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Updated: Feb 26, 2026
Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies
Published on: February 6, 2019
Proton radiotherapy outcomes in pediatric ependymoma: A long-term meta-analysis (PROPEL)
Gustavo A Viani1, Ana Carolina Hamamura2, Caio Viani Arruda3
1Hospital das Clínicas of Botucatu Medical School, University of State of São Paulo (UNESP), Botucatu, SP, Brazil; Latin America Cooperative Oncology Group (LACOG), Porto Alegre, Brazil; Master's Program in Applied Health Sciences at the University of Vassouras, Rio de Janeiro, Brazil.
Objectives:
To synthesize existing evidence on pencil-beam and passive-scattering proton therapy outcomes in pediatric intracranial ependymoma and to generate pooled estimates of five-year overall survival (OS), local control (LC), progression-free survival (PFS), and late toxicity profiles.
Materials And Methods:
We performed a random-effects meta-analysis (with fixed- and random-effects estimates converging when between-study heterogeneity was negligible) of eight retrospective single-center cohorts (2000-2025) encompassing 1100 children treated with 54-60 Gy(RBE) proton therapy. Primary endpoints were five-year OS, LC, and PFS. Secondary endpoints included growth hormone deficiency (GHD), hypothyroidism, radionecrosis, and secondary malignancies. Pooled proportions and 95 % confidence intervals (CIs) were calculated for each outcome. Between-study heterogeneity was assessed via Cochran's Q and I² statistics. Meta-regression evaluated the influence of surgical extent, proton dose, and delivery technique on oncologic endpoints.
Results:
Five-year OS was 83.1 % (95 % CI 80.7-85.4 %), LC 84.9 % (95 % CI 82.7-87.2 %), and PFS 74.1 % (95 % CI 71.3-76.9 %), each with negligible heterogeneity (I² = 0 %). Late toxicities were modest: GHD in 21.3 % (95 % CI 18.8-23.8 %), hypothyroidism in 15.0 % (95 % CI 12.9-17.1 %), ototoxicity grade 2 or higher in 5 % (95 % CI 3.5-6.5 %), radionecrosis in 2.0 % (95 % CI 1.5-3.5 %), and secondary malignancy in 0.65 % (95 % CI 0.17-1.13 %). Meta-regression identified subtotal resection as the sole predictor of inferior LC, and PFS (p < 0.01), whereas proton dose range and delivery modality had no significant effect (p > 0.1).
Conclusion:
PTB in pediatric intracranial ependymoma achieves excellent five-year OS, LC, and PFS with low rates of serious late effects. Surgical extent remains the principal determinant of outcome, underscoring the need for prospective trials of targeted dose escalation-particularly in cases of subtotal resection-using modern intensity-modulated proton techniques to optimize the therapeutic ratio.
