{"entity":{"id":"neuroblastoma","kind":"indication","name":"Neuroblastoma (paediatric)","aka":[],"tldr":"Neuroblastoma is a childhood nerve-cell cancer where anti-GD2 antibodies and, recently, GD2 CAR-T have improved survival in high-risk disease.","summary":"Neuroblastoma arises from developing sympathetic nerve cells, usually in the adrenal gland or along the spine, and is the most common cancer of infants and the most common extracranial solid tumour of childhood. It spans the widest clinical range in oncology: some infant tumours (stage MS) regress without treatment, while high-risk disease (about half of patients, defined by INRG stage, age over 18 months, MYCN amplification and other genomic features) is cured in only 50-60% despite the most intensive therapy given to children, which is where anti-GD2 antibodies and CAR-T have made their gains. ALK mutations (~10%) are the main druggable driver; MYCN, though not directly druggable, points to polyamine and ALK biology.\n\nHigh-risk therapy is a year-long sequence: five to six cycles of induction chemotherapy, surgery, myeloablative chemotherapy with autologous stem-cell rescue (tandem transplant in North America after ANBL0532; busulfan-melphalan single transplant in Europe after HR-NBL1), radiotherapy to the primary site, then anti-GD2 immunotherapy (dinutuximab or dinutuximab beta with GM-CSF; IL-2 abandoned after HR-NBL1) and isotretinoin. Anti-GD2 antibody raised survival by about 20 points (ANBL0032). Since December 2023, two years of oral eflornithine (DFMO) is approved as maintenance on the strength of an externally controlled study; naxitamab and irinotecan-temozolomide-dinutuximab treat relapse; lorlatinib is being added for ALK-aberrant tumours and 131I-MIBG tested in induction (ANBL1531).\n\nNeuroblastoma is also where CAR-T first produced lasting cures in a solid tumour: GD2-CART01 (Bambino Gesù, NEJM 2023) achieved 63% responses and 33% complete remissions in relapsed disease, with some remissions lasting more than a decade. The open questions are whether cell therapy can consolidate first-line remission, how to reduce the lifelong burden of hearing loss, infertility and second cancers in survivors, how to treat MYCN-amplified relapse, and how to bring anti-GD2 therapy to the majority of children in the world who cannot access it.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Neuroblastoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroblastoma"}],"tags":["paediatric","spike"],"related":["i-131"],"indications":[],"sections":[],"technologies":["radioligand-therapy","mibg-theranostics"],"targets":[],"drugs":[],"companies":["y-mabs"],"institutions":["mskcc","dana-farber"],"pathways":[],"terms":[],"trials":["nct04724369"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"paediatric","burden":"~7-8% of childhood cancers; ~800 US cases a year; median age at diagnosis ~18 months; 5-year survival >90% for low/intermediate risk and ~50-60% for high risk.","subtypes":["Very-low and low risk (L1, MS in infants; often observation or surgery alone)","Intermediate risk (L2, M in infants; moderate chemotherapy)","High risk (stage M >18 months, or MYCN-amplified at any age)","ALK-mutated or amplified (~10%; lorlatinib-responsive)","MYCN-amplified (~20%)","Relapsed/refractory (MIBG-avid vs non-avid; marrow vs soft-tissue)","Ganglioneuroblastoma / ganglioneuroma (differentiated spectrum)","Opsoclonus-myoclonus-associated (paraneoplastic)"],"biomarkers":["MYCN amplification","ALK mutation","Age, stage, ploidy","Segmental chromosome aberrations","INRG stage and image-defined risk factors","Age (<18 months)","MYCN amplification (FISH)","ALK mutation/amplification","11q aberration, 1p deletion, ploidy, segmental chromosomal aberrations","INPC histology","Urinary catecholamines (VMA/HVA)","123I-MIBG Curie score / 18F-MFBG PET","Bone marrow minimal residual disease (PHOX2B, TH qPCR)","GD2 expression (near-universal)"],"standardOfCare":[{"setting":"High-risk","approach":"Induction chemo → surgery → tandem transplant → RT → anti-GD2 + isotretinoin; lorlatinib if ALK-mutant.","refs":[],"guideline":{"version":"NCI PDQ: Neuroblastoma Treatment (COG risk groups)","url":"https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq"}},{"setting":"Very-low / low risk (L1, MS)","approach":"Observation with serial imaging for asymptomatic L1/MS (many regress); surgery alone for resectable L1; short chemotherapy only for symptoms or progression.","refs":[],"guideline":{"nccn":"COG/SIOPEN low-risk protocols (observation or surgery)","version":"COG ANBL1232 / SIOPEN LINES"}},{"setting":"Intermediate risk","approach":"2-8 cycles of moderate chemotherapy (carboplatin, etoposide, cyclophosphamide, doxorubicin) guided by response and biology; surgery; isotretinoin in some protocols.","refs":[]},{"setting":"High risk: induction","approach":"5-6 cycles (COG: topotecan-cyclophosphamide × 2 then cisplatin-etoposide, cyclophosphamide-doxorubicin-vincristine; SIOPEN: rapid COJEC); stem-cell harvest; ANBL1531 adds 131I-MIBG (randomised) or lorlatinib (ALK); ANBL17P1 adds dinutuximab to induction.","refs":["anbl1531","i131-mibg"],"guideline":{"nccn":"COG ANBL1531 backbone","version":"COG 2026"}},{"setting":"High risk: local control","approach":"Surgical resection of primary after induction (gross total where safe); external-beam radiotherapy 21.6 Gy to primary site (boost to residual) and MIBG-avid metastatic sites; proton therapy where available.","refs":[]},{"setting":"High risk: consolidation","approach":"Tandem autologous transplant (thiotepa-cyclophosphamide, then CEM) in North America (ANBL0532); single busulfan-melphalan transplant in Europe (HR-NBL1).","refs":[],"guideline":{"nccn":"COG standard (tandem); SIOPEN standard (BuMel)","version":"2026"}},{"setting":"High risk: post-consolidation","approach":"Anti-GD2 antibody (dinutuximab + GM-CSF + isotretinoin; dinutuximab beta in Europe, no IL-2) × 5-6 cycles; then eflornithine maintenance 2 years (US, 2023).","refs":[],"guideline":{"nccn":"Dinutuximab: FDA-approved standard; eflornithine: FDA-approved maintenance","version":"2026"}},{"setting":"Relapsed / refractory","approach":"Irinotecan-temozolomide + dinutuximab or naxitamab (ANBL1221); naxitamab + GM-CSF for marrow/bone disease; 131I-MIBG for MIBG-avid disease; lorlatinib for ALK; GD2 CAR-T (Italy, trials); DFMO-based maintenance; palliative radiotherapy.","refs":["i131-mibg"]},{"setting":"Survivorship","approach":"Audiology (platinum, DFMO), endocrine and fertility follow-up, cardiac surveillance (anthracycline), second-malignancy screening, neurocognitive support; lifelong late-effects clinic.","refs":[]}],"stateOfArt":["Anti-GD2 raised high-risk survival to ~60%.","GD2 CAR-T responses.","Anti-GD2 immunotherapy after transplant is standard worldwide (ANBL0032), with IL-2 removed after HR-NBL1 showed no benefit.","Tandem transplant (North America) and busulfan-melphalan (Europe) are the two evidence-based consolidation standards.","Eflornithine is the first oral maintenance therapy approved (December 2023), on an externally controlled study.","GD2 CAR-T produced durable complete remissions in relapsed neuroblastoma, the first such result in a childhood solid tumour.","ALK inhibition with lorlatinib for ALK-aberrant tumours and 131I-MIBG during induction are being tested in ANBL1531.","Risk-adapted de-escalation: many infants and low-risk patients are observed or cured with surgery alone."],"history":[{"year":1910,"title":"James Homer Wright describes neuroblastoma and its rosettes","refs":[]},{"year":1971,"title":"Spontaneous regression of stage IV-S (now MS) disease recognised (Evans staging)","refs":[]},{"year":1983,"title":"MYCN amplification linked to aggressive disease (Brodeur, Schwab)","refs":[]},{"year":1985,"title":"131I-MIBG therapy first used in relapsed neuroblastoma","refs":["mibg-theranostics"]},{"year":1999,"title":"CCG-3891: myeloablative therapy with autologous rescue and isotretinoin improve survival","refs":[]},{"year":2008,"title":"ALK mutations identified as a hereditary and somatic driver","refs":[]},{"year":2009,"title":"INRG classification unifies international risk grouping","refs":[]},{"year":2010,"title":"Anti-GD2 (ch14.18) improves EFS","refs":[]},{"year":2010,"title":"ANBL0032: anti-GD2 immunotherapy raises survival ~20 points (NEJM)","refs":[]},{"year":2015,"title":"Dinutuximab approved (US); dinutuximab beta in EU 2017","refs":[]},{"year":2017,"title":"HR-NBL1: busulfan-melphalan beats CEM; IL-2 adds no benefit (2018)","refs":[]},{"year":2019,"title":"ANBL0532: tandem transplant improves EFS (JAMA)","refs":[]},{"year":2020,"title":"Naxitamab approved for relapsed disease (accelerated)","refs":[]},{"year":2023,"title":"GD2 CAR-T phase 1/2 in NEJM","refs":[]},{"year":2023,"title":"GD2-CART01 in NEJM: durable CAR-T remissions in a solid tumour; eflornithine approved (13 Dec)","refs":[]},{"year":2025,"title":"Long-term GD2 CAR-T follow-up (Nature Medicine); naxitamab primary-refractory phase 2 (75% CR); eflornithine EU filing","refs":[]},{"year":2026,"title":"ANBL1531 MIBG randomisation maturing; ALK arm reports","refs":["anbl1531"]}],"pipeline":["anbl1531","i131-mibg","idea-mfbg-pet-replaces-mibg","mibg-theranostics","y-mabs"],"openProblems":["Relapsed high-risk disease.","Long-term toxicity of intensive therapy.","Relapsed high-risk neuroblastoma is rarely curable; MYCN-amplified relapse worst of all.","Anti-GD2 therapy causes severe neuropathic pain; less painful antibody formats (e.g., humanised, Fc-engineered) and CAR-T are needed.","Long-term toxicity of tandem transplant, cisplatin (hearing loss), and radiation in children who will live 70 years.","Eflornithine's approval rests on an external control; a randomised trial is unlikely, so uncertainty persists.","Access: anti-GD2 antibodies are expensive and unavailable in most low- and middle-income countries where most children with cancer live.","MYCN remains undruggable directly; polyamine and Aurora/BET strategies are indirect.","GD2 CAR-T needs randomised evidence and manufacturing at scale; only a few centres can deliver it.","Imaging burden: repeated MIBG scans with sedation; MFBG PET adoption is slow."]},"route":"/indications/neuroblastoma/","neighbours":{"isotope":[{"id":"i-123","kind":"isotope","name":"Iodine-123","route":"/isotopes/i-123/"},{"id":"i-131","kind":"isotope","name":"Iodine-131","route":"/isotopes/i-131/"}],"technology":[{"id":"mibg-theranostics","kind":"technology","name":"MIBG imaging and 131I-MIBG therapy","route":"/technologies/mibg-theranostics/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"},{"id":"spect-ct","kind":"technology","name":"SPECT/CT","route":"/technologies/spect-ct/"}],"company":[{"id":"y-mabs","kind":"company","name":"Y-mAbs Therapeutics","route":"/companies/y-mabs/"}],"institution":[{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"sahlgrenska","kind":"institution","name":"Sahlgrenska University Hospital / Sahlgrenska Center for Cancer Research","route":"/institutions/sahlgrenska/"}],"trial":[{"id":"anbl1531","kind":"trial","name":"COG ANBL1531","route":"/trials/anbl1531/"},{"id":"nct04724369","kind":"trial","name":"Open-Label Study of 18F-mFBG for Imaging Neuroblastoma","route":"/trials/nct04724369/"}],"drug":[{"id":"i131-mibg","kind":"drug","name":"131I-MIBG (iobenguane I-131) therapy","route":"/drugs/i131-mibg/"},{"id":"i-123-mibg","kind":"drug","name":"Iobenguane I-123","route":"/drugs/i-123-mibg/"}],"idea":[{"id":"idea-mfbg-pet-replaces-mibg","kind":"idea","name":"18F-MFBG PET replacing 123I-MIBG scintigraphy","route":"/ideas/idea-mfbg-pet-replaces-mibg/"}],"indication":[{"id":"neuroblastoma-high-risk","kind":"indication","name":"High-risk neuroblastoma","route":"/indications/neuroblastoma-high-risk/"}],"term":[{"id":"curie-siopen-score","kind":"term","name":"MIBG Curie and SIOPEN scores","route":"/terms/curie-siopen-score/"}],"person":[{"id":"katherine-matthay","kind":"person","name":"Katherine K. Matthay","route":"/people/katherine-matthay/"},{"id":"neeta-pandit-taskar","kind":"person","name":"Neeta Pandit-Taskar","route":"/people/neeta-pandit-taskar/"}],"target":[{"id":"norepinephrine-transporter","kind":"target","name":"Norepinephrine transporter (NET)","route":"/targets/norepinephrine-transporter/"}]}}