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.

Oral Manifestations: A Warning-Sign in Children with Hematological Disease Acute Lymphocytic Leukemia

“…Target systemic therapies are now combined with low-intensity radiotherapy only in specific patients. In addition, the radiotherapy technique is becoming more precise due to image guidance allowing a reduction in toxicity, while still controlling the disease [ 22 , 23 ]. In recent years, immunotherapy has evolved and the OS of these children has increased, although there are still several side effects of the disease/treatments [ 17 ].…”

Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma

“…Simply escalating the radiation dose has not been beneficial, likely because of increased toxicity to critical normal neural structures in the brainstem and thalamus [10] , and while re-irradiation at first progression may have some initial effect on tumor growth, eventually these tumors recur as well [11] . It has therefore been of particular interest to develop radiosensitizing strategies in DIPG that maximize the therapeutic ratio by targeting tumor-specific vulnerabilities to achieve selective, synergistic tumor cell killing at lower radiation doses, thereby sparing nearby normal, healthy tissues from radiotherapy-related side effects [ 12 , 13 ].…”

Dosiomics-Based Prediction of Radiation-Induced Valvulopathy after Childhood Cancer

“…Childhood cancer (CC) survival rates have risen over the past decades in high-income countries, owing to advances in oncology treatment [1][2][3]. Radiotherapy, in particular, radically improves cancer survival in many cases [4], and modern optimizations [5][6][7][8] have had a substantial impact in reducing toxicity and side risks. Meanwhile, during treatment with radiotherapy, healthy tissues cannot be avoided entirely; this can potentially lead childhood cancer survivors to suffer chronic damage; especially at risk are those who did not benefit from modern protocols.…”