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Childhood solid tumours (adrenal and sympathetic nervous system; kidney)

Neuroblastoma and Wilms tumour

How neuroblastoma and Wilms tumour care moved from surgery alone to risk-adapted therapy, anti-GD2 immunotherapy and doing less where safe.

Neuroblastoma, children under 1 year · 5-year relative survival · United States (as cited in the NCI PDQ summary)

86%→93%

1975 to 2020. Read these with the caveats under “Then and now”.Source

24 milestones, by decade

  • The NCI PDQ summary says that between 1975 and 2020 the 5-year survival rate for neuroblastoma in the United States rose from 86% to 93% in children younger than 1 year and from 34% to 83% in children aged 1 to 14 years. The sentence does not say whether the figures are relative or observed survival, and the PDQ warns that pooled figures hide very different outlooks by age, stage and tumour biology: for 2014 to 2020 it gives 5-year relative survival of 93% under 1 year, 78% at 1 to 4 years, 83% at 5 to 9 years and 86% at 10 to 14 years.
  • Large population studies of urine screening for neuroblastoma did not reduce deaths. In Quebec, 476,654 children born over five years were offered screening at 3 weeks and 6 months (participation 92%); there were 22 deaths from neuroblastoma before age 8, and standardised ratios against four unscreened control populations ranged from 0.90 to 1.40, each with a confidence interval that included 1. In Germany, screening at about 1 year of age was offered to 2,581,188 children; stage 4 disease occurred in 3.7 per 100,000 screened children and 3.8 per 100,000 controls, with an estimated 7 overdiagnosed cases per 100,000 children.
  • A 2015 history of Wilms tumour notes that Max Wilms published his monograph on mixed tumours of the kidney in 1899 at age 32, and that excellent reviews of the lesion existed before him. The same history states that by mid century Robert Gross achieved a 47% survival rate with surgery plus postoperative radiotherapy, and that with National Wilms Tumor Study Group protocols the survival rate reached 90% by the end of the twentieth century. The abstract does not define 'survival rate' or give a time point or series, so the two figures are the author's account and are not comparable registry values.

Evidence current to October 2026 · Checked against primary sources to the extent possible

A guided tour of 10 milestones. You can pause or step through it yourself.

Filter milestonesshowing all 24
Treatment type
Setting

The age of rays

  1. 1899 · Origin · UnderstandingMax Wilms publishes a monograph on mixed kidney tumours (1899)In 1899 the German surgeon Max Wilms published a monograph on mixed tumours of the kidney. The most common kidney cancer of infants and children now carries his name, although a 2015 history notes that excellent reviews of the lesion existed before his.Wilms M. Die Mischgeschwülste (Leipzig: Arthur Georgi, 1899; 3 volumes per the Wellcome Collection catalogue). Raffensperger 2015 (abstract) records that Wilms, a second-year surgical assistant aged 32, published it, that excellent reviews of this lesion preceded it, and that the commonest renal cancer of infants and children is named for him. No case numbers or outcomes are reported here, and no priority claim is made.

Chemotherapy

  1. 1966 · Treatment · Chemotherapy⚑ needs reviewActinomycin D and vincristine in Wilms tumour treatment, 1966-67In 1966 Sidney Farber published a JAMA paper on chemotherapy in leukaemia and Wilms tumour, and in 1967 a JAMA paper reported vincristine in the management of Wilms tumour. A 2016 history says Farber's group added the antibiotic dactinomycin (actinomycin D) and reached an 80 per cent survival rate in 1966.Farber (JAMA 1966) and Sullivan et al. (JAMA 1967, on vincristine replacing preoperative irradiation) are cited by title only; no results are taken from them. Nakayama 2016 (review abstract) gives survival of 32% with surgery alone (Ladd, 1940), 47% with surgery plus radiotherapy (Gross and Neuhauser, 1950) and 80% after dactinomycin was added (Farber, 1966). The FDA table dates dactinomycin for Wilms tumour 12-10-1964.

Molecular origins

  1. 1976 · Treatment · ChemotherapyNWTS-1: randomised trial of radiotherapy and chemotherapyThe first National Wilms' Tumor Study began in 1969 and randomised children to different combinations of surgery, radiotherapy and chemotherapy. Its 1976 report found that actinomycin D plus vincristine gave better results than either drug alone for children whose tumours were still confined to the abdomen. All of those children also had radiotherapy.NWTS-1 (begun 1969): 606 registered, 359 randomised, groups I to IV. Group I under 2 years: postoperative radiotherapy or none after 15 months of actinomycin D; both fared well. Groups II and III (all given postoperative radiotherapy): actinomycin D plus vincristine gave better results than either drug alone. Group IV: preoperative vincristine did not improve results. Mesoblastic nephroma 1%, bilateral tumours 5%, incorrect preoperative diagnosis 5%. The abstract gives no relapse or survival figures.
  2. 1978 · Understanding · UnderstandingNWTS-1 histology: anaplastic and sarcomatous tumours fare worseIn 1978 pathologists reviewing 427 tumours from the first National Wilms' Tumor Study found that tumours with markedly abnormal cells (anaplasia) or mostly sarcoma-like tissue were linked to worse outcomes. About 57 in 100 of those children died of tumour, compared with about 7 in 100 of the rest. Later studies stratified treatment by favourable or unfavourable histology.Detailed histological analysis of 427 NWTS-1 cases: 25 with anaplasia and 24 with predominantly sarcomatous lesions, of which 28 (57.1%) died of tumour, versus 26 of 378 (6.9%) with neither feature. Seven of ten tumour deaths in patients diagnosed before 2 years were associated with sarcomatous lesions. A 'clear cell' sarcoma pattern had a predilection for bony metastases. NWTS-5 anaplasia: 4-year EFS 69.5% in stage I versus 92.4% in stage I favourable histology.
  3. 1983 · Treatment · ChemotherapySIOP and UK trials of preoperative chemotherapy before nephrectomyIn Europe, children with Wilms tumour began to receive chemotherapy before surgery rather than operating first. A 1983 SIOP trial concluded that preoperative chemotherapy was as good as preoperative radiotherapy for preventing tumour rupture. A later UK trial of 205 children found that six weeks of chemotherapy first shifted tumours to a lower stage.SIOP 1977-1979: 164 eligible patients randomised to preoperative radiotherapy plus chemotherapy (76) or chemotherapy alone (88); authors concluded preoperative chemotherapy was as good for preventing rupture, and 43% of an unselected population could avoid radiotherapy. UKW3: 205 randomised, 186 with Wilms histology; stage III 9.8% (delayed surgery) versus 29.8% (immediate), P = 0.008 for trend; 5-year EFS 79.6% and OS 89.0%, reported as similar between groups.
  4. 1984 · Understanding · UnderstandingN-myc amplification linked to advanced neuroblastoma (1984)In 1984 researchers reported that a DNA region called N-myc (written MYCN today) was present in many extra copies in tumour tissue from 24 of 63 untreated patients with neuroblastoma, all of them with stage 3 or 4 disease. A 1985 study of 89 patients linked more copies to faster progression.Brodeur 1984: N-myc amplification in tumour tissue from 24 of 63 untreated patients (38%); 0 of 15 with stage 1 or 2 disease, 24 of 48 (50%) with stage 3 or 4 (P less than 0.001). Seeger 1985: 89 untreated primary tumours; estimated progression-free survival at 18 months 70%, 30% and 5% for 1, 3 to 10 and more than 10 copies (P less than 0.0001). Tissue series, not trials.
  5. 1984 · Understanding · UnderstandingShimada classification: histology and age predict outcomeIn 1984 a pathology study of neuroblastic tumours reported that how the tumour looks under the microscope, together with the patient's age, separated tumours with a good outlook from those with a poor one. In 1999 an international committee proposed a modified version for use worldwide.Shimada 1984: 295 pretreatment tumours (of 641 studied) divided into stroma-poor (235) and stroma-rich (60); with age, maturation and mitosis-karyorrhexis index, favorable stroma-poor tumours had 84% survival and unfavorable 4.5%; stroma-rich subgroups ranged from 100% (well differentiated) to 18% (nodular). INPC 1999 (227 cases, six pathologists): 3-year EFS 85% with favorable and 41% with unfavorable histology.
  6. 1988 · Understanding · UnderstandingInternational Neuroblastoma Staging System and response criteriaIn 1988 an international group agreed shared rules for diagnosing and staging neuroblastoma and for judging response to treatment, so that studies from different countries could be compared. The rules were revised in 1993 and the response criteria again in 2017.Consensus statement (J Clin Oncol 1988): diagnostic criteria, the International Neuroblastoma Staging System (INSS) and International Neuroblastoma Response Criteria (INRC), agreed by major groups in the United States, Europe and Japan. 1993 revisions: midline redefinition, age and marrow restrictions for stage 4S, MIBG scanning recommended. 2017 revision (13 countries): MIBG or FDG-PET, RECIST and standardised marrow assessment; marrow with 5% or less tumour is minimal disease.
  7. 1989 · De-escalation · ChemotherapyNWTS-3 and NWTS-4: shorter and pulse-intensive chemotherapyTwo US trials asked whether children with Wilms tumour could safely have less treatment. NWTS-3 (reported 1989) concluded that less intensive treatment did not worsen results for low-risk children. NWTS-4 (reported 1998) found that giving dactinomycin (and, in high-risk disease, doxorubicin) as a single dose per course, and stopping chemotherapy at six months rather than 15, gave similar relapse-free survival.NWTS-3: 1,439 eligible, randomised by stage and histology; 4-year survival 96.5% (607 stage I FH), 92.2% (278 stage II FH), 86.9% (275 stage III FH), 73.0% (279 high-risk); less intensive therapy did not worsen low-risk results. NWTS-4: 2-year RFS, pulse-intensive versus divided-dose, 91.3% v 91.4% (low-risk) and 87.3% v 90.0% (high-risk); 4-year RFS, 6 versus 15 months, 83.7% v 88.2% (low-risk) and 89.7% v 88.8% (high-risk FH).

Targeted therapy

  1. 1999 · Treatment · Cell therapy & transplantTransplant and isotretinoin in high-risk neuroblastoma (CCG-3891)Two linked randomized comparisons tested treatments for children with high-risk neuroblastoma. Children assigned to high-dose chemotherapy with their own purged bone marrow had better three-year event-free survival than those given more intensive chemotherapy, about one in three versus about one in five. Isotretinoin afterwards was also linked to better event-free survival.CCG-3891, two sequential randomizations. First (N=379): myeloablative chemotherapy, TBI and purged autologous BMT (n=189) vs three cycles of intensive chemotherapy (n=190); 3-year EFS 34% vs 22% (P=0.034). Second (n=130 vs 128, no progression after therapy): 13-cis-retinoic acid for 6 months vs none; 3-year EFS 46% vs 29% (P=0.027). Long-term report: 5-year EFS 30% vs 19% (P=0.04) and 42% vs 31% (not significant).
  2. 2002 · Reversal · Detection & preventionInfant urine screening did not reduce neuroblastoma mortality (2002)In 2002 two large studies evaluated urine screening of babies for neuroblastoma, in Quebec (about 477,000 births) and in Germany (over 2.5 million children offered screening). Neither found fewer deaths, and the German study estimated that screening found tumours that would not have benefited from earlier treatment.Quebec: screening at 3 weeks and 6 months offered to 476,654 births, 92% participation; cumulative neuroblastoma mortality 4.78 per 100,000 over nine years, with standardized incidence ratios for death of 0.90 to 1.40 against four unscreened control populations (confidence intervals include 1). Germany: screening at about 1 year offered to 2,581,188 children; stage 4 incidence 3.7 vs 3.8 and deaths 1.3 vs 1.2 per 100,000 (screened vs control); overdiagnosis estimated at 7 per 100,000. Population comparisons, not randomised.
  3. 2005 · Understanding · UnderstandingTumour markers: 1p/16q loss and 1q gain predict relapseIn 2005 the National Wilms Tumor Study Group reported that favourable-histology Wilms tumours with loss of parts of chromosomes 1p and 16q relapsed more often. A 2016 analysis added gain of chromosome 1q as a marker linked to worse survival. Later Children's Oncology Group studies used these markers to decide how intensively some children were treated.NWTS-5 favourable histology. Relative risk of relapse with LOH 1p 1.56 (P = .01) and 16q 1.49 (P = .01). Stage I-II, LOH at both sites: relapse RR 2.9 (P = .001), death RR 4.3 (P = .01); stage III-IV: RR 2.4 and 2.7. In 1,114 informative tumours, 1q gain was present in 28%; 8-year EFS 77% versus 90% without it (P < .001); multivariable relative risk of relapse 2.4. Reported as relative risks, not hazard ratios.
  4. 2008 · Understanding · UnderstandingINRG classification and staging: one risk language across groupsIn 2008 an international task force analysed outcomes of 8,800 children with neuroblastoma and proposed a shared way to group them by risk before treatment, using stage, age, tumour biology and microscopy. Its aim was to let trials run in different regions be compared. The Children's Oncology Group revised its own version in 2021.INRG Task Force: survival-tree analysis of 8,800 children diagnosed 1990 to 2002 found stage, age, histologic category, differentiation grade, MYCN status, 11q status and ploidy most significant; 18 months chosen as age cutoff; 16 pretreatment groups; 5-year EFS defines very low (above 85%) to high (below 50%) risk. INRGSS (L1, L2, M, MS): 5-year EFS 78% for L2 vs 90% for L1 (P = .0010; 661 patients). COG revision 2021 (N = 4,832) adds segmental chromosome aberrations.
  5. 2008 · De-escalation · Surgery⚑ needs reviewLow-risk neuroblastoma: observation or surgery aloneBetween 2008 and 2012 three prospective studies reported on doing less for low-risk neuroblastoma: observation without chemotherapy, or surgery alone. Survival was high in each, for example 99 in 100 at three years among infants in German trials whose tumours were observed, and many tumours shrank on their own. The studies are not directly comparable.Three prospective non-randomised cohorts. NB95-S/NB97 (340 eligible infants, no MYCN amplification): 93 observed with unresected tumour, 3-year OS 99%, metastases-free survival 94%; regression in 44. COG P9641 (915 eligible): surgery alone with restricted chemotherapy, 5-year EFS 89%, OS 97%. COG ANBL00P2 (87 infants aged 6 months or younger): 3-year EFS 97.7%, OS 100%; 10-year EFS 93.7%, OS 98.0%.
  6. 2008 · Treatment · ChemotherapyEuropean trials: rapid induction and busulfan-melphalan consolidationThree randomized European comparisons tested induction and high-dose chemotherapy for high-risk neuroblastoma. Rapid induction was linked to better five-year event-free survival in a 1990s trial, though three- and ten-year differences were not significant. Busulfan-melphalan gave better three-year event-free survival than carboplatin-etoposide-melphalan (50% against 38%). A later trial found no difference between two induction regimens.Three randomizations, each with its own result. (1) Rapid COJEC vs standard OPEC/OJEC induction (n=262, 1990 to 1999): 5-year EFS 30.2% vs 18.2% (P=0.022); 3-year EFS HR 0.86 (95% CI 0.66 to 1.14). (2) HR-NBL1, busulfan-melphalan vs carboplatin-etoposide-melphalan (n=598): 3-year EFS 50% (45 to 56) vs 38% (32 to 43), P=0.0005. (3) HR-NBL1.5, MSKCC N5 vs rapid COJEC (n=630): 3-year EFS 47% vs 44%, P=0.527.
  7. 2010 · Treatment · ImmunotherapyAnti-GD2 dinutuximab with cytokines after transplant (ANBL0032)In a randomized trial of children with high-risk neuroblastoma who had responded to earlier treatment, adding an antibody against GD2 and two cytokines to isotretinoin was linked to better outcomes. After two years about two in three children in the antibody group were free of relapse, progression or other events, compared with fewer than half given isotretinoin alone.COG ANBL0032: 226 eligible patients with high-risk neuroblastoma responding to induction and transplant, randomized 1:1 to isotretinoin alone or with ch14.18 (dinutuximab), GM-CSF and IL-2. Stopped early for efficacy: 2-year EFS 66% vs 46% (P=0.01); OS 86% vs 75% (P=0.02, unadjusted for interim analyses). Long-term follow-up: 5-year EFS 56.6% vs 46.1% (P=0.042); OS 73.2% vs 56.6% (P=0.045). FDA approval 10 March 2015.
  8. 2010 · De-escalation · ChemotherapyIntermediate-risk neuroblastoma: reduced chemotherapy (COG A3961)In 2010 the Children's Oncology Group reported that children with intermediate-risk neuroblastoma, given fewer and lower-dose chemotherapy cycles chosen by tumour biology, had about 96 in 100 alive at three years. This was a single-group study, not a head-to-head comparison with longer treatment.COG A3961: prospective, phase 3, nonrandomised trial (1997 to 2005) of 479 eligible patients with intermediate-risk neuroblastoma without MYCN amplification, assigned to four or eight cycles of reduced-dose chemotherapy by tumour biology. Goal: 3-year overall survival above 90%. Result: 96% overall (95% CI 94 to 97), 98% with favorable and 93% with unfavorable biologic features; 3-year EFS 88%. Severe adverse events without progression: 10 patients (2.1%). No comparison arm.

Immunotherapy

  1. 2015 · De-escalation · ChemotherapySIOP WT 2001: doxorubicin omitted in intermediate-risk stage II-IIIAn international trial of 583 children with stage II or III Wilms tumour tested leaving out doxorubicin, which can harm the heart. About 93 in 100 children given it and about 88 in 100 not given it had no relapse or other event at two years; five-year survival was roughly 96 in 100 in both groups.SIOP WT 2001, open-label non-inferiority phase 3: 583 children with stage II-III intermediate-risk Wilms tumour after 4 weeks of vincristine and actinomycin D, randomised to postoperative vincristine/actinomycin D with (291) or without (292) doxorubicin. 2-year EFS 92.6% (95% CI 89.6-95.7) versus 88.2% (84.5-92.1); difference 4.4% (0.4-9.3), within the 10% margin. 5-year OS 96.5% versus 95.8%. Median follow-up 60.8 months.
  2. 2016 · De-escalation · Chemotherapy⚑ needs reviewCOG AREN0532 and AREN0533: risk-adapted Wilms therapyFrom 2006 the Children's Oncology Group tested treatment matched to risk. Some children with very low-risk tumours had surgery alone, and some with lung spread skipped lung radiation if scans cleared. Children with a tumour change called combined 1p and 16q loss were given stronger treatment and had better event-free survival than an earlier comparison group.Non-randomised COG studies. AREN0532, very low-risk (stage I FH, under 550 g, under 2 years), nephrectomy only: 116 eligible, 4-year EFS 89.7% (95% CI 84.1-95.2), OS 100%. AREN0533, lung metastases: complete response, no lung radiotherapy, EFS 79.5%, OS 96.1% (133); incomplete response, regimen M, EFS 88.5%, OS 95.4% (159). Combined LOH 1p/16q, augmented therapy: 4-year EFS 87.3% (stage I-II) and 90.2% (III-IV) versus NWTS-5 68.8% and 61.3%.
  3. 2017 · Treatment · ChemotherapyRelapsed or refractory disease: randomised phase 2 chemo-immunotherapyRandomized phase 2 trials tested additions to chemotherapy for neuroblastoma that returned or did not respond. In the US trial, 9 of 17 children given dinutuximab with irinotecan and temozolomide responded, against 1 of 18 given temsirolimus; the design selected a regimen for further study. European trials of bevacizumab and dinutuximab beta reported signals needing confirmation.ANBL1221 (randomized phase 2 selection design): ORR 53% (95% CI 29.2 to 76.7; 9/17) with irinotecan-temozolomide-dinutuximab vs 6% (0.0 to 16.1; 1/18) with temsirolimus. BEACON-Neuroblastoma (3×2 factorial, n=160): ORR 26% vs 18% with vs without bevacizumab (RR 1.52, 0.83 to 2.77; P=0.17). BEACON Immuno (n=65, 1:2): ORR 30.2% vs 18.2% with vs without dinutuximab beta; median PFS 11.1 vs 3.8 months. Primary endpoint was response.
  4. 2017 · Treatment · ImmunotherapyDinutuximab beta in Europe: authorisation and the IL-2 questionIn Europe, the anti-GD2 antibody dinutuximab beta was authorised in May 2017 under exceptional circumstances. A large randomized trial reported in 2018 asked whether adding subcutaneous interleukin-2 helped: at three years about six in ten children in each group were free of relapse, progression or death, with no clear difference, and side effects were greater with interleukin-2.EC authorisation of dinutuximab beta (Qarziba) 8 May 2017 under exceptional circumstances. HR-NBL1/SIOPEN phase 3: 406 randomized (200 vs 206) to dinutuximab beta alone or with subcutaneous IL-2, all with isotretinoin. 3-year EFS 56% (95% CI 49 to 63) vs 60% (53 to 66), P=0.76; median follow-up 4.7 years. 62% vs 87% received allocated treatment (P<0.0001) because of toxicity.
  5. 2019 · Treatment · Cell therapy & transplantTandem vs single autologous transplant in high-risk neuroblastomaIn a randomized trial, children and young adults with high-risk neuroblastoma given two stem-cell transplants were more often free of relapse, progression, a second cancer or death at three years than those who had one: about six in ten against about five in ten. Only about half of eligible patients were randomized, so results may not generalize.COG ANBL0532 (phase 3, 142 centres): 652 eligible patients aged up to 30 years, 355 randomized to tandem transplant (thiotepa/cyclophosphamide, then dose-reduced carboplatin/etoposide/melphalan; n=176) or single transplant (carboplatin/etoposide/melphalan; n=179). 3-year EFS from randomization 61.6% (95% CI 54.3 to 68.9) vs 48.4% (41.0 to 55.7); one-sided log-rank P=0.006. The authors note the low randomization rate.

Precision & engineered

  1. 2020 · Treatment · ImmunotherapyNaxitamab: accelerated approval for relapsed or refractory diseaseIn November 2020 the US regulator granted accelerated approval to naxitamab, an anti-GD2 antibody given with GM-CSF, for relapsed or refractory high-risk neuroblastoma in bone or bone marrow. A later report from one of the supporting single-arm studies found about half of 52 evaluable patients responded. Approval depends on a confirmatory trial, still listed as ongoing in October 2026.FDA accelerated approval (21 CFR 601.41) on 25 November 2020; postmarketing requirement 3950-1 asks for a trial enrolling at least 80 patients with evaluable disease. Trial 201, which its authors cite as one of two single-arm studies supporting the approval (interim analysis after the approval, data cutoff 31 December 2021, efficacy population 52): ORR 50% (95% CI 36 to 64), CR 38%, PR 12%; 1-year PFS 35% (16 to 54); 1-year OS 93% (80 to 98).
  2. 2023 · Treatment · TargetedEflornithine maintenance to reduce relapse: FDA approval (2023)In December 2023 the US regulator approved eflornithine, a tablet, to reduce relapse risk in people with high-risk neuroblastoma who responded to earlier treatment including antibody therapy. The evidence was a single-arm study compared with matched patients from an earlier trial, not a randomized comparison. An advisory committee voted fourteen to six that evidence of improved event-free survival was sufficient.NMTRC003B (single-arm phase 2, oral DFMO up to 2 years) vs patient-level ANBL0032 data as external control. Overall: 92 DFMO vs 852 controls, EFS HR 0.50 (95% CI 0.29 to 0.84), OS HR 0.38 (0.19 to 0.76). Propensity-matched 3:1 (90 vs 270): EFS HR 0.48 (0.27 to 0.85), OS HR 0.32 (0.15 to 0.70). FDA approval 13 December 2023 (ODAC vote 14 yes, 6 no).

Then and now

  • 5-year relative survival · United States (as cited in the NCI PDQ summary)

    • 86%

      1975

    Children with neuroblastoma younger than 1 year, as worded in the NCI PDQ summary 'Neuroblastoma Treatment'. Race and sex are not stated.

    The PDQ sentence (General Information section, Health Professional version, page updated 28 April 2025) says '5-year survival rate' without saying whether it is relative or observed survival or whether the years are years of diagnosis; it cites the NCI NCCR*Explorer (last accessed 25 February 2025) and a 2014 Cancer paper on declining childhood cancer mortality, neither of which was opened. The page does not say how much of the change reflects treatment, changes in classification or case mix. Filed under the nearest metric. Do not subtract it from the other series on this page. SEER Cancer Stat Facts has no neuroblastoma page. Same sentence as the 2020 value for this age group; the 1975 to 2020 comparison is the PDQ's own.

    Source

  • 5-year relative survival · United States (as cited in the NCI PDQ summary)

    • 93%

      2020

    Children with neuroblastoma younger than 1 year, as worded in the NCI PDQ summary 'Neuroblastoma Treatment'. Race and sex are not stated.

    The PDQ sentence (General Information section, Health Professional version, page updated 28 April 2025) says '5-year survival rate' without saying whether it is relative or observed survival or whether the years are years of diagnosis; it cites the NCI NCCR*Explorer (last accessed 25 February 2025) and a 2014 Cancer paper on declining childhood cancer mortality, neither of which was opened. The page does not say how much of the change reflects treatment, changes in classification or case mix. Filed under the nearest metric. Do not subtract it from the other series on this page. SEER Cancer Stat Facts has no neuroblastoma page. Same sentence as the 1975 value for this age group.

    Source

  • 5-year relative survival · United States (as cited in the NCI PDQ summary)

    • 34%

      1975

    Children aged 1 to 14 years with neuroblastoma, as worded in the NCI PDQ summary 'Neuroblastoma Treatment'. Race and sex are not stated.

    The PDQ sentence (General Information section, Health Professional version, page updated 28 April 2025) says '5-year survival rate' without saying whether it is relative or observed survival or whether the years are years of diagnosis; it cites the NCI NCCR*Explorer (last accessed 25 February 2025) and a 2014 Cancer paper on declining childhood cancer mortality, neither of which was opened. The page does not say how much of the change reflects treatment, changes in classification or case mix. Filed under the nearest metric. Do not subtract it from the other series on this page. SEER Cancer Stat Facts has no neuroblastoma page. Same sentence as the 2020 value for this age group. Prognosis in this age group varies widely with stage and biology, so the pooled value hides high-risk and low-risk disease.

    Source

  • 5-year relative survival · United States (as cited in the NCI PDQ summary)

    • 83%

      2020

    Children aged 1 to 14 years with neuroblastoma, as worded in the NCI PDQ summary 'Neuroblastoma Treatment'. Race and sex are not stated.

    The PDQ sentence (General Information section, Health Professional version, page updated 28 April 2025) says '5-year survival rate' without saying whether it is relative or observed survival or whether the years are years of diagnosis; it cites the NCI NCCR*Explorer (last accessed 25 February 2025) and a 2014 Cancer paper on declining childhood cancer mortality, neither of which was opened. The page does not say how much of the change reflects treatment, changes in classification or case mix. Filed under the nearest metric. Do not subtract it from the other series on this page. SEER Cancer Stat Facts has no neuroblastoma page. Same sentence as the 1975 value for this age group. Prognosis in this age group varies widely with stage and biology, so the pooled value hides high-risk and low-risk disease.

    Source

  • 5-year relative survival · United States (National Childhood Cancer Registry, as cited in the NCI PDQ summary)

    • 93%

      2014-2020; younger than 1 year

    Children with neuroblastoma younger than 1 year, as worded in the NCI PDQ summary 'Neuroblastoma Treatment'.

    From the NCI PDQ 'Neuroblastoma Treatment' prognosis section: 'According to the National Childhood Cancer Registry (NCCR), the 5-year relative survival rates from 2014 to 2020' by age. The PDQ lists four age groups (younger than 1 year 93%, 1 to 4 years 78%, 5 to 9 years 83%, 10 to 14 years 86%) and gives approximately 85% for infants and children younger than 15 years; all are entered here. The PDQ does not say whether 2014-2020 are years of diagnosis. A different series from the 1975 and 2020 age-specific values (note that the 2014-2020 value for children younger than 1 year, 93%, equals the 2020 value but is a separate sentence and series), so do not combine or subtract. Prognosis varies strongly with stage and biology; the PDQ gives 5-year overall survival of 98% for low-risk and about 95% for intermediate-risk disease in a COG biology study (ANBL00B1), and a lower figure for high-risk disease, which these pooled values hide.

    Source

  • 5-year relative survival · United States (National Childhood Cancer Registry, as cited in the NCI PDQ summary)

    • 78%

      2014-2020; ages 1-4 years

    Children with neuroblastoma aged 1 to 4 years, as worded in the NCI PDQ summary 'Neuroblastoma Treatment'.

    From the NCI PDQ 'Neuroblastoma Treatment' prognosis section: 'According to the National Childhood Cancer Registry (NCCR), the 5-year relative survival rates from 2014 to 2020' by age. The PDQ lists four age groups (younger than 1 year 93%, 1 to 4 years 78%, 5 to 9 years 83%, 10 to 14 years 86%) and gives approximately 85% for infants and children younger than 15 years; all are entered here. The PDQ does not say whether 2014-2020 are years of diagnosis. A different series from the 1975 and 2020 age-specific values (note that the 2014-2020 value for children younger than 1 year, 93%, equals the 2020 value but is a separate sentence and series), so do not combine or subtract. Prognosis varies strongly with stage and biology; the PDQ gives 5-year overall survival of 98% for low-risk and about 95% for intermediate-risk disease in a COG biology study (ANBL00B1), and a lower figure for high-risk disease, which these pooled values hide.

    Source

  • 5-year relative survival · United States (National Childhood Cancer Registry, as cited in the NCI PDQ summary)

    • 83%

      2014-2020; ages 5-9 years

    Children with neuroblastoma aged 5 to 9 years, as worded in the NCI PDQ summary 'Neuroblastoma Treatment'.

    From the NCI PDQ 'Neuroblastoma Treatment' prognosis section: 'According to the National Childhood Cancer Registry (NCCR), the 5-year relative survival rates from 2014 to 2020' by age. The PDQ lists four age groups (younger than 1 year 93%, 1 to 4 years 78%, 5 to 9 years 83%, 10 to 14 years 86%) and gives approximately 85% for infants and children younger than 15 years; all are entered here. The PDQ does not say whether 2014-2020 are years of diagnosis. A different series from the 1975 and 2020 age-specific values (note that the 2014-2020 value for children younger than 1 year, 93%, equals the 2020 value but is a separate sentence and series), so do not combine or subtract. Prognosis varies strongly with stage and biology; the PDQ gives 5-year overall survival of 98% for low-risk and about 95% for intermediate-risk disease in a COG biology study (ANBL00B1), and a lower figure for high-risk disease, which these pooled values hide.

    Source

  • 5-year relative survival · United States (National Childhood Cancer Registry, as cited in the NCI PDQ summary)

    • 86%

      2014-2020; ages 10-14 years

    Children with neuroblastoma aged 10 to 14 years, as worded in the NCI PDQ summary 'Neuroblastoma Treatment'.

    From the NCI PDQ 'Neuroblastoma Treatment' prognosis section: 'According to the National Childhood Cancer Registry (NCCR), the 5-year relative survival rates from 2014 to 2020' by age. The PDQ lists four age groups (younger than 1 year 93%, 1 to 4 years 78%, 5 to 9 years 83%, 10 to 14 years 86%) and gives approximately 85% for infants and children younger than 15 years; all are entered here. The PDQ does not say whether 2014-2020 are years of diagnosis. A different series from the 1975 and 2020 age-specific values (note that the 2014-2020 value for children younger than 1 year, 93%, equals the 2020 value but is a separate sentence and series), so do not combine or subtract. Prognosis varies strongly with stage and biology; the PDQ gives 5-year overall survival of 98% for low-risk and about 95% for intermediate-risk disease in a COG biology study (ANBL00B1), and a lower figure for high-risk disease, which these pooled values hide.

    Source

  • 5-year relative survival · United States (National Childhood Cancer Registry, as cited in the NCI PDQ summary)

    • 85%

      2014-2020; all younger than 15 years (PDQ: 'approximately 85%')

    Infants and children with neuroblastoma younger than 15 years; the PDQ says 'approximately 85%', as worded in the NCI PDQ summary 'Neuroblastoma Treatment'.

    From the NCI PDQ 'Neuroblastoma Treatment' prognosis section: 'According to the National Childhood Cancer Registry (NCCR), the 5-year relative survival rates from 2014 to 2020' by age. The PDQ lists four age groups (younger than 1 year 93%, 1 to 4 years 78%, 5 to 9 years 83%, 10 to 14 years 86%) and gives approximately 85% for infants and children younger than 15 years; all are entered here. The PDQ does not say whether 2014-2020 are years of diagnosis. A different series from the 1975 and 2020 age-specific values (note that the 2014-2020 value for children younger than 1 year, 93%, equals the 2020 value but is a separate sentence and series), so do not combine or subtract. Prognosis varies strongly with stage and biology; the PDQ gives 5-year overall survival of 98% for low-risk and about 95% for intermediate-risk disease in a COG biology study (ANBL00B1), and a lower figure for high-risk disease, which these pooled values hide.

    Source

  • 5-year relative survival · United States (NCCR*Explorer, as cited in the NCI PDQ summary)

    • 93%

      not stated on the page (NCCR*Explorer last accessed 25 February 2025 per the PDQ)

    Children and adolescents younger than 20 years with Wilms tumor (nephroblastoma), as worded in the NCI PDQ summary 'Wilms Tumor and Other Childhood Kidney Tumors Treatment' (page updated 15 April 2025).

    The PDQ sentence names the measure ('5-year relative survival rate') but gives no period, race, sex or registry set beyond citing NCCR*Explorer. No earlier Wilms tumour value was found on any page read, so there is no 'then' comparator here and no trend should be inferred from this single value. A separate PDQ sentence says that since the 1980s the 5-year survival rate for favorable-histology Wilms tumor has been consistently greater than 90% (reference not opened). SEER Cancer Stat Facts has no Wilms tumour page. For history, see the attributed account in the hooks and the milestones.

    Source

  • Age-standardised mortality · United States

    • 5.1per 100,000

      1975

    • 2.2per 100,000

      2022

    Children and adolescents younger than 20 years, all cancers combined (not neuroblastoma or Wilms tumour alone).

    Not specific to neuroblastoma or Wilms tumour: this is the rate for all cancers combined in children and adolescents younger than 20 years, from the NCI fact sheet 'Cancer in Children and Adolescents' (page updated 27 August 2024), which gives 5.1 per 100,000 in 1975 and 2.2 in 2022 and describes a fall of more than 50%. The page does not say whether the rate is age-adjusted or which mortality data it uses. A death rate depends on how many children are diagnosed as well as on survival, and is not measured from diagnosis. No neuroblastoma-specific or Wilms-tumour-specific death rate was found on any page read (SEER Cancer Stat Facts has no page for either). Neither is a screened cancer: population screening for neuroblastoma was studied and not adopted, see 'today'. Read beside the survival values above; do not subtract them.

    Source

Survival figures are affected by earlier detection (lead time) and overdiagnosis, and by changes in who is diagnosed. For screened cancers, read them alongside mortality.

Evidence chains

A lane follows one defined population and setting, where each new trial tests against what was then standard. Compare only within a lane, and read every comparison as illustrative.

High-risk neuroblastoma: randomised consolidation and transplant comparisons

Children and young people with high-risk neuroblastoma who completed induction and met protocol criteria for randomisation (CCG-3891: high-risk neuroblastoma as defined in the paper; HR-NBL1: age 1 to 20 years; ANBL0532: age 30 years or younger). · Any setting · endpoint: EFS

Results are not comparable across trials.

Three different questions in three eras, all plotted as 3-year event-free survival: myeloablative therapy with purged autologous marrow and total-body irradiation versus intensive chemotherapy (CCG-3891, first randomisation), busulfan-melphalan versus carboplatin-etoposide-melphalan (HR-NBL1), and tandem versus single autologous transplant (ANBL0532). Induction regimens, graft source, conditioning, radiotherapy, later antibody and retinoid therapy, definitions of high risk and age limits differ, and ANBL0532 randomised only about half of eligible patients (355 of 652). The ANBL0532 value is from a one-sided log-rank test. Compare only each trial's own two arms; the chart is not a pooled or cumulative estimate. The CCG-3891 second randomisation (isotretinoin) and the two European induction randomisations (ENSG5, HR-NBL1.5) are not drawn here.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100EFS at 36 months (%)199920082019CCG-3891HR-NBL1/SIOPENANBL0532
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS at 36 months, rate, across 3 trials in this lane. CCG-3891 (1999): experimental 34 % vs control 22 %; HR-NBL1/SIOPEN (2008): experimental 50 % vs control 38 %; ANBL0532 (2019): experimental 61.6 % vs control 48.4 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
CCG-38911999EFS22 %34 %
HR-NBL1/SIOPEN2008EFS38 %50 %
ANBL05322019EFS48.4 %61.6 %

High-risk neuroblastoma: randomised maintenance immunotherapy

Children with high-risk neuroblastoma who had responded to induction and completed high-dose therapy (ANBL0032: response to induction and stem-cell transplantation, 226 eligible randomised patients; HR-NBL1: aged 1 to 20 years, enrolled at diagnosis, after high-dose therapy and radiotherapy to the primary site). · Maintenance · endpoint: EFS

Results are not comparable across trials.

The two randomisations ask different questions. ANBL0032 tested isotretinoin with or without ch14.18 (dinutuximab), GM-CSF and IL-2 and is plotted at the primary 2-year event-free survival, the earlier follow-up time (a 5-year update was published later). HR-NBL1 gave dinutuximab beta with isotretinoin to both arms and tested subcutaneous IL-2; it does not compare antibody with no antibody, and it is plotted at 3 years. The two plotted values are at different follow-up times, with different antibodies, cytokines, regions and induction regimens. The eflornithine milestone (2023) rests on a single-arm study compared with matched patients from ANBL0032, not a randomised comparison, so it is listed without a plotted pair. Compare only each trial's own arms. The CCG-3891 isotretinoin randomisation is not drawn here.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100EFS at 24 months (%)2010ANBL0032
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS at 24 months, rate, across 1 trial in this lane. ANBL0032 (2010): experimental 66 % vs control 46 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
ANBL00322010EFS46 %66 %
HR-NBL1/SIOPEN2017EFS (not plotted: different measure or time point)56 %60 %

Wilms tumour, NWTS-4 low-risk group: less intensive chemotherapy

Previously untreated children with low-risk Wilms tumour in NWTS-4: stages I to II favourable histology or stage I anaplastic histology for the dosing-schedule comparison; stage II favourable histology for the duration comparison. Treated in North America after upfront nephrectomy. · Any setting · endpoint: RFS

Results are not comparable across trials.

Two randomisations within one trial are shown for the same risk group: single-dose (pulse-intensive) versus divided-dose dactinomycin, relapse-free survival at 2 years, and stopping chemotherapy at 6 months versus continuing to 15 months, relapse-free survival at 4 years (stage II favourable histology only). The two use different follow-up times and populations, and the duration comparison was measured after a second randomisation. The abstract concludes the dosing arms have equivalent 2-year relapse-free survival. NWTS uses surgery-first staging and histology; SIOP trials use preoperative chemotherapy and a different staging basis and are plotted separately. High-risk NWTS-4 results are in their own lane. Compare only each comparison's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100RFS at 24 months (%)1989NWTS-4
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
RFS at 24 months, rate, across 1 trial in this lane. NWTS-4 (1989): experimental 91.3 % vs control 91.4 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
NWTS-41989RFS91.4 %91.3 %
NWTS-41989RFS (not plotted: different measure or time point)88.2 %83.7 %

Wilms tumour, NWTS-4 high-risk group: less intensive chemotherapy

Previously untreated children with higher-risk Wilms tumour in NWTS-4: stages III to IV favourable histology or stages I to IV clear cell sarcoma of the kidney for the dosing-schedule comparison; high-risk favourable-histology patients for the duration comparison. Treated in North America after upfront nephrectomy. · Any setting · endpoint: RFS

Results are not comparable across trials.

Two randomisations within one trial are shown for the higher-risk group: single-dose (pulse-intensive) versus divided-dose dactinomycin and doxorubicin, relapse-free survival at 2 years (this group includes clear cell sarcoma of the kidney), and stopping chemotherapy at 6 months versus continuing to 15 months, relapse-free survival at 4 years (favourable-histology patients only). The two use different follow-up times and populations, and the duration comparison was measured after a second randomisation. The abstract concludes the dosing arms have equivalent 2-year relapse-free survival. Compare only each comparison's own two arms; low-risk NWTS-4 results and SIOP trials are in separate lanes.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100RFS at 24 months (%)1989NWTS-4
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
RFS at 24 months, rate, across 1 trial in this lane. NWTS-4 (1989): experimental 87.3 % vs control 90 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
NWTS-41989RFS90 %87.3 %
NWTS-41989RFS (not plotted: different measure or time point)88.8 %89.7 %

Wilms tumour, SIOP intermediate risk: omitting doxorubicin

Children aged 6 months to 18 years with stage II-III, histological intermediate-risk Wilms tumour after 4 weeks of preoperative vincristine and actinomycin D and delayed nephrectomy (583 randomised; a newly defined high-risk blastemal subtype was excluded from randomisation). · Adjuvant · endpoint: EFS

Results are not comparable across trials.

A non-inferiority trial (primary endpoint 2-year event-free survival, 10% margin) in a SIOP risk group defined after preoperative chemotherapy. It is plotted separately from the NWTS-4 lanes because the staging basis, risk definitions and surgery-first versus preoperative-chemotherapy approach differ, and the arms here are standard versus experimental, with the experimental arm omitting a drug. The reported difference in 2-year event-free survival was 4.4% (95% CI 0.4 to 9.3), which did not exceed the predefined margin. Compare only this trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100EFS at 24 months (%)2015SIOP WT 2001
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS at 24 months, rate, across 1 trial in this lane. SIOP WT 2001 (2015): experimental 88.2 % vs control 92.6 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
SIOP WT 20012015EFS92.6 %88.2 %

Standard of care, then and now

How the usual sequence of treatment changed for one setting. Choose a point in time; each step links to the milestone behind it.

High-risk neuroblastoma: therapy after induction

Children with high-risk neuroblastoma who responded to induction chemotherapy · Maintenance

  1. Cell therapy & transplant1Single or tandem transplant (compared)Tandem vs single autologous transplant in high-risk neuroblastoma (2019)
  2. Targeted2Isotretinoin (13-cis-retinoic acid)Transplant and isotretinoin in high-risk neuroblastoma (CCG-3891) (1999)
  3. Immunotherapy3Anti-GD2 antibody with GM-CSF and IL-2Anti-GD2 dinutuximab with cytokines after transplant (ANBL0032) (2010)
  4. Immunotherapy4Dinutuximab beta (EU authorisation)Dinutuximab beta in Europe: authorisation and the IL-2 question (2017)
  5. Targeted5Eflornithine (relapse-risk reduction)Eflornithine maintenance to reduce relapse: FDA approval (2023) (2023)
2023. Based only on the cited trials; induction and radiotherapy not shown. Eflornithine was FDA-approved in December 2023 on a single-arm study with matched controls. Tandem versus single transplant was compared in a randomized trial (2019).
Text version
  • 1999: Myeloablative therapy, autologous transplant → Isotretinoin (13-cis-retinoic acid)
  • 2010: Myeloablative therapy, autologous transplant → Isotretinoin (13-cis-retinoic acid) → Anti-GD2 antibody with GM-CSF and IL-2
  • 2017: Myeloablative therapy, autologous transplant → Isotretinoin (13-cis-retinoic acid) → Anti-GD2 antibody with GM-CSF and IL-2 → Dinutuximab beta (EU authorisation)
  • 2023: Single or tandem transplant (compared) → Isotretinoin (13-cis-retinoic acid) → Anti-GD2 antibody with GM-CSF and IL-2 → Dinutuximab beta (EU authorisation) → Eflornithine (relapse-risk reduction)

Reversals and dead ends

Approaches that were abandoned or withdrawn, and trials whose results were later questioned, are part of the story.

  • 2002

    Infant urine screening did not reduce neuroblastoma mortality (2002)

    In 2002 two large studies evaluated urine screening of babies for neuroblastoma, in Quebec (about 477,000 births) and in Germany (over 2.5 million children offered screening). Neither found fewer deaths, and the German study estimated that screening found tumours that would not have benefited from earlier treatment.

    Quebec: screening at 3 weeks and 6 months offered to 476,654 births, 92% participation; cumulative neuroblastoma mortality 4.78 per 100,000 over nine years, with standardized incidence ratios for death of 0.90 to 1.40 against four unscreened control populations (confidence intervals include 1). Germany: screening at about 1 year offered to 2,581,188 children; stage 4 incidence 3.7 vs 3.8 and deaths 1.3 vs 1.2 per 100,000 (screened vs control); overdiagnosis estimated at 7 per 100,000. Population comparisons, not randomised.

Today and tomorrow

Standard of care today

Screening
Neuroblastoma screening. The NCI PDQ summary (page updated 28 April 2025) says current data do not support neuroblastoma screening in the general public: screening at 3 weeks, 6 months or 1 year did not reduce the incidence of advanced-stage disease with unfavourable biology in older children or overall neuroblastoma mortality, and Quebec screening detected many tumours with favourable features that would never have been detected clinically because they regress spontaneously. The two population studies are the Quebec programme (Woods 2002) and the German programme at about 1 year of age (Schilling 2002); their numbers are in the milestone material. This restates the PDQ text and is not a guideline recommendation. No FDA or EMA action concerns screening.
National Cancer Institute 2025Woods WG, Gao RN, Shuster JJ, Robison LL, Bernstein M, Weitzman S, et al 2002Schilling FH, Spix C, Berthold F, Erttmann R, Fehse N, Hero B, et al 2002
Localised

Low-risk neuroblastoma. PDQ text read:

  • the approach is observation or resection, with chemotherapy restricted to symptomatic patients with low-risk biology
  • 5-year overall survival was 98% for low-risk patients among more than 5,000 children in the COG biology study ANBL00B1. For infants younger than 6 months with isolated adrenal masses below a size limit given in the PDQ (3.1 cm if solid, 5 cm if at least 25% cystic), the PDQ describes observation without biopsy as the recommended approach
  • observation without biopsy is otherwise described as under study (COG ANBL1232, closed to accrual per the PDQ
  • see horizon). NCCN Neuroblastoma, Version 2.2024 (Bagatell et al, J Natl Compr Canc Netw 2024;22(6):413-433, PMID 39151455) is cited by identifier only: its text was not read, and a later version may exist. No FDA or EMA action is specific to this setting
National Cancer Institute 2025Bagatell R, Park JR, Acharya S, Aldrink J, Allison J, Alva E, et al 2024ClinicalTrials 2026
Any setting

Intermediate-risk neuroblastoma. PDQ text read:

  • chemotherapy is often given before definitive resection, using doxorubicin, cyclophosphamide, a platinum drug and etoposide, with the number of cycles set by clinical and tumour-biology risk factors and by response
  • 5-year overall survival was about 95% for intermediate-risk patients in ANBL00B1. In COG ANBL0531 the duration and intensity of chemotherapy were reduced in several subsets of intermediate-risk children and the PDQ reports no declines in outcomes. The PDQ also notes that staging and risk systems changed over the past 20 years, which makes older trial results hard to compare. NCCN Neuroblastoma, Version 2.2024 (Bagatell et al, J Natl Compr Canc Netw 2024;22(6):413-433, PMID 39151455) is cited by identifier only
  • its text was not read. No FDA or EMA action is specific to this setting
National Cancer Institute 2025Bagatell R, Park JR, Acharya S, Aldrink J, Allison J, Alva E, et al 2024
Any setting

High-risk neuroblastoma, first line. PDQ text read:

  • treatment is generally in three phases: induction (chemotherapy and surgical resection), consolidation (myeloablative therapy with autologous stem-cell transplant, and radiotherapy) and postconsolidation (dinutuximab with GM-CSF and isotretinoin)
  • the PDQ describes consolidation as tandem cycles of myeloablative therapy with stem-cell transplant plus radiotherapy and cites the randomised COG trial ANBL0532, in which a large proportion of patients were not randomised (Park 2019). FDA action read: 10 March 2015, dinutuximab (Unituxin) in combination with GM-CSF, interleukin-2 and isotretinoin for paediatric patients with high-risk neuroblastoma who reach at least a partial response to prior first-line multiagent, multimodality therapy
  • the letter has no accelerated-approval wording, so the type is an inference. EU, from the EMA pages read: Unituxin was authorised on 14 August 2015 and withdrawn on 20 March 2017 at the holder's request because of inability to supply enough product
  • Qarziba (dinutuximab beta) was authorised on 8 May 2017 under exceptional circumstances. In the SIOPEN randomisation HR-NBL1 (Ladenstein 2018), adding subcutaneous IL-2 to dinutuximab beta was not shown to improve outcomes. NCCN Neuroblastoma, Version 2.2024 (Bagatell et al, J Natl Compr Canc Netw 2024;22(6):413-433, PMID 39151455) is cited by identifier only
  • its text was not read
National Cancer Institute 2025Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, et al 2010Park JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, et al 2019Ladenstein R, Pötschger U, Valteau-Couanet D, Luksch R, Castel V, Yaniv I, et al 2018US Food and Drug Administration 2015U 2026European Medicines Agency 2017European Medicines Agency 2025Bagatell R, Park JR, Acharya S, Aldrink J, Allison J, Alva E, et al 2024
Maintenance

High-risk neuroblastoma, after immunotherapy. FDA action read:

  • 13 December 2023, eflornithine (Iwilfin) to reduce the risk of relapse in adult and paediatric patients with high-risk neuroblastoma who have shown at least a partial response to prior multiagent, multimodality therapy that included anti-GD2 immunotherapy
  • the letter has no accelerated-approval wording, so the type is an inference. The FDA announcement describes efficacy from an externally controlled comparison of the single-arm Study 3b (NMTRC003B) with an ANBL0032-derived control: 90 treated and 270 matched control patients, event-free survival hazard ratio 0.48 (95% CI 0.27 to 0.85) and overall survival hazard ratio 0.32 (95% CI 0.15 to 0.70) in the protocol-specified analysis, and it notes uncertainty from the external-control design. The PDQ says the earlier historical comparison and possible selection bias limit its validity. EU: the marketing authorisation application for Ifinwil was withdrawn on 18 July 2025
  • the EMA page records the company's reason (more time to address questions) and EMA's provisional opinion that effectiveness could not be demonstrated from the data provided
US Food and Drug Administration 2023US Food and Drug Administration 2023European Medicines Agency 2025Oesterheld J, Ferguson W, Kraveka JM, Bergendahl G, Clinch T, Lorenzi E, et al 2024National Cancer Institute 2025
Relapsed / refractory
Relapsed or refractory high-risk neuroblastoma. FDA action read: 25 November 2020, naxitamab (Danyelza) with GM-CSF for paediatric patients 1 year and older and adult patients with relapsed or refractory high-risk neuroblastoma in bone or bone marrow who showed a partial response, minor response or stable disease to prior therapy, under the accelerated approval regulations. The FDA list of ongoing cancer accelerated approvals (content current 19 October 2026) still includes it, with postmarketing requirement 3950-1 and a projected completion date of 30 September 2027; it does not appear on the FDA list of accelerated approvals with verified clinical benefit (content current 16 October 2026). Which registered trial is the confirmatory trial is not stated in the pages read. The EMA page for Danyelza was not found at the expected address, so its EU status is not established. PDQ text read lists chemotherapy with immunotherapy (temozolomide, irinotecan and dinutuximab), 131I-MIBG and newer agents including ALK inhibitors as options and says chemo-immunotherapy gives the best response rate and response duration among treatments for high-risk patients with progression. Randomised phase 2 trials (ANBL1221, BEACON-Neuroblastoma, BEACON Immuno) and the phase 2 naxitamab trial are covered in the milestone material.
US Food and Drug Administration 2020FDA 2026US Food and Drug Administration 2026U 2026National Cancer Institute 2025Mody R, Naranjo A, Van Ryn C, Yu AL, London WB, Shulkin BL, et al 2017Moreno L, Weston R, Owens C, Valteau-Couanet D, Gambart M, Castel V, et al 2024Gray JC, Weston R, Owens C, Canete A, Gambart M, De Wilde B, et al 2026Mora J, Chan GCF, Morgenstern DA, Amoroso L, Nysom K, Faber J, et al 2025
Localised

Wilms tumour, North America (COG). PDQ text read:

  • the COG approach is immediate surgery for unilateral tumours (both COG and SIOP treat infants younger than 6 months with primary nephrectomy), followed by risk-adapted postoperative chemotherapy and, in some patients, radiotherapy. The PDQ reports, with a level-of-evidence label of C2, that in AREN0532 and AREN0533 augmented therapy for favorable-histology tumours with combined 1p and 16q loss of heterozygosity gave a 4-year EFS of 87.3% for stage I and II disease (regimen DD-4A) and 90.2% for stage III and IV (regimen M), against 68.8% and 61.3% for NWTS-5 patients (comparisons with an earlier study, not randomised). It also reports that in AREN0532, 116 children met the very low-risk criteria and were treated with nephrectomy alone, with an estimated 4-year EFS of 89.7% and overall survival of 100%. The FDA pediatric oncology table (current as of February 2026) lists dactinomycin (Cosmegen) for Wilms tumour as part of a multi-phase, combination chemotherapy regimen with the date 12-10-1964 as printed
  • this is a table entry and no letter was read. AREN2231 is in horizon. NCCN Wilms Tumor, Version 2.2025 (Balis et al, J Natl Compr Canc Netw 2025;23(8):319-342, PMID 40763792) is cited by identifier only
  • its text was not read, and a later version may exist
PDQ Pediatric Treatment Editorial Board 2025Dix DB, Fernandez CV, Chi YY, Mullen EA, Geller JI, Gratias EJ, et al 2019Fernandez CV, Perlman EJ, Mullen EA, Chi YY, Hamilton TE, Gow KW, et al 2017U 2026Balis F, Green DM, Armstrong A, Aye J, Benedetti D, Brown B, et al 2025ClinicalTrials 2026
Neoadjuvant
Wilms tumour, Europe (SIOP-RTSG). PDQ text read: SIOP uses preoperative chemotherapy as the first step, which the PDQ says results in fewer tumour spills during surgery and a lower postoperative stage and changes tumour histology (fewer blastemal and mixed-histology tumours); and the PDQ notes that differences between COG and SIOP affect staging and classification, so the two groups' staging should not be set side by side as if identical. SIOP WT 2001 randomised 583 children with stage II-III intermediate-risk tumours after preoperative vincristine and actinomycin D to postoperative treatment with or without doxorubicin: 2-year EFS was 92.6% with doxorubicin and 88.2% without, a difference of 4.4% (95% CI 0.4 to 9.3) that did not exceed the predefined 10% margin. The UMBRELLA SIOP-RTSG 2016 position paper describes the current protocol and names the blastemal component surviving preoperative chemotherapy among its research focuses. No FDA or EMA action specific to Wilms tumour was read. NCCN Wilms Tumor, Version 2.2025 (Balis et al, J Natl Compr Canc Netw 2025;23(8):319-342, PMID 40763792) is cited by identifier only.
PDQ Pediatric Treatment Editorial Board 2025Pritchard-Jones K, Bergeron C, de Camargo B, van den Heuvel-Eibrink MM, Acha T, Godzinski J, et al 2015van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, van Tinteren H, Furtwängler R, Verschuur AC, et al 2017Balis F, Green DM, Armstrong A, Aye J, Benedetti D, Brown B, et al 2025

Trials to watch

  • COG ANBL2131 NCT06172296

    In newly diagnosed high-risk neuroblastoma (registry: up to age 30 years), does adding dinutuximab to induction chemotherapy improve event-free survival (the registered primary outcome) compared with standard induction? Registered as a randomised phase 3 trial of two arms (standard induction, or induction with dinutuximab). Registry status: recruiting; primary completion estimated 31 December 2029; no results posted on 21 October 2026.

  • COG ANBL1531 NCT03126916

    In newly diagnosed high-risk neuroblastoma, does adding 131I-MIBG (registry arms B and C) or the ALK inhibitor lorlatinib (arm E, for ALK-aberrant disease) to intensive therapy improve event-free survival (registered primary outcome, arms A, B, D and E)? Registered as a randomised phase 3 trial with five arms, one of which closed to accrual in December 2020. Registry status: recruiting; primary completion estimated 30 September 2030; no results posted on 21 October 2026. A 2021 pilot paper on 131I-MIBG feasibility refers to this trial but reports no results from it.

  • HR-NBL2 (SIOPEN) NCT04221035

    In high-risk neuroblastoma, does the SIOPEN trial's three sequential randomisations of induction chemotherapy (RAPID COJEC versus GPOH), high-dose consolidation (busulfan-melphalan versus thiotepa plus busulfan-melphalan) and radiotherapy (21.6 Gy versus 21.6 Gy plus a boost for macroscopic residual disease) improve event-free survival (the registered primary outcome)? Registry status: recruiting; primary completion estimated November 2026; the record was last updated on 26 June 2025; no results posted on 21 October 2026.

  • COG ANBL1232 NCT02176967

    In non-high-risk neuroblastoma (registry: up to 18 months of age), can response- and biology-based risk groups guide observation, surgery or limited chemotherapy, with 3-year overall survival per stratum as the registered primary outcome? Registered as a non-randomised phase 3 trial with 391 participants (actual). Registry status: active, not recruiting; primary completion 30 September 2026 (recorded as actual); no results posted on 21 October 2026.

  • COG AREN2231 NCT06401330

    In unilateral favorable-histology Wilms tumour (registry: up to age 30 years), does risk-adapted treatment based on histology, tumour biology and response, with many stage-specific arms that include observation for some stage I disease and the regimens EE-4A, DD-4A, UH-3, M, MVI and VIVA, change 4-year event-free survival (the registered primary outcome)? Registered as a randomised phase 3 trial, not a single two-arm comparison. Registry status: recruiting; primary completion estimated 13 February 2031; no results posted on 21 October 2026.

Pioneers

References

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Every figure was checked against its primary source to the extent possible. Items that could not be fully confirmed are marked “needs review”. Educational history, not medical advice.

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2005UnderstandingUnderstanding

majorAny setting

Tumour markers: 1p/16q loss and 1q gain predict relapse

In 2005 the National Wilms Tumor Study Group reported that favourable-histology Wilms tumours with loss of parts of chromosomes 1p and 16q relapsed more often. A 2016 analysis added gain of chromosome 1q as a marker linked to worse survival. Later Children's Oncology Group studies used these markers to decide how intensively some children were treated.

NWTS-5 favourable histology. Relative risk of relapse with LOH 1p 1.56 (P = .01) and 16q 1.49 (P = .01). Stage I-II, LOH at both sites: relapse RR 2.9 (P = .001), death RR 4.3 (P = .01); stage III-IV: RR 2.4 and 2.7. In 1,114 informative tumours, 1q gain was present in 28%; 8-year EFS 77% versus 90% without it (P < .001); multivariable relative risk of relapse 2.4. Reported as relative risks, not hazard ratios.

Standard before

NWTS-5 assigned stage- and histology-specific therapy; tumour LOH status was assayed in a biology study alongside the therapeutic trial and had not been used to assign treatment.

What changed

The AREN0532 and AREN0533 studies used combined LOH 1p/16q to assign augmented therapy. The NCI PDQ summary describes 1q gain as the single most powerful predictor of outcome in unilateral favourable-histology Wilms tumour, with 1p and 16q loss retaining some prognostic significance only in its absence.

Why it mattered

Markers measured on tumour tissue separated higher-risk disease from the large favourable-histology group, which allowed later trials to test augmented therapy for the marker-defined subsets.

Caveats

  • Relative risks of relapse and death, not hazard ratios; they come from a therapeutic-trial cohort and are associations affected by the stage-specific treatment received.
  • NWTS-5 numbers differ by report: the registry lists 3,031 enrolled, Dome 2006 gives 2,596 enrolled, and Grundy 2005 assayed 2,021 children. The 1q-gain analysis used 1,114 tumours informative for the markers.
  • In the 1q analysis, 1p loss lost significance after multivariable adjustment. The treatment consequence of the markers (augmentation for combined LOH 1p/16q) is covered in the COG AREN milestone.