According to the results of the largest study of its kind conducted to date, the risk of meningioma in survivors of childhood cancer increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate.

The authors note that the development of secondary primary neoplasms (SPNs) is a serious consequence of treatment for childhood cancer.  The most common SPNs seen in the UK are those of the CNS (mainly meningiomas); the relationship between the risk of developing these and the doses of previous treatment are not known.  To investigate this issue further, they carried out a population-based cohort and nested case-control study to investigate the risk of CNS SPNs in survivors of childhood cancer, and relate this to previous treatment and genetic susceptibility factors.

They used data from the British Childhood Cancer Survivor Study (BCCSS) – a national, population-based cohort of 17,980 individuals in Britain who were diagnosed with cancer at the age of <15 years, and who survived at least five years following diagnosis.  This cohort was linked to national, population-based cancer registries, identifying 247 individuals who developed a SPN of the CNS (137 meningiomas, 73 gliomas and 37 other CNS neoplasms). 

The main findings were as follows:

• The standardised incidence ratio (SIR) for gliomas overall was 10.8 (95% CI, 8.5 to 13.6). It was highest after leukaemia (SIR 16.7; 95% CI 10.1 to 26.1) and CNS first primary neoplasms (SIR 18.5; 95% CI 12.7 to 26.2).

• The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue.  For example, those receiving 0.01 to 9.99 Gy of radiation to the meningal tissue had a risk of CNS SNP twice that of those who received no radiotherapy.  The risk increased with dose, for example ≥ 40 Gy was associated with a 479-fold risk.

• The risk of meningioma also increased strongly, linearly, and independently with the increased cumulative exposure to intrathecal methotrexate (p=0.015, adjusted for radiation exposure).  The risk of meningioma among individuals receiving 1 to 39, 40 to 69, and at least 70 mg/m2 of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed.

The authors comment that the main limitations of their study relate to the findings for methotrexate.  They say that readers should be cautious when interpreting the data – firstly there were insufficient survivors exposed to intrathecal methotrexate without cranial irradiation to assess their risk of meningioma separately (possibility of residual confounding); secondly if the relationship is causal, then the same relationship for systemic methotrexate would be expected (this was not seen in the study).