Atypical teratoid/rhabdoid tumour (ATRT)
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.
Overview
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.
State of the art today
- 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 has produced responses in paediatric rhabdoid tumours and is moving into combinations.
- Germline testing is routine because a third of children carry a predisposition that affects the whole family.
Where it starts and where it drains
Gliomas infiltrate along white matter and can cross the corpus callosum, medulloblastoma sits in the cerebellum, and CNS lymphoma favours deep periventricular tissue; none spread through lymph nodes.
- Frontal lobe (glioblastoma commonest)
- Temporal lobe
- Corpus callosum (butterfly glioma)
- Lower-grade IDH-mutant glioma
- Cerebellum (medulloblastoma)ATRT-SHH (supratentorial and infratentorial, SHH and NOTCH signalling)
- Brainstem (diffuse midline glioma)
- Ventricles and ependymal lining (ependymoma)
- Sella and pituitary (pituitary tumours, craniopharyngioma)
- Deep periventricular tissue (CNS lymphoma)
No conventional lymphatics: gliomas spread along white matter tracts and, rarely, through cerebrospinal fluid; medulloblastoma can seed the spine.
Same organ: Glioma & glioblastoma, Primary CNS lymphoma, Medulloblastoma, Paediatric low-grade glioma, Diffuse midline glioma, H3 K27-altered (including DIPG), Ependymoma, Craniopharyngioma, Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma
Rare: a small fraction of childhood brain tumours overall, but among the most common malignant brain tumours in infants under one year (NCI PDQ).
- DNA methylation profilingEstablished
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
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.
Genetic counselling and testing of parents and siblings; surveillance imaging for synchronous or second rhabdoid tumours in the kidney and soft tissue.
No standard; tazemetostat (EZH2 inhibitor) in trials and compassionate use, aurora kinase A inhibition, re-irradiation where feasible; early palliative care.
Subtypes & biomarkers
top- 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)
- 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
Target prevalence in this cancer
- 1987ATRT described as distinct from medulloblastoma
Rorke and colleagues recognise the rhabdoid tumour of the CNS.
- 1998SMARCB1 (hSNF5/INI1) identified as the rhabdoid tumour gene
Versteege and colleagues (Nature) find biallelic loss, the first chromatin-remodelling tumour suppressor.
- 2016Three molecular subgroups defined
Johann and Torchia (Cancer Cell) describe ATRT-TYR, ATRT-SHH and ATRT-MYC by methylation and expression.
- 2020ACNS0333 reports improved survival with intensive therapy
COG phase 3 with high-dose chemotherapy and autologous rescue (JCO 2020).
- 2020Tazemetostat approved for SMARCB1-negative epithelioid sarcoma
First EZH2 inhibitor approval; paediatric rhabdoid tumour responses in the phase 1 programme.
Open problems, and what is being done about each
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.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- Bone-modifying agents (bisphosphonates, denosumab)Standard of care
- DordaviproneApproved
- HIPEC / PIPAC (intraperitoneal chemotherapy)Established
- Laser interstitial thermal therapy (LITT)Established
- Liquid biopsy (ctDNA)Standard of care
- Lutetium-177 vipivotide tetraxetanApproved
In trials- ACTIONRecruiting
- CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)Phase 1
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
- DESTINY-Breast12Positive
- DYNAMICPositive
- EF-14Positive
Ideas and roadmaps- A billion-dollar prize for the first durable cure of a lethal metastatic cancer
- A blood test for the pre-metastatic niche
- A global rapid tissue donation network for metastatic disease
- A national rapid research autopsy network for end-stage cancer
- A regulatory endpoint for drugs that block spread, not tumours
- A ring-fenced metastasis programme with metastasis-specific endpoints
Background: Blood-brain barrier (BBB), Circulating tumour DNA (ctDNA), EGFRvIII, Epithelial–mesenchymal transition & drug efflux, H3 K27M (diffuse midline glioma). Also on OnCo: Atlas: what treats advanced disease · Mechanics: invasion and metastasis.
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.
and how the field plans to fix it →What is being done about thisCost and accessAvailable now- HPV & HBV vaccinationStandard of care
- ImatinibApproved
- Trastuzumab biosimilarsApproved
In trials- Gefitinib vs gefitinib plus pemetrexed-carboplatin in EGFR-mutant lung cancer (Tata Memorial)Positive
- IARC India HPV vaccine dose study (one, two or three doses)Positive
- IMAGINE (varnimcabtagene autoleucel, Immuneel)Positive
- Low-dose nivolumab plus metronomic chemotherapy (Tata Memorial)Positive
- Low-dose olanzapine for cancer anorexia (Tata Memorial)Positive
- METRO PLUS (Tata Memorial Centre, Varanasi)Positive
Ideas and roadmaps- 90-day reliance approval for cancer drugs cleared by two stringent regulators
- A cheap old tablet to restore appetite
- A combination pricing rule so two-drug regimens are not priced as two monopolies
- A coordinated reserve and shared schedule for the world's medical isotope reactors
- A dedicated global financing window for cancer, modelled on the Global Fund
- A delinked market-entry reward paid by payers when a repurposed generic wins approval
Background: Accelerated approval, Biosimilar, Real-world evidence. Also on OnCo: Financial help and assistance navigator · Coverage by country · HTA decisions.
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.
and how the field plans to fix it →What is being done about thisRare cancers and small trialsAvailable now- AI trial matching & clinical decision supportEstablished
- Comprehensive genomic profilingStandard of care
- Dinutuximab (ch14.18) / dinutuximab betaApproved
- Eflornithine (DFMO)Approved
- LarotrectinibApproved
- Limb-salvage surgery and endoprosthetic reconstructionStandard of care
In trials- NCI-COG Pediatric MATCH (APEC1621)Active
- ACTIONRecruiting
- COG AALL1731Positive
- COG ANBL0032Positive
- DeFiPositive
- Euro Ewing 2012Positive
Ideas and roadmaps- A digital second-opinion network answering community oncologists within 72 hours
- A DRUP-style protocol for off-label generic targeted drugs in rare tumours
- A funded expert second opinion for every new high-stakes or rare cancer diagnosis
- A global first-in-human network for academic cancer trials with single ethics review
- A global open trials operating system any hospital can plug into
- A live 'seats available' feed for trial slots, like airline inventory
Background: Basket, umbrella, and platform trials, Centralisation and high-volume centres, FNCLCC grade (soft-tissue sarcoma), Histotype-tailored therapy, INRG staging and risk groups. Also on OnCo: Find a trial · Expert centres.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Landmark trials in OnCo
Expert centres
topCentres linked to this cancer in OnCo
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via DNA methylation profiling
- via Proton therapy
- via Proton therapy
- via DNA methylation profiling, Proton therapy
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia Proton therapy, Germline (hereditary) testing
- Children's Oncology Group (COG)Monrovia, CA, USvia this cancer, NCI-COG Pediatric MATCH (APEC1621)
- German Cancer Research Center (DKFZ)Heidelberg, DEvia this cancer, DNA methylation profiling
- via DNA methylation profiling, Germline (hereditary) testing
- via Proton therapy, Germline (hereditary) testing
- Shizuoka Cancer CenterNagaizumi, Shizuoka, JPvia Proton therapy, Germline (hereditary) testing
- via this cancer, Proton therapy
- A.C. Camargo Cancer CenterSão Paulo, BRvia Germline (hereditary) testing
- Aarhus University HospitalAarhus, DKvia Proton therapy
- via Proton therapy
- Alliance for Clinical Trials in OncologyChicago, IL, USvia Carboplatin
- American Society for Radiation OncologyArlington, VA, USvia Proton therapy
- Apollo Hospitals (Apollo Cancer Centres)Chennai, INvia Proton therapy
- via Proton therapy
- Catalan Institute of Oncology (ICO)L'Hospitalet de Llobregat, ESvia Germline (hereditary) testing
- Centre Antoine LacassagneNice, FRvia Proton therapy
- Centre François BaclesseCaen, FRvia Proton therapy
- Chang Gung Memorial HospitalTaoyuan, TWvia Proton therapy
- Christian Medical College, VelloreVellore, INvia Early integrated palliative care
- Cleveland Clinic Abu DhabiAbu Dhabi, AEvia Proton therapy
- via Proton therapy
- Edinburgh Cancer Centre / CRUK Scotland CentreEdinburgh, GBvia Germline (hereditary) testing
- Erasmus MC Cancer InstituteRotterdam, NLvia Proton therapy
- European Society for Radiotherapy and OncologyBrussels, BEvia Proton therapy
- via Germline (hereditary) testing
- via DNA methylation profiling
- German Breast Group (GBG)Neu-Isenburg, DEvia Carboplatin
- via Germline (hereditary) testing
- Groote Schuur Hospital / University of Cape TownCape Town, ZAvia Germline (hereditary) testing
- Hadassah Medical CenterJerusalem, ILvia Germline (hereditary) testing
- via Germline (hereditary) testing
- Hokkaido University HospitalSapporo, JPvia Proton therapy
- Hospital de Clínicas de Porto AlegrePorto Alegre, BRvia Germline (hereditary) testing
- Hospital Universitari i Politècnic La FeValencia, ESvia Germline (hereditary) testing
- via Germline (hereditary) testing
- via Germline (hereditary) testing
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensivevia Cisplatin
- Innovative Therapies for Children with Cancer (ITCC)Villejuif, FRvia NCI-COG Pediatric MATCH (APEC1621)
- Institute of Oncology LjubljanaLjubljana, SIvia Carboplatin
- King Hussein Cancer CenterAmman, JOvia Germline (hereditary) testing
- Korle Bu Teaching HospitalAccra, GHvia Germline (hereditary) testing
- Lagos University Teaching HospitalLagos, NGvia Germline (hereditary) testing
- Leiden University Medical CenterLeiden, NLvia Proton therapy
- Li Ka Shing FoundationHong Kong, HKvia Early integrated palliative care
- Maastricht UMC+ Comprehensive Cancer CenterMaastricht, NLvia Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- MovemberMelbourne, AUvia Germline (hereditary) testing
- via Proton therapy
- National Cancer Center Hospital EastKashiwa, Chiba, JPvia Proton therapy
- National Cancer Center KoreaGoyang, KRvia Proton therapy
- National Cancer Centre SingaporeSingapore, SGvia Proton therapy
- National Cancer Institute (NIH)Bethesda, MD, USvia NCI-COG Pediatric MATCH (APEC1621)
- National Taiwan University HospitalTaipei, TWvia Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- Peking Union Medical College HospitalBeijing, CNvia Germline (hereditary) testing
- via DNA methylation profiling
- via Proton therapy
- QIMR Berghofer Medical Research InstituteBrisbane, AUvia Germline (hereditary) testing
- Ramathibodi Hospital, Mahidol UniversityBangkok, THvia Germline (hereditary) testing
- Royal Adelaide HospitalAdelaide, AUvia Proton therapy
- Ruijin Hospital, Shanghai Jiao Tong UniversityShanghai, CNvia Proton therapy
- Shaare Zedek Medical CenterJerusalem, ILvia Germline (hereditary) testing
- via Proton therapy
- via this cancer
- via Germline (hereditary) testing
- via DNA methylation profiling
- via Proton therapy
- The Clatterbridge Cancer Centre NHS Foundation TrustLiverpool, GBvia Proton therapy
- The Hospital for Sick Children (SickKids)Toronto, ON, CAvia Germline (hereditary) testing
- via EZH2
- Tohoku University HospitalSendai, JPvia Germline (hereditary) testing
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- University of Malaya Medical CentreKuala Lumpur, MYvia Germline (hereditary) testing
- University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensivevia Proton therapy
- via Proton therapy
- via DNA methylation profiling
- UZ Leuven / Leuven Cancer InstituteLeuven, BEvia Proton therapy
- via Proton therapy
- Zhejiang Cancer HospitalHangzhou, CNvia Proton therapy
Questions to ask
topQuestions to ask your oncologist about Atypical teratoid/rhabdoid tumour
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 Loss of SMARCB1nuclear staining by immunohistochemistry, SMARCB1 or SMARCA4 sequencing, somatic and germline, Methylation subgroup, Metastatic stage on MRI and cerebrospinal-fluid cytology, Age), 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 ATRT-TYR, ATRT-SHH, ATRT-MYC.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Newly diagnosed, any age
- For my situation (newly diagnosed, any age), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Methotrexate, Cyclophosphamide, Cisplatin or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Germline SMARCB1 or SMARCA4 alteration
- For my situation (germline smarcb1 or smarca4 alteration), which of the standard options do you recommend and why?Why: Guideline options include: Genetic counselling and testing of parents and siblings; surveillance imaging for synchronous or second rhabdoid tumours in the kidney and soft tissue.
Relapsed or refractory
- For my situation (relapsed or refractory), which of the standard options do you recommend and why?Why: Guideline options include: No standard; tazemetostat (EZH2 inhibitor) in trials and compassionate use, aurora kinase A inhibition, re-irradiation where feasible; early palliative care.
- Am I a candidate for Tazemetostat, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Tazemetostat, DNA methylation profiling, Proton therapy, NCI-COG Pediatric MATCH (APEC1621)?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 “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”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “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”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
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topQuery for this cancer: (TITLE:"Atypical teratoid/rhabdoid tumour" OR ABSTRACT:"Atypical teratoid/rhabdoid tumour" OR TITLE:"ATRT" OR ABSTRACT:"ATRT" OR TITLE:"AT/RT" OR ABSTRACT:"AT/RT" OR TITLE:"Rhabdoid tumour of the CNS" OR ABSTRACT:"Rhabdoid tumour of the CNS" OR TITLE:"Rhabdoid tumour predisposition syndrome" OR ABSTRACT:"Rhabdoid tumour predisposition syndrome") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Atypical teratoid/rhabdoid tumour (ATRT), not a curated reading list.
Pages like this
not linked directly; found by shared links- CancerEpendymoma
Shares NCI-COG Pediatric MATCH (APEC1621), St. Jude Children's Research Hospital, Late effects and survivorship toxicity, SIOP Europe – European Society for Paediatric Oncology and the tags nci-coverage, paediatric, cns.
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Shares NCI-COG Pediatric MATCH (APEC1621), Late effects and survivorship toxicity, SIOP Europe – European Society for Paediatric Oncology, Early integrated palliative care and the tags nci-coverage, paediatric, cns.
- CancerPaediatric low-grade glioma
Shares NCI-COG Pediatric MATCH (APEC1621), Late effects and survivorship toxicity, SIOP Europe – European Society for Paediatric Oncology, Vincristine and the tags nci-coverage, paediatric, cns.
- CancerCraniopharyngioma
Shares St. Jude Children's Research Hospital, Late effects and survivorship toxicity, Children's Oncology Group (COG), Survivorship and late effects are neglected and the tags nci-coverage, paediatric, cns.
- TrialCOG ACNS0331
Shares Late effects and survivorship toxicity, Vincristine, Cyclophosphamide, Cisplatin and the tags nci-coverage, paediatric, cns.
- TrialTADPOLE (CDRB436G2201)
Shares Vincristine, Carboplatin and the tags nci-coverage, paediatric, cns.
- TrialACTION
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- TrialFIREFLY-1
Shares the tags nci-coverage, paediatric, cns.