Role of radiotherapy and chemotherapy in the risk of leukemia after childhood cancer: An international pooled analysis.
alkylating agents
chemotherapy
childhood cancers survivors
radiation dose to active bone marrow
radiotherapy
secondary leukemia
topoisomerase II inhibitors
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
revised:
09
10
2020
received:
22
05
2020
accepted:
12
10
2020
pubmed:
27
10
2020
medline:
8
9
2021
entrez:
26
10
2020
Statut:
ppublish
Résumé
Childhood cancer survivors are at increased risk for second primary leukemia (SPL), but there is little consensus on the magnitude of some risk factors because of the small size of previous studies. We performed a pooled analysis of all published studies with detailed treatment data, including estimated active bone marrow (ABM) dose received during radiation therapy and doses of specific chemotherapeutic agents for childhood cancer diagnosed from 1930 through 2000, in order to more thoroughly investigate treatment-related risks of SPL. A total of 147 SPL cases (of which 69% were acute myeloid leukemia [AML]) were individually matched to 522 controls, all from four case-control studies including patients from six countries (France, United Kingdom, United States, Canada, Italy and Netherlands). Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression, and the excess OR per Gray (EOR/Gy) was also calculated. After accounting for the other therapies received, topoisomerase II inhibitor was associated with an increased SPL risk (highest tertile vs none: OR = 10.0, 95% CI: 3.7-27.3). Radiation dose to the ABM was also associated with increased SPL risk among those not receiving chemotherapy (EOR/Gy = 1.6, 95% CI: 0.1-14.3), but not among those who received chemotherapy (CT). SPL were most likely to occur in the first decade following cancer treatment. Results were similar when analyses were restricted to AML. The evidence of interaction between radiation and CT has implications for leukemogenic mechanism. The results for topoisomerase II inhibitors are particularly important given their increasing use to treat childhood cancer.
Identifiants
pubmed: 33105035
doi: 10.1002/ijc.33361
pmc: PMC8174089
mid: NIHMS1706638
doi:
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2079-2089Subventions
Organisme : Intramural NIH HHS
ID : ZIA CP010131
Pays : United States
Informations de copyright
© 2020 UICC.
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