Modern Radiotherapy for Pediatric Brain Tumors

Abstract

Cancer is a leading cause of death in children with tumors of the central nervous system, the most commonly encountered solid malignancies in this population. Radiotherapy (RT) is an integral part of managing brain tumors, with excellent long-term survival overall. The tumor histology will dictate the volume of tissue requiring treatment and the dose. However, radiation in developing children can yield functional deficits and/or cosmetic defects and carries a risk of second tumors. In particular, children receiving RT are at risk for neurocognitive effects, neuroendocrine dysfunction, hearing loss, vascular anomalies and events, and psychosocial dysfunction. The risk of these late effects is directly correlated with the volume of tissue irradiated and dose delivered and is inversely correlated with age. To limit the risk of developing these late effects, improved conformity of radiation to the target volume has come from adopting a volumetric planning process. Radiation beam characteristics have also evolved to achieve this end, as exemplified through development of intensity modulated photons and the use of protons. Understanding dose limits of critical at-risk structures for different RT modalities is evolving. In this review, we discuss the physical basis of the most common RT modalities used to treat pediatric brain tumors (intensity modulated radiation therapy and proton therapy), the RT planning process, survival outcomes for several common pediatric malignant brain tumor histologies, RT-associated toxicities, and steps taken to mitigate the risk of acute and late effects from treatment.

Keywords: IMRT; childhood; late effects; pediatric brain tumors; proton; radiation; radiotherapy; survival; toxicity; treatment planning.

Figure 1

Single beam dose profiles for photons and protons. D_max, the peak of the 6 MV photon curve (black), occurs at a depth of about 1.5 cm for a 10 × 10 cm field. The characteristic Bragg peak of a monoenergetic proton beam (red) is centered at a depth of 14.5 cm. The distal edge, to the right of the vertical dashed line, is an area of great interest when limiting dose to normal tissues immediately beyond the tumor. The spread-out Bragg peak (SOBP; blue) represents a summation of Bragg peaks from multiple protons with varied energies. This allows tumors (green) to be covered adequately by depositing therapeutic doses of radiation over a longer path.

Figure 2

Comparison of dose distributions for a patient undergoing craniospinal irradiation to a dose of 36 Gy by three-dimensional conformal radiation therapy (3DCRT) (a), intensity modulated radiation therapy (IMRT) (b), or proton beam radiation therapy (PBRT) (c). Each pane shows the dose distribution in sagittal (top) and transverse (bottom) views. The target volume is indicated by the thick red line that encompasses the brain and spinal canal down to the thecal sac. Prescription dose (shaded yellow) and target coverage are similar across modalities, but higher entrance (posterior) dose is seen in the 3DCRT plan in comparison with IMRT or PBRT. The abdomen receives more low-dose radiation (shaded green, blue, and purple) using photon modalities compared with PBRT.

Figure 3

Immobilization device for RT. To create an immobilization device for each patient undergoing RT to treat a brain tumor, a hard sheet of plastic mesh (a) is warmed in a water bath before stretching it to conform to the contours of the head. The mesh then cools and hardens, forming a customized mask (b) that can be fixed to the table on which the patient lies during daily radiation treatments.

Figure 4

Dose distribution for treatment of standard-risk medulloblastoma shown in axial (a) and sagittal (b) views. A dose of 23.4 Gy (shaded purple) was delivered to the entire craniospinal axis, followed by 30.6 Gy to the tumor bed only (darkest blue line) for a total dose of 54 Gy (shaded yellow) to the tumor bed. Delivery of the prescription dose to the entire tumor bed is limited owing to proximity of the brainstem (white line), such that the entire target receives nearly the full 54 Gy. Note that multiple posterior beams from varied angles are used (a) to distribute dose deposited at the end of range near the brainstem.