Children's Oncology Group's 2013 blueprint for research: Bone tumors

In the US, approximately 650 children are diagnosed with osteosarcoma and Ewing sarcoma (ES) each year. Five‐year survival ranges from 65% to 75% for localized disease and <30% for patients with metastases. Recent findings include interval‐compressed five drug chemotherapy improves survival with localized ES. In osteosarcoma a large international trial investigating the addition of ifosfamide/etoposide or interferon to standard therapy has completed accrual. For ES an ongoing trial explores the addition of cyclophosphamide/topotecan to interval‐compressed chemotherapy. Trials planned by the Children's Oncology Group will investigate new target(s) including IGF‐1R and mTOR in ES, and RANKL and GD2 in osteosarcoma. Pediatr Blood Cancer 2013; 60: 1009–1015. © 2012 Wiley Periodicals, Inc.

[1]  S. Baruchel,et al.  A pilot study of low‐dose anti‐angiogenic chemotherapy in combination with standard multiagent chemotherapy for patients with newly diagnosed metastatic Ewing sarcoma family of tumors: A Children's Oncology Group (COG) Phase II study NCT00061893 , 2013, Pediatric blood & cancer.

[2]  J. Healey,et al.  Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  X. Chen,et al.  DNA Methylation and Gene Expression Profiling of Ewing Sarcoma Primary Tumors Reveal Genes That Are Potential Targets of Epigenetic Inactivation , 2012, Sarcoma.

[4]  S. Lipshultz,et al.  Phase II trial of trastuzumab in combination with cytotoxic chemotherapy for treatment of metastatic osteosarcoma with human epidermal growth factor receptor 2 overexpression: a report from the children's oncology group. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  C. Thiele,et al.  Epigenetic Changes in Pediatric Solid Tumors: Promising New Targets , 2012, Clinical Cancer Research.

[6]  William Wheeler,et al.  Detectable clonal mosaicism and its relationship to aging and cancer , 2012, Nature Genetics.

[7]  O. Delattre,et al.  A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion , 2012, Nature Genetics.

[8]  R. Khokha,et al.  Homotypic RANK signaling differentially regulates proliferation, motility and cell survival in osteosarcoma and mammary epithelial cells , 2012, Journal of Cell Science.

[9]  M. Ladanyi,et al.  Molecular pathogenesis of Ewing sarcoma: new therapeutic and transcriptional targets. , 2012, Annual review of pathology.

[10]  J. Lieb,et al.  Tumor-specific retargeting of an oncogenic transcription factor chimera results in dysregulation of chromatin and transcription. , 2012, Genome research.

[11]  D. Reinke,et al.  R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II Sarcoma Alliance for Research through Collaboration study. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  U. Dirksen,et al.  Preliminary efficacy of the anti-insulin-like growth factor type 1 receptor antibody figitumumab in patients with refractory Ewing sarcoma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  J. Toretsky,et al.  Investigation of the insulin‐like growth factor‐1 signaling pathway in localized Ewing sarcoma , 2011, Cancer.

[14]  R. Kurzrock,et al.  R1507, an Anti-Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antibody, and EWS/FLI-1 siRNA in Ewing's Sarcoma: Convergence at the IGF/IGFR/Akt Axis , 2011, PloS one.

[15]  S. Lessnick,et al.  Promiscuous partnerships in Ewing's sarcoma. , 2011, Cancer genetics.

[16]  Qing-Rong Chen,et al.  Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening. , 2011, Journal of the National Cancer Institute.

[17]  P. Lollini,et al.  Efficacy of and resistance to anti-IGF-1R therapies in Ewing's sarcoma is dependent on insulin receptor signaling , 2011, Oncogene.

[18]  Jason U Tilan,et al.  Dipeptidyl Peptidases as Survival Factors in Ewing Sarcoma Family of Tumors , 2011, The Journal of Biological Chemistry.

[19]  Richard Gorlick,et al.  Initial testing (stage 1) of the IGF‐1 receptor inhibitor BMS‐754807 by the pediatric preclinical testing program , 2011, Pediatric blood & cancer.

[20]  J. Khan,et al.  Ecteinascidin 743 interferes with the activity of EWS-FLI1 in Ewing sarcoma cells. , 2011, Neoplasia.

[21]  Aaron R Cooper,et al.  Ewing Tumors That Do Not Overexpress BMI-1 Are a Distinct Molecular Subclass with Variant Biology: A Report from the Children's Oncology Group , 2010, Clinical Cancer Research.

[22]  Helen X. Chen,et al.  Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. , 2010, The New England journal of medicine.

[23]  T. Triche,et al.  Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice. , 2010, The Journal of clinical investigation.

[24]  J. Schiffman,et al.  Recent advances in the molecular pathogenesis of Ewing's sarcoma , 2010, Oncogene.

[25]  Y. Iwamoto,et al.  Inhibition of the transcriptional function of p53 by EWS-Fli1 chimeric protein in Ewing Family Tumors. , 2010, Cancer letters.

[26]  S. Keir,et al.  Initial testing of a monoclonal antibody (IMC‐A12) against IGF‐1R by the pediatric preclinical testing program , 2010, Pediatric blood & cancer.

[27]  E. Kleinerman,et al.  Inhaled Granulocyte-Macrophage Colony Stimulating Factor for First Pulmonary Recurrence of Osteosarcoma: Effects on Disease-Free Survival and Immunomodulation. A Report From the Children's Oncology Group , 2010, Clinical Cancer Research.

[28]  T. Triche,et al.  Current treatment protocols have eliminated the prognostic advantage of type 1 fusions in Ewing sarcoma: a report from the Children's Oncology Group. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  U. Dirksen,et al.  Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  P. Choong,et al.  RANK-Fc inhibits malignancy via inhibiting ERK activation and evoking caspase-3-mediated anoikis in human osteosarcoma cells , 2010, Clinical & Experimental Metastasis.

[31]  R. Kurzrock,et al.  A Phase I Study of Weekly R1507, A Human Monoclonal Antibody Insulin-like Growth Factor-I Receptor Antagonist, in Patients with Advanced Solid Tumors , 2010, Clinical Cancer Research.

[32]  Sakae Tanaka,et al.  Systemic RANK‐Fc protein therapy is efficacious against primary osteosarcoma growth in a murine model via activity against osteoclasts , 2010, The Journal of pharmacy and pharmacology.

[33]  C. Hill,et al.  Emergent Properties of EWS/FLI Regulation via GGAA Microsatellites in Ewing's Sarcoma. , 2010, Genes & cancer.

[34]  S. Schuetze,et al.  Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study. , 2010, The Lancet. Oncology.

[35]  H. Kovar Downstream EWS/FLI1 - upstream Ewing's sarcoma , 2010, Genome Medicine.

[36]  K. Matthay,et al.  Flow cytometric detection of Ewing sarcoma cells in peripheral blood and bone marrow , 2010, Pediatric blood & cancer.

[37]  L. Wexler,et al.  Irinotecan and temozolomide for Ewing sarcoma: The Memorial Sloan‐Kettering experience , 2009, Pediatric blood & cancer.

[38]  A. Tolcher,et al.  Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  S. Lessnick,et al.  EWS/FLI and its downstream target NR0B1 interact directly to modulate transcription and oncogenesis in Ewing's sarcoma. , 2009, Cancer research.

[40]  S. Lessnick,et al.  GSTM4 is a microsatellite-containing EWS/FLI target involved in Ewing's sarcoma oncogenesis and therapeutic resistance , 2009, Oncogene.

[41]  P. Houghton,et al.  The insulin-like growth factor-1 receptor-targeting antibody, CP-751,871, suppresses tumor-derived VEGF and synergizes with rapamycin in models of childhood sarcoma. , 2009, Cancer research.

[42]  Lisa Mirabello,et al.  International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons , 2009, International journal of cancer.

[43]  A. Lazar,et al.  Ewing’s Sarcoma: Standard and Experimental Treatment Options , 2009, Current treatment options in oncology.

[44]  E. Álava,et al.  Stable interference of EWS–FLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target , 2009, British Journal of Cancer.

[45]  A. Üren,et al.  GLI1 Is a Direct Transcriptional Target of EWS-FLI1 Oncoprotein* , 2009, Journal of Biological Chemistry.

[46]  L. Mirabello,et al.  Osteosarcoma incidence and survival rates from 1973 to 2004 , 2009, Cancer.

[47]  Robert E. Brown,et al.  Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in Ewing family of tumors. , 2009, Annals of clinical and laboratory science.

[48]  K. Stegmaier,et al.  Phase II study of intermediate‐dose cytarabine in patients with relapsed or refractory Ewing sarcoma: A report from the Children's Oncology Group , 2009, Pediatric blood & cancer.

[49]  B. Pitard,et al.  Therapeutic efficacy of soluble receptor activator of nuclear factor-kappa B-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma , 2010 .

[50]  M. Kauer,et al.  EWS-FLI1 suppresses NOTCH-activated p53 in Ewing's sarcoma. , 2008, Cancer research.

[51]  J. Reubi,et al.  High Expression of Neuropeptide Y1 Receptors in Ewing Sarcoma Tumors , 2008, Clinical Cancer Research.

[52]  Stephen C. Haroldsen,et al.  Microsatellites as EWS/FLI response elements in Ewing's sarcoma , 2008, Proceedings of the National Academy of Sciences.

[53]  Natalie K. Wolf,et al.  IGF1 Is a Common Target Gene of Ewing's Sarcoma Fusion Proteins in Mesenchymal Progenitor Cells , 2008, PloS one.

[54]  M. Goodman,et al.  Changes in Incidence and Survival of Ewing Sarcoma Patients Over the Past 3 Decades: Surveillance Epidemiology and End Results Data , 2008, Journal of pediatric hematology/oncology.

[55]  S. Keir,et al.  Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF‐1 receptor by the pediatric preclinical testing program , 2008, Pediatric blood & cancer.

[56]  T. Triche,et al.  The EWS/FLI1 oncogenic transcription factor deregulates GLI1 , 2008, Oncogene.

[57]  D. West,et al.  Randomized comparison of every-two-week v. every-three-week chemotherapy in Ewing sarcoma family tumors (ESFT) , 2008 .

[58]  John H. Healey,et al.  Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma: A report from the Children’s Oncology Group , 2008 .

[59]  Stephen L. Lessnick,et al.  EWS/FLI Mediates Transcriptional Repression via NKX2.2 during Oncogenic Transformation in Ewing's Sarcoma , 2008, PloS one.

[60]  Paul A Meyers,et al.  Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival--a report from the Children's Oncology Group. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  S. Lessnick,et al.  A transcriptional profiling meta-analysis reveals a core EWS-FLI gene expression signature , 2008, Cell cycle.

[62]  D. Heymann,et al.  Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells. , 2007, Oncology reports.

[63]  J. Squire,et al.  Identification of cryptic microaberrations in osteosarcoma by high-definition oligonucleotide array comparative genomic hybridization. , 2007, Cancer genetics and cytogenetics.

[64]  Yuzhuo Wang,et al.  Modulation by decitabine of gene expression and growth of osteosarcoma U2OS cells in vitro and in xenografts: Identification of apoptotic genes as targets for demethylation , 2007, Cancer Cell International.

[65]  B. Pitard,et al.  Therapeutic relevance of osteoprotegerin gene therapy in osteosarcoma: blockade of the vicious cycle between tumor cell proliferation and bone resorption. , 2007, Cancer research.

[66]  M. Sydes,et al.  International collaboration is feasible in trials for rare conditions: the EURAMOS experience. , 2007, Cancer treatment and research.

[67]  O. Delattre,et al.  Mesenchymal stem cell features of Ewing tumors. , 2007, Cancer cell.

[68]  B. Le Goff,et al.  Human osteosarcoma cells express functional receptor activator of nuclear factor‐kappa B , 2007, The Journal of pathology.

[69]  M Beth McCarville,et al.  Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma , 2007, Pediatric blood & cancer.

[70]  S. Lessnick,et al.  NR0B1 Is Required for the Oncogenic Phenotype Mediated by EWS/FLI in Ewing's Sarcoma , 2006, Molecular Cancer Research.

[71]  P. Cohen,et al.  Insulin‐like growth factor binding protein 3 as an anticancer molecule in Ewing's sarcoma , 2006, International journal of cancer.

[72]  A. Martins,et al.  Insulin-Like Growth Factor I Receptor Pathway Inhibition by ADW742, Alone or in Combination with Imatinib, Doxorubicin, or Vincristine, Is a Novel Therapeutic Approach in Ewing Tumor , 2006, Clinical Cancer Research.

[73]  T. Golub,et al.  Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma. , 2006, Cancer cell.

[74]  S. Ferrari,et al.  Neoadjuvant chemotherapy with high-dose Ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: a joint study by the Italian and Scandinavian Sarcoma Groups. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[75]  E. Kleinerman,et al.  Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[76]  S. Knuutila,et al.  Gene amplifications in osteosarcoma—CGH microarray analysis , 2005, Genes, chromosomes & cancer.

[77]  M. Semik,et al.  Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[78]  M. Ladanyi,et al.  Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[79]  O. Delattre,et al.  EWS/FLI-1 Silencing and Gene Profiling of Ewing Cells Reveal Downstream Oncogenic Pathways and a Crucial Role for Repression of Insulin-Like Growth Factor Binding Protein 3 , 2004, Molecular and Cellular Biology.

[80]  P. Meltzer,et al.  Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[81]  P. Picci,et al.  Impact of IGF-I/IGF-IR circuit on the angiogenetic properties of Ewing's sarcoma cells. , 2003, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[82]  T. Taki,et al.  Aberrations of p16INK4A, p14ARF and p15INK4B genes in pediatric solid tumors. , 2003, International journal of oncology.

[83]  W. Winkelmann,et al.  Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[84]  A. Pappo,et al.  Treatment of Ewing sarcoma family of tumors: current status and outlook for the future. , 2003, Medical and pediatric oncology.

[85]  M. Link,et al.  Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[86]  S. Donaldson,et al.  Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. , 2003, The New England journal of medicine.

[87]  T. Golub,et al.  Supplemental Information for , 2002 .

[88]  S. Steinberg,et al.  Insulin‐like growth factor type 1 (IGF–1) and IGF binding protein–3 in patients with Ewing sarcoma family of tumors , 2001, Cancer.

[89]  C. Denny,et al.  Loss of p16 pathways stabilizes EWS/FLI1 expression and complements EWS/FLI1 mediated transformation , 2001, Oncogene.

[90]  M. Ringnér,et al.  Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks , 2001, Nature Medicine.

[91]  A. Llombart‐Bosch,et al.  Molecular Analysis of the 9p21 Locus and p53 Genes in Ewing Family Tumors , 2001, Laboratory Investigation.

[92]  P. Lollini,et al.  Inhibition of insulin-like growth factor I receptor increases the antitumor activity of doxorubicin and vincristine against Ewing's sarcoma cells. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[93]  M. Tan,et al.  Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[94]  A. Craft,et al.  Prognostic factors in Ewing's tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing's Sarcoma Study Group. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[95]  M. Ladanyi,et al.  Prognostic impact of P53 status in Ewing sarcoma , 2000, Cancer.

[96]  Y. Kaneko,et al.  Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma. , 2000, Cancer genetics and cytogenetics.

[97]  M. Ladanyi,et al.  Molecular Pathology and Molecular Pharmacology of Osteosarcoma , 2000 .

[98]  C. Arndt,et al.  Common musculoskeletal tumors of childhood and adolescence. , 1999, The New England journal of medicine.

[99]  W. Gerald,et al.  EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[100]  H. Kovar,et al.  Predictive potential of testing for bone marrow involvement in Ewing tumor patients by RT‐PCR: A preliminary evaluation , 1998, International journal of cancer.

[101]  D. Leroith,et al.  The Insulin-like Growth Factor-I Receptor Is Required for EWS/FLI-1 Transformation of Fibroblasts* , 1997, The Journal of Biological Chemistry.

[102]  H. Kovar,et al.  Among genes involved in the RB dependent cell cycle regulatory cascade, the p16 tumor suppressor gene is frequently lost in the Ewing family of tumors , 1997, Oncogene.

[103]  K. Matthay,et al.  A Phase I/IB trial of murine monoclonal anti‐GD2 antibody 14.G2a plus interleukin‐2 in children with refractory neuroblastoma , 1997, Cancer.

[104]  J. Sklar,et al.  Detection of circulating tumor cells in patients with Ewing's sarcoma and peripheral primitive neuroectodermal tumor. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[105]  P. Lollini,et al.  Insulin-like growth factor I receptor-mediated circuit in Ewing's sarcoma/peripheral neuroectodermal tumor: a possible therapeutic target. , 1996, Cancer research.

[106]  O. Delattre,et al.  Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients? , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[107]  G. Thomas,et al.  Sensitive detection of occult Ewing's cells by the reverse transcriptase-polymerase chain reaction. , 1995, British Journal of Cancer.

[108]  T. Lion,et al.  Detection of tumour cells in peripheral blood and bone marrow from ewing tumour patients by rt‐pcr , 1995, International journal of cancer.

[109]  D. Yee,et al.  Insulin-like growth factor I expression by tumors of neuroectodermal origin with the t(11;22) chromosomal translocation. A potential autocrine growth factor. , 1990, The Journal of clinical investigation.

[110]  E. Gehan,et al.  Ewing's sarcoma metastatic at diagnosis results and comparisons of two intergroup Ewing's sarcoma studies , 1990, Cancer.

[111]  M. Israel,et al.  Human neuroblastoma tumor cell lines correspond to the arrested differentiation of chromaffin adrenal medullary neuroblasts. , 1990, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[112]  N. Cheung,et al.  Localization of GD2-specific monoclonal antibody 3F8 in human osteosarcoma. , 1987, Cancer research.

[113]  J. Toretsky,et al.  The Role of IGF-1 R in Pediatric Malignancies , 2009 .

[114]  Xia Han,et al.  The mechanisms of differential sensitivity to an insulin-like growth factor-1 receptor inhibitor (BMS-536924) and rationale for combining with EGFR/HER2 inhibitors. , 2009, Cancer research.

[115]  A. Üren,et al.  A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing’s sarcoma , 2009 .

[116]  W. Winkelmann,et al.  Type I and type II insulin-like growth factor receptors and their function in human Ewing's sarcoma cells , 2005, Journal of Cancer Research and Clinical Oncology.

[117]  O. Delattre,et al.  Increased risk of systemic relapses associated with bone marrow micrometastasis and circulating tumor cells in localized ewing tumor. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[118]  W. Winkelmann,et al.  Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[119]  S. Ferrari,et al.  Prognostic factors in nonmetastatic Ewing's sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Istituto Ortopedico Rizzoli. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[120]  P. Pynsent,et al.  Overexpression of p53 protein in primary Ewing’s sarcoma of bone: relationship to tumour stage, response and prognosis , 1999, British Journal of Cancer.

[121]  L. Ries,et al.  Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. , 1999 .

[122]  R. Schneider-Stock,et al.  p53 and ras mutations in Ewing's sarcoma. , 1998, Pathology, research and practice.