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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.

SUBMITTER: Carbonara R

PROVIDER: S-EPMC6900940 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo compare the dosimetric differences in stereotactic radiosurgery between use of passively scattered protons (PSRS) versus photons (XSRS) for pituitary adenomas.Methods and materialsNine patients with pituitary adenomas were selected among patients receiving single-fraction proton stereotactic radiosurgery (PSRS) between 2016 and 2017. These cases were replanned with XSRS using volumetric-modulated arc therapy with 2.5 mm and 5 mm multileaf collimators (2.5XSRS and 5XSRS, respectively). PSRS was planned with a dedicated single scattering stereotactic proton unit delivered via 3 equally or unequally weighted isocentric fields. XSRS plans were created with optimization to spare organs at risk. Plans were generated using the original total treatment dose delivered in 1 fraction.ResultsPlans were evaluated for target volume dosimetry and estimated clinical toxicity. There was no significant difference in clinical target volume V100%, V95%, V90% or homogeneity index between treatment modalities. PSRS offered lower maximum dose (Dmax) to organs at risk and equivalent uniform dose (EUD) compared with 5XSRS and 2.5XSRS, respectively, for critical structures including optic nerve (right, Dmax 4.18, 5.32, 5.41; EUD 3.35, 4.08, 4.20) and hypothalamus (Dmax 1.71, 3.94, 3.77; EUD 0.94, 2.47, 2.39; P < .05 for PSRS vs 5XSRS and 2.5XSRS). The projected risk of secondary tumors in excess of baseline was lowest for PSRS plans (PSRS 5.28, 5XSRS 12.93, 2.5XSRS 12.66 cases per 10,000 patient-years; P = .008 for PSRS vs 5XSRS, PSRS vs 2.5XSRS, and P = .77 for 5XSRS vs 2.5XSRS).ConclusionsWe demonstrate that neither modality has empirically superior dosimetry and identify potential clinical advantages as well as limitations of each technique. PSRS, 5XSRS and 2.5XSRS demonstrate comparable target volume dosimetry for pituitary adenoma. PSRS compared with XSRS modalities offers modestly decreased maximum dose and EUD to critical proximal structures and decreases risk of radiation-induced secondary tumors by more than half.

Project description:PurposeProton radiotherapy (PRT) may lessen the neuropsychological risk traditionally associated with cranial radiotherapy for the treatment of pediatric brain tumors by reducing the dose to normal tissue compared with that of photon radiotherapy (XRT). We examined the change in intellectual scores over time in patients with pediatric medulloblastoma treated with craniospinal PRT versus XRT.MethodsIntelligence test scores were obtained for a sample of pediatric patients treated between 2007 and 2018 on the same medulloblastoma protocols that differed only in radiotherapy modality (PRT v XRT). Growth curve analyses compared change in scores over time since diagnosis between groups.ResultsLongitudinal intelligence data from 79 patients (37 PRT, 42 XRT) were examined. Groups were similar on most demographic/clinical variables, including sex (67.1% male), age at diagnosis (mean, 8.6 years), craniospinal irradiation dose (median, 23.4 Gy), length of follow-up (mean, 4.3 years), and parental education (mean, 14.3 years). Boost dose (P < .001) and boost margin (P = .001) differed between groups. Adjusting for covariates, the PRT group exhibited superior long-term outcomes in global intelligence quotient (IQ), perceptual reasoning, and working memory compared with the XRT group (all P < .05). The XRT group exhibited a significant decline in global IQ, working memory, and processing speed (all P < .05). The PRT group exhibited stable scores over time in all domains with the exception of processing speed (P = .003).ConclusionTo our knowledge, this is the first study to compare intellectual trajectories between pediatric patients treated for medulloblastoma with PRT versus those treated with XRT on comparable, contemporary protocols. PRT was associated with more favorable intellectual outcomes in most domains compared with XRT, although processing speed emerged as a vulnerable domain for both groups. This study provides the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.

Project description:PurposeTo simulate and analyze the dosimetric differences of intraoperative radiotherapy (IORT) or pre-operative single-fraction stereotactic radiosurgery (SRS) in addition to post-operative external beam radiotherapy (EBRT) in Glioblastoma (GB).MethodsImaging series of previously treated patients with adjuvant radiochemotherapy were analyzed. For SRS target definition, pre-operative MRIs were co-registered to planning CT scans and a pre-operative T1-weighted gross target volume (GTV) plus a 2-mm planning target volume (PTV) were created. For IORT, a modified (m)GTV was expanded from the pre-operative volume, in order to mimic a round cavity as during IORT. Dose prescription was 20 Gy, homogeneously planned for SRS and calculated at the surface for IORT, to cover 99% and 90% of the volumes, respectively. For tumors > 2cm in maximum diameter, a 15 Gy dose was prescribed. Plan assessment was performed after calculating the 2-Gy equivalent doses (EQD2) for both boost modalities and including them into the EBRT plan. Main points of interest encompass differences in target coverage, brain volume receiving 12 Gy or more (V12), and doses to various organs-at-risk (OARs).ResultsSeventeen pre-delivered treatment plans were included in the study. The mean GTV was 21.72 cm3 (SD ± 19.36) and mGTV 29.64 cm3 (SD ± 25.64). The mean EBRT and SRS PTV were 254.09 (SD ± 80.0) and 36.20 cm3 (SD ± 31.48), respectively. Eight SRS plans were calculated to 15 Gy according to larger tumor sizes, while all IORT plans to 20 Gy. The mean EBRT D95 was 97.13% (SD ± 3.48) the SRS D99 99.91% (SD ± 0.35) and IORT D90 83.59% (SD ± 3.55). Accounting for only-boost approaches, the brain V12 was 49.68 cm3 (SD ± 26.70) and 16.94 cm3 (SD ± 13.33) (p<0.001) for SRS and IORT, respectively. After adding EBRT results respectively to SRS and IORT doses, significant lower doses were found in the latter for mean Dmax of chiasma (p=0.01), left optic nerve (p=0.023), right (p=0.008) and left retina (p<0.001). No significant differences were obtained for brainstem and cochleae.ConclusionDose escalation for Glioblastoma using IORT results in lower OAR exposure as conventional SRS.

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

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