The Evolving Role of Radiotherapy for Pediatric Cancers With Advancements in Molecular Tumor Characterization and Targeted Therapies

Abstract

Ongoing rapid advances in molecular diagnostics, precision imaging, and development of targeted therapies have resulted in a constantly evolving landscape for treatment of pediatric cancers. Radiotherapy remains a critical element of the therapeutic toolbox, and its role in the era of precision medicine continues to adapt and undergo re-evaluation. Here, we review emerging strategies for combining radiotherapy with novel targeted systemic therapies (for example, for pediatric gliomas or soft tissue sarcomas), modifying use or intensity of radiotherapy when appropriate via molecular diagnostics that allow better characterization and individualization of each patient's treatments (for example, de-intensification of radiotherapy in WNT subgroup medulloblastoma), as well as exploring more effective targeted systemic therapies that may allow omission or delay of radiotherapy. Many of these strategies are still under investigation but highlight the importance of continued pre-clinical and clinical studies evaluating the role of radiotherapy in this era of precision oncology.

Keywords: medulloblastoma; molecular diagnostics; pediatric cancer; pediatric glioma; pediatric sarcomas; precision medicine & genomics; radiation therapy (radiotherapy); targeted therapies.

Figure 1

Schematic of MAPK signaling pathway and potential targets and therapeutics for pediatric LGG. FGFR, fibroblast growth factor receptor; LGG, low-grade glioma; MAPK, mitogen-activated protein kinase; RTK, receptor tyrosine kinase; TRK, tropomyosin receptor kinase.

Figure 2

Distribution of pediatric LGG histologies and genetic alterations by location in the brain. Reproduced with permission from Filbin and Sturm (12). DA, diffuse astrocytoma; DNT, dysembryoplastic neuroepithelial tumors; GG, ganglioglioma; LGG, low-grade glioma; PA, pilocytic astrocytoma; PXA, pleomorphic xanthoastrocytomas; SEGA, subependymal giant cell astrocytoma.

Figure 3

Current treatment paradigms for medulloblastoma, as well as approaches under investigation in clinical trials incorporating molecular risk stratification. Investigational approaches are indicated in red. CSI, craniospinal irradiation; GTR, gross total resection; NTR, near total resection; SHH, sonic hedgehog; STR, subtotal resection.