# Atypical teratoid/rhabdoid tumour (ATRT)

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

## TL;DR

ATRT is an aggressive brain tumour of babies and toddlers caused by loss of a single gene, SMARCB1, part of the machinery that opens and closes DNA. Intensive chemotherapy with stem-cell rescue, and radiotherapy where age allows, now cure a meaningful share of children who once had little chance, and drugs aimed at the epigenetic consequence of SMARCB1 loss (EZH2 inhibitors) are in trials.

## Summary

Atypical teratoid/rhabdoid tumour is a WHO grade 4 embryonal tumour defined by biallelic inactivation of SMARCB1 (INI1) or, rarely, SMARCA4, both core subunits of the SWI/SNF chromatin-remodelling complex. It is one of the genetically simplest human cancers, often with no other recurrent mutation, yet it splits into three epigenetic subgroups (ATRT-TYR, ATRT-SHH, ATRT-MYC) with different locations, ages and outcomes. About a third of children carry a germline SMARCB1 or SMARCA4 alteration (rhabdoid tumour predisposition syndrome), which matters for siblings and for the risk of synchronous renal or soft-tissue rhabdoid tumours. Median age at diagnosis is under two years, which limits radiotherapy.

Outcomes were dismal until intensive multimodal protocols were adopted. The COG trial ACNS0333 combined maximal resection, induction chemotherapy (including high-dose methotrexate), three cycles of high-dose chemotherapy with autologous stem-cell rescue, and focal radiotherapy adapted to age, and reported markedly better survival than historical controls (JCO 2020). The European EU-RHAB registry-based regimen (conventional chemotherapy with intraventricular methotrexate, radiotherapy for older children) gives comparable results and forms the basis of the SIOPE ATRT01 trial. Extent of resection, age, metastatic disease and subgroup all predict outcome.

The biology points to therapy: loss of SMARCB1 leaves the PRC2 methyltransferase EZH2 unopposed, and the EZH2 inhibitor tazemetostat, already approved for SMARCB1-negative epithelioid sarcoma in adults, has shown responses in children with ATRT and other rhabdoid tumours in a paediatric phase 1 and is being combined with chemotherapy. Other avenues include CDK4/6 inhibition, aurora kinase A inhibitors (alisertib) and the EZHIP-independent dependency on the residual SWI/SNF subunit BRG1. Methylation-based subgrouping is expected to stratify the next generation of trials.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: AT/RT; Rhabdoid tumour of the CNS; Rhabdoid tumour predisposition syndrome
- Tags: nci-coverage; paediatric; cns
- Group: paediatric
- Burden: Rare: a small fraction of childhood brain tumours overall, but among the most common malignant brain tumours in infants under one year (NCI PDQ).
- Subtypes: ATRT-TYR (infants, infratentorial, melanosomal markers); ATRT-SHH (supratentorial and infratentorial, SHH and NOTCH signalling); ATRT-MYC (older children, supratentorial, MYC expression; overlaps with extracranial rhabdoid tumours); SMARCA4-deficient ATRT (rare, often germline)
- Biomarkers: Loss of SMARCB1 (INI1) nuclear staining by immunohistochemistry; SMARCB1 or SMARCA4 sequencing, somatic and germline; Methylation subgroup (TYR, SHH, MYC); Metastatic stage on MRI and cerebrospinal-fluid cytology; Age (radiotherapy eligibility); Extent of resection

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/atrt/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/atrt/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/atrt/#what-it-is [4 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/atrt/#finding-it [6 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/atrt/#treating-it [3 settings, 2 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/atrt/#evidence [2 trials, 2 key papers, 5 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/atrt/#science [3 targets, 4 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/atrt/where-you-are/ [3 centres]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/atrt/#living-with-it [15 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/atrt/coming/ [6 medicines, 1 trial, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/atrt/data/ [41 connected records]

## Standard of care

- Newly diagnosed, any age: Maximal safe resection followed by an intensive multimodal protocol: ACNS0333-style induction, high-dose chemotherapy with autologous stem-cell rescue, and age-adapted focal radiotherapy; or the EU-RHAB regimen with intraventricular methotrexate. Enrolment in SIOPE ATRT01 or a COG successor where available. ([Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Vincristine](https://onco.cc/drugs/vincristine/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [ACNS0333](https://onco.cc/trials/acns0333/))
- Germline SMARCB1 or SMARCA4 alteration: Genetic counselling and testing of parents and siblings; surveillance imaging for synchronous or second rhabdoid tumours in the kidney and soft tissue. ([Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/))
- Relapsed or refractory: No standard; EZH2 inhibition with tazemetostat was explored in trials and compassionate use until the drug was withdrawn from all markets in March 2026; aurora kinase A inhibition, re-irradiation where feasible; early palliative care. ([Tazemetostat](https://onco.cc/drugs/tazemetostat/), [Early integrated palliative care](https://onco.cc/technologies/palliative-care/))

## State of the art

- Intensive multimodal therapy (ACNS0333, EU-RHAB) turned ATRT from an almost uniformly fatal infant tumour into one that is cured in a meaningful share of children.
- Three methylation subgroups (TYR, SHH, MYC) explain much of the heterogeneity and are being built into trial stratification.
- SMARCB1 loss creates an EZH2 dependency; tazemetostat produced responses in paediatric rhabdoid tumours before its 2026 withdrawal, so the dependency is validated but a next EZH2 inhibitor is needed.
- Germline testing is routine because a third of children carry a predisposition that affects the whole family.

## Open problems

- Infants too young for radiotherapy and children with metastatic or ATRT-MYC disease still do poorly; SIOPE ATRT01 and COG successors are testing intensified and subgroup-directed therapy.
- Long-term neurocognitive and endocrine cost of intensive therapy in the first years of life; proton therapy and radiation-sparing arms aim to reduce it.
- Translating the EZH2 dependency into cures: tazemetostat combinations with chemotherapy are in early trials.
- Rarity: international registries (EU-RHAB) and shared protocols are the only route to adequately powered trials.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Atypical_teratoid_rhabdoid_tumor
- NCI PDQ: childhood CNS atypical teratoid/rhabdoid tumour: https://www.cancer.gov/types/brain/hp/child-cns-atrt-treatment-pdq
- ACNS0333: intensive multimodal therapy for ATRT (JCO 2020): https://doi.org/10.1200/JCO.19.01776
- EU-RHAB registry outcomes (Neuro-Oncology 2020): https://doi.org/10.1093/neuonc/noz244

## Connected records

- cancers: [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Central nervous system germ cell tumours (germinoma and non-germinomatous)](https://onco.cc/cancers/cns-germ-cell-tumours/), [Childhood cancers (all types)](https://onco.cc/cancers/childhood-cancers/), [Choroid plexus carcinoma](https://onco.cc/cancers/choroid-plexus-carcinoma/), [Ependymoma](https://onco.cc/cancers/ependymoma/), [Epithelioid sarcoma](https://onco.cc/cancers/epithelioid-sarcoma/), [Medulloblastoma](https://onco.cc/cancers/medulloblastoma/), [Poorly differentiated chordoma (SMARCB1-deficient)](https://onco.cc/cancers/poorly-differentiated-chordoma/), [Wilms tumour (nephroblastoma)](https://onco.cc/cancers/wilms-tumor/)
- technologies: [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [Early integrated palliative care](https://onco.cc/technologies/palliative-care/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Proton therapy](https://onco.cc/technologies/proton-therapy/)
- targets: [ASCL1](https://onco.cc/targets/ascl1/), [EZH2](https://onco.cc/targets/ezh2/), [SMARCB1](https://onco.cc/targets/smarcb1/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Tazemetostat](https://onco.cc/drugs/tazemetostat/), [Vincristine](https://onco.cc/drugs/vincristine/)
- companies: [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/)
- institutions: [German Cancer Research Center (DKFZ)](https://onco.cc/institutions/dkfz/), [SIOP Europe (European Society for Paediatric Oncology)](https://onco.cc/institutions/siop-europe/), [St. Jude Children's Research Hospital](https://onco.cc/institutions/st-jude/)
- pathways: [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Hedgehog signalling](https://onco.cc/pathways/hedgehog/), [MYC](https://onco.cc/pathways/myc/), [SWI/SNF chromatin remodelling](https://onco.cc/pathways/swi-snf-chromatin/)
- terms: [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/)
- key papers: [ACNS0333: high-dose chemotherapy and three-dimensional conformal radiation for atypical teratoid/rhabdoid tumour](https://onco.cc/key-papers/paper-acns0333-atrt-high-dose-chemotherapy-reddy-jco-2020/), [Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors](https://onco.cc/key-papers/paper-fruhwald-neuro-oncol/)
- trials: [ACNS0333](https://onco.cc/trials/acns0333/), [NCI-COG Pediatric MATCH (APEC1621)](https://onco.cc/trials/pediatric-match/)
- journals: [Brain tumor pathology](https://onco.cc/journals/brain-tumor-pathology/), [CNS oncology](https://onco.cc/journals/cns-oncology/), [Journal of neuro-oncology](https://onco.cc/journals/journal-of-neuro-oncology/)

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JSON: https://onco.cc/api/v1/entities/atrt.json