High incidence of secondary brain tumours after radiotherapy and antimetabolites

Brain tumours rarely occur in survivors of childhood acute lymphoblastic leukaemia after cranial radiotherapy. An unusually high frequency of brain tumours seen among children enrolled in one of our leukaemia treatment protocols, Total Therapy Study XII, prompted us to identify the potential causes...

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Published in:The Lancet (British edition) 1999-07, Vol.354 (9172), p.34-39
Main Authors: Relling, Mary V, Rubnitz, Jeffrey E, Rivera, Gaston K, Boyett, James M, Hancock, Michael L, Felix, Carolyn A, Kun, Larry E, Walter, Andrew W, Evans, William E, Pui, Ching-Hon
Format: Article
Language:English
Subjects:
Adolescent
Antimetabolites, Antineoplastic - adverse effects
Antimetabolites, Antineoplastic - therapeutic use
Biological and medical sciences
Brain
Brain Neoplasms - etiology
Brain tumors
Child
Child, Preschool
Children & youth
Combined Modality Therapy
Cranial Irradiation
Female
Follow-Up Studies
Humans
Incidence
Leukemia
Leukemia, Lymphoid - therapy
Male
Medical sciences
Metabolites
Neoplasms, Radiation-Induced - etiology
Neoplasms, Second Primary - etiology
Neurology
Pharmacokinetics
Radiation
Remission Induction
Risk Factors
Therapy
Tumors
Tumors of the nervous system. Phacomatoses
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creator Relling, Mary V
Rubnitz, Jeffrey E
Rivera, Gaston K
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Hancock, Michael L
Felix, Carolyn A
Kun, Larry E
Walter, Andrew W
Evans, William E
Pui, Ching-Hon
description Brain tumours rarely occur in survivors of childhood acute lymphoblastic leukaemia after cranial radiotherapy. An unusually high frequency of brain tumours seen among children enrolled in one of our leukaemia treatment protocols, Total Therapy Study XII, prompted us to identify the potential causes of this complication. We assessed clinical, biological, and pharmacokinetic features in all 52 children who received prophylactic cranial radiotherapy. We compared the cumulative incidence of brain tumours between subgroups, and with that of 421 children who received radiotherapy in previous studies. The incidence of brain tumours among irradiated children (six of 52, 12·8% [SE 5·0]) was high compared with patients in the same study who did not receive radiotherapy (none of 101; p=0·0008) and with other protocols that included cranial radiotherapy (p
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An unusually high frequency of brain tumours seen among children enrolled in one of our leukaemia treatment protocols, Total Therapy Study XII, prompted us to identify the potential causes of this complication. We assessed clinical, biological, and pharmacokinetic features in all 52 children who received prophylactic cranial radiotherapy. We compared the cumulative incidence of brain tumours between subgroups, and with that of 421 children who received radiotherapy in previous studies. The incidence of brain tumours among irradiated children (six of 52, 12·8% [SE 5·0]) was high compared with patients in the same study who did not receive radiotherapy (none of 101; p=0·0008) and with other protocols that included cranial radiotherapy (p&lt;0·0001). Of the six children, four had erythrocyte concentrations of thioguanine nucleotide metabolites higher than the 70th percentile for the entire cohort, and three had a genetic defect in thiopurine catabolism. The 8–year cumulative incidence of brain tumour among children with defective versus wild-type thiopurine methyltransferase phenotype was 42·9% (SE 20·6) versus 8·3% (4·7; p=0·0077). This protocol differed from previous protocols, in that more intensive systemic antimetabolite therapy was given before and during radiotherapy. These data support the elimination of prophylactic radiotherapy for acute lymphoblastic leukaemia except in patients at high risk of central-nervous-system relapse. Underlying genetic characteristics and treatment variables may be associated with an increased risk of radiation-associated brain tumours.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(98)11079-6</identifier><identifier>PMID: 10406363</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Adolescent ; Antimetabolites, Antineoplastic - adverse effects ; Antimetabolites, Antineoplastic - therapeutic use ; Biological and medical sciences ; Brain ; Brain Neoplasms - etiology ; Brain tumors ; Child ; Child, Preschool ; Children &amp; youth ; Combined Modality Therapy ; Cranial Irradiation ; Female ; Follow-Up Studies ; Humans ; Incidence ; Leukemia ; Leukemia, Lymphoid - therapy ; Male ; Medical sciences ; Metabolites ; Neoplasms, Radiation-Induced - etiology ; Neoplasms, Second Primary - etiology ; Neurology ; Pharmacokinetics ; Radiation ; Remission Induction ; Risk Factors ; Therapy ; Tumors ; Tumors of the nervous system. 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An unusually high frequency of brain tumours seen among children enrolled in one of our leukaemia treatment protocols, Total Therapy Study XII, prompted us to identify the potential causes of this complication. We assessed clinical, biological, and pharmacokinetic features in all 52 children who received prophylactic cranial radiotherapy. We compared the cumulative incidence of brain tumours between subgroups, and with that of 421 children who received radiotherapy in previous studies. The incidence of brain tumours among irradiated children (six of 52, 12·8% [SE 5·0]) was high compared with patients in the same study who did not receive radiotherapy (none of 101; p=0·0008) and with other protocols that included cranial radiotherapy (p&lt;0·0001). Of the six children, four had erythrocyte concentrations of thioguanine nucleotide metabolites higher than the 70th percentile for the entire cohort, and three had a genetic defect in thiopurine catabolism. 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subjects Adolescent
Antimetabolites, Antineoplastic - adverse effects
Antimetabolites, Antineoplastic - therapeutic use
Biological and medical sciences
Brain
Brain Neoplasms - etiology
Brain tumors
Child
Child, Preschool
Children & youth
Combined Modality Therapy
Cranial Irradiation
Female
Follow-Up Studies
Humans
Incidence
Leukemia
Leukemia, Lymphoid - therapy
Male
Medical sciences
Metabolites
Neoplasms, Radiation-Induced - etiology
Neoplasms, Second Primary - etiology
Neurology
Pharmacokinetics
Radiation
Remission Induction
Risk Factors
Therapy
Tumors
Tumors of the nervous system. Phacomatoses
title High incidence of secondary brain tumours after radiotherapy and antimetabolites
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