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Pakistan National Guidelines for Pediatric High-Grade Gliomas
Farrah Bashir1, Bilal Mazhar Qureshi2, Khurram Minhas3
1Dr. Farrah Bashir, FCPS Aga Khan University Hospital, Karachi, Pakistan.
Insights
Pediatric high-grade glioma (pHGG) is a rare, aggressive brain tumor. Early diagnosis and multidisciplinary care are crucial, especially for rare genetic forms like Constitutional Mismatch Repair Deficiency (CMMRD) associated HGG.
Area of Science:
- Pediatric Neuro-oncology
- Cancer Genetics
- Central Nervous System Tumors
Background:
- Pediatric high-grade glioma (pHGG) is a highly malignant brain tumor comprising 10% of pediatric gliomas.
- Despite multimodal treatment, pHGG frequently recurs, leading to poor outcomes.
- A subset of pHGG is linked to cancer predisposition syndromes, notably Constitutional Mismatch Repair Deficiency (CMMRD), also known as Biallelic Mismatch Repair Deficiency (bMMRD).
Purpose of the Study:
- To highlight the critical role of multidisciplinary teams in managing pediatric high-grade glioma.
- To emphasize the unique challenges and considerations in treating pHGG associated with CMMRD.
- To underscore the importance of specialized care in resource-limited settings.
Main Methods:
- Review of current treatment paradigms for pediatric high-grade glioma.
- Discussion of the genetic basis and clinical implications of CMMRD in pHGG.
- Consideration of treatment modifications, such as avoiding temozolomide in CMMRD-pHGG.
Main Results:
- Effective pHGG management requires a coordinated multidisciplinary team.
- CMMRD-associated pHGG presents with high mutational burden and distinct treatment considerations.
- TMZ use is cautioned in CMMRD-pHGG due to limited efficacy and potential for secondary malignancies.
Conclusions:
- Optimal management of pediatric high-grade glioma necessitates a comprehensive multidisciplinary approach.
- Understanding genetic predispositions like CMMRD is vital for tailored treatment strategies.
- Addressing resource limitations in low-middle-income countries is essential for improving pHGG patient outcomes.
Abstract:
Pediatric high-grade glioma (pHGG) is highly malignant central nervous system tumor and constitute 10% of the pediatric gliomas. Effective treatment needs a functioning multi-disciplinary team including pediatric neuro oncologist, neurosurgeon, neuroradiologist, neuropathologist and radiation oncologist. Despite surgical resection, radiotherapy and chemotherapy, most HGG will recur resulting in early death. A significant proportion of HGG occurs in context of cancer predisposition syndromes like Constitutional Mismatch Repair Deficiency (CMMRD) also known as Biallelic Mismatch Repair Deficiency (bMMRD) characterized by high mutational burden. The incidence of HGG with CMMRD is one per million patients. bMMRD is caused by homozygous germline mutations in one of the four Mis Match Repair (MMR) genes (PMS2, MLH1, MSH2, and MSH6). The use of TMZ is now avoided in CMMRD related HGG due to its limited response and known ability to increase the accumulation of somatic mutations in these patients, increasing the risk of secondary tumors. HGG should be managed under the care of multidisciplinary team to receive optimum treatment. This is particularly important for low middle-income countries (LMIC) with limited resources like Pakistan.
