Clinical and Molecular Characteristics of 100 Atypical Teratoid Rhabdoid Tumor Patients from Low- and Middle-Income...

Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive, rare pediatric central nervous system malignancy. Prognostic factors for optimizing risk stratification and management in a large uniformly treated cohort are lacking.

We conducted a single-center retrospective cohort study analyzing clinical and outcome data for 100 newly diagnosed ATRT patients aged <18 years treated at the Children's Cancer Hospital, Egypt, from 2008 to 2022. They were treated uniformly as per the Dana-Farber Cancer Institute modified IRS-III protocol. Molecular subgroups (MYC, SHH, and TYR) were determined via a DNA methylation array for patients who had sufficient DNA material available for the methylation analysis. Treatment toxicities were graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

The median age at diagnosis was 1.88 years (IQR 0.99, 3.01); 28% were under 1 year of age, 45% were between 1 and 3 years old, and 26% were above 3 years of age. At diagnosis, 39% of patients had metastatic disease. A total of 60% of patients had gross residual disease following surgical excision. In multivariable analysis, age < 1 year and metastatic disease had a significant impact on event-free survival (EFS) (p = 0.047 and p = 0.002, respectively); however, only metastatic disease had a significantly negative effect on overall survival (OS) and cumulative incidence of relapse (CIR) (p = 0.002 for OS and p < 0.001 for CIR). DNA methylation was performed for 69 patients who were classified as having a TYR (n = 13), SHH (n = 34), MYC (n = 17), or non-ATRT diagnosis (n = 5). In the cohort of the 64 patients with ATRT defined by methylation, no significant survival differences were observed. Treatment-related deaths were reported in 28% of our studied group. Gram-negative septicemia was the most common cause of toxic death. The 5-year EFS and OS of the whole cohort were 12% and 13%, respectively.

In this cohort, no significant survival differences were observed among the methylation subgroups. The higher treatment-related mortality in our cohort compared to the original protocol's toxic-related deaths suggested that intensive and lengthy chemotherapy regimens may need modification for our population. The need for a short intensified approach, including a limited induction cycle followed by an intensified high-dose consolidation therapy, may be more appropriate for our patients with low socioeconomic status to avoid a repeated and prolonged course of protracted neutropenia.