Atypical Teratoid/Rhabdoid Tumors (ATRT): Improved Survival in Children 3 Years of Age and Older With Radiation Therapy and High-Dose Alkylator-Based Chemotherapy

PurposeTo describe clinical features, therapeutic approaches, and prognostic factors in pediatric patients with atypical teratoid/rhabdoid tumors (ATRT) treated at St Jude Children's Research Hospital (SJCRH).Patients and MethodsPrimary tumor samples from patients diagnosed with ATRT at SJCRH between July 1984 and June 2003 were identified. Pathology review included histologic, immunohistochemical analysis, and fluorescence in situ hybridization for SMARCB1 (also known as hSNF5/INI1) deletion. Clinical records of patients with pathologic confirmation of ATRT were reviewed.ResultsThirty-seven patients were diagnosed with ATRT at SJCRH during the 19-year study interval. Six patients were excluded from this clinical review based on pathologic or clinical criteria. Of the remaining 31 patients, 22 were younger than 3 years. Posterior fossa primary lesions and metastatic disease at diagnosis were more common in younger patients with ATRT. All patients underwent surgical resection; 30 received subsequent chemotherapy. The majority of patients aged 3 years or older received postoperative craniospinal radiation. Two-year event-free (EFS) and overall survival (OS) of children aged 3 years or older (EFS, 78% + 14%; OS, 89% ± 11%) were significantly better than those for younger patients (EFS, 11% ± 6%; OS, 17% ± 8%); EFS, P = .009 and OS, P = .0001. No other clinical characteristics were predictive of survival. Three of four patients 3 years or older with progressive disease were successfully rescued with ifosfamide, carboplatin, and etoposide therapy.ConclusionChildren presenting with ATRT before the age of 3 years have a dismal prognosis. ATRT presenting in older patients can be cured using a combination of radiation and high-dose alkylating therapy. Older patients with relapsed ATRT can have salvage treatment using ICE chemotherapy.

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Clinical characteristics, treatment, and survival outcome in pediatric patients with atypical teratoid/rhabdoid tumors: a retrospective study by the Japan Children’s Cancer Group

Journal of Neurosurgery Pediatrics ◽

10.3171/2019.9.peds19367 ◽

2020 ◽

Vol 25 (2) ◽

pp. 111-120 ◽

Cited By ~ 2

Author(s):

Kai Yamasaki ◽

Chikako Kiyotani ◽

Keita Terashima ◽

Yuko Watanabe ◽

Masayuki Kanamori ◽

...

Keyword(s):

Multimodal Therapy ◽

Pediatric Patients ◽

Positive Impact ◽

Conditioning Regimen ◽

High Dose ◽

Primary Therapy ◽

Female Ratio ◽

Atypical Teratoid ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

OBJECTIVEThe prognosis of atypical teratoid/rhabdoid tumors (ATRTs) has improved in recent years with the use of multimodal therapy, mainly in cases not involving metastatic disease. The authors wanted to obtain historical control data and evaluate the suitable treatments in Japanese children with ATRTs that were proven negative for INI-1 immunostaining.METHODSThe authors retrospectively collected clinical information on 38 pediatric patients with ATRTs treated from 2005 to 2016 and analyzed the data for this series.RESULTSThe median age of the patient population was 1.3 years, and the male/female ratio was approximately 2:1. Twenty-three patients (60.5%) had metastases. The effects of treatment on prognosis were analyzed for 34 patients after exclusion of 4 patients who could not receive curative treatment. At a median follow-up of 40.9 months, the mean (± SD) progression-free survival (PFS) and overall survival (OS) were 66.6% ± 8.3% and 45.9% ± 8.7% at 2 years and 44.2% ± 9.9% and 34.2% ± 8.9% at 5 years, respectively. The metastasis stage at diagnosis (M0–1 vs M2–4) (HR 2.68, 95% CI 1.08–6.65; p = 0.0338) and gross tumor resection (yes vs no) (HR 3.49, 95% CI 1.01–12.1; p = 0.0481) were prognostic factors for PFS but not for OS. Postoperative chemotherapy was performed in all 34 cases. High-dose chemotherapy was performed in 19 (55.8%) of 34 patients and showed a positive impact on OS (HR 0.31, 95% CI 0.11–0.86; p = 0.0254); the most commonly used regimen was a double-conditioning regimen of thiotepa plus melphalan. Local radiotherapy had a positive impact on both PFS and OS; however, craniospinal irradiation (CSI) performed in 12 patients as the primary therapy was associated with a poor outcome. Disseminated recurrence within 12 months from diagnosis was the most common pattern of treatment failure regardless of CSI.CONCLUSIONSThere has been an improvement in outcomes for pediatric ATRT patients since the introduction of multimodal therapy in Japan, mainly in patients without metastases. Even if selection bias is taken into consideration, CSI did not contribute to an improved prognosis. Novel treatment approaches are required for pediatric ATRT patients with metastases.

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Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors

Neuro-Oncology ◽

10.1093/neuonc/noz244 ◽

2019 ◽

Vol 22 (7) ◽

pp. 1006-1017 ◽

Cited By ~ 10

Author(s):

Michael C Frühwald ◽

Martin Hasselblatt ◽

Karolina Nemes ◽

Susanne Bens ◽

Mona Steinbügl ◽

...

Keyword(s):

Risk Factors ◽

Dna Methylation ◽

Germline Mutations ◽

High Dose ◽

Single Nucleotide Variants ◽

Molecular Subgroup ◽

Atypical Teratoid ◽

Independent Risk Factors ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

Abstract Background Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. Methods Clinical, genetic, and treatment data of 143 patients from 13 European countries were analyzed (2009–2017). Therapy consisted of surgery, anthracycline-based induction, and either radiotherapy or high dose chemotherapy following a consensus among European experts. Fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and sequencing were employed for assessment of somatic and germline mutations in SWItch/sucrose nonfermentable related, matrix associated, actin dependent regulator of chromatin, subfamily B (SMARCB1). Molecular subgroups (ATRT-SHH, ATRT-TYR, and ATRT-MYC) were determined using DNA methylation arrays, resulting in profiles of 84 tumors. Results Median age at diagnosis of 67 girls and 76 boys was 29.5 months. Five-year overall survival (OS) and event-free survival (EFS) were 34.7 ± 4.5% and 30.5 ± 4.2%, respectively. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRTs (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC (17/84). Age <1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission, and omission of radiotherapy were negative prognostic factors in univariate analyses (P < 0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 y + non-TYR; 5-y OS = 0%), intermediate risk (<1 y + ATRT-TYR or ≥1 y + non-TYR; 5-y OS = 32.5 ± 8.7%), and standard risk (≥1 y + ATRT-TYR, 5-y OS = 71.5 ± 12.2%). Conclusions Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials.

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