# Low-risk neuroblastoma (INRG very low and low risk, including stage MS)

Source: https://onco.cc/cancers/neuroblastoma-low-risk/  
OnCo record `neuroblastoma-low-risk` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Low-risk neuroblastoma is the form found in infants and young children whose tumour has not spread beyond its site or, in the special stage MS pattern, has spread only to the liver, skin and a little marrow. Many of these tumours shrink and disappear on their own, so treatment is surgery, or simply watching, and almost every child survives.

## Summary

Neuroblastoma arises from sympathetic nervous system precursors, most often in the adrenal, and the same histology spans one of the widest ranges of behaviour in oncology. The International Neuroblastoma Risk Group (INRG) classification of 2009 assigns pretreatment risk from image-defined risk factors (stage L1 or L2), metastatic pattern (M or MS), age, MYCN status, 11q aberration, ploidy and histology. Very low and low risk covers L1 tumours without MYCN amplification at any age, L2 tumours in infants without unfavourable biology, and stage MS in infants under 18 months: metastases confined to skin, liver and less than 10 percent of marrow, which regress spontaneously. Screening programmes in Japan, Quebec and Germany in the 1980s and 1990s found many more infant tumours than ever came to clinical attention and did not reduce deaths, proof that a large fraction of infant neuroblastoma regresses unseen.

The Children's Oncology Group trial P9641 treated children with low-risk disease by surgery alone, reserving chemotherapy for symptoms or incomplete resection with unfavourable biology: five-year event-free survival was 89 percent and overall survival 97 percent, with almost every child who relapsed rescued. The German NB97 trial observed infants with localised unresected tumours and saw spontaneous regression in around half. COG ANBL1232 then went further, observing small adrenal masses in infants under six months without biopsy, and expectant observation of L2 tumours in children under 18 months with favourable biology; the SIOPEN LINES study runs the same strategy in Europe. Stage MS infants are watched unless a rapidly enlarging liver threatens breathing or the kidneys, when a short course of carboplatin and etoposide or low-dose cyclophosphamide is given.

The problems are of judgement rather than drugs: telling a tumour that will regress from one that will grow, deciding when the surgical risk to the kidney or spinal cord of an L2 tumour outweighs the risk of watching, and recognising the minority of infants with MS disease who carry MYCN amplification or 11q loss and behave as high risk. Telomere maintenance status and segmental chromosomal aberrations are being added to the biology, urinary catecholamines and ultrasound carry the follow-up, and the late effects of the chemotherapy given to the small group who need it, particularly hearing and fertility, are being tracked so that even that can be reduced.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Very low-risk neuroblastoma; Stage MS neuroblastoma; Stage 4S neuroblastoma; Localised neuroblastoma in infants
- Tags: subtype-page; paediatric
- Group: paediatric
- Burden: Roughly a third of neuroblastoma, mostly in infants, is low risk: localised disease or the special metastatic pattern of infancy, without MYCN amplification, and cured in almost every case with little or no treatment.
- Subtypes: INRG very low risk: L1 neuroblastoma without MYCN amplification (surgery or observation); INRG low risk: L2 neuroblastoma in infants without unfavourable biology (observation or surgery); Stage MS neuroblastoma in infants under 18 months without MYCN amplification (observation, short chemotherapy if symptomatic); Ganglioneuroblastoma intermixed and ganglioneuroma (maturing spectrum; surgery or observation); Perinatal adrenal neuroblastoma found on antenatal or postnatal ultrasound (expectant observation)
- Biomarkers: INRG stage (L1, L2, MS) from image-defined risk factors; MYCN amplification (must be absent); 11q aberration; DNA ploidy; INPC histology; Urinary catecholamine metabolites (HVA, VMA); Age at diagnosis

## Standard of care

- L1 tumours and small adrenal masses in infants: Observation with serial ultrasound and urinary catecholamines, or surgical resection; no chemotherapy. ([INRG staging and risk groups](https://onco.cc/terms/inrg-staging/), [Active surveillance](https://onco.cc/technologies/active-surveillance/), [Ultrasound](https://onco.cc/technologies/ultrasound/), [MRI](https://onco.cc/technologies/mri/), [MYCN amplification](https://onco.cc/terms/mycn-amplification/))
- L2 tumours in infants with favourable biology: Expectant observation or surgery; short carboplatin and etoposide or cyclophosphamide only for symptoms or threat to organs. ([Active surveillance](https://onco.cc/technologies/active-surveillance/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [INRG staging and risk groups](https://onco.cc/terms/inrg-staging/))
- Stage MS: Observation; carboplatin and etoposide or low-dose cyclophosphamide for a rapidly enlarging liver or respiratory compromise. ([Active surveillance](https://onco.cc/technologies/active-surveillance/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Ultrasound](https://onco.cc/technologies/ultrasound/))
- Follow-up: Ultrasound and urinary catecholamines, tapering over years; late-effects follow-up for the few who received chemotherapy. ([Ultrasound](https://onco.cc/technologies/ultrasound/), [MRI](https://onco.cc/technologies/mri/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/))

## State of the art

- Surgery alone, or observation alone, cures almost every child with low-risk neuroblastoma; five-year overall survival was 97 percent in P9641.
- Small adrenal masses in young infants are observed without biopsy, and about half regress.
- Biology (MYCN, 11q, ploidy) rather than stage decides who is watched and who is treated.

## Open problems

- Distinguishing tumours that will regress from those that will grow without biopsy.
- When surgery to the kidney or spinal canal is riskier than watching.
- Identifying the few stage MS infants with MYCN amplification or 11q loss who behave as high risk.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Neuroblastoma
- Wikipedia: Neuroblastoma: https://en.wikipedia.org/wiki/Neuroblastoma
- NCI PDQ: Neuroblastoma Treatment: https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq

## Connected records

- cancers: [High-risk neuroblastoma](https://onco.cc/cancers/neuroblastoma-high-risk/), [Intermediate-risk neuroblastoma](https://onco.cc/cancers/neuroblastoma-intermediate-risk/), [Neuroblastoma (paediatric)](https://onco.cc/cancers/neuroblastoma/)
- technologies: [Active surveillance](https://onco.cc/technologies/active-surveillance/), [MRI](https://onco.cc/technologies/mri/), [Ultrasound](https://onco.cc/technologies/ultrasound/)
- institutions: [Children's Oncology Group (COG)](https://onco.cc/institutions/childrens-oncology-group/), [SIOP Europe (European Society for Paediatric Oncology)](https://onco.cc/institutions/siop-europe/)
- terms: [INRG staging and risk groups](https://onco.cc/terms/inrg-staging/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/), [MYCN amplification](https://onco.cc/terms/mycn-amplification/), [Segmental chromosomal aberrations and ploidy (neuroblastoma)](https://onco.cc/terms/segmental-chromosomal-aberrations/), [Urinary catecholamine metabolites (VMA and HVA)](https://onco.cc/terms/urinary-catecholamines/)
- ideas: [18F-MFBG PET replacing 123I-MIBG scintigraphy](https://onco.cc/ideas/idea-mfbg-pet-replaces-mibg/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Etoposide](https://onco.cc/drugs/etoposide/)

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