Proton therapy for newly diagnosed pediatric diffuse intrinsic pontine glioma
Diffuse intrinsic pontine glioma (DIPG) is a type of brain malignancy with a very poor prognosis. Although various radiation and chemotherapy protocols have been attempted, only conventional radiotherapy has yielded improvements in survival. In this study, we aimed to compare proton therapy versus conventional photon radiotherapy in terms of the outcomes of pediatric patients with DIPG.
This retrospective review included 12 pediatric patients with newly diagnosed DIPG who received a total proton therapy dose of 54 Gy (relative biological effectiveness) in 30 fractions at the University of Tsukuba Hospital between 2011 and 2017 (proton group). We additionally reviewed the medical records of 10 patients with DIPG who previously underwent conventional photon radiotherapy at our institute (historical cohort).
The median progression-free survival (PFS) duration was 5 months (range 1–11 months), and the 6-, 12-, and 18-month PFS rates were 50%, 33%, and 25%, respectively. The median overall survival (OS) duration was 9 months (range 4–48 months), and the 6-, 12-, 18-, and 24-month OS rates were 66.8%, 50%, 41%, and 20%, respectively. There were no significant differences in survival between the proton and historical groups (PFS, p = 0.169 and OS, p = 0.16).
Proton therapy was well tolerated by the majority of patients. No severe adverse events, including radiation necrosis, were recorded. Proton therapy did not yield superior survival outcomes vs. conventional photon radiotherapy in patients with DIPG at our institution. Further research is needed to identify the factors associated with better survival in this population.
KeywordsProton therapy Diffuse intrinsic pontine glioma Radiotherapy Reirradiation
We would like to thank Editage (www.editage.com) for the English language editing.
All authors contributed to the study conception and design. Material preparation and data collection were performed by AM, MM, TT, HF, and SI. The first draft of the manuscript was written by AM, MM, and EI and all authors commented on previous versions of the manuscript. HS, and AMa critically supervised the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study was approved by the Ethics Committee of the University of Tsukuba Hospital.
- 1.Nakata K, Ito Y, Magadi W, Bonaventure A, Stiller CA, Katanoda K, Matsuda T, Miyashiro I, Pritchard-Jones K, Rachet B (2017) Childhood cancer incidence and survival in Japan and England: a population-based study (1993-2010). Cancer Sci 109:422–434. https://doi.org/10.1111/cas.13457 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Mandell LR, Kadota R, Freeman C et al (1999) There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 43:959–964CrossRefGoogle Scholar
- 8.Zaghloul MS, Eldebawy E, Ahmed S, Mousa AG, Amin A, Refaat A, Zaky I, Elkhateeb N, Sabry M (2014) Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): a randomized controlled trial. Radiother Oncol 111:35–40. https://doi.org/10.1016/j.radonc.2014.01.013 CrossRefPubMedGoogle Scholar
- 9.Frappaz D, Schell M, Thiesse P, Marec-Bérard P, Mottolese C, Perol D, Bergeron C, Philip T, Ricci AC, Galand-Desme S, Szathmari A, Carrie C (2008) Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial. Neuro Oncol 10:599–607. https://doi.org/10.1215/15228517-2008-029 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Gokce-Samar Z, Beuriat PA, Faure-Conter C, Carrie C, Chabaud S, Claude L, di Rocco F, Mottolese C, Szathmari A, Chabert C, Frappaz D (2016) Pre-radiation chemotherapy improves survival in pediatric diffuse intrinsic pontine gliomas. Childs Nerv Syst 32:1415–1423. https://doi.org/10.1007/s00381-016-3153-8 CrossRefPubMedGoogle Scholar
- 12.Khuong-Quang D-A, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E, Bartels U, Albrecht S, Schwartzentruber J, Letourneau L, Bourgey M, Bourque G, Montpetit A, Bourret G, Lepage P, Fleming A, Lichter P, Kool M, von Deimling A, Sturm D, Korshunov A, Faury D, Jones DT, Majewski J, Pfister SM, Jabado N, Hawkins C (2012) K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124:439–447. https://doi.org/10.1007/s00401-012-0998-0 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Zhang J, Baker SJ, St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253. https://doi.org/10.1038/ng.1102 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Fukushima H, Fukushima T, Suzuki R, Iwabuchi A, Hidaka K, Shinkai T, Masumoto K, Muroi A, Yamamoto T, Nakao T, Oshiro Y, Mizumoto M, Sakurai H, Sumazaki R (2017) Comorbidity and quality of life in childhood cancer survivors treated with proton beam therapy. Pediatr Int 59:1039–1045. https://doi.org/10.1111/ped.13323 CrossRefPubMedGoogle Scholar