Next-Generation Sequencing (NGS) in Paediatric Oncology: Transforming Diagnosis and Treatment

The integration of Next-Generation Sequencing (NGS) in paediatric oncology has marked a significant leap forward in diagnosing and treating childhood cancers. This technology allows for a deeper understanding of the genetic mutations driving cancer in children, which is crucial given the genetic complexity and heterogeneity of paediatric tumors.

With NGS, paediatric oncologists can now provide more precise, targeted treatments, tailored to the unique genetic profile of each patient's cancer.

The Role of NGS in Paediatric Oncology

In the past, cancer diagnosis and treatment in children relied heavily on traditional methods, such as biopsies and standard chemotherapy regimens. However, paediatric cancers differ significantly from adult cancers in their genetic makeup, and conventional approaches often fell short in effectively targeting these tumors. NGS has changed the landscape by offering comprehensive genomic profiling, which identifies specific genetic alterations, or "actionable targets," that can be treated with precision medicine.

In paediatric cancers like sarcomas and neuroblastomas, NGS has proven invaluable. Studies have shown that 85% of paediatric tumors have at least one actionable mutation, allowing oncologists to implement more effective treatments, such as targeted therapies that inhibit specific cancer-causing pathways. For example, NGS has helped reclassify certain tumors based on genetic mutations, leading to better treatment decisions and improved outcomes.

NGS in Diagnosis and Personalized Treatment

NGS not only enhances diagnostic accuracy but also helps predict how aggressive a tumor might be and what treatments are likely to be effective. In paediatric central nervous system (CNS) tumors, NGS has played a crucial role in refining classifications, improving prognostic predictions, and identifying targetable mutations that may not have been detected through traditional histological methods.

Moreover, NGS allows for the identification of somatic (tumor-specific) mutations and germline (heritable) mutations, enabling oncologists to determine whether the cancer is linked to a genetic predisposition. This has opened new doors for genetic counseling and early cancer screening, not just for the patient but for family members who might be at risk of developing similar conditions.

Impact on Treatment Decisions and Clinical Outcomes

One of the most significant contributions of NGS in paediatric oncology is its ability to inform treatment decisions. In a recent study, 43% of paediatric cancer patients whose tumors were sequenced using NGS had genetic alterations that could be matched with targeted therapies. This shift towards personalized medicine has led to improved disease control and survival rates, particularly in high-risk or relapsed paediatric cancers.

For example, in cases where conventional chemotherapy failed to control tumor growth, targeted therapies based on NGS findings have shown to extend progression-free survival and overall survival in paediatric patients with certain mutations. This is a game-changer for children with aggressive cancers, offering them a better chance at long-term survival and reduced treatment toxicity compared to traditional therapies.

Challenges and Future Directions

While the benefits of NGS are clear, there are still challenges to be addressed.

• The cost of NGS testing, particularly in low- and middle-income countries, can be prohibitive, and the infrastructure for conducting these tests and interpreting the results is not universally available.
• While NGS has identified numerous actionable mutations, not all paediatric cancer patients have access to the targeted therapies required to treat these mutations.

Efforts are being made to overcome these challenges through global collaborations and clinical trials, which aim to make NGS more accessible and expand the range of available targeted therapies. As more paediatric oncology centers adopt NGS, we can expect to see continued improvements in cancer outcomes for children worldwide.

In the future, continued advancements in NGS and precision medicine will further enhance our ability to fight paediatric cancer, bringing us closer to a world where every child has access to life-saving, personalized treatment options.