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Lookup NU author(s): Professor Deborah TweddleORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026. More than 50% of patients with high-risk neuroblastoma (HRNB) will relapse despite intensive multimodal therapy. Most relapses occur within 2 years of diagnosis. Overall survival at relapse is 20% at 4 years, but long-term survival can be achieved in a patient subset. A biopsy at relapse with in-depth molecular characterization should now become accepted as standard of care to confirm active neuroblastoma and identify potential targets for biomarker-based targeted therapy or immunotherapy. No clear consensus currently exists about optimal therapy because the field lacks umbrella trials covering all phases of relapse treatment (re-induction, consolidation, maintenance) in a homogenous strategy. Recruitment into clinical trials (e.g. BEACON2) should be prioritized. Current evidence supports starting re-induction therapy with a camptothecin-based chemotherapy regimen combined with monoclonal antibody therapy targeting GD2 or VEGF (or ALK inhibitors if ALK -aberrant) as the first choice. The RIST regimen is a promising first choice for MYCN -amplified disease. After an objective response to re-induction therapy, GD2-directed immunotherapy or cellular therapies harnessing the immune system (haploidentical stem cell transplantation, CAR T cells) are of high interest as a consolidation strategy. Long-term maintenance therapy must be feasible as outpatient treatment, have a low toxicity profile and be well-tolerable to suit patients with relapsed HRNB. For optimal care, new options must be tested as maintenance therapy in randomized trials. The most promising salvage options for patients responding insufficiently to treatment are the chemotherapy combinations, topotecan/vincristine/doxorubicin (TVD), topotecan/cyclophosphamide/etoposide (TCE), ifosfamide/carboplatin/etoposide (ICE) or topotecan/cyclophosphamide (TopoCy), or [131I]-mIBG therapy. Early-phase clinical trials are also a possible option in this setting.
Author(s): Castelli S, Schulze F, Thole-Kliesch TM, Astrahantseff K, Barone G, Beck-Popovic M, Berlanga P, Corbacioglu S, Fischer M, Gambart M, George SL, Chesler L, Gray JC, Hero B, Kunkele A, Flaadt T, Lang P, Lode HN, Molenaar JJ, Schleiermacher G, Rosswog C, Moreno L, Owens C, Rubio-San-Simon A, Schulte JH, Simon T, Tweddle DA, Deubzer HE, Eggert A
Publication type: Review
Publication status: Published
Journal: European Journal of Cancer
Year: 2026
Volume: 236
Print publication date: 11/03/2026
Online publication date: 29/01/2026
Acceptance date: 21/01/2026
ISSN (print): 0959-8049
ISSN (electronic): 1879-0852
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.ejca.2026.116254
DOI: 10.1016/j.ejca.2026.116254
