Dataset Information

An analysis of the diagnosis, clinical characteristics, treatment, and survival outcomes of 36 extracranial malignant rhabdoid tumor patients.

ABSTRACT:

Background

Extracranial malignant Rhabdoid tumors (eMRTs) are rare but aggressive lesions in young children. This work aimed to review and analyze the diagnosis, clinical characteristics, treatment, and survival of eMRTs so as to summarize experience for future therapy.

Methods

A total of 36 eMRT cases were treated between January 2008 and August 2019 according to Shanghai Children's Medical Center (SCMC) multimodal protocol of mixed surgery, radiation and chemotherapy involving vincristine, carboplatin, doxorubicin, etoposide, cyclophosphamide and ifosfamide. We collected information including: age at diagnosis, tumor location, disease stage, therapy, outcomes, etc. Overall survival (OS) and event free survival (EFS) were calculated and risk factors for survival were analyzed.

Results

The patients had a median age of 1.80 years at diagnosis (range, 1.4 m-13.42 years), and were followed up for 9.17 months in median (range, 4 d-11.14 y). A total of 16 patients achieved complete remission (CR), and 7 survived without reoccurrence till December 2019. The 3-year EFS was 17.4% (95% CI: 11.0-23.8%) with a 3-year OS of 23.4% (95% CI: 15.8-31.0%). Recurrence was found only in children younger than the median age (1.80 y). Localized staging (Log Rank P=0.039 for OS and P=0.021) and older age (Log Rank P=0.016 for OS and P=0.002 for EFS) were associated with improved outcome. Younger age (Cox regression, OS, OR =2.610, 95% CI: 1.147-5.937, P=0.022; EFS, OR =3.401, 95% CI: 1.495-7.752, P=0.004) were independent risk factors for death and recurrence.

Conclusions

Those eMRTs treated according to SCMC protocol turned out to have poor outcomes. Higher staging at diagnosis and reoccurrence in younger patients remain major threats to the prognosis.

SUBMITTER: Shan Y

PROVIDER: S-EPMC8261579 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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An analysis of the diagnosis, clinical characteristics, treatment, and survival outcomes of 36 extracranial malignant rhabdoid tumor patients.

Shan Yuhua Y Cai Jiaoyang J Han Yali Y Xie Chenjie C Gao Honxiang H Zhang Lei L Li Jingjing J Tian Ruicheng R Liang Yu Y Wang Jing J Chen Changcheng C Ji Bin B Tang Jingyan J Xu Min M Gu Song S

Translational pediatrics 20210601 6

<h4>Background</h4>Extracranial malignant Rhabdoid tumors (eMRTs) are rare but aggressive lesions in young children. This work aimed to review and analyze the diagnosis, clinical characteristics, treatment, and survival of eMRTs so as to summarize experience for future therapy.<h4>Methods</h4>A total of 36 eMRT cases were treated between January 2008 and August 2019 according to Shanghai Children's Medical Center (SCMC) multimodal protocol of mixed surgery, radiation and chemotherapy involving v ...[more]

PMID: 34295774

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Project description:Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005-2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option.

Project description:Abstract BACKGROUND Prognosis of patients with recurrent medulloblastoma and atypical teratoid rhabdoid tumor (ATRT) is dismal despite intensive therapy including high-dose chemotherapy with stem cell rescue. An evolving alternative approach to conventional chemotherapy is to target neovascularisation by interfering with tumor angiogenesis at various levels. We report on 32 patients with recurrent medulloblastoma and ATRT treated with an antiangiogenic combination therapy. PATIENTS AND METHODS From 11/2006 to 02/2018, 32 patients were diagnosed with recurrent embryonal tumors, 20 with a recurrent medulloblastoma (14 first, 6 multiple recurrences) and 12 with recurrent ATRT (6 first, 6 multiple), three had germ line mutations. Treatment consisted of an antiangiogenic multidrug-regime including IV bevacizumab, oral thalidomide, celecoxib, fenofibrate, and etoposide alternating with cyclophosphamide, and augmented with intraventricular therapy (etoposide and aqueous or liposomal cytarabine). Median age at start of antiangiogenic therapy was 10 (1–24) years for medulloblastoma and 3 (1–12) years for ATRT. RESULTS As of 05/2018, 10/20 patients with medulloblastoma are alive, eight in CR, six off therapy for 96, 79, 77, 34, 12, and 4 months. 5-year-OS is 54.5 ± 11.2% and 5-year-EFS is 25.0 ± 9.7%. One patient died of an accident in CR 23 months after initiation of antiangiogenic therapy. 6/12 patients with ATRT are alive and in CR for 123, 90, 45, 9, 6 and 3 months after start of antiangiogenic therapy, the first three off therapy. OS for the whole cohort was 47.7 ± 16.6% at 3 years and 31.8 ± 17.1% at 5-years with a median OS of 22.8 months (KI 0.0–66.8). Therapy was generally well tolerated and toxicities were manageable. CONCLUSION The proposed antiangiogenic regimen is currently being evaluated for medulloblastomas in an international phase II protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290). The same approach seems to be also efficacious in recurrent ATRTs and warrants further evaluation.

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Dataset Information

An analysis of the diagnosis, clinical characteristics, treatment, and survival outcomes of 36 extracranial malignant rhabdoid tumor patients.

Background

Methods

Results

Conclusions

Publications

An analysis of the diagnosis, clinical characteristics, treatment, and survival outcomes of 36 extracranial malignant rhabdoid tumor patients.

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