How proton therapy fits into the management of adult intracranial tumors

Abstract

Intracranial tumors include a challenging array of primary and secondary parenchymal and extra-axial tumors which cause neurologic morbidity consequential to location, disease extent, and proximity to critical neurologic structures. Radiotherapy can be used in the definitive, adjuvant, or salvage setting either with curative or palliative intent. Proton therapy (PT) is a promising advance due to dosimetric advantages compared to conventional photon radiotherapy with regards to normal tissue sparing, as well as distinct physical properties, which yield radiobiologic benefits. In this review, the principles of efficacy and safety of PT for a variety of intracranial tumors are discussed, drawing upon case series, retrospective and prospective cohort studies, and randomized clinical trials. This manuscript explores the potential advantages of PT, including reduced acute and late treatment-related side effects and improved quality of life. The objective is to provide a comprehensive review of the current evidence and clinical outcomes of PT. Given the lack of consensus and directives for its utilization in patients with intracranial tumors, we aim to provide a guide for its judicious use in clinical practice.

Keywords: CNS tumors; brain tumors; proton therapy.

Figure 1.

Case example illustrating the dose to bilateral hippocampus for patient with a left temporal glioma. (A) Intensity-modulated proton therapy treatment plan with isodose distribution and bilateral hippocampus delineated (B) demonstrates a substantially lower risk of neurocognitive impairment than a photon therapy plan (non-coplanar volumetric modulated arc therapy [VMAT]) with isodose distribution (C) due to the rapid dose-fall at the (left) ipsilateral hippocampus and lack of exit or entrance dose at the contralateral (right) hippocampus. Adapted from Gondi et al., dose–response relationship from Wechsler Memory Scale-III World Lists (WMS-WL) Delayed Recall at 18 months and the dose to 40% of bilateral hippocampus. Footnote: EQD₂ = equivalent total dose in 2-Gy fractions. WMS-WL = Wechsler Memory Scale-III World Lists. Gy = Gray. RBE = relative biological effectiveness

Figure 2.

Craniospinal irradiation isodose dose distributions for a variety of radiotherapy techniques including 3D conformal radiotherapy, volumetrically modulated radiation therapy, tomotherapy, and intensity-modulated proton therapy (IMPT) demonstrating significantly reduced vertebral body and extracranial organ doses with IMPT compared to all other photon modalities. Footnote:3D CRT, Three-dimensional conformal radiation therapy. VMAT, Volumetric modulated arc therapy. TOMO, Tomotherapy. IMPT, Intensity-modulated proton therapy.