Mushtaq Naureen, Bashir Farrah, Zahid Soha, Riaz Quratulain, Javed Gohar, Tariq Maria, Qureshi Bilal Mazhar, Hilal Kiran, Ramaswamy Vijay, Hawkins Cynthia, Minhas Khurram, Bouffet Eric
Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan.
Department of Pediatric Oncology, Indus Hospital, Karachi, Pakistan.
Pediatr Blood Cancer. 2025 Apr;72(4):e31555. doi: 10.1002/pbc.31555. Epub 2025 Jan 21.
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.
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.
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).
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.
髓母细胞瘤（MB）是儿童最常见的恶性脑肿瘤。在高收入国家，MB的分子亚组分类已成为治疗决策的主要决定因素。在低收入和中等收入国家（LMICs），亚组分类仍然非常有限，并且在这种情况下，其与纳入风险分层（低风险、标准风险、高风险和极高风险）的治疗的相关性尚未得到评估。我们描述了巴基斯坦一家三级医疗中心的分子研究结果及其对预后的影响。
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至18岁儿童。通过与多伦多病童医院合作，利用NanoString进行亚组分类。
本研究纳入了37例患者（30例男性）；中位年龄为9岁。20例患者（54.1%）为高风险，其中12例有转移性疾病。30例儿童有明确的分子亚组：4例翼状胬肉（WNT）（10.8%），6例音猬因子（SHH）（16.2%），3例3组（8.1%），17例4组（45.9%）MB。3例患者（8.1%）分子亚组分类不确定，4例患者（10.8%）未进行亚组分类。所有患者均接受了手术；26例患者在AKUH接受了放射治疗，9例被转诊至外部接受放疗；24例患者在AKUH接受了化疗（10例在AKUH以外）。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%，而极高风险患者的OS显著较低，为0%（p < 0.001）。
尽管1例WNT患者有转移性疾病，8例4组患者为高风险，但WNT和4组患者的预后良好。我们的研究表明，分子亚组分类有助于准确预测生存率，提示在LMIC环境中进行针对性检测和治疗的潜在益处。
