Perinatal and early life risk factors for childhood brain tumors: Is instrument-assisted delivery associated with higher risk?

BACKGROUND: The childhood peak of brain tumors suggests that early-life exposures might have a role in their etiology. Hence, we examined in the Greek National Registry for Childhood Hematological Malignancies and Solid tumors (NARECHEM-ST) whether perinatal and early-life risk factors influence the risk of childhood brain tumors. METHODS: In a nationwide case-control study, we included 203 cases (0-14 years) with a diagnosis of brain tumor in NARECHEM-ST (2010-2016) and 406 age-, sex-, and center-matched hospital controls. Information was collected via interviews with the guardians and we analyzed the variables of interest in multivariable conditional logistic regression models. RESULTS: Instrument-assisted delivery was associated with higher (OR: 7.82, 95%CI: 2.18-28.03), whereas caesarean delivery with lower (OR: 0.67, 95%CI: 0.45-0.99) risk of childhood brain tumors, as compared to spontaneous vaginal delivery. Maternal alcohol consumption during pregnancy (OR: 2.35, 95%CI: 1.45-3.81) and history of living in a farm (OR: 4.98, 2.40-10.32) increased the odds of childhood brain tumors. Conversely, higher birth order was associated with lower risk (OR for 2nd vs. 1st child: 0.60, 95%CI: 0.40-0.89 and OR for 3rd vs. 1st: 0.34, 95%CI: 0.18-0.63). Birth weight, gestational age, parental age, history of infertility, smoking during pregnancy, allergic diseases, and maternal diseases during pregnancy showed no significant associations. CONCLUSIONS: Perinatal and early-life risk factors, and specifically indicators of brain trauma, exposure to toxic agents and immune system maturation, might be involved in the pathogenesis of childhood brain tumors. Larger studies should aim to replicate our findings and examine associations with tumor subtypes.

Incidence and survival of gliomatosis cerebri: a population-based cancer registration study.

Gliomatosis cerebri (GC) comprises a rare widespread infiltrating growth pattern of diffuse gliomas. We explored the incidence patterns and survival rates of GC in a population-based registration sample from the Surveillance, Epidemiology and End, Results database (1973-2012). GC cases (n = 176) were identified based on their International Classification of Diseases in Oncology (ICD-O-3) morphology code (9381). We calculated age-adjusted incidence rates (AIR) and evaluated temporal trends. Survival was assessed with Kaplan-Meier curves and Cox regression models. The annual AIR of GC was 0.1/million. We noted increasing trends in the preceding registration years (1973-2002; annually, + 7%) and a tendency of clinical/radiological approaches to substitute the gold-standard histological assessment for diagnosis. GC was diagnosed in the entire age spectrum (range 1-98 years), but higher incidence rates (0.43/million) were noted among the elderly (≥ 65 years). A slight male preponderance was identified (male-to-female ratio: 1.4). Median overall survival was 9 months with a 5 year survival rate of 18%. Increasing age, primary tumor location not restricted to the cerebral hemispheres and rural residence at diagnosis were identified as negative prognostic factors, whereas receipt of radiotherapy, surgical treatment, race and method of diagnosis were not associated with outcome. This first comprehensive overview of GC epidemiology exemplifies the rarity of the disease, provides evidence for male preponderance and increased incidence among the elderly and shows lower survival rates compared to the published single center reports. Expansion of registration to histological and molecular characteristics would allow emergence of clinical prognostic factors at the population level.

The use of short-echo-time 1H MRS for childhood cerebellar tumours prior to histopathological diagnosis.

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) measures concentrations of metabolites in vivo and provides a powerful method for identifying tumours. MRS has not entered routine clinical use partly due to the difficulty of analysing the spectra. OBJECTIVE: To create a straightforward method for interpreting short-echo-time MRS of childhood cerebellar tumours. MATERIALS AND METHODS: Single-voxel MRS (1.5-T Siemens Symphony NUM4, TR/TE 1,500/30 ms) was performed at presentation in 30 children with cerebellar tumours. The MRS results were analysed for comparison with histological diagnosis. Peak heights for N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mIns) were determined and receiver operator characteristic curves used to select ratios that best discriminated between the tumour types. The method was implemented by a group of clinicians and scientists, blinded to the results. RESULTS: A total of 27 MRS studies met the quality control criteria. NAA/Cr >4.0 distinguished all but one of the astrocytomas from the other tumours. A combination of Cr/Cho <0.75 and mIns/NAA <2.1 separated all the medulloblastomas from the ependymomas. CONCLUSION: Peak height ratios from short-echo-time MRS can accurately predict the histopathology of childhood cerebellar tumours.