Medulloblastoma Molecular Subgrouping and Outcomes Data of a Single Center From a Low- and Middle-Income Country

IF 2.4 3区医学 Q2 HEMATOLOGY Pediatric Blood & Cancer Pub Date : 2025-01-21 DOI:10.1002/pbc.31555

Naureen Mushtaq, Farrah Bashir, Soha Zahid, Quratulain Riaz, Gohar Javed, Maria Tariq, Bilal Mazhar Qureshi, Kiran Hilal, Vijay Ramaswamy, Cynthia Hawkins, Khurram Minhas, Eric Bouffet

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Abstract

Introduction

Medulloblastoma (MB) is the most common malignant childhood brain tumor. Molecular subgrouping of MB has become a major determinant of management in high-income countries. Subgrouping is still very limited in low- and middle-income countries (LMICs), and its relevance to management with the incorporation of risk stratification (low risk, standard risk, high risk, and very high risk) has yet to be evaluated in this setting. We describe molecular findings from a tertiary care center in Pakistan and their implications for outcome.

Methods

Children aged between 3 and 18 years diagnosed with MB from April 2014 to December 2020 at Aga Khan University Hospital (AKUH) were included. Subgrouping was performed by NanoString through a collaboration with The Hospital for Sick Children, Toronto.

Results

Thirty-seven patients (30 males) were included in this study; median age was 9 years. Twenty patients (54.1%) were high-risk, including 12 with metastatic disease. In 30 children, there was a clear molecular subgroup: 4 wingless (WNT) (10.8%), 6 sonic hedgehog (SHH) (16.2%), 3 Group 3 (8.1%), and 17 Group 4 (45.9%) MBs. Molecular subgrouping was inconclusive for three patients (8.1%) and not done in four patients (10.8%). All patients underwent surgery; 26 patients received radiation therapy at AKUH, and 9 were referred outside for radiotherapy; 24 patients received chemotherapy at AKUH (10 outside AKUH). Overall survival (OS) at 5 years was 100%, 66.7%, 66.7%, and 88.2% for WNT, SHH, Group 3, and Group 4 patients, respectively (p = 0.668). Low- and standard-risk patients had a 5-year OS of 100%, whereas very high-risk patients exhibited a significantly lower OS of 0% (p < 0.001).

Conclusion

WNT and Group 4 patients had excellent results despite one WNT patient having metastatic disease and eight Group 4 patients being high risk. Our study depicts that molecular subgrouping aids in accurately predicting survival, suggesting the potential benefit of tailored testing and treatment in the LMIC setting.

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来自中低收入国家单一中心的成神经管细胞瘤分子亚群和结局数据

髓母细胞瘤（Medulloblastoma， MB）是儿童最常见的恶性脑肿瘤。MB的分子亚群已成为高收入国家管理的主要决定因素。在低收入和中等收入国家（LMICs），亚分组仍然非常有限，在这种情况下，还需要评估其与纳入风险分层（低风险、标准风险、高风险和极高风险）的管理的相关性。我们描述了巴基斯坦三级护理中心的分子发现及其对结果的影响。方法：纳入2014年4月至2020年12月在阿迦汗大学医院（AKUH）诊断为MB的3 - 18岁儿童。NanoString通过与多伦多病童医院的合作进行了分组。结果：本研究纳入37例患者，其中男性30例；中位年龄为9岁。高危患者20例（54.1%），其中12例有转移性疾病。在30例患儿中，存在明确的分子亚群：无翅（WNT） 4例（10.8%），音猬（SHH） 6例（16.2%），3组（8.1%）3例，4组（45.9%）17例。3例（8.1%）患者分子亚组不确定，4例（10.8%）患者未进行分子亚组。所有患者均接受手术治疗；26例患者在AKUH接受放射治疗，9例患者转诊外接受放射治疗；24例患者在AKUH接受化疗（10例在AKUH外）。WNT、SHH、3组和4组患者的5年总生存率（OS）分别为100%、66.7%、66.7%和88.2% （p = 0.668）。低风险和标准风险患者的5年OS为100%，而高危患者的5年OS明显较低，为0% (p)。结论：尽管1例WNT患者有转移性疾病，8例4组患者有高风险，但WNT和4组患者的结果很好。我们的研究表明，分子亚分组有助于准确预测生存，这表明在LMIC环境中定制检测和治疗的潜在益处。

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来源期刊

Pediatric Blood & Cancer 医学-小儿科

CiteScore

4.90

自引率

9.40%

发文量

546

审稿时长

1.5 months

期刊介绍： Pediatric Blood & Cancer publishes the highest quality manuscripts describing basic and clinical investigations of blood disorders and malignant diseases of childhood including diagnosis, treatment, epidemiology, etiology, biology, and molecular and clinical genetics of these diseases as they affect children, adolescents, and young adults. Pediatric Blood & Cancer will also include studies on such treatment options as hematopoietic stem cell transplantation, immunology, and gene therapy.