Proton versus Photon Radiotherapy for Pediatric Central Nervous System Malignancies: A Systematic Review and Meta-Analysis of Dosimetric Comparison Studies

Abstract

Background Radiotherapy (RT) plays a fundamental role in the treatment of pediatric central nervous system (CNS) malignancies, but its late sequelae are still a challenging question. Despite developments in modern high-conformal photon techniques and proton beam therapy (PBT) are improving the normal tissues dose-sparing while maintaining satisfactory target coverage, clinical advantages supporting the optimal treatment strategy have to be better evaluated in long-term clinical studies and assessed in further radiobiological analyses. Our analysis aimed to systematically review current knowledge on the dosimetric advantages of PBT in the considered setting, which should be the basis for future specific studies. Materials and Methods A PubMed and Google Scholar search was conducted in June 2019 to select dosimetric studies comparing photon versus proton RT for pediatric patients affected by CNS tumors. Then, a systematic review and meta-analysis according to the PRISMA statement was performed. Average and standard deviation values of Conformity Index, Homogeneity Index, and mean and maximum doses to intracranial and extracranial organs at risk (OARs) were specifically evaluated for secondary dosimetric comparisons. The standardized mean differences (SMDs) for target parameters and the mean differences (MDs) for OARs were summarized in forest plots (P < 0.05 was considered statistically significant). Publication bias was also assessed by the funnel plot and Egger's regression test. Results Among the 88 identified papers, a total of twelve studies were included in the meta-analysis. PBT showed dosimetric advantages in target homogeneity (significant especially in the subgroup comparing PBT and 3D conformal RT), as well as in the dose sparing of almost all analyzed OARs (significantly superior results for brainstem, normal brain, and hippocampal dose constraints and for extracranial OARs parameters, excluding the kidneys). Publication bias was observed for Conformity Index. Conclusion Our analysis supports the evidence of dosimetric advantages of PBT over photon RT, especially in the dose sparing of normal growing tissues. Confirmations from wider well-designed studies are required.

Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects

“…Proton radiation therapy has been used for cancer treatment since the 1960s, but until recently its use was limited by the number of available facilities 5 . Proton radiotherapy can decrease toxicity by reducing radiation exposure of healthy brain tissue, while delivering equivalent anti-tumor efficacy compared with X-ray radiotherapy 6,7 . In that regard, a recent pivotal study in children with medulloblastoma identified superior intellectual outcomes in patients treated with proton compared with photon radiotherapy 8 .…”

Demographic profile and early clinical experience of treating children and young adults with image guided proton beam therapy in India

“…One 15-year-old girl with an intracranial germinoma received whole ventricular irradiation (WVI).On analysis of the technique of PBT planning, MFO was used in 21 patients (of which 17 were non-CNS tumors), SFO was used in 11 patients (all of them being CNS tumors) and hybrid planswere used in 15 patients (including all 13 patients of CSI). Median number of fractions received was 30 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) for CNS patients to a median dose of 54CGE(40-55.8Gy) and 32 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) for non-CNS patients to a median dose of 59.4CGE (30.6-70.4). One patient of recurrent para-meningeal RMS received hyperfractionation with 52.8CGE in 40 fractions with a twice daily fractionation.…”

Review of Conventional and High Dose Rate Brain Radiation (FLASH): Neurobehavioural, Neurocognitive and Assessment Issues in Rodent Models

“…Xrays are commonly used, but in recent years there has been increasing availability and use of proton radiation, with the opening of new proton centres. Proton radiation has advantages over X-rays in its ability to spare exposure of normal brain tissue while maintaining equivalent antitumour efficacy [3,4]. This relative tissue sparing by protons is due to their differing physical interactions with matter.…”