Population-Based Risks of CNS Tumors in Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study

Abstract

Purpose CNS tumours are the most common second primary neoplasm observed after childhood cancer in Britain, but the relationship of risk to dose of previous radiotherapy and chemotherapy is uncertain. Methods The British Childhood Cancer Survivor Study is a national population-based cohort study of 17980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national population-based cancer registries identified 247 second primary neoplasms of the CNS. Cohort and nested case-control studies were undertaken. Results There were 137 meningiomas, 73 gliomas and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01-9.99,10.00-19.99,20.00-29.99,30.00-39.99 and ≥40Gy had a risk 2,8,52,568 and 479-fold that experienced by those whose meningeal tissue was unexposed, respectively. The risk of meningioma among individuals receiving 1-39,40-69 and at least 70mg/m2 of intrathecal methotrexate was 15,11 and 36-fold that experienced by those unexposed, respectively. The standardised incidence ratio for gliomas was 10·8 (95% confidence interval: 8·5, 13·6). The risk of glioma/primitive neuroectodermal tumours increased linearly with dose of radiation and those with CNS tissue exposed to at least 40Gy experienced a risk 4-fold that experienced by those with CNS tissue unexposed. Conclusion The largest ever study of CNS tumours in childhood cancer survivors indicates the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and increased dose of intrathecal methotrexate.

Distinguishing Grade I Meningioma From Higher Grade Meningiomas Without Biopsy

“…Additionally, we feel that the relatively high proportion of Grade II/III tumors may reflect a referral bias to our institution. Because past therapeutic radiation [12], BMI in females [13] and hormone replacement therapy [14] have been associated with the development of meningioma, we felt that assessing the association of these factors with the meningioma grade may be important. It should be noted that obesity is associated with higher adipose aromatase activity, estrogen, androgens, and insulin-like growth factor [15].…”

Postoperative imaging for detection of recurrent arteriovenous malformations in children

“…30 Consistent with this conclusion, the largest study of population-based risk of malignancy after radiation exposure by dose demonstrated no significant increase in the relative risk of malignancy after exposure to 0.01-9.99 Gy. 27 Additionally, neurological and nonneurological risks of DSA in the infant population were recently reviewed at our institution with no increase in morbidity in this population. 11 All of this accumulating evidence suggests that the additional risk of favoring DSA over MRI/MRA in a follow-up protocol after AVM treatment is minimal, and unlikely to surpass the risk of hemorrhage from an undetected recurrence.…”

Proton Radiotherapy for Childhood Tumors: an Overview of Early Clinical Results

“…Unfortunately, radiation exposure is a major contributor to treatment related late morbidity for long-term survivors. Children are particularly susceptible to the late effects of radiation, even at low doses, as demonstrated in epidemiologic studies of exposed populations [2,3]. The reasons for this include the sensitivity of developing and growing tissues, the longer life expectancy resulting in a larger window of opportunity for expressing radiation damage, and the large number of long-term survivors.…”