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Pharmacotherapeutic Management of Wilms Tumor: An Update

  • Radna Minou Oostveen
  • Kathy Pritchard-Jones
Leading Article

Abstract

Although differences exist in treatment and risk-stratification strategies for children with Wilms tumor (WT) between the European [International Society of Paediatric Oncology (SIOP)] and American [Children’s Oncology Group (COG)] study groups, outcomes are very similar, with an overall survival of > 85%. Future strategies aim to de-intensify treatment and reduce toxicity for children with a low risk of relapse and intensify treatment for children with high-risk disease. For metastatic WT, response of lung nodules to chemotherapy is used as a marker to modify treatment intensity. For recurrent WT, a unified approach based on the use of agents that were not used for primary therapy is being introduced. Irinotecan is being explored as a new strategy in both metastatic and relapsed WT. Introduction of biology-driven approaches to risk stratification and new drug treatments has been slower in WT than in some other childhood cancers. While several new biological pathways have been identified recently in WT, their individual rarity has hampered their translation into clinical utility. Identification of robust prognostic factors requires extensive international collaborative studies because of the low proportion who relapse or die. Molecular profiling studies are in progress that should ultimately improve both risk classification and signposting to more targeted therapies for the small group for whom current therapies fail. Accrual of patients with WT to early-phase trials has been low, and the efficacy of these new agents has so far been very disappointing. Better in vitro model systems to test mechanistic dependence are needed so available new agents can be more rationally prioritized for recruitment of children with WT to early-phase trials.

Notes

Acknowledgements

The authors thank Suzanne Tugnait for her contribution to the final editing of the manuscript.

Compliance with Ethical Standards

Funding

RMO is funded by the Great Ormond Street Hospital Children’s Charity (grant reference W1090). KPJ is funded in part by the National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Hospital Children’s Charity, Cancer Research UK (grant no. C1188/A4614) and the Children’s Cancer and Leukaemia Group (Bethany’s Wish, grant reference CCLGA 2017 02).

Conflict of interest

Radna Minou Oostveen and Kathy Pritchard-Jones have no conflicts of interest that might be relevant to the contents of this manuscript.

References

  1. 1.
    Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya A, Bray F, et al. International incidence of childhood cancer, 2001–10: a population-based registry study. Lancet Oncol. 2017;18(6):719–31.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Nakata K, Ito Y, Magadi W, Bonaventure A, Stiller CA, Katanoda K, et al. Childhood cancer incidence and survival in Japan and England: a population-based study (1993–2010). Cancer Sci. 2018;109(2):422–34.PubMedCrossRefGoogle Scholar
  3. 3.
    Scott RH, Stiller CA, Walker L, Rahman N. Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genetics. 2006;43(9):705–15.CrossRefGoogle Scholar
  4. 4.
    Brok J, Treger TD, Gooskens SL, van den Heuvel-Eibrink MM, Pritchard-Jones K. Biology and treatment of renal tumours in childhood. Eur J Cancer. 2016;68:179–95.PubMedCrossRefGoogle Scholar
  5. 5.
    Gadd S, Huff V, Walz AL, Ooms AHAG, Armstrong AE, Gerhard DS, et al. A Children’s Oncology Group and TARGET initiative exploring the genetic landscape of wilms tumor. Nature Genetics. 2017;49(10):1487–94.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Deng C, Dai R, Li X, Liu F. Genetic variation frequencies in Wilms’ tumor: a meta-analysis and systematic review. Cancer Sci. 2016;107(5):690–9.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Yu X, Li Z, Chan MTV, Wu WKK. The roles of microRNAs in Wilms’ tumors. Tumor Biol. 2016;37(2):1445–50.CrossRefGoogle Scholar
  8. 8.
    Green DM. Controversies in the management of Wilms tumour—immediate nephrectomy or delayed nephrectomy? Eur J Cancer. 2007;43(17):2453–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Mitchell C, Pritchard-Jones K, Shannon R, Hutton C, Stevens S, Machin D, et al. Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms’ tumour: results of a randomised trial (UKW3) by the UK Children’s Cancer Study Group. Eur J Cancer. 2006;42(15):2554–62.PubMedCrossRefGoogle Scholar
  10. 10.
    Dome JS, Graf N, Geller JI, Fernandez CV, Mullen EA, Spreafico F, et al. Advances in Wilms tumor treatment and biology: progress through international collaboration. J Clin Oncol. 2015;33(27):2999–3007.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Pritchard-Jones K, Dome JS. Renal tumors of childhood. Berlin, Heidelberg: Springer; 2014. p. 53–76.CrossRefGoogle Scholar
  12. 12.
    Vujanić GM, Gessler M, Ooms AHAG, Collini P, Coulomb-l’Hermine A, D’Hooghe E, et al. The UMBRELLA SIOP–RTSG 2016 Wilms tumour pathology and molecular biology protocol. Nature Rev Urol. 2018;15(11):693–701.CrossRefGoogle Scholar
  13. 13.
    Lopes RI, Lorenzo A. Recent advances in the management of Wilms’ tumor. F1000Research. 2017;6:670.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Dome JS, Cotton CA, Perlman EJ, Breslow NE, Kalapurakal JA, Ritchey ML, et al. Treatment of anaplastic histology Wilms’ tumor: results from the fifth national Wilms’ tumor study. J Clin Oncol. 2006;24(15):2352–8.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Grundy PE, Breslow NE, Li S, Perlman E, Beckwith JB, Ritchey ML, et al. Loss of heterozygosity for chromosomes 1p and 16q Is an Adverse prognostic factor in favorable-histology Wilms tumor: a report from the national Wilms tumor study group. J Clin Oncol. 2005;23(29):7312–21.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Spreafico F, Pritchard Jones K, Malogolowkin MH, Bergeron C, Hale J, de Kraker J, et al. Treatment of relapsed Wilms tumors: lessons learned. Expert Rev Anticancer Therapy. 2009;9(12):1807–15.CrossRefGoogle Scholar
  17. 17.
    Ladd WE. Embryoma of the kidney (Wilms’ tumor). Ann Surg. 1938;108(5):885–902.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Randolph J. Treatment of mixed tumors of the kidney in childhood. In: Gross RE, Neuhauser EBD, editors. Pediatrics, vol. 6. 1950. p. 843–52 (1998;102(Supplement 1):209–10).Google Scholar
  19. 19.
    Green DM, Jaffe N, Paed D. The role of chemotherapy in the treatment of Wilms’ tumor. Cancer. 1979;44(1):52–7.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Larsen E, Perez-Atayde A, Green DM, Retik A, Clavell LA, Sallan SE. Surgery only for the treatment of patients with stage I (Cassady) Wilms’ tumor. Cancer. 1990;66(2):264–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Green DM, Breslow NE, Beckwith JB, Takashima J, Kelalis P, D’Angio GJ. Treatment outcomes in patients less than 2 years of age with small, stage I, favorable-histology Wilms’ tumors: a report from the National Wilms’ Tumor Study. J Clin Oncol. 1993;11(1):91–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Shamberger RC, Anderson JR, Breslow NE, Perlman EJ, Beckwith JB, Ritchey ML, et al. Long-term outcomes of infants with very low risk Wilms tumor treated with surgery alone on national Wilms Tumor study-5. Ann Surg. 2010;251(3):555–8.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Green DM, Breslow NE, Beckwith JB, Ritchey ML, Shamberger RC, Haase GM, et al. Treatment With nephrectomy only for small, stage I/favorable histology Wilms’ tumor: a report from the national Wilms’ tumor study group. J Clin Oncol. 2001;19(17):3719–24.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Green DM. The treatment of stages I–IV favorable histology Wilms’ tumor. J Clin Oncol. 2004;22(8):1366–72.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Fernandez CV, Perlman EJ, Mullen EA, Chi Y-Y, Hamilton TE, Gow KW, et al. Clinical outcome and biological predictors of relapse after nephrectomy only for very low-risk Wilms tumor: a report from children’s oncology group AREN0532. Ann Surg. 2017;265(4):835–40.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Perlman EJ, Grundy PE, Anderson JR, Jennings LJ, Green DM, Dome JS, et al. WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk Wilms tumors treated with surgery alone: a children’s oncology group study. J Clin Oncol. 2011;29(6):698–703.PubMedCrossRefGoogle Scholar
  27. 27.
    Jones B, Breslow NE, Takashima J. Toxic deaths in the Second National Wilms’ tumor study. J Clin Oncol. 1984;2(9):1028–33.PubMedCrossRefGoogle Scholar
  28. 28.
    Coppes MJ, Tournade MF, Lemerle J, Weitzman S, Rey A, Burger D, et al. Preoperative care of infants with nephroblastoma the international society of pediatric oncology 6 experience. Cancer. 1992;69(11):2721–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Green DM, Finklestein JZ, Norkool P, D’Angio JG. Severe hepatic toxicity after treatment with single-dose dactinomycin and vincristine. A report of the national Wilms’ tumor study. Cancer. 1988;62(2):270–3.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Bisogno G, Kraker JD, Weirich A, Masiero L, Ludwig R, Tournade MF, et al. Veno-occlusive disease of the liver in children treated for Wilms tumor. Med Pediatric Oncol. 1997;29(4):245–51.CrossRefGoogle Scholar
  31. 31.
    D’Angio GJ, Evans AE, Breslow N, Beckwith B, Bishop H, Feigl P, et al. The treatment of Wilms’ tumor: results of the national Wilms’ tumor study. Cancer. 1976;38(2):633–46.PubMedCrossRefGoogle Scholar
  32. 32.
    Medical Research Council’s Working Party on Embryonal Tumours in C. Management of nephroblastoma in childhood: clinical study of two forms of maintenance chemotherapy. Arch Dis Child. 1978;53(2):112–9.CrossRefGoogle Scholar
  33. 33.
    Pritchard J, Imeson J, Barnes J, Cotterill S, Gough D, Marsden HB, et al. Results of the United Kingdom Children’s Cancer Study Group first Wilms’ tumor study. J Clin Oncol. 1995;13(1):124–33.PubMedCrossRefGoogle Scholar
  34. 34.
    Pritchard-Jones K, Kelsey A, Vujanic G, Imeson J, Hutton C, Mitchell C. Older age is an adverse prognostic factor in stage I, favorable histology Wilms’ tumor treated with vincristine monochemotherapy: a study by the united kingdom children’s cancer study group, Wilm’s Tumor Working Group. J Clin Oncol. 2003;21(17):3269–75.PubMedCrossRefGoogle Scholar
  35. 35.
    Davidoff AM. Wilms tumor. Adv Pediatrics. 2012;59(1):247–67.CrossRefGoogle Scholar
  36. 36.
    Gratias EJ, Dome JS, Jennings LJ, Chi Y-Y, Tian J, Anderson J, et al. Association of chromosome 1q gain with inferior survival in favorable-histology Wilms tumor: a report from the Children’s Oncology Group. J Clin Oncol. 2016;34(26):3189–94.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Lindsay FA, Shamberger RC, Henderson TO, Lisa D. Decision analysis to compare treatment strategies for stage I/favorable histology Wilms tumor. Pediatric Blood Cancer. 2010;54(7):879–84.Google Scholar
  38. 38.
    Pritchard-Jones K. Nephrectomy-only for Wilms tumour: negotiating the tangled web requires multi-professional input. Pediatric Blood Cancer. 2010;54(7):865–6.PubMedGoogle Scholar
  39. 39.
    Ceppi F, Langlois-Pelletier C, Gagné V, Rousseau J, Ciolino C, Lorenzo SD, et al. Polymorphisms of the vincristine pathway and response to treatment in children with childhood acute lymphoblastic leukemia. Pharmacogenomics. 2014;15(8):1105–16.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Plasschaert SLA, Groninger E, Boezen M, Kema I, Vries EGE, Uges D, et al. Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic Leukemia. Clin Pharmacol Ther. 2004;76(3):220–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Gregers J, Gréen H, Christensen IJ, Dalhoff K, Schroeder H, Carlsen N, et al. Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia. Pharmacogenomics J. 2015;15(4):372–9.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Walsh C, Bonner JJ, Johnson TN, Neuhoff S, Ghazaly EA, Gribben JG, et al. Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer. Br J Clin Pharmacol. 2016;81(5):989–98.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Veal GJ, Cole M, Errington J, Parry A, Hale J, Pearson ADJ, et al. Pharmacokinetics of Dactinomycin in a pediatric patient population: a United Kingdom Children’s Cancer Study Group Study. Clin Cancer Res. 2005;11(16):5893–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Sredni ST, Gadd S, Huang C-C, Breslow N, Grundy P, Green DM, et al. Subsets of very low risk Wilms tumor show distinctive gene expression, histologic, and clinical features. Clin Cancer Res. 2009;15(22):6800–9.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Pritchard-Jones K, Bergeron C, de Camargo B, van den Heuvel-Eibrink MM, Acha T, Godzinski J, et al. Omission of doxorubicin from the treatment of stage II–III, intermediate-risk Wilms’ tumour (SIOP WT 2001): an open-label, non-inferiority, randomised controlled trial. Lancet. 2015;386(9999):1156–64.PubMedCrossRefGoogle Scholar
  46. 46.
    van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, van Tinteren H, Furtwängler R, Verschuur AC, et al. Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol. Nature Rev Urol. 2017;14:743.CrossRefGoogle Scholar
  47. 47.
    Chagtai T, Zill C, Dainese L, Wegert J, Savola S, Popov S, et al. Gain of 1q As a prognostic biomarker in Wilms Tumors (WTs) treated with preoperative chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 Trial: A SIOP Renal Tumours Biology Consortium Study. J Clin Oncol. 2016;34(26):3195–203.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    The SRTSG, Spreafico F, van den Heuvel-Eibrink MM, Pritchard-Jones K, Bergeron C, Godzinski J, et al. Paediatric renal tumours: perspectives from the SIOP–RTSG. Nature Rev Urol. 2016;14:3.Google Scholar
  49. 49.
    Dome JS, Fernandez CV, Mullen EA, Kalapurakal JA, Geller JI, Huff V, et al. Children’s Oncology Group’s 2013 blueprint for research: renal tumors. Pediatric Blood Cancer. 2013;60(6):994–1000.PubMedCrossRefGoogle Scholar
  50. 50.
    Cresswell GD, Apps JR, Chagtai T, Mifsud B, Bentley CC, Maschietto M, et al. Intra-tumor genetic heterogeneity in Wilms Tumor: clonal evolution and clinical implications. EBioMedicine. 2016;9:120–9.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Walz AL, Ooms A, Gadd S, Gerhard DS, Smith MA, Guidry Auvil JM, et al. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors. Cancer Cell. 2015;27(2):286–97.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Gadd S, Huff V, Huang C-C, Ruteshouser EC, Dome JS, Grundy PE, et al. Clinically relevant subsets identified by gene expression patterns support a revised ontogenic model of Wilms tumor: a Children’s Oncology Group Study. Neoplasia (New York, NY). 2012;14(8):742–56.CrossRefGoogle Scholar
  53. 53.
    Drost J, Clevers H. Organoids in cancer research. Nature Rev Cancer. 2018;18(7):407–18.CrossRefGoogle Scholar
  54. 54.
    Drost J, Clevers H. Translational applications of adult stem cell-derived organoids. Development. 2017;144(6):968–75.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Smets AMJB, Tinteren HV, Bergeron C, Camargo BD, Graf N, Pritchard-Jones K, et al. The contribution of chest CT-scan at diagnosis in children with unilateral Wilms’ tumour. Results of the SIOP 2001 study. Eur J Cancer. 2012;48(7):1060–5.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Grundy PE, Green DM, Dirks AC, Berendt AE, Breslow NE, Anderson JR, et al. Clinical significance of pulmonary nodules detected by CT and Not CXR in patients treated for favorable histology Wilms tumor on national Wilms tumor studies-4 and 5: a report from the Children’s Oncology Group. Pediatric Blood Cancer. 2012;59(4):631–5.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Owens CM, Veys PA, Pritchard J, Levitt G, Imeson J, Dicks-Mireaux C. Role of chest computed tomography at diagnosis in the management of Wilms’ tumor: a study by the United Kingdom Children’s Cancer Study Group. J Clin Oncol. 2002;20(12):2768–73.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Dix DB, Seibel NL, Chi Y-Y, Khanna G, Gratias E, Anderson JR, et al. Treatment of stage IV favorable histology Wilms tumor with lung metastases: a report from the Children’s Oncology Group AREN0533 Study. J Clin Oncol. 2018;36(16):1564–70.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Daw NC, Anderson JR, Hoffer FA, Geller JI, Kalapurakal JA, Perlman EJ, et al. A phase 2 study of vincristine and irinotecan in metastatic diffuse anaplastic Wilms tumor: results from the Children’s Oncology Group AREN0321 study. J Clin Oncol. 2014;32(15_suppl):10032.Google Scholar
  60. 60.
    Verschuur A, Tinteren HV, Graf N, Bergeron C, Sandstedt B, Kraker JD. Treatment of pulmonary metastases in children with stage IV nephroblastoma with risk-based use of pulmonary radiotherapy. J Clin Oncol. 2012;30(28):3533–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Warmann SW, Furtwängler R, Blumenstock G, Armeanu S, Nourkami N, Leuschner I, et al. Tumor biology influences the prognosis of nephroblastoma patients with primary pulmonary metastases: results from SIOP 93-01/GPOH and SIOP 2001/GPOH. Ann Surg. 2011;254(1):155–62.PubMedCrossRefGoogle Scholar
  62. 62.
    Pein F, Pinkerton R, Tournade MF, Brunat-Mentigny M, Levitt G, Margueritte G, et al. Etoposide in relapsed or refractory Wilms’ tumor: a phase II study by the French Society of Pediatric Oncology and the United Kingdom Children’s Cancer Study Group. J Clin Oncol. 1993;11(8):1478–81.PubMedCrossRefGoogle Scholar
  63. 63.
    Pein F, Tournade MF, Zucker JM, Brunat-Mentigny M, Deville A, Boutard P, et al. Etoposide and carboplatin: a highly effective combination in relapsed or refractory Wilms’ tumor—a phase II study by the French Society of Pediatric Oncology. J Clin Oncol. 1994;12(5):931–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Tournade MF, Lemerle J, Brunat-Mentigny M, Bachelot C, Roche H, Taboureau O, et al. Ifosfamide is an active drug in Wilms’ tumor: a phase II study conducted by the French Society of Pediatric Oncology. J Clin Oncol. 1988;6(5):793–6.PubMedCrossRefGoogle Scholar
  65. 65.
    De Camargo B, Melaragno R, Silva NSE, Mendoncla N, Alvares MN, Morinaka E, et al. Phase II study of carboplatin as a single drug for relapsed Wilms’ tumor: experience of the Brazilian Wilms’ tumor study group. Med Pediatric Oncol. 1994;22(4):258–60.CrossRefGoogle Scholar
  66. 66.
    Ha TC, Spreafico F, Graf N, Dallorso S, Dome JS, Malogolowkin M, et al. An international strategy to determine the role of high dose therapy in recurrent Wilms’ tumour. Eur J Cancer. 2013;49(1):194–210.PubMedCrossRefGoogle Scholar
  67. 67.
    Hol JA, den Heuvel-Eibrink MM, Graf N, Pritchard-Jones K, Brok J, Tinteren H, et al. Irinotecan for relapsed Wilms tumor in pediatric patients: SIOP experience and review of the literature—a report from the SIOP Renal Tumor Study Group. Pediatric Blood Cancer. 2018;65(2):e26849.CrossRefGoogle Scholar
  68. 68.
    Mavinkurve-Groothuis AMC, van den Heuvel-Eibrink MM, Tytgat GA, van Tinteren H, Vujanic G, Pritchard-Jones KLP, et al. Treatment of relapsed Wilms tumour (WT) patients: experience with topotecan. A report from the SIOP Renal Tumour Study Group (RTSG). Pediatric Blood Cancer. 2015;62(4):598–602.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Metzger ML, Stewart CF III, Freeman BB, Billups CA, Hoffer FA, Wu J, et al. Topotecan is active against Wilms’ tumor: results of a multi-institutional phase II study. J Clin Oncol. 2007;25(21):3130–6.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Green DM, Cotton CA, Malogolowkin M, Breslow NE, Perlman E, Miser J, et al. Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group. Pediatric Blood Cancer. 2007;48(5):493–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Malogolowkin M, Cotton CA, Green DM, Breslow NE, Perlman E, Miser J, et al. Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group. Pediatric Blood Cancer. 2008;50(2):236–41.PubMedCrossRefGoogle Scholar
  72. 72.
    Hale J, Hobson R, Moroz V, Sartori P. Results of UK children’s cancer and leukemia group (CCLG) protocol for relapsed Wilms tumor (UKWR): unified relapse strategy improves outcome. In: Proceeding of the 40th Meeting of International Society of Pediatric Oncology (Abstract O154). 2008:16.Google Scholar
  73. 73.
    Maschietto M, Charlton J, Perotti D, Radice P, Geller JI, Pritchard-Jones K, et al. The IGF signalling pathway in Wilms tumours—A report from the ENCCA Renal Tumours Biology-driven drug development workshop. Oncotarget. 2014;5(18):8014–26.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Perotti D, Hohenstein P, Bongarzone I, Maschietto M, Weeks M, Radice P, et al. Is Wilms tumor a candidate neoplasia for treatment with WNT/β-catenin pathway modulators?—a report from the renal tumors biology-driven drug development workshop. Mol Cancer Ther. 2013;12(12):2619–27.PubMedCrossRefGoogle Scholar
  75. 75.
    Williams RD, Chagtai T, Alcaide-German M, Apps J, Wegert J, Popov S, et al. Multiple mechanisms of MYCN dysregulation in Wilms tumour. Oncotarget. 2015;6(9):7232–43.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Brok J, Pritchard-Jones K, Geller JI, Spreafico F. Review of phase I and II trials for Wilms’ tumour—can we optimise the search for novel agents? Eur J Cancer. 2017;79:205–13.PubMedCrossRefGoogle Scholar
  77. 77.
    Geller JI, Pressey JG, Smith MA, Kudgus RA, Schoon R, McGovern RM, et al. ADVL1522: a phase 2 study of IMGN901 (lorvotuzumab mertansine; IND# 126953, NSC# 783609) in children with relapsed or refractory Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST), and synovial sarcoma: a Children’s Oncology Group study. J Clin Oncol. 2017;35(15_suppl):10537.CrossRefGoogle Scholar
  78. 78.
    Malempati S, Weigel B, Ingle AM, Ahern CH, Carroll JM, Roberts CT, et al. Phase I/II Trial and pharmacokinetic study of cixutumumab in pediatric patients with refractory solid tumors and ewing sarcoma: a report from the Children’s Oncology Group. J Clin Oncol. 2012;30(3):256–62.PubMedCrossRefGoogle Scholar
  79. 79.
    Weigel B, Malempati S, Reid JM, Voss SD, Cho SY, Chen HX, et al. Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: a report from the Children’s Oncology Group. Pediatric Blood Cancer. 2014;61(3):452–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Fouladi M, Perentesis JP, Wagner LM, Vinks AA, Reid JM, Ahern C, et al. A phase I study of cixutumumab (IMC-A12) in combination with temsirolimus (CCI-779) in children with recurrent solid tumors: a Children’s Oncology Group Phase I Consortium Report. Clin Cancer Res. 2015;21(7):1558–65.PubMedCrossRefGoogle Scholar
  81. 81.
    Frappaz D, Federico SM, Pearson ADJ, Gore L, Macy ME, DuBois SG, et al. Phase 1 study of dalotuzumab monotherapy and ridaforolimus–dalotuzumab combination therapy in paediatric patients with advanced solid tumours. Eur J Cancer. 2016;62:9–17.PubMedCrossRefGoogle Scholar
  82. 82.
    Wagner-Bohn A, Paulussen M, Vieira Pinheiro JP, Gerss J, Stoffregen C, Boos J. Phase II study of gemcitabine in children with solid tumors of mesenchymal and embryonic origin. Anti-Cancer Drugs. 2006;17(7):859–64.PubMedCrossRefGoogle Scholar
  83. 83.
    Geoerger B, Chisholm J, Le Deley M-C, Gentet J-C, Zwaan CM, Dias N, et al. Phase II study of gemcitabine combined with oxaliplatin in relapsed or refractory paediatric solid malignancies: an innovative therapy for children with Cancer European Consortium Study. Eur J Cancer. 2011;47(2):230–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Su JM, Li X-N, Thompson P, Ou C-N, Ingle AM, Russell H, et al. Phase 1 study of valproic acid in pediatric patients with refractory solid or CNS tumors: a Children’s Oncology Group Report. Clin Cancer Res. 2011;17(3):589–97.PubMedCrossRefGoogle Scholar
  85. 85.
    Muscal JA, Thompson PA, Horton TM, Ingle AM, Ahern CH, McGovern RM, et al. A phase I trial of vorinostat and bortezomib in children with refractory or recurrent solid tumors: a Children’s Oncology Group phase I consortium study (ADVL0916). Pediatric Blood Cancer. 2013;60(3):390–5.PubMedCrossRefGoogle Scholar
  86. 86.
    Fouladi M, Furman WL, Chin T III, Freeman BB, Dudkin L, Stewart CF, et al. Phase I study of depsipeptide in pediatric patients with refractory solid Tumors: a Children’s Oncology Group Report. J Clin Oncol. 2006;24(22):3678–85.PubMedCrossRefGoogle Scholar
  87. 87.
    Robison NJ, Campigotto F, Chi SN, Manley PE, Turner CD, Zimmerman MA, et al. A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer. Pediatric Blood Cancer. 2014;61(4):636–42.PubMedCrossRefGoogle Scholar
  88. 88.
    Villablanca JG, Krailo MD, Ames MM, Reid JM, Reaman GH, Reynolds CP. Phase I trial of oral fenretinide in children with high-risk solid tumors: a report from the Children’s Oncology Group (CCG 09709). J Clin Oncol. 2006;24(21):3423–30.PubMedCrossRefGoogle Scholar
  89. 89.
    Adamson PC, Matthay KK, O’Brien M, Reaman GH, Sato JK, Balis FM. A phase 2 trial of all-trans-retinoic acid in combination with interferon-α2a in children with recurrent neuroblastoma or Wilms tumor: a Pediatric Oncology Branch, NCI and Children’s Oncology Group Study. Pediatric Blood Cancer. 2007;49(5):661–5.PubMedCrossRefGoogle Scholar
  90. 90.
    Mossé YP, Lipsitz E, Fox E, Teachey DT, Maris JM, Weigel B, et al. Pediatric phase I trial and pharmacokinetic study of MLN8237, an investigational oral selective small-molecule inhibitor of aurora kinase A: a Children’s Oncology Group Phase I Consortium Study. Clin Cancer Res. 2012;18(21):6058–64.PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.UCL Great Ormond Street Hospital Institute of Child HealthLondonUK

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