With advances in highly conformal external-beam radiotherapy (EBRT) and steep radiation dose gradients, radiosensitive tissues can be better spared exposure to ionizing radiation and resulting toxicities. New practice recommendations by a working group of pediatric radiation oncologists from across Europe emphasize the importance of radiation dose distributions involving spinal vertebrae as a risk factor for spinal development problems and identify ways to minimize risk. But more research is urgently needed and the authors called for multicenter clinical studies to better identify optimal vertebral radiotherapy dose distributions in children treated for cancer.
Inhomogeneous radiation dose distributions across children’s developing vertebrae during cancer treatment can alter local gene expression, metabolism, endocrine signaling, and ultimately, normal spinal development, leading to spinal cord hypoplasia or growth restriction and problems such as scoliosis, kyphosis (the pronounced outward spinal curvature that causes back hunching) and lordosis (inward spinal curvature).1 The spine of newborns is only approximately 30% ossified. Vertebral ossification begins in the vertebral body and the dorsal halves of the vertebral arch, and as ossification progresses throughout early childhood, it displaces cartilage outward.1 By age 16 years, secondary ossification of vertebral body rim begins.1
Children with neuroblastomas, medulloblastomas and other brain or spine cancers frequently undergo craniospinal EBRT.1,2 Because children’s bodies are smaller than those of adults, other radiotherapy-target organ volumes also are more frequently in closer proximity to their spines than is the case with adults.1 The incidence of some cancers is greater among young children (younger than 10 years for CNS tumors and younger than 5 years for renal tumors), for whom radiation-associated impairment of spinal development can be more marked.1
As early as 1973, researchers knew that pediatric radiotherapy dose could impact spinal growth, particularly among children receiving more than 35 Gy whole spine radiotherapy.1 In general, the younger the age of a patient at the time of irradiation, the more pronounced the potential long-term spinal development impacts can be. Infants (children younger than 1 year) are most affected. Radiotherapy for Wilms tumors earlier than age 1 is associated with adolescent growth restriction, with attained height decreases of up to 8 cm by age 15 years.1,3
“Radiation of extensive thoracic spinal segments can cause thoracic cage and lung underdevelopment, which considerably increases the risk of future respiratory insufficiency,” the investigators noted.1 Poor bone mass accumulation during development is also a risk factor for early-onset osteoporosis and bone fracture in adulthood.1,4
More recent advances in highly conformal and intensity-modulated EBRT delivery have improved the precision of radiation dose distributions and now better allow for more homogeneous dose delivery to vertebrae. But vertebral dose inhomogeneities do still occur and because of improving 5-year and long-term survival rates among children treated for cancer, the potential long-term quality-of-life impacts of spinal developmental disruptions are receiving more scrutiny.1