BACKGROUND: The goal of this study was to evaluate outcomes in children with relapsed, molecularly characterized intracranial ependymoma treated with or without craniospinal irradiation (CSI) as part of a course of repeat radiation therapy (re-RT). METHODS: This was a retrospective cohort study of 31 children. Patients with distant relapse received CSI as part of re-RT. For patients with locally recurrent ependymoma, those treated before 2012 were re-irradiated with focal re-RT. In 2012, institutional practice changed to offer CSI, followed by boost re-RT to the site of resected or gross disease. RESULTS: Median follow-up was 5.5 years. Of 9 patients with distant relapse after initial RT, 2-year freedom from progression (FFP) and overall survival (OS) were 12.5% and 62.5%, respectively. There were 22 patients with local failure after initial RT. In these patients, use of CSI during re-RT was associated with improvement in 5-year FFP (83.3% with CSI vs 15.2% with focal re-RT only, P = 0.030). In the subgroup of patients with infratentorial primary disease, CSI during re-RT also improved 5-year FFP (100% with CSI, 10.0% with focal re-RT only, P = 0.036). Twenty-three patients had known molecular status; all had posterior fossa group A tumors (n = 17) or tumors with a RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) fusion (n = 6). No patient developed radiation necrosis after fractionated re-RT, though almost all survivors required assistance throughout formal schooling. Five out of 10 long-term survivors have not developed neuroendocrine deficits. CONCLUSIONS: Re-irradiation with CSI is a safe and effective treatment for children with locally recurrent ependymoma and improves disease control compared with focal re-irradiation, with the benefit most apparent for those with infratentorial primary tumors.

Department of Pediatric Haematology and Oncology 2nd Medical School Charles University and University Hospital Motol Prague Czech Republic

Division of Haematology Oncology Hospital for Sick Children Toronto Canada

Division of Neurosurgery Hospital for Sick Children Toronto Canada

Pediatric Laboratory Medicine Hospital for Sick Children Toronto Canada

Radiation Medicine Program Princess Margaret Cancer Centre University Health Network Toronto Canada

Radiotherapy Research Group University of Leeds Leeds United Kingdom

Zobrazit více v PubMed

Ries LAG, Smith MA, J.G. G, et al. . Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975–1995, National Cancer Institute, SEER Program. NIH Publication Number 99–4649 Bethesda, MD: National Cancer Institute, SEER Program; 1999.

CBTRUS. Statistical Report: Primary Brain Tumors in the United States, 1997–2001. Hinsdale, IL: Published by the Central Brain Tumor Registry of the United States; 2004.

Tamburrini G, D’Ercole M, Pettorini BL, Caldarelli M, Massimi L, Di Rocco C. Survival following treatment for intracranial ependymoma: a review. Childs Nerv Syst. 2009;25(10):1303–1312. PubMed

Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA. Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol. 2009;10(3):258–266. PubMed PMC

Reni M, Gatta G, Mazza E, Vecht C. Ependymoma. Crit Rev Oncol Hematol. 2007;63(1):81–89. PubMed

Sangra M, Thorp N, May P, Pizer B, Mallucci C. Management strategies for recurrent ependymoma in the paediatric population. Childs Nerv Syst. 2009;25(10):1283–1291. PubMed

Merchant TE, Boop FA, Kun LE, Sanford RA. A retrospective study of surgery and reirradiation for recurrent ependymoma. Int J Radiat Oncol Biol Phys. 2008;71(1):87–97. PubMed

Bouffet E, Hawkins CE, Ballourah W, et al. . Survival benefit for pediatric patients with recurrent ependymoma treated with reirradiation. Int J Radiat Oncol Biol Phys. 2012;83(5):1541–1548. PubMed

Tsang DS, Burghen E, Klimo P Jr, Boop FA, Ellison DW, Merchant TE. Outcomes after reirradiation for recurrent pediatric intracranial ependymoma. Int J Radiat Oncol Biol Phys. 2018;100(2):507–515. PubMed

Pajtler KW, Mack SC, Ramaswamy V, et al. . The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol. 2017;133(1):5–12. PubMed PMC

Bayliss J, Mukherjee P, Lu C, et al. . Lowered H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas. Sci Transl Med. 2016;8(366):366ra161. PubMed PMC

Panwalkar P, Clark J, Ramaswamy V, et al. . Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. Acta Neuropathol. 2017;134(5):705–714. PubMed PMC

Pajtler KW, Witt H, Sill M, et al. . Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell. 2015;27(5):728–743. PubMed PMC

Massimino M, Miceli R, Giangaspero F, et al. . Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma. Neuro Oncol. 2016;18(10):1451–1460. PubMed PMC

The pediatrician’s role in development and implementation of an Individual Education Plan (IEP) and/or an Individual Family Service Plan (IFSP). American Academy of Pediatrics. Committee on children with disabilities. Pediatrics. 1999;104(1 Pt 1):124–127. PubMed

Ramaswamy V, Hielscher T, Mack SC, et al. . Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis. J Clin Oncol. 2016;34(21):2468–2477. PubMed PMC

Godfraind C, Kaczmarska JM, Kocak M, et al. . Distinct disease-risk groups in pediatric supratentorial and posterior fossa ependymomas. Acta Neuropathol. 2012;124(2):247–257. PubMed PMC

Mendrzyk F, Korshunov A, Benner A, et al. . Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin Cancer Res. 2006;12(7 Pt 1):2070–2079. PubMed

Messahel B, Ashley S, Saran F, et al. ; Children’s Cancer Leukaemia Group Brain Tumour Committee Relapsed intracranial ependymoma in children in the UK: patterns of relapse, survival and therapeutic outcome. Eur J Cancer. 2009;45(10):1815–1823. PubMed

Lobón M, Bautista F, Riet F, et al. . Re-irradiation of recurrent pediatric ependymoma: modalities and outcomes: a twenty-year survey. SpringerPlus. 2016;5(1):1–9. PubMed PMC

Eaton BR, Chowdhry V, Weaver K, et al. . Use of proton therapy for re-irradiation in pediatric intracranial ependymoma. Radiother Oncol. 2015;116(2):301–308. PubMed

Antony R, Wong KE, Patel M, et al. . A retrospective analysis of recurrent intracranial ependymoma. Pediatr Blood Cancer. 2014;61(7):1195–1201. PubMed

Combs SE, Thilmann C, Debus J, Schulz-Ertner D. Local radiotherapeutic management of ependymomas with fractionated stereotactic radiotherapy (FSRT). BMC Cancer. 2006;6:222. PubMed PMC

Zacharoulis S, Ashley S, Moreno L, Gentet JC, Massimino M, Frappaz D. Treatment and outcome of children with relapsed ependymoma: a multi-institutional retrospective analysis. Childs Nerv Syst. 2010;26(7):905–911. PubMed

Hoffman LM, Plimpton SR, Foreman NK, et al. . Fractionated stereotactic radiosurgery for recurrent ependymoma in children. J Neurooncol. 2014;116(1):107–111. PubMed PMC

Brown AP, Barney CL, Grosshans DR, et al. . Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys. 2013;86(2):277–284. PubMed PMC

Song S, Park HJ, Yoon JH, et al. . Proton beam therapy reduces the incidence of acute haematological and gastrointestinal toxicities associated with craniospinal irradiation in pediatric brain tumors. Acta Oncol. 2014;53(9):1158–1164. PubMed

Zhang R, Howell RM, Giebeler A, Taddei PJ, Mahajan A, Newhauser WD. Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient. Phys Med Biol. 2013;58(4):807–823. PubMed PMC

St Clair WH, Adams JA, Bues M, et al. . Advantage of protons compared to conventional X-ray or IMRT in the treatment of a pediatric patient with medulloblastoma. Int J Radiat Oncol Biol Phys. 2004;58(3):727–734. PubMed

Seravalli E, Bosman M, Lassen-Ramshad Y, et al. . Dosimetric comparison of five different techniques for craniospinal irradiation across 15 European centers: analysis on behalf of the SIOP-E-BTG (radiotherapy working group). Acta Oncol. 2018;57(9):1240–1249. PubMed

Brodin NP, Munck Af Rosenschöld P, Aznar MC, et al. . Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma. Acta Oncol. 2011;50(6):806–816. PubMed

Mailhot Vega RB, Kim J, Bussière M, et al. . Cost effectiveness of proton therapy compared with photon therapy in the management of pediatric medulloblastoma. Cancer. 2013;119(24):4299–4307. PubMed

Individualized therapeutic approaches for relapsed and refractory pediatric ependymomas: a single institution experience