Multimodal therapy in children and adolescents with newly diagnosed atypical teratoid rhabdoid tumor: individual pooled data analysis and review of the literature

Abstract

Atypical teratoid rhabdoid tumour (ATRT) is a malignant tumour of the central nervous system with a dismal prognosis. There is no consensus on optimal treatment and different multimodal strategies are currently being used in an attempt to improve outcomes. To evaluate the impact of high-dose chemotherapy followed by autologous stem-cell rescue (HD48 SCR), radiotherapy (RT) at first line, intrathecal chemotherapy (IT) and extent of surgical resection upon recurrence-free survival (RFS) and overall survival (OS). An online database search identified prospective and retrospective studies focused on the treatment of children and adolescents with newly diagnosed ATRT. Clinical, therapeutic and outcome data were extracted and an individual pooled data analysis was conducted. Out of 389 publications, 12 manuscripts were included in our review. Data from 332 patients were analysed. Median age at diagnosis was 37 months (range 1-231). HD-SCR, RT and IT had been administered to 28.6% (58/203), 49.6% (118/238) and 21% (65/310) of the patients, respectively. Gross total resection (GTR) had been achieved in 46.5% (152/327) of the cases. In the multivariate analysis, hazard ratios (95% Confidence Interval) for HD-SCR were: RFS-HR = 0.570 (0.357-0.910) p = 0.019, and OS-HR = 0.388 (0.214-0.704) p = 0.002; and for RT: RFS-HR = 0.551 (0.351-0.866) p = 0.01, and OS-HR = 0.393 (0.216-0.712) p = 0.002. IT and GTR were not significantly associated with improved RFS or OS in the multivariate analysis. In our pooled data review, HD-SCR and RT at first line were associated with improved outcomes in children and adolescents with newly diagnosed ATRT.

Long-term survival following additive radiotherapy in patients with atypical teratoid rhabdoid tumors

“…Based on their outcomes, the authors concluded that early administration of RT prior to tandem highdose CTX (HDCT) with autologous SCT improved patient outcome, even in the patients who were very young [27]. In a more recent study, Schrey et al [28] analyzed the data of 332 patients from various prospective and retrospective series and found that early HDCT followed by SCT and RT may improve the survival of children with newly diagnosed ATRT.…”

Atypical teratoid/rhabdoid tumors in children treated with multimodal therapies: The necessity of upfront radiotherapy after surgery

“…Nevertheless, RT has been deferred or omitted because of the risk of adverse effects, especially for patients under 3 years of age. Less than half of the patients in these studies ultimately received RT as an initial treatment . However, analysis of 144 patients identified in the SEER database who were treated between 1973 and 2008 showed that RT increased survival (the hazard ratio for RT vs. non‐RT as the initial treatment was 0.1 with a 95% confidence interval of 0.01–0.73) .…”

“…Unfortunately, since there are no common therapeutic strategies for these tumors, treatment approaches for ATRT vary among institutions, as well as between countries. Additionally, the preferred treatment modality depends on the extent of tumor progression and the patient's age …”

Acid ceramidase is a novel drug target for pediatric brain tumors

“…In this study, we focus on three malignant brain tumors – atypical rhabdoid/teratoid tumor (ATRT), glioblastoma, and medulloblastoma. In particular, ATRT is associated with a miserable prognosis, with medial survival at 9 to 17 months [2]. No guidelines exist for optimal treatment and different multimodal protocols are presently being studied to improve outcomes [2].…”

“…In particular, ATRT is associated with a miserable prognosis, with medial survival at 9 to 17 months [2]. No guidelines exist for optimal treatment and different multimodal protocols are presently being studied to improve outcomes [2]. For pediatric glioblastoma, most institutions employ surgery and adjuvant radiotherapy, but the role of chemotherapy remains investigational [3, 4].…”