Background: 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. Methods: 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. Results: 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 andp= 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 andp< 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. Conclusions: 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.
背景：非典型畸胎样横纹肌样瘤（ATRT）是一种高度侵袭性、罕见的儿童中枢神经系统恶性肿瘤。目前缺乏针对大型统一治疗队列中优化风险分层和管理的预后因素研究。方法：我们开展了一项单中心回顾性队列研究，分析了2008年至2022年间在埃及儿童癌症医院接受治疗的100例新诊断ATRT患儿（年龄<18岁）的临床及预后数据。所有患者均按照丹娜-法伯癌症研究所改良IRS-III方案接受统一治疗。对具备足够DNA样本的患者通过DNA甲基化阵列确定分子亚型（MYC、SHH和TYR）。治疗相关毒性根据不良事件通用术语标准（CTCAE）v5.0进行分级。结果：诊断时中位年龄为1.88岁（四分位距0.99-3.01），其中28%患儿年龄<1岁，45%为1-3岁，26%>3岁。诊断时39%患者存在转移性疾病。60%患者在手术切除后存在肉眼可见残留病灶。多变量分析显示，年龄<1岁和转移性疾病对无事件生存期（EFS）有显著影响（p值分别为0.047和0.002）；但仅转移性疾病对总生存期（OS）和累积复发率（CIR）有显著负面影响（OS的p=0.002，CIR的p<0.001）。对69例患者进行DNA甲基化分析，鉴定出TYR亚型13例、SHH亚型34例、MYC亚型17例，另有5例被重新诊断为非ATRT肿瘤。在经甲基化确认的64例ATRT患者队列中，各亚型间未观察到显著生存差异。研究队列中28%患者发生治疗相关死亡，革兰氏阴性菌败血症是最常见的毒性致死原因。全队列5年EFS和OS分别为12%和13%。结论：本队列研究中未发现甲基化亚型间存在显著生存差异。与原始方案相比，本队列较高的治疗相关死亡率提示，针对本地区人群可能需要调整强化及长疗程化疗方案。对于社会经济地位较低的患者群体，采用短期强化治疗方案（包括有限周期的诱导化疗后接强化大剂量巩固治疗）可能更为适宜，以避免反复长期的中性粒细胞减少症。
肿瘤(癌症)患者之家