High Prevalence of Weight Gain in Childhood Brain Tumor Survivors and Its Association With Hypothalamic-Pituitary Dysfunction.

PURPOSE: Childhood brain tumor survivors (CBTS) are at risk for developing obesity, which negatively influences cardiometabolic health. The prevalence of obesity in CBTS may have been overestimated in previous cohorts because of inclusion of children with craniopharyngioma. On the contrary, the degree of weight gain may have been underestimated because of exclusion of CBTS who experienced weight gain, but were neither overweight nor obese. Weight gain may be an indicator of underlying hypothalamic-pituitary (HP) dysfunction. We aimed to study prevalence of and risk factors for significant weight gain, overweight, or obesity, and its association with HP dysfunction in a national cohort of noncraniopharyngioma and nonpituitary CBTS. METHODS: Prevalence of and risk factors for significant weight gain (body mass index [BMI] change ≥ +2.0 standard deviation score [SDS]), overweight, or obesity at follow-up, and its association with HP dysfunction were studied in a nationwide cohort of CBTS, diagnosed in a 10-year period (2002-2012), excluding all craniopharyngioma and pituitary tumors. RESULTS: Of 661 CBTS, with a median age at follow-up of 7.3 years, 33.1% had significant weight gain, overweight, or obesity. Of the CBTS between 4 and 20 years of age, 28.7% were overweight or obese, compared with 13.2% of the general population between 4 and 20 years of age. BMI SDS at diagnosis, diagnosis of low-grade glioma, diabetes insipidus, and central precocious puberty were associated with weight gain, overweight, or obesity. The prevalence of HP dysfunction was higher in overweight and obese CTBS compared with normal-weight CBTS. CONCLUSION: Overweight, obesity, and significant weight gain are prevalent in CBTS. An increase in BMI during follow-up may be a reflection of HP dysfunction, necessitating more intense endocrine surveillance.

Brain computer tomography in critically ill patients--a prospective cohort study.

BACKGROUND: Brain computer tomography (brain CT) is an important imaging tool in patients with intracranial disorders. In ICU patients, a brain CT implies an intrahospital transport which has inherent risks. The proceeds and consequences of a brain CT in a critically ill patient should outweigh these risks. The aim of this study was to critically evaluate the diagnostic and therapeutic yield of brain CT in ICU patients. METHODS: In a prospective observational study data were collected during one year on the reasons to request a brain CT, expected abnormalities, abnormalities found by the radiologist and consequences for treatment. An "expected abnormality" was any finding that had been predicted by the physician requesting the brain CT. A brain CT was "diagnostically positive", if the abnormality found was new or if an already known abnormality was increased. It was "diagnostically negative" if an already known abnormality was unchanged or if an expected abnormality was not found. The treatment consequences of the brain CT, were registered as "treatment as planned", "treatment changed, not as planned", "treatment unchanged". RESULTS: Data of 225 brain CT in 175 patients were analyzed. In 115 (51%) brain CT the abnormalities found were new or increased known abnormalities. 115 (51%) brain CT were found to be diagnostically positive. In the medical group 29 (39%) of brain CT were positive, in the surgical group 86 (57%), p 0.01. After a positive brain CT, in which the expected abnormalities were found, treatment was changed as planned in 33%, and in 19% treatment was changed otherwise than planned. CONCLUSIONS: The results of this study show that the diagnostic and therapeutic yield of brain CT in critically ill patients is moderate. The development of guidelines regarding the decision rules for performing a brain CT in ICU patients is needed.

PARP inhibition sensitizes childhood high grade glioma, medulloblastoma and ependymoma to radiation.

Poly ADP-ribose polymerase (PARP) is a protein involved in single strand break repair. Recently, PARP inhibitors have shown considerable promise in the treatment of several cancers, both in monotherapy and in combination with cytotoxic agents. Synthetic lethal action of PARP inhibitors has been observed in tumors with mutations in double strand break repair pathways. In addition, PARP inhibition potentially enhances sensitivity of tumor cells to DNA damaging agents, including radiotherapy. Aim of this study is to determine the radiosensitizing properties of the PARP inhibitor Olaparib in childhood medulloblastoma, ependymoma and high grade glioma (HGG). Increased PARP1 expression was observed in medulloblastoma, ependymoma and HGG, as compared to non-neoplastic brain tissue. Pediatric high grade glioma, medulloblastoma and ependymoma gene expression profiling revealed that high PARP1 expression is associated with poor prognosis. Cell growth inhibition assays with Olaparib resulted in differential sensitivity, with IC50 values ranging from 1.4 to 8.4 µM, irrespective of tumor type and PARP1 protein expression. Sensitization to radiation was observed in medulloblastoma, ependymoma and HGG cell lines with subcytotoxic concentrations of Olaparib, which coincided with persistence of double strand breaks. Combining PARP inhibitors with radiotherapy in clinical studies in childhood high grade brain tumors may improve therapeutic outcome.