High incidence of secondary brain tumours after radiotherapy and antimetabolites

Mary V. Relling, Jeffrey E. Rubnitz, Gaston K. Rivera, James M. Boyett, Michael L. Hancock, Carolyn A. Felix, Larry E. Kun, Andrew W. Walter, William E. Evans, Ching Hon Pui

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322 Citations (Scopus)

Abstract

Background. 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. Methods. 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. Findings. 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 < 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. Interpretation. 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.

Original languageEnglish (US)
Pages (from-to)34-39
Number of pages6
JournalLancet
Volume354
Issue number9172
DOIs
StatePublished - Jul 3 1999

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Antimetabolites
Brain Neoplasms
Radiotherapy
Incidence
thiopurine methyltransferase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Thioguanine
Clinical Protocols
Survivors
Leukemia
Therapeutics
Nucleotides
Central Nervous System
Pharmacokinetics
Erythrocytes
Radiation
Phenotype
Recurrence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Relling, M. V., Rubnitz, J. E., Rivera, G. K., Boyett, J. M., Hancock, M. L., Felix, C. A., ... Pui, C. H. (1999). High incidence of secondary brain tumours after radiotherapy and antimetabolites. Lancet, 354(9172), 34-39. https://doi.org/10.1016/S0140-6736(98)11079-6

High incidence of secondary brain tumours after radiotherapy and antimetabolites. / 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.

In: Lancet, Vol. 354, No. 9172, 03.07.1999, p. 34-39.

Research output: Contribution to journalArticle

Relling, MV, Rubnitz, JE, Rivera, GK, Boyett, JM, Hancock, ML, Felix, CA, Kun, LE, Walter, AW, Evans, WE & Pui, CH 1999, 'High incidence of secondary brain tumours after radiotherapy and antimetabolites', Lancet, vol. 354, no. 9172, pp. 34-39. https://doi.org/10.1016/S0140-6736(98)11079-6
Relling MV, Rubnitz JE, Rivera GK, Boyett JM, Hancock ML, Felix CA et al. High incidence of secondary brain tumours after radiotherapy and antimetabolites. Lancet. 1999 Jul 3;354(9172):34-39. https://doi.org/10.1016/S0140-6736(98)11079-6
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. / High incidence of secondary brain tumours after radiotherapy and antimetabolites. In: Lancet. 1999 ; Vol. 354, No. 9172. pp. 34-39.
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AU - Hancock, Michael L.

AU - Felix, Carolyn A.

AU - Kun, Larry E.

AU - Walter, Andrew W.

AU - Evans, William E.

AU - Pui, Ching Hon

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