Intermediate-risk neuroblastoma
Intermediate-risk neuroblastoma sits between the tumours that go away on their own and the high-risk disease that needs everything. A few cycles of moderate chemotherapy followed by surgery cure most children, and trials have spent twenty years showing how few cycles are enough.
Overview
The intermediate-risk group takes in L2 tumours in children with unfavourable histology or 11q aberration, L2 tumours in children over 18 months, metastatic stage M disease in infants under 18 months, and stage MS with unfavourable biology, all without MYCN amplification. These tumours will not regress reliably and cannot be removed safely at diagnosis, but they respond to chemotherapy and rarely relapse after it. The question the trials have asked is not which drug but how little: each cycle of carboplatin, etoposide, cyclophosphamide and doxorubicin adds hearing loss, infertility and cardiac risk to a child who will live for seventy years.
COG A3961, reported in the New England Journal of Medicine in 2010, gave 479 children four or eight cycles of that four-drug chemotherapy according to histology and ploidy and operated when the tumour became resectable: three-year overall survival was 96 percent and event-free survival 88 percent, establishing a biology-based reduction of therapy. ANBL0531 then cut further, giving two cycles to the most favourable subset and adding response-based escalation for the rest, with three-year event-free survival 83.2 percent and overall survival 94.9 percent; infants with stage M disease and children with 11q loss or unfavourable histology needed the longer course. SIOPEN's LINES trial applies the same approach in Europe, and infants with stage MS disease who need treatment for a bulky liver receive the same drugs briefly.
Radiotherapy is used only for life-threatening disease that does not respond, and the residual mass after chemotherapy is often left in place when resection would risk the kidney or a nerve root. Children with 11q aberration or unfavourable histology, and infants with stage M disease and diploid tumours, are the ones who still relapse and the ones whose therapy the next trials will not shorten. Telomere maintenance mechanisms (ATRX, TERT) and ALK mutations are being tested as additions to the classification, and long-term follow-up of hearing, kidney function and fertility is what tells the groups whether the reductions were worth it.
State of the art
- Biology (11q, ploidy, histology) sets the number of cycles; response allows escalation.
- Radiotherapy and high-dose therapy are avoided altogether.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Four to eight cycles of moderate chemotherapy gave 96 percent three-year survival in A3961, and ANBL0531 cut therapy to two cycles for the most favourable children.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Check before combiningFood and drink: Doxorubicin
Cumulative dose: risk rises steeply above 400-550 mg/m² (see the anthracycline calculator).
- Check before combiningKidneys: Carboplatin
Dose by Calvert formula using GFR (see the calculators).
- Check before combiningKidneys: Etoposide
Reduce to 75% for CrCl 15-50.
- Check before combiningLiver: Doxorubicin
Reduce by 50% for bilirubin 20-50 µmol/L and 75% for 50-85 µmol/L.
- Good to knowCardiotoxicity (LVEF decline, cardiomyopathy)
Heart damage from cancer treatment: anthracyclines weaken the heart muscle permanently in a dose-related way, trastuzumab does so reversibly, and some kinase inhibitors raise blood pressure or disturb rhythm. Heart function (LVEF) is monitored by ultrasound during treatment.
See all on the product pages:CarboplatinCyclophosphamideDoxorubicinEtoposide·Printable cards in the navigator
Anatomy and lymph node drainage
- Renal cortex (RCC)
- Renal pelvis and ureter (upper tract urothelial)
- Bladder lining (non-muscle-invasive)
- Bladder muscle wall (muscle-invasive)
- Adrenal cortex
- Adrenal medulla and sympathetic chain (neuroblastoma)
- Developing kidney (Wilms tumour)
- Nodes: renal hilar
- Nodes: para-aortic and paracaval
- Nodes: obturator and iliac (bladder)
Renal cell carcinoma comes from the kidney's filtering cortex, urothelial cancer from the lining of the collecting system and bladder, and the adrenal on top hosts cortical and medullary (neuroblastoma) tumours.
- Renal cortex (RCC)
- Renal pelvis and ureter (upper tract urothelial)
- Bladder lining (non-muscle-invasive)
- Bladder muscle wall (muscle-invasive)
- Adrenal cortex
- Adrenal medulla and sympathetic chain (neuroblastoma)L2 neuroblastoma over 18 months, or with unfavourable histology or 11q aberration, without MYCN amplification · Stage M neuroblastoma in infants under 18 months without MYCN amplification · Stage MS neuroblastoma with 11q aberration or unfavourable biology · Intermediate-risk neuroblastoma with favourable biology (two to four cycles) · Intermediate-risk neuroblastoma with unfavourable biology (up to eight cycles)
- Developing kidney (Wilms tumour)L2 neuroblastoma over 18 months, or with unfavourable histology or 11q aberration, without MYCN amplification
- renal hilar
- para-aortic and paracaval
- obturator and iliac (bladder)
Same organ: Non-muscle-invasive bladder cancer, Muscle-invasive and advanced bladder cancer, Bladder & urothelial cancer, Clear cell renal cell carcinoma, Papillary renal cell carcinoma, Chromophobe renal cell carcinoma, Renal cell carcinoma, Wilms tumour (nephroblastoma), Neuroblastoma (paediatric), Low-risk neuroblastoma (INRG very low and low risk, including stage MS), High-risk neuroblastoma, Adrenocortical carcinoma, Pheochromocytoma and paraganglioma (PPGL), Urethral cancer, Penile cancer
About one neuroblastoma in ten is intermediate risk: unresectable localised disease or metastatic disease in infants, without MYCN amplification, cured in about nine in ten children with a few cycles of moderate chemotherapy.
- MRIStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Two to eight cycles of carboplatin, etoposide, cyclophosphamide and doxorubicin by biology and response (A3961, ANBL0531), then surgery when resectable.
MRI or CT and MIBG scan after chemotherapy; resection of the residual primary where safe, otherwise observation of the residual mass.
Radiotherapy to the primary or to a compressing lesion; escalation to high-risk therapy if biology proves unfavourable.
Hearing, kidney, cardiac and fertility follow-up for the chemotherapy given.
Subtypes & biomarkers
top- L2 neuroblastoma over 18 months, or with unfavourable histology or 11q aberration, without MYCN amplification
- Stage M neuroblastoma in infants under 18 months without MYCN amplification
- Stage MS neuroblastoma with 11q aberration or unfavourable biology
- Intermediate-risk neuroblastoma with favourable biology (two to four cycles)
- Intermediate-risk neuroblastoma with unfavourable biology (up to eight cycles)
- INRG stage (L2, M in infants, MS)
- MYCN amplification (must be absent)
- 11q aberration
- DNA ploidy
- INPC histology
- ALK mutation
- Urinary catecholamine metabolites
How often this target appears
- 2009INRG classification defines the intermediate-risk group by stage, age and biology
- 2010A3961: biology-based reduction to four or eight cycles gives 96 percent three-year survival
- 2019ANBL0531: further response-based reduction, two cycles for the most favourable children
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 4 changes by month →- 2026-09-17This recordIntermediate-risk neuroblastomaFacts on this page last checked
When this page itself was last checked or edited.
- 2019MilestoneINRG staging and risk groupsANBL0531: further response-based reduction, two cycles for the most favourable children
A milestone in how this cancer is treated.
- 2010MilestoneCarboplatinA3961: biology-based reduction to four or eight cycles gives 96 percent three-year survival
A milestone in how this cancer is treated.
- 2009MilestoneINRG staging and risk groupsINRG classification defines the intermediate-risk group by stage, age and biology
A milestone in how this cancer is treated.
What is in development for Intermediate-risk neuroblastoma, drawn from the whole corpus: 1 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Ideas not yet in a trial · 1
Open problems and what is being done
Children with 11q aberration or unfavourable histology still relapse and cannot have therapy shortened.
Whether telomere maintenance and ALK status should change risk assignment.
Measuring the late effects of even moderate chemotherapy over decades.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- Cardio-oncologyEstablished
- CyclophosphamideApproved
- Cytotoxic chemotherapyStandard of care
- IMRT / IGRT (modern external beam)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Side effects by symptom · Immune-related side effects · Toxicity compare · Survivorship planner.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Expert centres
topExpert centres
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - | |
Dresden · cancer center | Germany | none recorded | 0 | 728 | 7,984 | - | |
| United Kingdom | none recorded | 0 | 693 | 7,168 | - | ||
Aarhus · hospital | Denmark | none recorded | 0 | 624 | 4,497 | - | |
Freiburg im Breisgau · cancer center | Germany | none recorded | 0 | 549 | 5,261 | - | |
Geneva · hospital | Switzerland | none recorded | 0 | 441 | 6,485 | - | |
Madison, WI · cancer center | United States | 0 | 424 | 10,177 | - | ||
Bangkok · hospital | Thailand | none recorded | 0 | 422 | 3,241 | - | |
Sapporo · hospital | Japan | none recorded | 0 | 412 | 2,961 | - | |
Bordeaux · cancer center | France | none recorded | 0 | 410 | 4,462 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Intermediate-risk neuroblastoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Intermediate-risk neuroblastoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example INRG stage, MYCN amplification, 11q aberration, DNA ploidy, INPC histology), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include L2 neuroblastoma over 18 months, or with unfavourable histology or 11q aberration, without MYCN amplification, Stage M neuroblastoma in infants under 18 months without MYCN amplification, Stage MS neuroblastoma with 11q aberration or unfavourable biology.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Chemotherapy
- For my situation (chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Two to eight cycles of carboplatin, etoposide, cyclophosphamide and doxorubicin by biology and response (A3961, ANBL0531), then surgery when resectable.
- Am I a candidate for Carboplatin, Etoposide, Cyclophosphamide or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Response assessment and surgery
- For my situation (response assessment and surgery), which of the standard options do you recommend and why?Why: Guideline options include: MRI or CT and MIBG scan after chemotherapy; resection of the residual primary where safe, otherwise observation of the residual mass.
Non-responding or life-threatening disease
- For my situation (non-responding or life-threatening disease), which of the standard options do you recommend and why?Why: Guideline options include: Radiotherapy to the primary or to a compressing lesion; escalation to high-risk therapy if biology proves unfavourable.
Follow-up
- For my situation (follow-up), which of the standard options do you recommend and why?Why: Guideline options include: Hearing, kidney, cardiac and fertility follow-up for the chemotherapy given.
Any stage
- Are there clinical trials I could join, for example of INRG staging and risk groups, 18F-MFBG PET replacing 123I-MIBG scintigraphy, MIBG imaging and 131I-MIBG therapy, Cardio-oncology?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Children with 11q aberration or unfavourable histology still relapse and cannot have therapy shortened”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Whether telomere maintenance and ALK status should change risk assignment”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Intermediate-risk neuroblastoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
11targets
1drugs
4institutions
2terms
6ideas
1Latest papers
topQuery for this cancer: (TITLE:"Intermediate-risk neuroblastoma" OR ABSTRACT:"Intermediate-risk neuroblastoma" OR TITLE:"INRG intermediate-risk neuroblastoma" OR ABSTRACT:"INRG intermediate-risk neuroblastoma" OR TITLE:"Unresectable localised neuroblastoma" OR ABSTRACT:"Unresectable localised neuroblastoma" OR TITLE:"Stage M neuroblastoma in infants" OR ABSTRACT:"Stage M neuroblastoma in infants") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Intermediate-risk neuroblastoma, not a curated reading list.
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