GPOH Guidelines for Diagnosis and First-line Treatment of Patients with Neuroblastic Tumors, update 2025

Abstract

The clinical course of neuroblastoma is more heterogeneous than any other malignant disease. Many low-risk patients experience regression after limited or even no chemotherapy. However, more than half of high-risk patients die from disease despite intensive multimodal treatment. Precise disease characterization for each patient at diagnosis is key for risk-adapted treatment. The guidelines presented here incorporate results from national and international clinical trials to produce recommendations for diagnosing and treating neuroblastoma patients in German hospitals outside of clinical trials.

Zusammenfassung

Der klinische Verlauf von Neuroblastomen ist sehr variabel. Bei Patienten mit günstigem Risikoprofil werden regelhaft Spontanregression der Tumoren beobachtet. Bei Hochrisiko-Neuroblastom können dagegen nur ca. 50% der Patienten durch eine intensive multimodale Therapie geheilt werden. Eine exakte Risikoklassifizierung jedes einzelnen Patienten ist von entscheidender Bedeutung eine korrekte risikoadaptierte Therapie. Die hier vorgestellten Empfehlungen berücksichtigen Ergebnisse von nationalen und internationalen klinischen Studien und definieren den gegenwärtigen Standard für die Behandlung von Patienten mit Neuroblastomen in Deutschland außerhalb von klinischen Studien.

Keywords

neuroblastoma - treatment recommendation - ganglioneuroma - neuroblastic tumors - GPOH - pediatric oncology

Schlüsselwörter

Neuroblastom - Therapieempfehlungen - Neuroblastische Tumoren - Ganglioneurom - GPOH - Kinderonkologie

Publikationsverlauf

Artikel online veröffentlicht:
09. Mai 2025

• References

• 1 Cohn SL, Pearson AD, London WB. et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 2009; 27: 289-297
• 2 Hero B, Simon T, Spitz R. et al. Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol 2008; 26: 1504-1510
• 3 Pinto NR, Applebaum MA, Volchenboum SL. et al. Advances in Risk Classification and Treatment Strategies for Neuroblastoma. J Clin Oncol 2015; 33: 3008-3017
• 4 Ackermann S, Cartolano M, Hero B. et al. A mechanistic classification of clinical phenotypes in neuroblastoma. Science 2018; 362: 1165-1170
• 5 Cangemi G, Barco S, Reggiardo G. et al. Interchangeability between 24-hour collection and single spot urines for vanillylmandelic and homovanillic acid levels in the diagnosis of neuroblastoma. Pediatr Blood Cancer 2013; 60: E170-172
• 6 Korber F, Schafer JF. [Radiological imaging of neuroblastoma]. Radiologe 2021; 61: 639-648
• 7 Kembhavi SA, Rangarajan V, Shah S. et al. Prospective observational study on diagnostic accuracy of whole-body MRI in solid small round cell tumours. Clin Radiol 2014; 69: 900-908
• 8 Atkin KL, Ditchfield MR. The role of whole-body MRI in pediatric oncology. J Pediatr Hematol Oncol 2014; 36: 342-352
• 9 Siegel MJ, Acharyya S, Hoffer FA. et al. Whole-body MR imaging for staging of malignant tumors in pediatric patients: results of the American College of Radiology Imaging Network 6660 Trial. Radiology 2013; 266: 599-609
• 10 Goo HW, Choi SH, Ghim T. et al. Whole-body MRI of paediatric malignant tumours: comparison with conventional oncological imaging methods. Pediatr Radiol 2005; 35: 766-773
• 11 Schafer JF, Granata C, von Kalle T. et al. Whole-body magnetic resonance imaging in pediatric oncology – recommendations by the Oncology Task Force of the ESPR. Pediatr Radiol 2020; 50: 1162-1174
• 12 Gassenmaier S, Bares R, Barreuther M. et al. (123)Iodine-metaiodobenzylguanidine scintigraphy versus whole-body magnetic resonance imaging with diffusion-weighted imaging in children with high-risk neuroblastoma – pilot study. Pediatr Radiol 2021; 51: 1223-1230
• 13 Gassenmaier S, Tsiflikas I, Fuchs J. et al. Feasibility and possible value of quantitative semi-automated diffusion weighted imaging volumetry of neuroblastic tumors. Cancer Imaging 2020; 20: 89
• 14 Ishiguchi H, Ito S, Kato K. et al. Diagnostic performance of (18)F-FDG PET/CT and whole-body diffusion-weighted imaging with background body suppression (DWIBS) in detection of lymph node and bone metastases from pediatric neuroblastoma. Ann Nucl Med 2018; 32: 348-362
• 15 Park JR, Bagatell R, Cohn SL. et al. Revisions to the International Neuroblastoma Response Criteria: A Consensus Statement From the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol 2017; 35: 2580-2587
• 16 Lassmann M, Biassoni L, Monsieurs M. et al. The new EANM paediatric dosage card. Eur J Nucl Med Mol Imaging 2007; 34: 796-798
• 17 Olivier P, Colarinha P, Fettich J. et al. Guidelines for radioiodinated MIBG scintigraphy in children. Eur J Nucl Med Mol Imaging 2003; 30: B45-50
• 18 Matthay KK, Shulkin B, Ladenstein R. et al. Criteria for evaluation of disease extent by (123)I-metaiodobenzylguanidine scans in neuroblastoma: a report for the International Neuroblastoma Risk Group (INRG) Task Force. Br J Cancer 2010; 102: 1319-1326
• 19 Schmidt M, Decarolis B, Franzius C. et al. Durchfuhrung und Befundung der 123I-mIBG-Szintigraphie bei Kindern und Jugendlichen mit Neuroblastom (Version 3) – DGN-Handlungsempfehlung (S1-Leitlinie), Stand: 2/2020 – AWMF-Registernummer: 031-040. Nuklearmedizin 2022; 61: 96-110
• 20 Lassmann M, Treves ST. Group ESPDHW Paediatric radiopharmaceutical administration: harmonization of the 2007 EANM paediatric dosage card (version 1.5.2008) and the 2010 North American consensus guidelines. Eur J Nucl Med Mol Imaging 2014; 41: 1036-1041
• 21 Rufini V, Giordano A, Di Giuda D. et al. [123I]MIBG scintigraphy in neuroblastoma: a comparison between planar and SPECT imaging. Q J Nucl Med 1995; 39: 25-28
• 22 Rogasch JMM, Amthauer H, Furth C. et al. I-123-MIBG scintigraphy in patients with neuroblastoma. Nuklearmedizin 2018; 57: 35-39
• 23 Lewington V, Lambert B, Poetschger U. et al. 123I-mIBG scintigraphy in neuroblastoma: development of a SIOPEN semi-quantitative reporting ,method by an international panel. Eur J Nucl Med Mol Imaging 2017; 44: 234-241
• 24 Pandit-Taskar N, Zanzonico P, Staton KD. et al. Biodistribution and Dosimetry of (18)F-Meta-Fluorobenzylguanidine: A First-in-Human PET/CT Imaging Study of Patients with Neuroendocrine Malignancies. J Nucl Med 2018; 59: 147-153
• 25 Wang P, Li T, Liu Z. et al. [(18)F]MFBG PET/CT outperforming [(123)I]MIBG SPECT/CT in the evaluation of neuroblastoma. Eur J Nucl Med Mol Imaging 2023; 50: 3097-3106
• 26 Samim A, Blom T, Poot AJ. et al. [(18)F]mFBG PET-CT for detection and localisation of neuroblastoma: a prospective pilot study. Eur J Nucl Med Mol Imaging 2023; 50: 1146-1157
• 27 Borgwardt L, Brok JS, Andersen KF. et al. [(18)F]mFBG long axial field of view PET-CT without general anaesthesia reveals concise extension of neuroblastoma in a 9-month-old boy. Eur J Nucl Med Mol Imaging 2023; 50: 2563-2564
• 28 Geoerger B, Hero B, Harms D. et al. Metabolic activity and clinical features of primary ganglioneuromas. Cancer 2001; 91: 1905-1913 10.1002/1097-0142(20010515)91:10<1905::aid-cncr1213>3.0.co;2-4
• 29 Decarolis B, Simon T, Krug B. et al. Treatment and outcome of Ganglioneuroma and Ganglioneuroblastoma intermixed. BMC Cancer 2016; 16: 542
• 30 Melzer HI, Coppenrath E, Schmid I. et al. (1)(2)(3)I-MIBG scintigraphy/SPECT versus (1)(8)F-FDG PET in paediatric neuroblastoma. Eur J Nucl Med Mol Imaging 2011; 38: 1648-1658
• 31 Sharp SE, Shulkin BL, Gelfand MJ. et al. 123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma. J Nucl Med 2009; 50: 1237-1243
• 32 Scanga DR, Martin WH, Delbeke D. Value of FDG PET imaging in the management of patients with thyroid, neuroendocrine, and neural crest tumors. Clin Nucl Med 2004; 29: 86-90
• 33 Schafer JF, Gatidis S, Schmidt H. et al. Simultaneous whole-body PET/MR imaging in comparison to PET/CT in pediatric oncology: initial results. Radiology 2014; 273: 220-231
• 34 Fu Z, Ren J, Zhou J. et al. Comparing the diagnostic value of 18F-FDG PET/CT scan and bone marrow biopsy in newly diagnosed pediatric neuroblastoma and ganglioneuroblastoma. Frontiers in oncology 2022; 12: 1031078
• 35 Liu J, Li C, Yang X. et al. The Diagnostic Value of (18)F-FDG PET/CT Bone Marrow Uptake Pattern in Detecting Bone Marrow Involvement in Pediatric Neuroblastoma Patients. Contrast media & molecular imaging 2022; 2022: 7556315
• 36 Sun L, Zhang B, Peng R. Diagnostic Performance of (18)F-FDG PET(CT) in Bone-Bone Marrow Involvement in Pediatric Neuroblastoma: A Systemic Review and Meta-Analysis. Contrast media & molecular imaging 2021; 2021: 8125373
• 37 Bleeker G, Tytgat GA, Adam JA. et al. 123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma. Cochrane Database Syst Rev 2015; 2015: CD009263
• 38 Gains JE, Sebire NJ, Moroz V. et al. Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue. Eur J Nucl Med Mol Imaging 2018; 45: 402-411
• 39 Kroiss A, Putzer D, Uprimny C. et al. Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine: a clarification. Eur J Nucl Med Mol Imaging 2012; 39: 543
• 40 Kong G, Hofman MS, Murray WK. et al. Initial Experience With Gallium-68 DOTA-Octreotate PET/CT and Peptide Receptor Radionuclide Therapy for Pediatric Patients With Refractory Metastatic Neuroblastoma. J Pediatr Hematol Oncol 2016; 38: 87-96
• 41 Kroiss A, Putzer D, Uprimny C. et al. Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine. Eur J Nucl Med Mol Imaging 2011; 38: 865-873
• 42 Piccardo A, Lopci E, Conte M. et al. Comparison of 18F-dopa PET/CT and 123I-MIBG scintigraphy in stage 3 and 4 neuroblastoma: a pilot study. Eur J Nucl Med Mol Imaging 2012; 39: 57-71
• 43 Kiratli PO, Tuncel M, Bar-Sever Z. Nuclear Medicine in Pediatric and Adolescent Tumors. Semin Nucl Med 2016; 46: 308-323
• 44 Cheung NK, Heller G, Kushner BH. et al. Detection of neuroblastoma in bone marrow by immunocytology: is a single marrow aspirate adequate?. Med Pediatr Oncol 1999; 32: 84-87 10.1002/(sici)1096-911x(199902)32:2<84::aid-mpo2>3.0.co;2-1
• 45 Burchill SA, Beiske K, Shimada H. et al. Recommendations for the standardization of bone marrow disease assessment and reporting in children with neuroblastoma on behalf of the International Neuroblastoma Response Criteria Bone Marrow Working Group. Cancer 2017; 123: 1095-1105
• 46 Schumacher-Kuckelkorn R, Atra A, Belli ML. et al. The reliability of bone marrow cytology as response criterion in metastatic neuroblastoma. Pediatr Blood Cancer 2021; 68: e28819
• 47 Swerts K, Ambros PF, Brouzes C. et al. Standardization of the immunocytochemical detection of neuroblastoma cells in bone marrow. J Histochem Cytochem 2005; 53: 1433-1440
• 48 Viprey VF, Corrias MV, Kagedal B. et al. Standardisation of operating procedures for the detection of minimal disease by QRT-PCR in children with neuroblastoma: quality assurance on behalf of SIOPEN-R-NET. Eur J Cancer 2007; 43: 341-350
• 49 Stutterheim J, Zappeij-Kannegieter L, Versteeg R. et al. The prognostic value of fast molecular response of marrow disease in patients aged over 1 year with stage 4 neuroblastoma. Eur J Cancer 2011; 47: 1193-1202
• 50 Cheung IY, Feng Y, Cheung NK. Early negative minimal residual disease in bone marrow after immunotherapy is less predictive of late or non-marrow relapse among patients with high-risk stage 4 neuroblastoma. Pediatr Blood Cancer 2013; 60: E32-34
• 51 Cai JY, Tang YJ, Jiang LM. et al. Prognostic influence of minimal residual disease detected by flow cytometry and peripheral blood stem cell transplantation by CD34+ selection in childhood advanced neuroblastoma. Pediatr Blood Cancer 2007; 49: 952-957
• 52 van Wezel EM, Decarolis B, Stutterheim J. et al. Neuroblastoma messenger RNA is frequently detected in bone marrow at diagnosis of localised neuroblastoma patients. Eur J Cancer 2016; 54: 149-158
• 53 Shimada H, Ambros IM, Dehner LP. et al The International Neuroblastoma Pathology Classification (the Shimada system). Cancer 1999; 86: 364-372 10.1002/(SICI)1097-0142(19990715)86:2<364::AID-CNCR21>3.0.CO;2-7 [pii]
• 54 Schwab M, Ellison J, Busch M. et al. Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma. Proc Natl Acad Sci U S A 1984; 81: 4940-4944
• 55 Brodeur GM, Seeger RC, Schwab M. et al. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 1984; 224: 1121-1124
• 56 Ambros PF, Ambros IM, Brodeur GM. et al. International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br J Cancer 2009; 100: 1471-1482
• 57 Caron H. Allelic loss of chromosome 1 and additional chromosome 17 material are both unfavourable prognostic markers in neuroblastoma. Med Pediatr Oncol 1995; 24: 215-221
• 58 Attiyeh EF, London WB, Mosse YP. et al. Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med 2005; 353: 2243-2253
• 59 Spitz R, Hero B, Simon T. et al. Loss in chromosome 11q identifies tumors with increased risk for metastatic relapses in localized and 4S neuroblastoma. Clin Cancer Res 2006; 12: 3368-3373
• 60 Meeser A, Bartenhagen C, Werr L. et al. Reliable assessment of telomere maintenance mechanisms in neuroblastoma. Cell Biosci 2022; 12: 160
• 61 Oberthuer A, Juraeva D, Hero B. et al. Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers. Clin Cancer Res 2015; 21: 1904-1915
• 62 Janoueix-Lerosey I, Schleiermacher G, Michels E. et al. Overall genomic pattern is a predictor of outcome in neuroblastoma. J Clin Oncol 2009; 27: 1026-1033
• 63 George RE, Sanda T, Hanna M. et al. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 2008; 455: 975-978
• 64 Fischer M, Moreno L, Ziegler DS. et al. Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Lancet Oncol 2021; 22: 1764-1776
• 65 Bellini A, Potschger U, Bernard V. et al Frequency and Prognostic Impact of ALK Amplifications and Mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1). J Clin Oncol 2021; 39: 3377-3390
• 66 Goldsmith KC, Park JR, Kayser K. et al. Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results. Nat Med 2023; 29: 1092-1102
• 67 Lodrini M, Graef J, Thole-Kliesch TM. et al. Targeted Analysis of Cell-free Circulating Tumor DNA is Suitable for Early Relapse and Actionable Target Detection in Patients with Neuroblastoma. Clin Cancer Res 2022; 28: 1809-1820
• 68 Lodrini M, Wunschel J, Thole-Kliesch TM. et al. Circulating Cell-Free DNA Assessment in Biofluids from Children with Neuroblastoma Demonstrates Feasibility and Potential for Minimally Invasive Molecular Diagnostics. Cancers 2022; 14
• 69 Brodeur GM, Pritchard J, Berthold F. et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993; 11: 1466-1477
• 70 Monclair T, Brodeur GM, Ambros PF. et al. The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol 2009; 27: 298-303
• 71 Cecchetto G, Mosseri V, De Bernardi B. et al. Surgical risk factors in primary surgery for localized neuroblastoma: the LNESG1 study of the European International Society of Pediatric Oncology Neuroblastoma Group. J Clin Oncol 2005; 23: 8483-8489
• 72 Brisse HJ, McCarville MB, Granata C. et al. Guidelines for imaging and staging of neuroblastic tumors: consensus report from the International Neuroblastoma Risk Group Project. Radiology 2011; 261: 243-257
• 73 Simon T, Hero B, Benz-Bohm G. et al. Review of image defined risk factors in localized neuroblastoma patients: Results of the GPOH NB97 trial. Pediatr Blood Cancer 2008; 50: 965-969
• 74 Irtan S, Brisse HJ, Minard-Colin V. et al. Minimally invasive surgery of neuroblastic tumors in children: Indications depend on anatomical location and image-defined risk factors. Pediatr Blood Cancer 2015; 62: 257-261
• 75 Iwanaka T, Arai M, Ito M. et al. Surgical treatment for abdominal neuroblastoma in the laparoscopic era. Surg Endosc 2001; 15: 751-754
• 76 Fuchs J. The role of minimally invasive surgery in pediatric solid tumors. Pediatr Surg Int 2015; 31: 213-228
• 77 Hassan SF, Mathur S, Magliaro TJ. et al. Needle core vs open biopsy for diagnosis of intermediate- and high-risk neuroblastoma in children. J Pediatr Surg 2012; 47: 1261-1266
• 78 Jarzembowski JA, Lal DR, Shimada H. Re: Needle core vs open biopsy for diagnosis of intermediate- and high-risk neuroblastoma in children. J Pediatr Surg 2012; 47: 2162-2163 author reply 2163-2165
• 79 Kirkpatrick AW, Roberts DJ, De Waele J. et al. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med 2013; 39: 1190-1206
• 80 Muller-Berghaus J, Kurowski C, Gharib M. et al. Artificial abdominal hernia for the treatment of hepatomegaly in a neonate with stage 4S neuroblastoma. Pediatr Hematol Oncol 1999; 16: 453-458
• 81 Holsten T, Schuster T, Grabhorn E. et al. Liver transplantation as a potentially lifesaving measure in neuroblastoma stage 4S. Pediatr Hematol Oncol 2017; 34: 17-23
• 82 Twist CJ, Naranjo A, Schmidt ML. et al. Defining Risk Factors for Chemotherapeutic Intervention in Infants With Stage 4S Neuroblastoma: A Report From Children’s Oncology Group Study ANBL0531. J Clin Oncol 2019; 37: 115-124
• 83 De Bernardi B, Gerrard M, Boni L. et al. Excellent outcome with reduced treatment for infants with disseminated neuroblastoma without MYCN gene amplification. J Clin Oncol 2009; 27: 1034-1040
• 84 Danner-Koptik K, Kletzel M, Dilley KJ. Exostoses as a long-term sequela after pediatric hematopoietic progenitor cell transplantation: potential causes and increase risk of secondary malignancies from Ann & Robert H. Lurie Children’s Hospital of Chicago. Biol Blood Marrow Transplant 2013; 19: 1267-1270
• 85 Bhatti P, Veiga LH, Ronckers CM. et al. Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study. Radiat Res 2010; 174: 741-752
• 86 Rubino C, Adjadj E, Guerin S. et al. Long-term risk of second malignant neoplasms after neuroblastoma in childhood: role of treatment. Int J Cancer 2003; 107: 791-796
• 87 Danner-Koptik KE, Majhail NS, Brazauskas R. et al. Second malignancies after autologous hematopoietic cell transplantation in children. Bone Marrow Transplant 2013; 48: 363-368
• 88 Fischer J, Pohl A, Volland R. et al. Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months. BMC Cancer 2017; 17: 520
• 89 Simon T, Spitz R, Faldum A. et al. New definition of low-risk neuroblastoma using stage, age, and 1p and MYCN status. J Pediatr Hematol Oncol 2004; 26: 791-796
• 90 Berthold F, Rosswog C, Christiansen H. et al. Clinical and molecular characterization of patients with stage 4(M) neuroblastoma aged less than 18 months without MYCN amplification. Pediatr Blood Cancer 2021; 68: e29038
• 91 Simon T, Hero B, Faldum A. et al. Infants with stage 4 neuroblastoma: the impact of the chimeric anti-GD2-antibody ch14.18 consolidation therapy. Klin Padiatr 2005; 217: 147-152
• 92 Simon T, Hero B, Dupuis W. et al. The incidence of hearing impairment after successful treatment of neuroblastoma. Klin Padiatr 2002; 214: 149-152
• 93 Dhyani P, Quispe C, Sharma E. et al. Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine. Cancer Cell Int 2022; 22: 206
• 94 Oshiro Y, Mizumoto M, Okumura T. et al. Clinical results of proton beam therapy for advanced neuroblastoma. Radiat Oncol 2013; 8: 142
• 95 Merchant TE. Clinical controversies: proton therapy for pediatric tumors. Semin Radiat Oncol 2013; 23: 97-108
• 96 Hattangadi JA, Rombi B, Yock TI. et al. Proton radiotherapy for high-risk pediatric neuroblastoma: early outcomes and dose comparison. Int J Radiat Oncol Biol Phys 2012; 83: 1015-1022
• 97 Hill-Kayser C, Tochner Z, Both S. et al. Proton versus photon radiation therapy for patients with high-risk neuroblastoma: the need for a customized approach. Pediatr Blood Cancer 2013; 60: 1606-1611
• 98 Taylor S, Lim P, Ahmad R. et al. Risk of radiation-induced second malignant neoplasms from photon and proton radiotherapy in paediatric abdominal neuroblastoma. Phys Imaging Radiat Oncol 2021; 19: 45-52
• 99 Jazmati D, Butzer S, Hero B. et al. Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry. Frontiers in oncology 2020; 10: 617506
• 100 Matthay KK, Villablanca JG, Seeger RC. et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group. N Engl J Med 1999; 341: 1165-1173
• 101 Matthay KK, Reynolds CP, Seeger RC. et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study. J Clin Oncol 2009; 27: 1007-1013
• 102 Park JR, Villablanca JG, London WB. et al. Outcome of high-risk stage 3 neuroblastoma with myeloablative therapy and 13-cis-retinoic acid: a report from the Children’s Oncology Group. Pediatr Blood Cancer 2009; 52: 44-50
• 103 Erratum Errata. Journal of Clinical Oncology 2014; 32: 1862-1863
• 104 Kohler JA, Imeson J, Ellershaw C. et al. A randomized trial of 13-Cis retinoic acid in children with advanced neuroblastoma after high-dose therapy. Br J Cancer 2000; 83: 1124-1127
• 105 Zwaveling S, Tytgat GA, van der Zee DC. et al. Is complete surgical resection of stage 4 neuroblastoma a prerequisite for optimal survival or may >95% tumour resection suffice?. Pediatr Surg Int 2012; 28: 953-959
• 106 von Schweinitz D, Hero B, Berthold F. The impact of surgical radicality on outcome in childhood neuroblastoma. Eur J Pediatr Surg 2002; 12: 402-409
• 107 Simon T, Haberle B, Hero B. et al. Role of surgery in the treatment of patients with stage 4 neuroblastoma age 18 months or older at diagnosis. J Clin Oncol 2013; 31: 752-758
• 108 Castel V, Tovar JA, Costa E. et al. The role of surgery in stage IV neuroblastoma. J Pediatr Surg 2002; 37: 1574-1578
• 109 Salim A, Mullassery D, Pizer B. et al. Neuroblastoma: a 20-year experience in a UK regional centre. Pediatr Blood Cancer 2011; 57: 1254-1260
• 110 von Allmen D, Grupp S, Diller L. et al Aggressive surgical therapy and radiotherapy for patients with high-risk neuroblastoma treated with rapid sequence tandem transplant. J Pediatr Surg 2005; 40: 936-941 discussion 941
• 111 McGregor LM, Rao BN, Davidoff AM. et al. The impact of early resection of primary neuroblastoma on the survival of children older than 1 year of age with stage 4 disease: the St. Jude Children's Research Hospital Experience. Cancer 2005; 104: 2837-2846
• 112 Koivusalo AI, Pakarinen MP, Rintala RJ. et al. Surgical treatment of neuroblastoma: twenty-three years of experience at a single institution. Surg Today 2014; 44: 517-525
• 113 Yeung F, Chung PH, Tam PK. et al. Is complete resection of high-risk stage IV neuroblastoma associated with better survival. J Pediatr Surg 2015; 50: 2107-2111
• 114 Englum BR, Rialon KL, Speicher PJ. et al. Value of surgical resection in children with high-risk neuroblastoma. Pediatr Blood Cancer 2015; 62: 1529-1535
• 115 La Quaglia MP, Kushner BH, Su W. et al The impact of gross total resection on local control and survival in high-risk neuroblastoma. J Pediatr Surg 2004; 39: 412-417 discussion 412-417
• 116 La Quaglia MP, Kushner BH, Heller G. et al Stage 4 neuroblastoma diagnosed at more than 1 year of age: gross total resection and clinical outcome. J Pediatr Surg 1994; 29: 1162-1165 discussion 1165-1166
• 117 Koh CC, Sheu JC, Liang DC. et al. Complete surgical resection plus chemotherapy prolongs survival in children with stage 4 neuroblastoma. Pediatr Surg Int 2005; 21: 69-72
• 118 Hsu WM, Jen YM, Lee H. et al. The influence of biologic factors on the surgical decision in advanced neuroblastoma. Ann Surg Oncol 2006; 13: 238-244
• 119 Adkins ES, Sawin R, Gerbing RB. et al. Efficacy of complete resection for high-risk neuroblastoma: a Children’s Cancer Group study. J Pediatr Surg 2004; 39: 931-936
• 120 Tsuchida Y, Yokoyama J, Kaneko M. et al. Therapeutic significance of surgery in advanced neuroblastoma: a report from the study group of Japan. J Pediatr Surg 1992; 27: 616-622
• 121 Escobar MA, Grosfeld JL, Powell RL. et al. Long-term outcomes in patients with stage IV neuroblastoma. J Pediatr Surg 2006; 41: 377-381
• 122 Holmes K, Potschger U, Pearson ADJ. et al. Influence of Surgical Excision on the Survival of Patients With Stage 4 High-Risk Neuroblastoma: A Report From the HR-NBL1/SIOPEN Study. J Clin Oncol 2020; 38: 2902-2915
• 123 Simon T, Hero B, Bongartz R. et al. Intensified external-beam radiation therapy improves the outcome of stage 4 neuroblastoma in children > 1 year with residual local disease. Strahlenther Onkol 2006; 182: 389-394
• 124 Philip T, Ghalie R, Pinkerton R. et al. A phase II study of high-dose cisplatin and VP-16 in neuroblastoma: a report from the Societe Francaise d'Oncologie Pediatrique. J Clin Oncol 1987; 5: 941-950
• 125 Kushner BH, LaQuaglia MP, Bonilla MA. et al. Highly effective induction therapy for stage 4 neuroblastoma in children over 1 year of age. J Clin Oncol 1994; 12: 2607-2613
• 126 Berthold F, Hero B. Neuroblastoma: current drug therapy recommendations as part of the total treatment approach. Drugs 2000; 59: 1261-1277
• 127 Castel V, Canete A, Navarro S. et al. Outcome of high-risk neuroblastoma using a dose intensity approach: improvement in initial but not in long-term results. Med Pediatr Oncol 2001; 37: 537-542
• 128 Frappaz D, Perol D, Michon J. et al. The LMCE5 unselected cohort of 25 children consecutively diagnosed with untreated stage 4 neuroblastoma over 1 year at diagnosis. Br J Cancer 2002; 87: 1197-1203
• 129 Tweddle DA, Pinkerton CR, Lewis IJ. et al. OPEC/OJEC for stage 4 neuroblastoma in children over 1 year of age. Med Pediatr Oncol 2001; 36: 239-242
• 130 De Bernardi B, Nicolas B, Boni L. et al. Disseminated neuroblastoma in children older than one year at diagnosis: comparable results with three consecutive high-dose protocols adopted by the Italian Co-Operative Group for Neuroblastoma. J Clin Oncol 2003; 21: 1592-1601
• 131 Berthold F, Boos J, Burdach S. et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol 2005; 6: 649-658
• 132 Pritchard J, Cotterill SJ, Germond SM. et al. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group. Pediatr Blood Cancer 2005; 44: 348-357
• 133 Kushner BH, Kramer K, LaQuaglia MP. et al. Reduction from seven to five cycles of intensive induction chemotherapy in children with high-risk neuroblastoma. J Clin Oncol 2004; 22: 4888-4892
• 134 Pearson AD, Pinkerton CR, Lewis IJ. et al. High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial. Lancet Oncol 2008; 9: 247-256
• 135 Valteau-Couanet D, Michon J, Boneu A. et al. Results of induction chemotherapy in children older than 1 year with a stage 4 neuroblastoma treated with the NB 97 French Society of Pediatric Oncology (SFOP) protocol. J Clin Oncol 2005; 23: 532-540
• 136 Cheung NK, Kushner BH, LaQuaglia M. et al. N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age. Med Pediatr Oncol 2001; 36: 227-230
• 137 Garaventa A, Poetschger U, Valteau-Couanet D. et al. Randomized Trial of Two Induction Therapy Regimens for High-Risk Neuroblastoma: HR-NBL1.5 International Society of Pediatric Oncology European Neuroblastoma Group Study. J Clin Oncol 2021; 39: 2552-2563
• 138 Berthold F, Faldum A, Ernst A. et al. Extended induction chemotherapy does not improve the outcome for high-risk neuroblastoma patients: results of the randomized open-label GPOH trial NB2004-HR. Ann Oncol 2020; 31: 422-429
• 139 Kushner BH, Kramer K, Modak S. et al. Irinotecan plus temozolomide for relapsed or refractory neuroblastoma. J Clin Oncol 2006; 24: 5271-5276
• 140 Vassal G, Giammarile F, Brooks M. et al. A phase II study of irinotecan in children with relapsed or refractory neuroblastoma: a European cooperation of the Societe Francaise d'Oncologie Pediatrique (SFOP) and the United Kingdom Children Cancer Study Group (UKCCSG). Eur J Cancer 2008; 44: 2453-2460
• 141 Wagner LM, Villablanca JG, Stewart CF. et al. Phase I trial of oral irinotecan and temozolomide for children with relapsed high-risk neuroblastoma: a new approach to neuroblastoma therapy consortium study. J Clin Oncol 2009; 27: 1290-1296
• 142 Kushner BH, Kramer K, Modak S. et al. High-dose carboplatin-irinotecan-temozolomide: treatment option for neuroblastoma resistant to topotecan. Pediatr Blood Cancer 2011; 56: 403-408
• 143 Bagatell R, London WB, Wagner LM. et al. Phase II study of irinotecan and temozolomide in children with relapsed or refractory neuroblastoma: a Children's Oncology Group study. J Clin Oncol 2011; 29: 208-213
• 144 Rubie H, Chisholm J, Defachelles AS. et al. Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: a joint Societe Francaise des Cancers de l'Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study. J Clin Oncol 2006; 24: 5259-5264
• 145 Rubie H, Geoerger B, Frappaz D. et al. Phase I study of topotecan in combination with temozolomide (TOTEM) in relapsed or refractory paediatric solid tumours. Eur J Cancer 2010; 46: 2763-2770
• 146 Peinemann F, Tushabe DA, van Dalen EC. et al. Rapid COJEC versus standard induction therapies for high-risk neuroblastoma. Cochrane Database Syst Rev 2015; 2015: CD010774
• 147 Ladenstein R, Valteau-Couanet D, Brock P. et al. Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study. J Clin Oncol 2010; 28: 3516-3524
• 148 Kim ES, Agarwal S, Shohet JM. G-CSF Is a Cancer Stem Cell-Specific Growth Factor-Response. Cancer Res 2015; 75: 3992
• 149 Agarwal S, Lakoma A, Chen Z. et al. G-CSF Promotes Neuroblastoma Tumorigenicity and Metastasis via STAT3-Dependent Cancer Stem Cell Activation. Cancer Res 2015; 75: 2566-2579
• 150 Maris JM, Healy J, Park J. et al. G-CSF Is a Cancer Stem Cell-Specific Growth Factor-Letter. Cancer Res 2015; 75: 3991
• 151 Amoroso L, Erminio G, Makin G. et al. Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study. Cancer research and treatment : official journal of Korean Cancer Association 2018; 50: 148-155
• 152 Mody R, Naranjo A, Van Ryn C. et al. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol 2017; 18: 946-957
• 153 Mody R, Yu AL, Naranjo A. et al. Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. J Clin Oncol 2020; 38: 2160-2169
• 154 Wieczorek A, Zaniewska-Tekieli A, Ehlert K. et al. Dinutuximab beta combined with chemotherapy in patients with relapsed or refractory neuroblastoma. Frontiers in oncology 2023; 13: 1082771
• 155 Lerman BJ, Li Y, Carlowicz C. et al. Progression-Free Survival and Patterns of Response in Patients With Relapsed High-Risk Neuroblastoma Treated With Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor. J Clin Oncol 2023; 41: 508-516
• 156 Kreissman SG, Seeger RC, Matthay KK. et al. Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial. Lancet Oncol 2013; 14: 999-1008
• 157 Modak S, Cheung IY, Kushner BH. et al. Plerixafor plus granulocyte-colony stimulating factor for autologous hematopoietic stem cell mobilization in patients with metastatic neuroblastoma. Pediatr Blood Cancer 2012; 58: 469-471
• 158 Son MH, Kang ES, Kim DH. et al. Efficacy and toxicity of plerixafor for peripheral blood stem cell mobilization in children with high-risk neuroblastoma. Pediatr Blood Cancer 2013; 60: E57-59
• 159 Vettenranta K, Mottonen M, Riikonen P. The use of plerixafor in harvesting autologous stem cells in the pediatric setting. Pediatr Blood Cancer 2012; 59: 197-198
• 160 Berthold F, Ernst A, Hero B. et al. Long-term outcomes of the GPOH NB97 trial for children with high-risk neuroblastoma comparing high-dose chemotherapy with autologous stem cell transplantation and oral chemotherapy as consolidation. Br J Cancer 2018; 119: 282-290
• 161 Ladenstein R, Potschger U, Hartman O. et al. 28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures. Bone Marrow Transplant 2008; 41: S118-127
• 162 Ladenstein R, Potschger U, Pearson AD. et al. Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial. Lancet Oncol 2017; 18: 500-514
• 163 Seddon BM, Cassoni AM, Galloway MJ. et al. Fatal radiation myelopathy after high-dose busulfan and melphalan chemotherapy and radiotherapy for Ewing's sarcoma: a review of the literature and implications for practice. Clin Oncol (R Coll Radiol) 2005; 17: 385-390
• 164 Carrie C, Le Deley MC, Claude L. et al. The radiosensitization effect and toxicity of busulfan containing chemotherapy before radiotherapy for Ewing’s sarcomas. Strahlentherapie Und Onkologie 2009; 185: 31-31
• 165 French S, DuBois SG, Horn B. et al. 131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma. Pediatr Blood Cancer 2013; 60: 879-884
• 166 Ferry I, Kolesnikov-Gauthier H, Oudoux A. et al. Feasibility of Busulfan Melphalan and Stem Cell Rescue After 131I-MIBG and Topotecan Therapy for Refractory or Relapsed Metastatic Neuroblastoma: The French Experience. J Pediatr Hematol Oncol 2018; 40: 426-432
• 167 Giardino S, Piccardo A, Conte M. et al. (131) I-Meta-iodobenzylguanidine followed by busulfan and melphalan and autologous stem cell rescue in high-risk neuroblastoma. Pediatr Blood Cancer 2021; 68: e28775
• 168 Park JR, Kreissman SG, London WB. et al. Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial. JAMA 2019; 322: 746-755
• 169 Hovi L, Saarinen UM, Siimes MA. Growth failure in children after total body irradiation preparative for bone marrow transplantation. Bone Marrow Transplant 1991; 8: 10-13
• 170 Toporski J, Garkavij M, Tennvall J. et al. High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma. Biol Blood Marrow Transplant 2009; 15: 1077-1085
• 171 Lang P, Pfeiffer M, Muller I. et al. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr 2006; 218: 321-326
• 172 Hale GA, Arora M, Ahn KW. et al. Allogeneic hematopoietic cell transplantation for neuroblastoma: the CIBMTR experience. Bone Marrow Transplant 2013; 48: 1056-1064
• 173 Flaadt T, Ladenstein RL, Ebinger M. et al. Anti-GD2 Antibody Dinutuximab Beta and Low-Dose Interleukin 2 After Haploidentical Stem-Cell Transplantation in Patients With Relapsed Neuroblastoma: A Multicenter, Phase I/II Trial. J Clin Oncol 2023; 41: 3135-3148
• 174 Matthay KK, DeSantes K, Hasegawa B. et al. Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma. J Clin Oncol 1998; 16: 229-236
• 175 Matthay KK, Quach A, Huberty J. et al. Iodine-131--metaiodobenzylguanidine double infusion with autologous stem-cell rescue for neuroblastoma: a new approaches to neuroblastoma therapy phase I study. J Clin Oncol 2009; 27: 1020-1025
• 176 Matthay KK, Weiss B, Villablanca JG. et al. Dose escalation study of no-carrier-added 131I-metaiodobenzylguanidine for relapsed or refractory neuroblastoma: new approaches to neuroblastoma therapy consortium trial. J Nucl Med 2012; 53: 1155-1163
• 177 Matthay KK, Tan JC, Villablanca JG. et al. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol 2006; 24: 500-506
• 178 DuBois SG, Chesler L, Groshen S. et al. Phase I study of vincristine, irinotecan, and (1)(3)(1)I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial. Clin Cancer Res 2012; 18: 2679-2686
• 179 Gaze MN, Chang YC, Flux GD. et al. Feasibility of dosimetry-based high-dose 131I-meta-iodobenzylguanidine with topotecan as a radiosensitizer in children with metastatic neuroblastoma. Cancer Biother Radiopharm 2005; 20: 195-199
• 180 Kanold J, Paillard C, Tchirkov A. et al. Allogeneic or haploidentical HSCT for refractory or relapsed solid tumors in children: toward a neuroblastoma model. Bone Marrow Transplant 2008; 42: S25-30
• 181 de Kraker J, Hoefnagel KA, Verschuur AC. et al. Iodine-131-metaiodobenzylguanidine as initial induction therapy in stage 4 neuroblastoma patients over 1 year of age. Eur J Cancer 2008; 44: 551-556
• 182 Mastrangelo S, Rufini V, Ruggiero A. et al. Treatment of advanced neuroblastoma in children over 1 year of age: the critical role of (1)(3)(1)I-metaiodobenzylguanidine combined with chemotherapy in a rapid induction regimen. Pediatr Blood Cancer 2011; 56: 1032-1040
• 183 Yanik GA, Levine JE, Matthay KK. et al. Pilot study of iodine-131-metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma. J Clin Oncol 2002; 20: 2142-2149
• 184 Schmidt M, Simon T, Hero B. et al Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for The German Neuroblastoma Trial NB2004. Nuklearmedizin 2006; 45: 145-151 quiz N139-140
• 185 Klingebiel T, Bader P, Bares R. et al. Treatment of neuroblastoma stage 4 with 131I-meta-iodo-benzylguanidine, high-dose chemotherapy and immunotherapy. A pilot study. Eur J Cancer 1998; 34: 1398-1402
• 186 Matthay KK, Yanik G, Messina J. et al. Phase II study on the effect of disease sites, age, and prior therapy on response to iodine-131-metaiodobenzylguanidine therapy in refractory neuroblastoma. J Clin Oncol 2007; 25: 1054-1060
• 187 Sudbrock F, Schmidt M, Simon T. et al. Dosimetry for 131I-MIBG therapies in metastatic neuroblastoma, phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging 2010; 37: 1279-1290
• 188 Dahllof G, Borgstrom P, Lundell G. et al. Severe oral mucositis after therapeutic administration of [131I]MIBG in a child with neuroblastoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 92: 420-423
• 189 Garaventa A, Bellagamba O, Lo Piccolo MS. et al. 131I-metaiodobenzylguanidine (131I-MIBG) therapy for residual neuroblastoma: a mono-institutional experience with 43 patients. Br J Cancer 1999; 81: 1378-1384
• 190 Arumugam S, Manning-Cork NJ, Gains JE. et al. The Evidence for External Beam Radiotherapy in High-Risk Neuroblastoma of Childhood: A Systematic Review. Clin Oncol (R Coll Radiol) 2019; 31: 182-190
• 191 Casey DL, Kushner BH, Cheung NK. et al. Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma. Int J Radiat Oncol Biol Phys 2016; 96: 393-400
• 192 Gatcombe HG, Marcus RB, Katzenstein HM. et al. Excellent local control from radiation therapy for high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 2009; 74: 1549-1554
• 193 Kushner BH, Wolden S, LaQuaglia MP. et al. Hyperfractionated low-dose radiotherapy for high-risk neuroblastoma after intensive chemotherapy and surgery. J Clin Oncol 2001; 19: 2821-2828
• 194 Mazloom A, Louis CU, Nuchtern J. et al. Radiation therapy to the primary and postinduction chemotherapy MIBG-avid sites in high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 2014; 90: 858-862
• 195 Pai Panandiker AS, McGregor L, Krasin MJ. et al. Locoregional tumor progression after radiation therapy influences overall survival in pediatric patients with neuroblastoma. Int J Radiat Oncol Biol Phys 2010; 76: 1161-1165
• 196 Pai Panandiker AS, Beltran C, Billups CA. et al. Intensity modulated radiation therapy provides excellent local control in high-risk abdominal neuroblastoma. Pediatr Blood Cancer 2013; 60: 761-765
• 197 Haas-Kogan DA, Swift PS, Selch M. et al. Impact of radiotherapy for high-risk neuroblastoma: a Children's Cancer Group study. Int J Radiat Oncol Biol Phys 2003; 56: 28-39
• 198 Robbins JR, Krasin MJ, Pai Panandiker AS. et al. Radiation therapy as part of local control of metastatic neuroblastoma: the St Jude Children's Research Hospital experience. J Pediatr Surg 2010; 45: 678-686
• 199 Casey DL, Kushner BH, Cheung NV. et al. Dose-escalation is needed for gross disease in high-risk neuroblastoma. Pediatr Blood Cancer 2018; 65: e27009
• 200 Wei Z, Li J, Jin Y. et al. The application and value of radiotherapy at the primary site in patients with high-risk neuroblastoma. Br J Radiol 2022; 95: 20211086
• 201 Liu KX, Naranjo A, Zhang FF. et al. Prospective Evaluation of Radiation Dose Escalation in Patients With High-Risk Neuroblastoma and Gross Residual Disease After Surgery: A Report From the Children's Oncology Group ANBL0532 Study. J Clin Oncol 2020; 38: 2741-2752
• 202 Ding YY, Panzer J, Maris JM. et al. Transverse myelitis as an unexpected complication following treatment with dinutuximab in pediatric patients with high-risk neuroblastoma: A case series. Pediatr Blood Cancer 2018; 65
• 203 Gillis AM, Sutton E, Dewitt KD. et al. Long-term outcome and toxicities of intraoperative radiotherapy for high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 2007; 69: 858-864
• 204 Oertel S, Niethammer AG, Krempien R. et al. Combination of external-beam radiotherapy with intraoperative electron-beam therapy is effective in incompletely resected pediatric malignancies. Int J Radiat Oncol Biol Phys 2006; 64: 235-241
• 205 Sugito K, Kusafuka T, Hoshino M. et al. Intraoperative radiation therapy for advanced neuroblastoma: the problem of securing the IORT field. Pediatr Surg Int 2007; 23: 1203-1207
• 206 Gaze MN, Boterberg T, Dieckmann K. et al. Results of a quality assurance review of external beam radiation therapy in the International Society of Paediatric Oncology (Europe) Neuroblastoma Group's High-risk Neuroblastoma Trial: a SIOPEN study. Int J Radiat Oncol Biol Phys 2013; 85: 170-174
• 207 Casey DL, Pitter KL, Kushner BH. et al. Radiation Therapy to Sites of Metastatic Disease as Part of Consolidation in High-Risk Neuroblastoma: Can Long-term Control Be Achieved?. Int J Radiat Oncol Biol Phys 2018; 100: 1204-1209
• 208 Polishchuk AL, Li R, Hill-Kayser C. et al. Likelihood of bone recurrence in prior sites of metastasis in patients with high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 2014; 89: 839-845
• 209 Jazmati D, Butzer S, Hero B. et al. Long-term follow-up of children with neuroblastoma receiving radiotherapy to metastatic lesions within the German Neuroblastoma Trials NB97 and NB 2004. Strahlenther Onkol 2021; 197: 683-689
• 210 Xiang M, Chang DT, Pollom EL. Second cancer risk after primary cancer treatment with three-dimensional conformal, intensity-modulated, or proton beam radiation therapy. Cancer 2020; 126: 3560-3568
• 211 Kahalley LS, Peterson R, Ris MD. et al. Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma. J Clin Oncol 2020; 38: 454-461
• 212 Simon T, Hero B, Faldum A. et al. Consolidation treatment with chimeric anti-GD2-antibody ch14.18 in children older than 1 year with metastatic neuroblastoma. J Clin Oncol 2004; 22: 3549-3557
• 213 Cheung NK, Kushner BH, Cheung IY. et al. Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. J Clin Oncol 1998; 16: 3053-3060
• 214 Handgretinger R, Anderson K, Lang P. et al. A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma. Eur J Cancer 1995; 31A: 261-267
• 215 Yu AL, Uttenreuther-Fischer MM, Huang CS. et al Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma. J Clin Oncol 1998; 16: 2169-2180
• 216 Simon T, Berthold F, Borkhardt A. et al. Treatment and outcomes of patients with relapsed, high-risk neuroblastoma: results of German trials. Pediatr Blood Cancer 2011; 56: 578-583
• 217 Yu AL, Gilman AL, Ozkaynak MF. et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010; 363: 1324-1334
• 218 Yu AL, Gilman AL, Ozkaynak MF. et al. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032. Clin Cancer Res 2021; 27: 2179-2189
• 219 Zeng Y, Fest S, Kunert R. et al. Anti-neuroblastoma effect of ch14.18 antibody produced in CHO cells is mediated by NK-cells in mice. Mol Immunol 2005; 42: 1311-1319
• 220 Siebert N, Eger C, Seidel D. et al. Pharmacokinetics and pharmacodynamics of ch14.18/CHO in relapsed/refractory high-risk neuroblastoma patients treated by long-term infusion in combination with IL-2. MAbs 2016; 8: 604-616
• 221 Ladenstein R, Potschger U, Valteau-Couanet D. et al. Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1). Cancers 2020; 12
• 222 Ladenstein R, Potschger U, Valteau-Couanet D. et al. Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial. Lancet Oncol 2018; 19: 1617-1629
• 223 Ladenstein RL, Poetschger U, Valteau-Couanet D. et al. Randomization of dose-reduced subcutaneous interleukin-2 (scIL2) in maintenance immunotherapy (IT) with anti-GD2 antibody dinutuximab beta (DB) long-term infusion (LTI) in front–line high-risk neuroblastoma patients: Early results from the HR-NBL1/SIOPEN trial. Journal of Clinical Oncology 2019; 37: 10013-10013
• 224 Wieczorek A, Manzitti C, Garaventa A. et al. Clinical Phenotype and Management of Severe Neurotoxicity Observed in Patients with Neuroblastoma Treated with Dinutuximab Beta in Clinical Trials. Cancers 2022; 14
• 225 Lode HN, Ehlert K, Huber S. et al. Long-term, continuous infusion of single-agent dinutuximab beta for relapsed/refractory neuroblastoma: an open-label, single-arm, Phase 2 study. Br J Cancer 2023; 129: 1780-1786
• 226 Mueller I, Ehlert K, Endres S. et al. Tolerability, response and outcome of high-risk neuroblastoma patients treated with long-term infusion of anti-GD(2) antibody ch14.18/CHO. MAbs 2018; 10: 55-61
• 227 Mora J, Castaneda A, Gorostegui M. et al. Naxitamab Combined with Granulocyte-Macrophage Colony-Stimulating Factor as Consolidation for High-Risk Neuroblastoma Patients in First Complete Remission under Compassionate Use-Updated Outcome Report. Cancers 2023; 15
• 228 Duke ES, Bradford D, Sinha AK. et al. US Food and Drug Administration Approval Summary: Eflornithine for High-Risk Neuroblastoma After Prior Multiagent, Multimodality Therapy. J Clin Oncol 2024; 42: 3047-3057
• 229 Sholler GLS, Ferguson W, Bergendahl G. et al. Maintenance DFMO Increases Survival in High Risk Neuroblastoma. Sci Rep 2018; 8: 14445
• 230 Oesterheld J, Ferguson W, Kraveka JM. et al. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons. J Clin Oncol 2024; 42: 90-102
• 231 Rosswog C, Fassunke J, Ernst A. et al. Genomic ALK alterations in primary and relapsed neuroblastoma. Br J Cancer 2023; 128: 1559-1571
• 232 Mosse YP, Lim MS, Voss SD. et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol 2013; 14: 472-480
• 233 Simon T, Hero B, Hunneman DH. et al. Tumour markers are poor predictors for relapse or progression in neuroblastoma. Eur J Cancer 2003; 39: 1899-1903
• 234 Bertolini P, Lassalle M, Mercier G. et al Platinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss. J Pediatr Hematol Oncol 2004; 26: 649-655 00043426-200410000-00007 [pii]
• 235 Garaventa A, Gambini C, Villavecchia G. et al. Second malignancies in children with neuroblastoma after combined treatment with 131I-metaiodobenzylguanidine. Cancer 2003; 97: 1332-1338
• 236 Grewal S, Merchant T, Reymond R. et al. Auditory late effects of childhood cancer therapy: a report from the Children's Oncology Group. Pediatrics 2010; 125: e938-950
• 237 Laverdiere C, Cheung NK, Kushner BH. et al. Long-term complications in survivors of advanced stage neuroblastoma. Pediatr Blood Cancer 2005; 45: 324-332
• 238 Gurney JG, Tersak JM, Ness KK. et al. Hearing loss, quality of life, and academic problems in long-term neuroblastoma survivors: a report from the Children's Oncology Group. Pediatrics 2007; 120: e1229-1236
• 239 Nathan PC, Ness KK, Greenberg ML. et al. Health-related quality of life in adult survivors of childhood Wilms tumor or neuroblastoma: A report from the childhood cancer survivor study. Pediatr Blood Cancer 2007; 49: 704-715
• 240 Picco P, Garaventa A, Claudiani F. et al. Primary hypothyroidism as a consequence of 131-I-metaiodobenzylguanidine treatment for children with neuroblastoma. Cancer 1995; 76: 1662-1664
• 241 Quach A, Ji L, Mishra V. et al. Thyroid and hepatic function after high-dose 131 I-metaiodobenzylguanidine (131 I-MIBG) therapy for neuroblastoma. Pediatr Blood Cancer 2011; 56: 191-201
• 242 van Santen HM, de Kraker J, van Eck BL. et al. Improved radiation protection of the thyroid gland with thyroxine, methimazole, and potassium iodide during diagnostic and therapeutic use of radiolabeled metaiodobenzylguanidine in children with neuroblastoma. Cancer 2003; 98: 389-396
• 243 Benz-Bohm G, Hero B, Gossmann A. et al. Focal nodular hyperplasia of the liver in longterm survivors of neuroblastoma: how much diagnostic imaging is necessary?. Eur J Radiol 2010; 74: e1-5
• 244 Trahair T, Sorrentino S, Russell SJ. et al. Spinal Canal Involvement in Neuroblastoma. J Pediatr 2017; 188: 294-298
• 245 Kasahara K, Nakagawa T, Kubota T. Neuronal loss and expression of neurotrophic factors in a model of rat chronic compressive spinal cord injury. Spine (Phila Pa 1976) 2006; 31: 2059-2066
• 246 Boglino C, Martins AG, Ciprandi G. et al. Spinal cord vascular injuries following surgery of advanced thoracic neuroblastoma: an unusual catastrophic complication. Med Pediatr Oncol 1999; 32: 349-352
• 247 Simon T, Niemann CA, Hero B. et al. Short- and long-term outcome of patients with symptoms of spinal cord compression by neuroblastoma. Dev Med Child Neurol 2012; 54: 347-352
• 248 De Bernardi B, Balwierz W, Bejent J. et al. Epidural compression in neuroblastoma: Diagnostic and therapeutic aspects. Cancer Lett 2005; 228: 283-299
• 249 Kraal K, Blom T, Tytgat L. et al. Neuroblastoma With Intraspinal Extension: Health Problems in Long-Term Survivors. Pediatr Blood Cancer 2016; 63: 990-996
• 250 Davis DD, Kane SM. Palliation Radiation Therapy of the Spinal Cord. In. StatPearls: Treasure Island (FL); 2024
• 251 Paulino AC. Palliative radiotherapy in children with neuroblastoma. Pediatr Hematol Oncol 2003; 20: 111-117
• 252 Retrosi G, Bishay M, Kiely EM. et al. Morbidity after ganglioneuroma excision: is surgery necessary?. Eur J Pediatr Surg 2011; 21: 33-37
• 253 De Bernardi B, Gambini C, Haupt R. et al. Retrospective study of childhood ganglioneuroma. J Clin Oncol 2008; 26: 1710-1716
• 254 Geraci AP, de Csepel J, Shlasko E. et al. Ganglioneuroblastoma and ganglioneuroma in association with neurofibromatosis type I: report of three cases. J Child Neurol 1998; 13: 356-358
• 255 Duhem-Tonnelle V, Vinchon M, Defachelles AS. et al. Mature neuroblastic tumors with spinal cord compression: report of five pediatric cases. Childs Nerv Syst 2006; 22: 500-505
• 256 Okamatsu C, London WB, Naranjo A. et al. Clinicopathological characteristics of ganglioneuroma and ganglioneuroblastoma: a report from the CCG and COG. Pediatr Blood Cancer 2009; 53: 563-569
• 257 Cheung NK, Zhang J, Lu C. et al. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA 2012; 307: 1062-1071
• 258 Valentijn LJ, Koster J, Zwijnenburg DA. et al. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat Genet 2015; 47: 1411-1414
• 259 Kushner BH, Kramer K, LaQuaglia MP. et al. Neuroblastoma in adolescents and adults: the Memorial Sloan-Kettering experience. Med Pediatr Oncol 2003; 41: 508-515
• 260 Mosse YP, Deyell RJ, Berthold F. et al. Neuroblastoma in older children, adolescents and young adults: a report from the International Neuroblastoma Risk Group project. Pediatr Blood Cancer 2014; 61: 627-635
• 261 Sorrentino S, Gigliotti AR, Sementa AR. et al. Neuroblastoma in the adult: the Italian experience with 21 patients. J Pediatr Hematol Oncol 2014; 36: e499-505