Ritter J (Hrsg.): Pädiatrische Hämatologie und Onkologie. |
Springer-Verlag 2006, 847 |
|
| Graubner UB, Porzig S, Jorch N, Kolb R, Wessalowski R, Escherich G, Janka GE |
Impact of reduction of therapy on infectious complications in childhood acute lymphoblastic leukemia. [+] |
Pediatric blood & cancer 2008, 50: 259 |
|
| BACKGROUND: Infections are a major cause of morbidity and mortality in childhood acute lymphoblastic leukemia (ALL) and only limited information is available on infectious complications. PATIENTS AND METHODS: We investigated infectious complications in 293 children during different treatment phases of the multicenter protocol COALL-06-97. We also evaluated whether therapy reduction in prognostically good risk patients receiving either the low risk or high risk treatment arm would lead to fewer infectious complications. RESULTS: Thirty of 293 patients had no infections; 263 patients had 682 infectious complications (median 2, range 1-9), five of them lethal. Two thirds of the infections occurred during periods of neutropenia. The most frequent infectious episodes were fever of unknown origin (FUO): 483/682 (70.8%), microbiologically documented infections (MDI): 100/682 (14.6%), (61 gram-positive, 36 gram-negative, 3 fungal isolates), and clinically documented infections (CDI): 99/682 (14.5%). With standard reinduction, 44% low risk and 57% high risk patients had infections versus 26% low risk and 38% high risk patients with reduced reinduction therapy (P < 0.01). CONCLUSIONS: Most patients treated with intensive combination therapy for ALL experience one to several serious infections during treatment. The wide range in number of infectious episodes and the lack of infections in a small subset of patients in spite of uniform treatment suggest genetic as well as possibly environmental factors to have a role. Moderate reduction of chemotherapy may significantly reduce the rate of infectious episodes. |
| Graf N |
Nephroblastom. |
Leitlinie der Gesellschäft für Pädiatrische Onkologie und Hämatologie AWMF online 2010 |
|
| Grabow D, Spix C, Blettner M, Kaatsch P |
Strategy for long-term surveillance at the German Childhood Cancer Registry - an update. [+] |
Klin padiatr 2011, 223: 159 |
|
| BACKGROUND:
The objective of this paper is to provide information about the quality (e.g. completeness, response) of long-term surveillance in German paediatric oncology and haematology based on the structures implemented by the German Childhood Cancer Registry (GCCR).
METHODS:
The GCCR contacts parents or patients to collect and update information on a minimal set of follow-up health status data (e.g. late relapses, subsequent neoplasms, current address) and exchanges this information regularly with the appropriate clinical trials.
RESULTS:
Between 2006 and 2010, GCCR approached a total of about 20,000 patients (contact at the age of 16 years, inquiry concerning the health status) in the context of long-term surveillance. 11,000 addresses of former patients had to be researched via municipal registrar's offices. The response rates ranged from 56% to 68%, the research in municipal offices provided 93-96% valid addresses. Of 46,115 patients diagnosed between 1980 and 2009, 25,283 are in long-term surveillance in 2010.
DISCUSSION:
Long-term surveillance requires considerable logistic effort at GCCR and requires that thousands of letters be mailed each year in order to ensure regularly updated information. Long-term surveillance is indispensable for a better understanding of late effects, subsequent neoplasms and quality of life of former childhood cancer patients. |
| Grabow D, Lacher C, Kaatsch P |
Former childhood cancer patients need a competent help desk. |
Klin padiatr 2011, 223: 187 |
|
| Grace RF, Long M, Kalish LA, Neufeld EJ |
Applicability of 2009 international consensus terminology and criteria for immune thrombocytopenia to a clinical pediatric population. [+] |
Pediatric blood & cancer 2012, 58: 216 |
|
| Since pediatric immune thrombocytopenia (ITP) is relatively infrequent, comparisons among clinical studies are critical but have previously been limited by differences in terminology. In 2009, an international working group (IWG) developed consensus criteria to enhance comparability in future studies in adults and children. |
| Grace RF, Bennett CM, Ritchey AK, Jeng M, Thornburg CD, Lambert MP, Neier M, Recht M, Kumar M, Blanchette V, Klaassen RJ, Buchanan GR, Kurth MH, Nugent DJ, Thompson AA, Stine K, Kalish LA, Neufeld EJ |
Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia. [+] |
Pediatric blood & cancer 2012, 58: 221 |
|
| Treatment choice in pediatric immune thrombocytopenia (ITP) is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies. |
| Greaves M |
Childhood leukaemia. |
BMJ 2002, 324: 283 |
|
| Greten TF, Manns MP, Reinisch I, Kaatsch P |
Hepatocellular carcinoma occurring after successful treatment of childhood cancer with high dose chemotherapy and radiation. |
Gut 2005, 54: 732 |
|
| Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, Donaldson SS, Byrne J, Robison LL |
Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009 Jun 1; 27: 2677 |
|
| This study was undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on fertility. |
| Grigull L, Beier R, Schrauder A, Kirschner P, Loening L, Jack T, Welte K, Sykora K, Schrappe M |
Invasive fungal infections are responsible for one-fifth of the infectious deaths in children with ALL. |
Mycoses 2003, 46: 441 |
|
| Grimer R, Cannon S, Taminiau A, Bielack S, Kempf-Bielack B, Windhager R, Dominkus M, Saeter G, Bauer H, Meller I, Szendroi M, Folleras G, San Julian M, van der Eijken |
Osteosarcoma over the age of forty. |
Eur J Cancer 2003, 39: 157 |
|
| Grimer RJ, Bielack S, Flege S, Cannon SR, Foleras G, Andreeff I, Sokolov T, Taminiau A, Dominkus M, San-Julian M, Kollender Y, Gosheger G, European Musculo Skeletal Oncology Society |
Periosteal osteosarcoma--a European review of outcome. [+] |
European journal of cancer (Oxford, England : 1990) 2005, 41: 2806 |
|
| Periosteal osteosarcoma is a rare primary malignant bone tumour. Treatment is by surgical excision, but controversy remains about the value of chemotherapy. The members of the European Musculo Skeletal Oncology Society (EMSOS) collaborated to produce a dataset of 119 patients. The predominant site for the tumour was the femur, followed by the tibia. All but 2 patients underwent surgery, with 9 requiring amputation and the others having limb salvage. A total of 81 patients had chemotherapy, of whom 50 had neoadjuvant chemotherapy. There was no standard chemotherapy regime, but all patients receiving chemotherapy were given doxorubicin combined with at least one other agent. The overall survival was 89% at 5 years and 83% at 10 years. Eight patients developed local recurrence, of whom 5 died. Survival was related to appearance of local recurrence (P < 0.0001) but no other single factor. The use of chemotherapy was not shown to be a prognostic factor, but was used in two-thirds of the patients in this study. |
| Grois N, Flucher-Wolfram B, Heitger A, Mostbeck G, Hofmann J, Gadner H |
Diabetes insipidus in Langerhans cell histiocytosis. |
Med Pediatr Oncol 1995, 24: 248 |
|
| Grois N, Favara B, Mostbeck G, Prayer D |
Central nervous system disease in Langerhans cell histiocytosis. |
Hematol Oncol Clin North Am 1998, 12: 287 |
|
| Groll A, Ritter J, Müller F |
Prevention of fungal infections in children and adolescents with cancer. |
Klinische Pädiatrie 2001, 213 Suppl 1:A50-A68 |
|
| Groll AH, Ritter J, Muller FM |
Guidelines for Prevention of Pneumocystis carinii Pneumonitis in Children and Adolescents with Cancer. |
Klin Pädiatr 2001, 213 Suppl 1:A38 |
|
| Groll AH, Ritter J |
Diagnosis and management of fungal infections and pneumocystis pneumonitis in pediatric cancer patients. |
Klin Pädiatr 2005, 217 Suppl 1:S37 |
|
| van Grotel M, Meijerink JP, Beverloo HB, Langerak AW, Buys-Gladdines JG, Schneider P, Poulsen TS, den Boer ML, Horstmann M, Kamps WA, Veerman AJ, van Wering ER, van Noesel MM, Pieters R |
The outcome of molecular-cytogenetic subgroups in pediatric T-cell acute lymphoblastic leukemia: a retrospective study of patients treated according to DCOG or COALL protocols. [+] |
Haematologica 2006, 91: 1212 |
|
| BACKGROUND AND OBJECTIVES: Subgroups of T-cell acute lymphoblastic leukemia (T-ALL), defined according to recurrent cytogenetic aberrations, may have different prognoses. The aim of this study was to determine the prognostic relevance of molecular-cytogenetic abnormalities in pediatric patients using quantitative real-time polymerase chain reaction and fluorescence in situ hybridization. DESIGN AND METHODS: The patients were assigned to TAL1, HOX11/TLX1, HOX11L2/TLX3, or CALM-AF10 subgroups. The cytogenetic subgroups were characterized in relation to immunophenotype and the expression of aberrantly expressed transcription factors. RESULTS: In our cohort study, CALM-AF10 was associated with an immature immunophenotype and poor outcome (p=0.005). HOX11L2 was associated with both immunophenotypically immature cases as well as cases committed to the gammadelta-lineage. HOX11L2 was significantly associated with poor outcome (p=0.01), independently of the expression of CD1 or the presence of NOTCH1 mutations. TAL1 abnormalities were associated with alphabeta-lineage commitment, and tended to be associated with a good outcome. Cells in HOX11 cases resembled early CD1-positive cortical thymocytes without expression of Cytbeta and TCR molecules. In relation to the expression of early T-cell transcription factors, high TAL1 levels were found in immunophenotypically-advanced cases, whereas high LYL1 levels were found in immature subgroups. INTERPRETATION AND CONCLUSIONS: The reported outcomes for HOX11L2-rearranged T-ALL cases are conflicting; the prognostic impact may depend on the therapy given. In our cohort, this cytogenetic aberration was associated with a poor outcome. Our data on CALM-AF10 rearranged T-ALL, albeit based on only three patients, suggest that this type of leukemia is associated with a poor outcome. |
| Grotzer MA, von Hoff K, von Bueren AO, Shalaby T, Hartmann W, Warmuth-Metz M, Emser A, Kortmann RD, Kuehl J, Pietsch T, Rutkowski S |
Which clinical and biological tumor markers proved predictive in the prospective multicenter trial HIT'91--implications for investigating childhood medulloblastoma. [+] |
Klinische Padiatrie 2007, 219: 312 |
|
| BACKGROUND: Most recent studies analyzing candidate biological prognostic factors in childhood medulloblastoma (MB) are limited by small patient numbers due to dependence on fresh-frozen tumor material. By contrast, large archives of formalin-fixed, paraffin-embedded MB samples exist from homogeneously treated patients. PATIENTS AND METHODS: We have optimized RNA and DNA isolation from formalin-fixed paraffin-embedded MB samples. We then analyzed archived tumor samples from well-documented patients treated within the prospective randomized multicenter trial HIT'91 for DNA amplification of c-myc and N-myc, and mRNA expression of c-myc and trkC. RESULTS: TrkC and c-myc mRNA expression were identified as independent prognostic factors by multivariate analysis. Three risk groups were identified: 1) Favorable risk group: All 8 patients (2 metastatic) with elevated trkC and reduced c-myc mRNA expression (compared to levels of human cerebellum) remained relapse-free (7-year EFS 100%). 2) Poor risk group: 10 of 15 patients with metastatic disease and high c-myc and low trkC mRNA expression relapsed (7-year EFS 33%). 3) Intermediate risk group: The 7-year EFS of the remaining 78 patients was 65%. CONCLUSIONS: While the collection of fresh-frozen tumor samples is remaining a major challenge in large clinical trials, routinely processed paraffin-embedded tissue samples can be used to quantitate biological prognostic factors on the DNA and RNA level. Upon prospective validation of cut-off levels, this may lead to better risk-based stratification systems for children with medulloblastoma. |
| Grotegut S, Kappler R, Tarimoradi S, Lehembre F, Christofori G, Von Schweinitz D |
Hepatocyte growth factor protects hepatoblastoma cells from chemotherapy-induced apoptosis by AKT activation. [+] |
International journal of oncology 2010, 36: 1261 |
|
| Hepatocyte growth factor/scatter factor (HGF) is a ubiquitously expressed molecule that elicits pleiotropic functions on epithelial cells, including mitogenic, motogenic, differentiating, angiogenic and morphogenic effects. In hepatoblastoma (HB), post-operative residual tumor growth and tumor recurrences are often associated with markedly elevated serum levels of HGF, suggesting a link between this molecule and tumor malignancy. Here, we demonstrate that HGF has no impact on overall cell viability and proliferation of HB cells, although signal transduction occurs downstream of HGF, such as c-Met phosphorylation, activation of phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK-1/2 signaling. Instead of being mitogenic, HGF confers anti-apoptotic properties upon serum starvation and moreover protects HB cells against strong apoptotic inducers such as cisplatin and camptothecin, thereby contributing to chemotherapeutic resistance. This effect is mainly dependent on the PI3K/AKT signaling pathway, since inhibition by wortmannin resulted in abrogation of HGF-mediated survival, whereas inhibition of the MAPK pathway had no effect. Together, these findings highlight the importance of HGF in tumor cell survival and suggest that HGF and its cognate receptor c-Met should be considered as a candidate for combined therapeutic strategies of advanced pediatric liver tumors. |
| Grundy RG, Wilne SA, Weston CL, Robinson K, Lashford LS, Ironside J, Cox T, Chong WK, Campbell RH, Bailey CC, Gattamaneni R, Picton S, Thorpe N, Mallucci C, English MW, Punt JA, Walker DA, Ellison DW, Machin D, Children's Cancer and Leukaemia Group (formerly UKCCSG) Brain Tumour Committee |
Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study. [+] |
The lancet oncology 2007, 8: 696 |
|
| BACKGROUND: Over half of childhood intracranial ependymomas occur in children younger than 5 years. As an adjuvant treatment, radiotherapy can be effective, but has the potential to damage the child's developing nervous system at a crucial time-with a resultant reduction in IQ and cognitive impairment, endocrinopathy, and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with intracranial ependymoma. METHODS: Between December, 1992, and April, 2003, we enrolled 89 children with ependymoma who were aged 3 years or younger at diagnosis, of whom nine had metastatic disease on pre-operative imaging. After maximal surgical resection, children received alternating blocks of myelosuppressive and non-myelosuppressive chemotherapy every 14 days for an intended duration of 1 year. Radiotherapy was withheld unless local imaging (ie, from the child's treatment centre) showed progressive disease. FINDINGS: 50 of the 80 patients with non-metastatic disease progressed, 34 of whom were irradiated for progression. The 5-year cumulative incidence of freedom from radiotherapy for the 80 non-metastatic patients was 42% (95% CI 32-53). With a median follow-up of 6 years (range 1.5-11.3), overall survival for the non-metastatic patients at 3 years was 79.3% (95% CI 68.5-86.8) and at 5 years 63.4% (51.2-73.4). The corresponding values for event-free survival were 47.6% (36.2-58.1) and 41.8% (30.7-52.6). There was no significant difference in event-free or overall survival between complete and incomplete surgical resection, nor did survival differ according to histological grade, age at diagnosis, or site of disease. In 47 of 59 (80%) patients who progressed, relapse resulted from local control only. The median time to progression for the 59 patients who progressed was 1.6 years (range 0.1-10.2 years). The median age at irradiation of the whole group was 3.6 years (range 1.5-11.9). For the 80 non-metastatic patients, the 23 who achieved the highest relative dose intensity of chemotherapy had the highest post-chemotherapy 5-year overall survival of 76% (95% CI 46.6-91.2), compared with 52% (33.3-68.1) for the 32 patients who achieved the lowest relative dose intensity of chemotherapy. INTERPRETATION: This protocol avoided or delayed radiotherapy in a substantial proportion of children younger than 3 years without compromising survival. These results suggest, therefore, that primary chemotherapy strategies have an important role in the treatment of very young children with intracranial ependymoma. |
| Guardiola P, Socié G, Pasquini R, Dokal I, Ortega JJ, van Weel-Sipman M, Marsh J, Locatelli F, Souillet G, Cahn JY, Ljungman P, Miniero R, Shaw J, Vermylen C, Archimbaud E, Bekassy AN, Krivan G, Di Bartolomeo P, Bacigalupo A, Gluckman E |
Allogeneic stem cell transplantation for Fanconi Anaemia. Severe Aplastic Anaemia Working Party of the EBMT and EUFAR. European Group for Blood and Marrow Transplantation. [+] |
Bone Marrow Transplant 1998, 21 Suppl 2:S24 |
|
| Fanconi anaemia is a hereditary disorder characterised by chromosomal breaks increased by cross-linking agents. Bone marrow transplantation is the treatment of choice when a HLA identical sibling donor has been identified. The use of low-dose cyclophosphamide with thoraco-abdominal irradiation for the conditioning regimen of FA patients has lead to a dramatic improvement of survival, with a long-term survival of 75% at our institution. However, if most patients are completely cured of their haematological disease, there is concern about an increased frequency of secondary tumours, mostly head and neck squamous cell carcinomas of poor prognosis. Results of BMT using alternative donors (HLA mismatched related and unrelated donors) have also improved during the last decade. A better selection of the donor via high-resolution techniques for class-II HLA matching, and more recently the use of T cell depleted grafts are probably the main explanations. Despite a short follow-up and the small number of patients analysed, transplants using HLA matched family cord blood give some promising results. On the other hand, first results with unrelated cord blood remind that this approach is clearly an experimental one that has to be evaluated through international registries and prospective studies. New approaches including autologous stem cell transplantations and gene therapy are currently explored. |
| Guardiola P, Pasquini R, Dokal I, Ortega JJ, van Weel-Sipman M, Marsh JC, Ball SE, Locatelli F, Vermylen C, Skinner R, Ljungman P, Miniero R, Shaw PJ, Souillet G, Michallet M, Bekassy AN, Krivan G, Di Bartolomeo P, Heilmann C, Zanesco L, Cahn JY, Arcese W, Bacigalupo A, Gluckman E |
Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation. [+] |
Blood 2000, 95: 422 |
|
| Allogeneic stem cell transplantation is the only treatment that can restore a normal hematopoiesis in Fanconi anemia (FA). In this retrospective multicenter study, we analyzed the results of this approach using HLA-matched unrelated bone marrow donors, and tried to identify covariates predicting the outcome of the transplant. From January 1985 to June 1998, 69 FA patients were transplanted with unrelated HLA-matched donors. Patients' characteristics before and after transplant were provided by the European group blood and marrow transplant registry and were analyzed in collaboration with the European Fanconi Anemia Registry. The 3-year probability of survival was 33%. Extensive malformations, a positive recipient cytomegalovirus serology, the use of androgens before transplant, and female donors were associated with a worse outcome. Primary graft failures were observed more frequently when female donors were used, mainly because the grafts contained lower nucleated cell doses per kilogram of recipient body weight compared with grafts coming from male donors. The probability of grade III-IV acute graft-versus-host disease (GVHD) was 34%. Elevated serum alanine/aspartate transaminases before transplantation; limb, urogenital tract, or nephrologic malformations; and non-T-cell-depleted grafts were predictors of severe acute GVHD. This study shows the dramatic impact of preexisting congenital malformations on the outcome of FA patients transplanted with HLA-matched unrelated donors. If the use of T-cell depletion has led to a dramatic reduction of acute GVHD incidence, no significant outcome improvement was observed with this approach, mainly because of an increased risk of graft failure. (Blood. 2000;95:422-429) |
| Guggemos A, Eckert C, Szczepanski T, Hanel C, Taube T, van der, Graf-Einsiedel H, Henze G, Seeger K |
Assessment of clonal stability of minimal residual disease targets between 1st and 2nd relapse of childhood precursor B-cell acute lymphoblastic leukemia. |
haematologica 2003, 88: 736 |
|
| Gunther P, Troger J, Graf N, Waag K, Schenk J |
MR volumetric analysis of the course of nephroblastomatosis under chemotherapy in childhood. |
Pediatr Radiol 2004, 34: 660 |
|
| Gururangan S, McLaughlin C, Quinn J, Rich J, Reardon D, Halperin EC, Herndon J, Fuchs H, George T, Provenzale J, Watral M, McLendon RE, Friedman A, Friedman HS, Kurtzberg J, Vredenbergh J, Martin PL |
High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas. [+] |
J Clin Oncol 2003, 21: 2187 |
|
| PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. RESULTS: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. CONCLUSION: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma. |
| Gutjahr P |
Krebs? Mein Kind? Leukämie und bösartige Tumoren bei Kindern. |
S. Hirzel Verlag Stuttgart - Leipzig 2000, 53 |
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| Gutjahr P |
Krebs bei Kindern und Jugendlichen. |
Deutscher Ärzte-Verlag Köln 5. Aufl. 2004 |
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| Gutjahr P |
Tumoren des Zentralnervensystems, in: Gutjahr P (Hrsg.): Krebs bei Kindern und Jugendlichen. |
Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 373 |
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| Gutjahr P |
Retinoblastome, in: Gutjahr P (Hrsg.): Krebs bei Kindern und Jugendlichen. |
Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 499 |
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| Göhring G, Karow A, Steinemann D, Wilkens L, Lichter P, Zeidler C, Niemeyer C, Welte K, Schlegelberger B |
Chromosomal aberrations in congenital bone marrow failure disorders--an early indicator for leukemogenesis? [+] |
Annals of hematology 2007, 86: 733 |
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| As chromosomal instability may contribute to leukemogenesis in patients with congenital bone marrow failure (CBMF) disorders, it was the aim of this study to characterize chromosomally aberrant clones that arise during the clinical course of disease by means of R-banding and fluorescence in situ hybridization (FISH) analyses. In addition, multicolor-FISH and array-comparative genomic hybridization (CGH) were applied to characterize clonal chromosome aberrations in more detail. Between January 2004 and December 2005, we prospectively analyzed 90 samples of 73 patients with proven or suspected CBMF disorders enrolled in a German Study Network of CBMF diseases. Clonal aberrations could be identified in four of 73 patients examined. In one child with congenital thrombocytopenia, Jacobsen syndrome [del(11)(q24)c] was diagnosed, and thus a CBMF could be excluded. In a girl with Shwachman-Diamond syndrome, two independent clones, one with an isochromosome i(7)(q10), another with a complex aberrant karyotype, were identified. Simultaneously, transition into a myelodysplastic syndrome (MDS) occurred. The brother, who was also afflicted with Shwachman-Diamond syndrome, showed an isochromosome i(7q) as a single aberration. In the fourth patient with severe congenital neutropenia, an add(21)(q22) marker containing a low-level amplification of the AML1 gene was identified at the time point of transition into acute myelogenous leukemia (AML). In summary, we suggest that follow-up of patients with CBMF using chromosome and FISH analyses will be helpful for the early detection of transition into MDS or AML and thus should be an integral part of the clinical management of these patients. |
| Göbel U, Bamberg M, Calaminus G, Gnekow A, Herrmann H, Lenard H, Spaar H, Niethammer D, Kühl J, Harms D |
Improved prognosis of intracranial germ cell tumors by intensified therapy. |
Klin Pädiatr 1993, 205: 217 |
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| Göbel U, Calaminus G, Teske C, Bamberg M, Bokkerink J, Haas R, Holschneider A, Janka-Schaub G, Jürgens H, Mittler U |
BEP/VIP in children and adolescents with malignant non-testicular germ cell tumors. A comparison of the results of treatment of therapy studies MAKEI 83/86 and 89P/89. |
Klin Pädiatr 1993, 205: 231 |
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| Göbel U, Calaminus G, Harms D |
Ovarielle Keimzelltumoren bei Kindern und Jugendlichen:Ergebnisse der Studien MAKEI 1983/86 und 89 der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH). |
GPOH 1995, 23 |
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| Göbel U, Calaminus G, Harms D |
[Germ cell tumors in children and adolescents]. [+] |
Praxis 1995 Sep 26; 84: 1063 |
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| 3.7% of the diagnoses in the Pediatric Tumour Registry (Zentrales Tumor-Register) of the German Society for Pediatric Oncology and Haematology (Gesellschaft für Pädiatrische Onkologie und Hämatologie) concern germ cell tumors. The annual incidence has increased from 0.22 in 1980 to 0.60 per 100,000 children in 1992. The most common localizations are the coccygeal region (25%), followed by the testes (20%), the ovaries (20%) or the brain (20%). Some malignant germ cell tumors tend to secret the tumour markers Alpha-1-Feto-protein and HCG, and may then be diagnosed clinically due to the increased serum or spinal fluid levels. In the cases of extensive tumors growth and secreting intracranial germ cell tumors, a preoperative chemotherapy is favourable. The latest chemotherapy regime containing Cis-Platinum allows us to achieve long term remission in 80% of cases. Risk factors for the regime include histology, localization stage, and incomplete resection of the primary tumors. |
| Göbel U |
Teratome und andere Keimzelltumoren. |
Therapie der Krankheiten im Kindes- und Jugendalter 1997, 507 |
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| Göbel U, Calaminus G, Blohm M, Booss D, Felberbauer F, Hofmann U, Holschneider AM, Willnow U, Harms D |
Extracranial non-testicular teratoma in childhood and adolescence: introduction of a risk score for stratification of therapy. [+] |
Klinische Padiatrie 1997, 209: 228 |
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| PATIENTS AND METHODS: According to previous literature incomplete tumor resection, coccygeal or ovarian primary site and immaturity are known risk factors for relapse in teratoma. To establish a risk score points are allocated for resection, primary site and histology in the following manner and added: incomplete resection 4 points, primary site coccyx 3 points, ovary 2 points, other site 1 point, histological grading 0-3 points. This score system is evaluated on 270 extracranial non-testicular teratoma cases collected between 1982 and 1995 in the MAKEI cooperative treatment protocols of the German Society of Pediatric Oncology and Hematology. Treatment was resection alone (230 patients) or resection followed by postoperative adjuvant chemotherapy (40 patients). RESULTS: Patients treated with surgery alone: 28/230 (12%) patients relapsed, 14/230 (6%) patients showed highly malignant histology (mostly yolk sac tumor) in relapse. Mortality in case of relapse was 6/28 (21%). Patients scoring > or = 6 points (n = 45) had a relapse rate of 21/45 (47%) resulting in a 23%-mortality (5/21). Patients scoring < 6 points (n = 185) had a 4%-relapse risk (8/185) resulting in 13%-mortality (1/8) (p < 0.01). Patients treated with surgery and adjuvant chemotherapy: 7/40 patients (18%) suffered a relapse, none of them showing malignant histology. Mortality rate in case of relapse was 3/7 (43%). Patients scoring > or = 6 points initially treated with adjuvant chemotherapy (n = 18) had a relapse rate of 7/18 (39%), compared to patients scoring < 6 points (n = 22), in whom no relapses occurred (p < 0.01). There were no highly malignant relapses in the group treated with adjuvant chemotherapy. Regardless of the scored points the difference in highly malignant relapse histology comparing the group treated with surgery and adjuvant chemotherapy to the group treated with surgery was statistically significant (p = 0.02). CONCLUSION: The risk score system marks a high risk group including 63/270 (23%) of all evaluated extracranial non-testicular teratoma cases (scoring > or = 6 points). In this group 28/35 (80%) of relapses and 8/9 (89%) of tumor deaths occurred. For this high risk group a randomized trial will be suggested to evaluate the effect of adjuvant chemotherapy on the rate of malignant relapses. It should also be investigated, if adjuvant chemotherapy will influence relapse rate and mortality. |
| Göbel U, Calaminus G, Haas H |
Keimzelltumoren. |
Diagnostische und therapeutische Standards in der Pädiatrischen Onkologie 1997, 69 |
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| Göbel U, Calaminus G, Haas H |
Keimzelltumoren im Kindesalter, in Schmoll, H.-J, Höffken, K, Possinger, K. (Hrsg.). |
Kompendium internistischer Onkologie, Berlin, Springer 1997, 2 |
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| Göbel U, Calaminus G, Haas R |
Keimzelltumoren. |
Uroonkologie 1997, 598 |
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| Göbel U, Calaminus G, Engert J, Kaatsch P, Gadner H, Bokkerink J, Hass R, Waag K, Blohm M, Dippert S, Teske C, Harms D |
Teratomas in infancy and childhood. |
Med Pediatr Oncol 1998, 31: 8 |
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| Göbel U, Calaminus G, Waag K, Jonat W, Harms D |
Extracranial non-testicular teratoma in childhood and adolescents-the German experience. |
Germ Cell Tumors 1998,IV: 233 |
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| Göbel U, Calaminus G, Haas R |
Keimzelltumoren im Kindesalter (Solide Tumoren im Kindesalter). |
Kompendium internistischer Onkologie In Schmoll, H -J , Höffken,K , Possinger,K (eds), Berlin, Springer 1999, 2 |
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| Göbel U, Schneider D, Calaminus G, Harms D |
Tumoren im Kindesalter. Maligne Keimzelltumoren. |
Onkologie systematisch (Diagnostik und interdisziplinäre Therapie maligner Tumoren) 1999, 396 |
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| Göbel U, Calaminus G, Bamberg M, Engert J, Haas H, Jonat W, Kortmann R, Schneider D, Harms D |
Keimzelltumoren bei Kindern und Jugendlichen. |
Der Onkologe 2000, 6 |
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| Göbel U, Calaminus G, Engert J, Haas R, Jonat W, Harms D |
Malignant extracranial non-testicular germ cell tumors (GCTs)-the German experience. |
Germ Cell Tumors 2000,IV: 205 |
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| Göbel U, Schneider D, Calaminus G, Haas R, Schmidt P, Harms D |
Germ-cell tumors in childhood and adolescence. GPOH MAKEI and the MAHO study groups. |
Ann Oncol 2000, 11: 263 |
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| Göbel U, Schneider D, Calaminus G, Jürgens H, Spaar H, Sternschulte W, Waag K, Harms D |
Multimodal treatment of malignant sacrococcygeal germ cell tumors. |
J Clin Oncol 2001, 19: 1943 |
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