Late Effects in Pediatric Brain Tumor Survivors
A study on renal, skeletal and metabolic sequelae and neurological outcome 
Acta Universitatis Tamperensis No. 1739

By Sari Pietila
July 2012
Tampere University Press
ISBN: 9789514488276
139 pages
$87.50 Paper original

Background: Brain tumors are the most common solid tumors in children and the second most common form of cancer occurring in childhood. In Finland about 40–50 childhood brain tumors are diagnosed yearly. Treatment modalities include surgery, radiotherapy and chemotherapy. As a result of improvements in diagnosis and treatment, the number of long-term survivors has increased. These survivors are at high risk of chronic health conditions later in life. Adverse late effects may be due to the tumor itself or consequences of the treatment.

Aims: The aim of this study was to assess the renal consequences of treatment, the risk of hypertension, bone health, prevalence of obesity and metabolic changes, and neurological outcome, and to identify factors associated with problems discovered in childhood brain tumor survivors.

Subjects and Methods: A total of 104 primary brain tumor patients diagnosed at under 17 years of age between 1983–1997 were treated in Tampere University Hospital. When the study began in summer 1998, 24 of them had died. Of the 80 survivors 75 potentially eligible patients were invited to attend this cross-sectional study. Fifty-two (69%) participated in the study and were examined at a mean age of 14.2 years (range 3.8–28.7 years) after a mean follow-up time of 7.5 years (1.5–15.1 years). Diagnosed brain tumors included both benign and malignant tumors. The most common single tumor type was pilocytic astrocytoma. All 52 participants had undergone one or more surgical procedures. Twenty (38%) were treated with radiotherapy and 17 (33%) with chemotherapy; 14 (27%) received both. Thirteen (25%) had a residive or residual tumor upon evaluation. Thirty (58 %) had had hydrocephalus; all except one had been shunted. One third of all patients had needed shunt revisions, 10 (19% of all) more than one.

Results: Five out of 14 patients treated with cisplatin had renal glomerular dysfunction (GFR<87 ml/min/1.73m2) immediately after treatment. They had received high cumulative doses of cisplatin. During the study recovery from renal glomerular dysfunction was observed in one case; 4/14 (29%) thus had abnormal GFR at the time of study. There were several signs of tubular dysfunction in the cisplatin group. Hypomagnesemia was found in 71%. In addition, low plasma phosphate and potassium, hyperuricemia, metabolic alkalosis and tubular proteinuria were more common in patients who had received cisplatin. After cisplatin treatment renal glomerular dysfunction appeared overall to be permanent, and persistent and even progressive changes in renal tubular function were seen.

Approximately every fifth patient had elevated blood pressure. This was associated with cisplatin treatment, cranial irradiation, renal glomerular dysfunction and hypomagnesemia. The risk of elevated blood pressure was higher if the patients had been exposed to both cisplatin and cranial irradiation.

Fifteen out of 46 (33%) had low total body bone mineral density (Z-score < -2.0). Craniospinal irradiation was significantly associated with low Z-score.

Ten (19%) were overweight and four (8%) were obese. Dual-energy X-ray absorptiometry showed 16/46 (35%) to be obese. Central obesity was found in 11 (21%). Thirteen (25%) had hypercholesterolemia, 14 (27%) had raised low-density lipoprotein cholesterol, nine (17%) reduced high-density lipoprotein cholesterol, five (10%) raised triglycerides, four (8%) metabolic syndrome, two (4%) hyperinsulinemia and five (10%) hyperuricemia. Cranial irradiation, hypothalamic/hypophyseal damage, growth hormone deficiency and/or impaired mobility were associated with a higher risk of obesity and metabolic changes. Growth hormone supplementation alleviated adverse metabolic outcomes among brain tumor survivors with growth hormone deficiency.

The neurological status was abnormal in 36/52 (69%) cases. While all were ambulatory, only 50% showed normal motor function. Twenty-nine percent showed clumsiness/mild asymmetry, 21% hemiparesis. The median full-scale IQ was 85 (39–110) in 21 of the 30 participants between 6 and 16 years of age; in 29% IQ was <70. Thirty of the 44 school-aged subjects attended school with normal syllabus, 32% needed special education. Six of the 16 patients over 18 years of age were working. According to structured interview 87% coped normally in daily living. Regarding quality of life, 71% lived an active life with minor disabilities, while 29% had major neurological, cognitive and social disabilities, 8% being incapable of self-care.

Supratentorial/hemispheric tumor location, tumor reoperations, shunt revisions and chemotherapy were associated with neurological, cognitive and social disabilities.

Conclusions: Most of the childhood brain tumor survivors lived an active life with minor disabilities, but a wide range of adverse renal, vascular, metabolic, skeletal and neurological late effects with multifactorial etiology were observed. Neurological and neurocognitive impairment had the most notable impact on their daily life. The significance of the other observed late effects might be emphasized as the survivors age. With regular follow-up and early intervention it might be possible to improve the quality of life and diminish morbidity in later years. All survivors need life-long, tailor-made multiprofessional support and follow-up.

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