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Published in: Strahlentherapie und Onkologie 9/2013

01-09-2013 | Original article

Incidence and clinical course of radionecrosis in children with brain tumors

A 20-year longitudinal observational study

Authors: V. Strenger, MD, H. Lackner, R. Mayer, P. Sminia, P. Sovinz, M. Mokry, A. Pilhatsch, M. Benesch, W. Schwinger, M. Seidel, D. Sperl, S. Schmidt, C. Urban

Published in: Strahlentherapie und Onkologie | Issue 9/2013

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Abstract

Radionecrosis (RN) in children treated for brain tumors represents a potentially severe long-term complication. Its diagnosis is challenging, since magnetic resonance imaging (MRI) cannot clearly discriminate between RN and tumor recurrence. A retrospective single-center study was undertaken to describe the incidence and clinical course of RN in a cohort of 107 children treated with external radiotherapy (RT) for various brain tumors between 1992 and 2012. During a median follow-up of 4.6 years (range 0.29–20.1 years), RN was implied by suspicious MRI findings in in 5 children (4.7 %), 5–131 months after RT. Suspicion was confirmed histologically (1 patient) or substantiated by FDG positron-emission tomography (FDG-PET, 2 patients) or by FDG-PET and MR spectroscopy (1 patient). Before developing RN, all 5 patients had received cytotoxic chemotherapy in addition to RT. In addition to standard treatment protocols, 2 patients had received further chemotherapy for progression or relapse. Median radiation dose expressed as the biologically equivalent total dose applied in 2 Gy fractions (EQD2) was 51.7 Gy (range 51.0–60.0 Gy). At RN onset, 4 children presented with neurological symptoms. Treatment of RN included resection (n = 1), corticosteroids (n = 2) and a combination of corticosteroids, hyperbaric oxygen (HBO) and bevacizumab (n = 1). One patient with asymptomatic RN was not treated. Complete radiological regression of the lesions was observed in all patients. Clinical symptoms normalized in 3 patients, whereas 2 developed permanent severe neurological deficits. RN represents a severe long-term treatment complication in children with brain tumors. The spectrum of clinical presentation is wide; ranging from asymptomatic lesions to progressive neurological deterioration. FDG-PET and MR spectroscopy may be useful for distinguishing between RN and tumor recurrence. Treatment options in patients with symptomatic RN include conservative management (steroids, HBO, bevacizumab) and surgical resection.
Literature
1.
go back to reference Ashamalla HL, Thom SR, Goldwein JW (1996) Hyperbaric oxygen therapy for the treatment of radiation-induced sequelae in children. The University of Pennsylvania experience. Cancer 77:2407–2412PubMedCrossRef Ashamalla HL, Thom SR, Goldwein JW (1996) Hyperbaric oxygen therapy for the treatment of radiation-induced sequelae in children. The University of Pennsylvania experience. Cancer 77:2407–2412PubMedCrossRef
2.
go back to reference Baack T, Wenz F (2012) Secondary cancers after radiotherapy may appear early and atypical. Strahlenther Onkol 188:91–92 (author reply 2–3)PubMedCrossRef Baack T, Wenz F (2012) Secondary cancers after radiotherapy may appear early and atypical. Strahlenther Onkol 188:91–92 (author reply 2–3)PubMedCrossRef
3.
go back to reference Bakardjiev AI, Barnes PD, Goumnerova LC et al (1996) Magnetic resonance imaging changes after stereotactic radiation therapy for childhood low grade astrocytoma. Cancer 78:864–873PubMedCrossRef Bakardjiev AI, Barnes PD, Goumnerova LC et al (1996) Magnetic resonance imaging changes after stereotactic radiation therapy for childhood low grade astrocytoma. Cancer 78:864–873PubMedCrossRef
4.
go back to reference Barendsen GW (1982) Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys 8:1981–1997PubMedCrossRef Barendsen GW (1982) Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys 8:1981–1997PubMedCrossRef
5.
go back to reference Benesch M, Lackner H, Sovinz P et al (2006) Late sequela after treatment of childhood low-grade gliomas: a retrospective analysis of 69 long-term survivors treated between 1983 and 2003. J Neurooncol 78:199–205PubMedCrossRef Benesch M, Lackner H, Sovinz P et al (2006) Late sequela after treatment of childhood low-grade gliomas: a retrospective analysis of 69 long-term survivors treated between 1983 and 2003. J Neurooncol 78:199–205PubMedCrossRef
6.
go back to reference Bolling T, Schuck A, Pape H et al (2007) Register for the evaluation of side effects after radiation in childhood and adolescence—first results. Klin Padiatr 219:139–145PubMedCrossRef Bolling T, Schuck A, Pape H et al (2007) Register for the evaluation of side effects after radiation in childhood and adolescence—first results. Klin Padiatr 219:139–145PubMedCrossRef
7.
go back to reference Brandes AA, Tosoni A, Spagnolli F et al (2008) Disease progression or pseudoprogression after concomitant radiochemotherapy treatment: pitfalls in neurooncology. Neuro Oncol 10:361–367PubMedCrossRef Brandes AA, Tosoni A, Spagnolli F et al (2008) Disease progression or pseudoprogression after concomitant radiochemotherapy treatment: pitfalls in neurooncology. Neuro Oncol 10:361–367PubMedCrossRef
8.
go back to reference Brandsma D, Stalpers L, Taal W et al (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9:453–461PubMedCrossRef Brandsma D, Stalpers L, Taal W et al (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9:453–461PubMedCrossRef
9.
go back to reference Calaminus G, Bamberg M, Harms D et al (2005) AFP/beta-HCG secreting CNS germ cell tumors: long-term outcome with respect to initial symptoms and primary tumor resection. Results of the cooperative trial MAKEI 89. Neuropediatrics 36:71–77PubMedCrossRef Calaminus G, Bamberg M, Harms D et al (2005) AFP/beta-HCG secreting CNS germ cell tumors: long-term outcome with respect to initial symptoms and primary tumor resection. Results of the cooperative trial MAKEI 89. Neuropediatrics 36:71–77PubMedCrossRef
10.
go back to reference Chao ST, Suh JH, Raja S et al (2001) The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. Int J Cancer 96:191–197PubMedCrossRef Chao ST, Suh JH, Raja S et al (2001) The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. Int J Cancer 96:191–197PubMedCrossRef
11.
go back to reference Chuba PJ, Aronin P, Bhambhani K et al (1997) Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer 80:2005–2012PubMedCrossRef Chuba PJ, Aronin P, Bhambhani K et al (1997) Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer 80:2005–2012PubMedCrossRef
12.
go back to reference Dietrich U, Wanke I, Mueller T et al (2001) White matter disease in children treated for malignant brain tumors. Childs Nerv Syst 17:731–738PubMedCrossRef Dietrich U, Wanke I, Mueller T et al (2001) White matter disease in children treated for malignant brain tumors. Childs Nerv Syst 17:731–738PubMedCrossRef
13.
go back to reference Fouladi M, Chintagumpala M, Laningham FH et al (2004) White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor. J Clin Oncol 22:4551–4560PubMedCrossRef Fouladi M, Chintagumpala M, Laningham FH et al (2004) White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor. J Clin Oncol 22:4551–4560PubMedCrossRef
14.
go back to reference Joiner MC, Bentzen SM (2009) Fractionation: the linear-quadratic approach. In: Joiner MC, Kogel AJ van der (Hrsg) Basic clinical radiobiology. Hodder Arnold, London, S 102–119 Joiner MC, Bentzen SM (2009) Fractionation: the linear-quadratic approach. In: Joiner MC, Kogel AJ van der (Hrsg) Basic clinical radiobiology. Hodder Arnold, London, S 102–119
15.
go back to reference Kortmann RD, Kuhl J, Timmermann B et al (2001) Current and future strategies in interdisciplinary treatment of medulloblastomas, supratentorial PNET (primitive neuroectodermal tumors) and intracranial germ cell tumors in childhood. Strahlenther Onkol 177:447–461PubMedCrossRef Kortmann RD, Kuhl J, Timmermann B et al (2001) Current and future strategies in interdisciplinary treatment of medulloblastomas, supratentorial PNET (primitive neuroectodermal tumors) and intracranial germ cell tumors in childhood. Strahlenther Onkol 177:447–461PubMedCrossRef
16.
go back to reference Kumar AJ, Leeds NE, Fuller GN et al (2000) Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 217:377–384PubMed Kumar AJ, Leeds NE, Fuller GN et al (2000) Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 217:377–384PubMed
17.
go back to reference Langsenlehner T, Renner W, Gerger A et al (2011) Impact of VEGF gene polymorphisms and haplotypes on radiation-induced late toxicity in prostate cancer patients. Strahlenther Onkol 187:784–791PubMedCrossRef Langsenlehner T, Renner W, Gerger A et al (2011) Impact of VEGF gene polymorphisms and haplotypes on radiation-induced late toxicity in prostate cancer patients. Strahlenther Onkol 187:784–791PubMedCrossRef
18.
go back to reference Levin VA, Bidaut L, Hou P et al (2011) Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 79:1487–1495PubMedCrossRef Levin VA, Bidaut L, Hou P et al (2011) Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 79:1487–1495PubMedCrossRef
19.
go back to reference Mayer R, Hamilton-Farrell MR, Kleij AJ van der et al (2005) Hyperbaric oxygen and radiotherapy. Strahlenther Onkol 181:113–123PubMedCrossRef Mayer R, Hamilton-Farrell MR, Kleij AJ van der et al (2005) Hyperbaric oxygen and radiotherapy. Strahlenther Onkol 181:113–123PubMedCrossRef
20.
go back to reference Mayer R, Sminia P (2008) Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys 70:1350–1360PubMedCrossRef Mayer R, Sminia P (2008) Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys 70:1350–1360PubMedCrossRef
21.
go back to reference Muscal JA, Jones JY, Paulino AC et al (2009) Changes mimicking new leptomeningeal disease after intensity-modulated radiotherapy for medulloblastoma. Int J Radiat Oncol Biol Phys 73:214–221PubMedCrossRef Muscal JA, Jones JY, Paulino AC et al (2009) Changes mimicking new leptomeningeal disease after intensity-modulated radiotherapy for medulloblastoma. Int J Radiat Oncol Biol Phys 73:214–221PubMedCrossRef
22.
go back to reference Packer RJ, Meadows AT, Rorke LB et al (1987) Long-term sequelae of cancer treatment on the central nervous system in childhood. Med Pediatr Oncol 15:241–253PubMedCrossRef Packer RJ, Meadows AT, Rorke LB et al (1987) Long-term sequelae of cancer treatment on the central nervous system in childhood. Med Pediatr Oncol 15:241–253PubMedCrossRef
23.
go back to reference Rabin BM, Meyer JR, Berlin JW et al (1996) Radiation-induced changes in the central nervous system and head and neck. Radiographics 16:1055–1072PubMed Rabin BM, Meyer JR, Berlin JW et al (1996) Radiation-induced changes in the central nervous system and head and neck. Radiographics 16:1055–1072PubMed
24.
go back to reference Ruben JD, Dally M, Bailey M (2006) Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys 65:499–508PubMedCrossRef Ruben JD, Dally M, Bailey M (2006) Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys 65:499–508PubMedCrossRef
25.
go back to reference Shrieve DC (2011) Radiation dose, fractionation and normal tissue injury. In: Shrieve DC, Loeffler JS (Hrsg) Human radiation injury. Lippincott Williams & Wilkins, Philadelphia, S 32–42 Shrieve DC (2011) Radiation dose, fractionation and normal tissue injury. In: Shrieve DC, Loeffler JS (Hrsg) Human radiation injury. Lippincott Williams & Wilkins, Philadelphia, S 32–42
26.
go back to reference Sminia P, Mayer R (2012) External beam radiotherapy of recurrent glioma: radiation tolerance of the human brain. Cancers 4:379–399CrossRef Sminia P, Mayer R (2012) External beam radiotherapy of recurrent glioma: radiation tolerance of the human brain. Cancers 4:379–399CrossRef
27.
go back to reference Strenger V, Sovinz P, Lackner H et al (2008) Intracerebral cavernous hemangioma after cranial irradiation in childhood. Incidence and risk factors. Strahlenther Onkol 184:276–280PubMedCrossRef Strenger V, Sovinz P, Lackner H et al (2008) Intracerebral cavernous hemangioma after cranial irradiation in childhood. Incidence and risk factors. Strahlenther Onkol 184:276–280PubMedCrossRef
28.
go back to reference Timmermann B, Kortmann RD, Kuhl J et al (2002) Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. J Clin Oncol 20:842–849PubMedCrossRef Timmermann B, Kortmann RD, Kuhl J et al (2002) Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. J Clin Oncol 20:842–849PubMedCrossRef
Metadata
Title
Incidence and clinical course of radionecrosis in children with brain tumors
A 20-year longitudinal observational study
Authors
V. Strenger, MD
H. Lackner
R. Mayer
P. Sminia
P. Sovinz
M. Mokry
A. Pilhatsch
M. Benesch
W. Schwinger
M. Seidel
D. Sperl
S. Schmidt
C. Urban
Publication date
01-09-2013
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 9/2013
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-013-0408-0

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