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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
High-risk neuroblastoma has spread widely in a child over 18 months old or carries extra copies of the MYCN gene. Treatment lasts about 18 months and uses every tool: chemotherapy, surgery, high-dose chemotherapy with stem cell rescue, radiotherapy, and the anti-GD2 antibody dinutuximab, which raised survival in ANBL0032; eflornithine, given afterwards, was approved in 2023 to lower relapse.
High-risk disease is stage M neuroblastoma in a child over 18 months, MYCN-amplified disease at any age and stage, and a few L2 and infant M cases with unfavourable genetics. Treatment runs in blocks. Induction with five or six cycles (cyclophosphamide and topotecan, cisplatin and etoposide, cyclophosphamide with doxorubicin and vincristine in the COG regimen; rapid COJEC in Europe) brings most children to a partial response and clears the marrow; surgery removes the primary; consolidation with myeloablative chemotherapy and autologous stem cell rescue follows; radiotherapy to the primary site and residual metastases; then post-consolidation immunotherapy with an anti-GD2 antibody and isotretinoin for six months. CCG-3891, reported in 1999, established both myeloablative therapy with autologous marrow rescue and 13-cis-retinoic acid maintenance: three-year event-free survival 34 percent against 22 percent with transplant, and 46 percent against 29 percent with retinoic acid.
ANBL0032 randomised 226 children after transplant to isotretinoin alone or with the chimeric anti-GD2 antibody ch14.18 (dinutuximab), GM-CSF and interleukin-2: two-year event-free survival 66 percent against 46 percent and overall survival 86 percent against 75 percent, and dinutuximab was approved in March 2015. SIOPEN HR-NBL1 showed that busulfan and melphalan beat carboplatin, etoposide and melphalan as the myeloablative regimen, three-year event-free survival 50 percent against 38 percent, and that adding interleukin-2 to dinutuximab beta brought toxicity without benefit. COG ANBL0532 showed tandem transplant with thiotepa-cyclophosphamide then carboplatin-etoposide-melphalan beat a single transplant, three-year event-free survival 61.6 percent against 48.4 percent. Eflornithine (DFMO), an ornithine decarboxylase inhibitor that lowers MYCN-driven polyamine synthesis, was approved in December 2023 as two years of maintenance after immunotherapy on the basis of the NMTRC003 and 003B single-arm studies compared with matched ANBL0032 controls, the first approval in neuroblastoma on an external control. Naxitamab, a humanised anti-GD2 antibody given with GM-CSF, was granted accelerated approval in November 2020 for relapsed or refractory disease in bone or marrow.
| Setting | Approach | Guideline |
|---|---|---|
| Induction | Five or six cycles of cyclophosphamide-topotecan, cisplatin-etoposide and cyclophosphamide-doxorubicin-vincristine (COG) or rapid COJEC (SIOPEN); iodine-131 MIBG and, for ALK-mutant disease, lorlatinib within ANBL1531; surgery after induction. | not mapped |
| Consolidation | Busulfan-melphalan (HR-NBL1) or tandem thiotepa-cyclophosphamide then carboplatin-etoposide-melphalan (ANBL0532) with autologous stem cell rescue. | not mapped |
| Local control | Radiotherapy to the primary site bed and residual MIBG-avid metastases after transplant. | not mapped |
| Post-consolidation | Dinutuximab with GM-CSF and isotretinoin for five cycles (ANBL0032; interleukin-2 dropped after HR-NBL1), then two years of eflornithine maintenance. | not mapped |
| Relapsed or refractory | Irinotecan-temozolomide with dinutuximab (ANBL1221) or naxitamab with GM-CSF; iodine-131 MIBG for avid disease; lorlatinib for ALK-mutant disease; GD2 CAR T-cells in trials. | not mapped |
| Survivorship | Hearing, cardiac, renal, endocrine, fertility and second-cancer follow-up for life. | not mapped |