Current treatment strategies for first relapse of high-risk neuroblastoma
Current treatment strategies for first relapse of high-risk neuroblastoma
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.
Castelli, Sveva
e59978d7-0ed2-422f-984c-2b1d9681c6bc
Thole-Kliesch, Theresa M.
Gray, Juliet
12d5e17c-97bb-4d6d-8fc4-3914b730ed42
the SIOPEN New Drug Development, Immunotherapy and Relapse Groups
4 February 2026
Castelli, Sveva
e59978d7-0ed2-422f-984c-2b1d9681c6bc
Thole-Kliesch, Theresa M.
Gray, Juliet
12d5e17c-97bb-4d6d-8fc4-3914b730ed42
Castelli, Sveva, Schulze, Franziska and Thole-Kliesch, Theresa M.
,
et al. and the SIOPEN New Drug Development, Immunotherapy and Relapse Groups
(2026)
Current treatment strategies for first relapse of high-risk neuroblastoma.
European Journal of Cancer, 236, [116254].
(doi:10.1016/j.ejca.2026.116254).
Abstract
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.
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EJC-D-25-04465_Resubmission_FINAL-CLEAN_18.01.2026
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Accepted/In Press date: 21 January 2026
e-pub ahead of print date: 29 January 2026
Published date: 4 February 2026
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Local EPrints ID: 510057
URI: http://eprints.soton.ac.uk/id/eprint/510057
ISSN: 0959-8049
PURE UUID: 846440dc-0ffe-4fe9-b4a3-6b27c5290138
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Date deposited: 16 Mar 2026 17:53
Last modified: 17 Mar 2026 02:39
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Contributors
Author:
Sveva Castelli
Author:
Franziska Schulze
Author:
Theresa M. Thole-Kliesch
Corporate Author: et al.
Corporate Author: the SIOPEN New Drug Development, Immunotherapy and Relapse Groups
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