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| Authors (year) | Tumor histology | Patient number | Dosimetric study assessment | Mean total target dose (Gy/RBE/CGE) (dose/fraction) | Evaluation of at least one target parameter: CI (or CN), HI | Dmean/Dmax for OARs (Gy or %) with mean and SD | Conclusions |
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| Stoker et al. (2018) [14] | Primary brain tumors requiring hippocampal-avoidance- (HA-) WBRT | 10/20 | Dosimetric comparison between VMAT and IMPT for HA-WBRT | 36 Gy (1.8 Gy/die) HA-WBRT | HI | Dmax and Dmean reported for the normal brain, hippocampi, cochlea, and lens and Dmean for the brainstem | HA-IMPT can match or improve dosimetric benefits obtained with VMAT. |
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| Freund et al. (2015) [12] | Glioma
Ependymoma | 8
5 | Dosimetric comparison between VMAT, PSPT, and IMPT and risk of cerebral radionecrosis assessment | 54 Gy (RBE) (1.8 Gy/die) | CI, HI | Dmax and Dmean evaluated and reported for the normal brain | Both PSPT and IMPT plans significantly improved the maximum dose to the brain. A significant lower risk of brain radionecrosis was observed with PBT. |
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| Howell et al. (2012) [13] | Medulloblastoma | 18 | Comparison of dose distributions and DVHs between photon and proton CSI | 23.4 Gy (1.8 Gy/fr) | CI, HI | Dmean and/or Dmax not reported for the analyzed OARs | Both photon and proton plans provided good target coverage; PBT dose distributions were more homogeneous. Proton CSI improved normal tissue sparing. |
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| Correia et al. (2019) [11] | Intracranial germ-cell tumor | 11 | Comparison of dose distributions and DVHs between WV-RT/TB IMRT, VMAT, and PBS-PT | 24 Gy (RBE) WV-RT plus boost up to 40 Gy (1.6 Gy/fr) | HI and inhomogeneity coefficient | Dmean and Dmax reported (%) for the brainstem, chiasm, normal brain, pituitary gland, circle of Willis, bilateral cochlea, hippocampus, lens, and lacrimal gland | PBS-PT was superior to photons in conformality and OAR sparing. |
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| Boehling et al. (2012) [10] | Craniopharyngioma | 10 | Comparison of dose distributions and DVHs between IMRT, 3D-PRT, and IMPT | 50.4 Gy (CGE) (1.8 Gy/fr) | CN, HI | Dmean and Dmax reported for the vascular OARs, brainstem, and normal brain | PBT was able to avoid excess integral dose to a variety of normal structures at all dose levels while maintaining equal target coverage. |
| Takizawa et al. (2017) [31] | Ependymoma Germinoma | 6
6 | Comparison of dose distributions and DVHs between PBT, 3D-CRT, and IMRT | Median of 52.2 Gy for ependymoma and median of 30.6 Gy for germinoma | Not reported | Normal brain dose reported for each patient and as a percentage of the prescription dose (visual inspection of raw data) | PBT reduces the average dose to normal brain tissue as compared to 3D-CRT and IMRT. |
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| MacDonald et al. (2008) [26] | Ependymoma | 2/17 | Comparison of dose distributions and DVHs between IMPT, 3D-PBT, and IMRT | 55.8 Gy | Not reported | Dmean for the brain, brainstem, pituitary gland, optic chiasm, and cochlea evaluated and reported for each patient (Gy) | Dose distributions for PBT were compared favourably with IMRT plans. IMPT allows further sparing of some critical structures. |
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| Beltran et al. (2012) [16] | Craniopharyngioma | 14 | Dosimetric comparison between IMRT, double-scatter (DS) PT, and IMPT | 54 Gy (1.8 Gy/die) | CI | Not reported (other dosimetric parameters are reported) | PBT significantly reduced the dose to the whole brain. IMPT was the most conformal treatment that improved OAR dose sparing, but it was highly sensitive to target changes. |
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| Dennis et al. (2013) [17] | Low-grade glioma | 11 | Dosimetric (DVH) comparison between IMRT and PBT. SMN risk assessment | 54 Gy (1.8 Gy/die) | Not reported | Dmean for the brainstem, pituitary gland, optic chiasm, and lacrimal gland evaluated and reported for each patient (Gy) | PBT improved the reduction of doses to normal tissues, especially when tumors were in close proximity to critical structures. IMRT had a twofold higher risk of SMNs as compared to PBT. |
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| Mu et al. (2005) [18] | Medulloblastoma | 5 | Dosimetric comparison between conventional photons, IMRT, electrons, and PBT. SMN risk assessment | 23.4 Gy (1.8 Gy/die) | Not reported | Dmean evaluated and reported for the thyroid, esophagus, heart, lungs, and liver | IMPT significantly reduced mean doses to OARs, except for the lungs (not significantly). IMPT reduced SMN risk. |
| Zhang et al. (2014) [19] | Medulloblastoma | 17 | Dosimetric comparison between PSPT CSI and field-in-field photon CSI. SMN risk assessment | 23.4 Gy (1.8 Gy/die) | Not reported | Dmean evaluated and reported for the thyroid, heart, lungs, and liver | PSPT CSI provided lower doses to OARs, superior predicted outcomes, and lower predicted risks of SMNs and cardiac mortality than field-in-field photon CSI. |
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| Yoon et al. (2011) [15] | Various CNS tumors | 10 | Comparison of dose distributions, DVHs, and SMN risk between CSI with 3D-CRT, TOMO, and PBT. SMN risk assessment | 36 Gy (1.8 Gy/fr) to the spine; total target dose ranged between 54 and 60.6 Gy | CI, HI | Dmean evaluated and reported for the lens, thyroid, esophagus, lungs, liver, and kidneys | PBT provided the best HI and a superior CI than 3D-CRT (no significant difference compared to TOMO). OAR doses with PBT were lower than those obtained with 3D-CRT or TOMO. Lower SMN risk was reported with PBT. |
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