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Project properties

Title	Eating behaviour after childhood craniopharyngioma in relation to diagnostic characteristics and therapy – Multicentre studies on patients with childhood craniopharyngioma (HIT Endo, KRANIOPHARYNGEOM 2000/2007)
Keywords	obesity craniopharyngioma brain tumour
Researchers	prof. dr. H. Müller A. Sterkenburg A. Hoffmann
Nature of the research	Evaluation of eating behavior by the IEG instrument. Out of a total cohort of 517 patients with childhood craniopharngioma recruited in the multicenter studies HIT-Endo and KRANIOPHARYNGEOM 2000/2007 101 patients were evaluated by the IEG in terms of their eating behavior. The IEG score for the different domains of eating behavior will be compared to existing normal values and furthermore a BMI-matched normal cohort will be analyzed as control cohort. Patient subgroups with pathological patterns of their eating behavior will be analyzed for disease and treatment related risk factors.
Fields of study	endocrinology pediatrics neurology

Background / introduction

Craniopharyngiomas (CP) are rare embryogenic malformations of the sellar area with low-grade histological malignancy (incidence: 0.5-2.0/106/y). Despite high survival rates (92%), the quality of life (QoL) is frequently impaired in long-term survivors due to sequelae caused by the anatomical proximity of CP to the optic nerve, pituitary gland, and hypothalamus [1-8]. In our cross-sectional study HIT-ENDO we analyzed 290 patients with CR in regard to hypothalamic involvement (HI), growth, obesity and QoL. 59% of all patients presented with HI at the time of diagnosis. Severe long-term obesity was related to HI and found to be a major risk factor for reduced QoL. Aware of possible bias due to retrospective analysis in our cross-sectional study, in KRANIOPHARYNGEOM 2000 we prospectively recruited 119 patients between 2001 and 2006 from 52 participating centers in Germany, Austria and Switzerland. We observed a 3-yrs-event free survival (EFS) of 0.44 ± 0.06, indicating high recurrence rates after complete resection (n=45; 3-yrs-EFS: 0.62 ± 0.09) and high progression rates after incomplete resection (n=64; 3-yrs-EFS: 0.30 ± 0.07). The study was supported by the Deutsche Kinderkrebsstiftung and conducted by the German Society for Paediatric Oncology (GPOH).

Research question / problem definition

Data on possible risk factors for severe obesity after childhood craniopharyngioma are published: We and others could show that hypothalamic tumor involvement results in obesity due to decreased physical activity, increased daytime sleepiness, reduced metabolic rates, and metabolic syndrome (hyperinsulinism). Cases of childhood craniopharyngioma with pathologic eating behavior have been published. However, it is still unknown in which patients and to what extent pathological eating behavior occurs in childhood craniopharyngioma. The proposed study would be the first analyses of a large cohort of childhood craniopharyngioma patients, which could clarify the frequency and impact of pathological patterns of eating behavior.
The proposed project has also the aim to analyze the impact of diagnostic characteristics, clinical manifestations and therapy on eating behavior in childhood craniopharyngioma. Date on the parameters to be analyzed (tumor localization and surgical hypothalamic lesions as categorized by reference panel, OS, EFS, QoL, surgical and radio-oncological therapy, endocrine and ophthalmological parameters baseline and during follow-up) were prospectively collected with a high grade of completeness (>80%).
The main question of the study is to analyze characteristic patterns of eating behavior in childhood craniopharyngioma patients and to relate these patterns to disease associated risk factors.

Workplan

To elucidate the eating behavior of patients with childhood craniopharyngioma related to tumor- and treatment-associated (risk)factors we plan to:
1. check the existing data sets (IEG) for plausibility
2. collect data on eating behavior of BMI-matched “normal” controls using the IEG instrument, in collaboration with the Childrens Hospital Oldenburg, Klinikum Oldenburg,
3. describe specific patterns of eating behavior in patients with childhood craniopharyngioma,
4. define the parameters which should be included in a multivariate analysis on factors that influence eating behavior of patients with childhood craniopharyngioma.
5. perform multivariate analysis,
6. identify independent risk factors for pathological patterns of eating behavior in patients with childhood craniopharyngioma during follow-up,
7. define risk profiles and cohorts at risk for pathological eating behavior,
8. correlate eating behavior with existing data on health-related quality of life in the patient cohort,
discuss possible recommendations for treatment strategies in patients at risk based on the results of the project.
9. discuss possible recommendations for treatment strategies in patients at risk based on the results of the project.
10. summarize the findings in a report – and publish it.
11. collaborate with the Institute for Medical Biostatistics at the University of Münster, Germany,
12. collaborate with the task force for Quality of Life assessment (HIT-Leben, Dr. G. Calaminus, University of Münster, Germany) in the German Network for Brain Tumor Studies (HIT) of the German Society for Pediatric Oncology and Hematology (GPOH),

The project will be conducted in the personal and scientific context of the study team of KRANIOPHARYNGEOM 2000/2007 (study assistants: Mrs. U. Gebhardt, PhD; Anikka Hoffmann, M.D., PhD; documentarist: Mrs. Schirawski; Study Nurse: K. Gerstmann, K. Skatschkow; coordinator: Prof. Dr. H. Müller). Biostatistical support is provided by University of Münster, Germany (Prof. Dr. A. Faldum). The evaluation of QoL assessments (PEDQOL) will be supported by the HIT-Leben task force (Dr. G. Calaminus; Mrs. Teske, Dipl. Psych. A. Wiener). Free meals and lodging at the Klinikum Oldenburg gGmbH will be provided for the time of the project.
We suggest that applicants interested in the project first contact the study team KRANIOPHARYNGEOM 2000/2007 (e-mail: Mueller.hermann@klinikum-oldenburg.de; tel.: 0049-441-4032013) before officially applicating for the project.

References

Internet sources of information:
www.kraniopharyngeom.net
www.kinderkrebsinfo.de/kranio2007 (study protocol)
www.klinikum-oldenburg.de/kinderonkologie
www.kinderkrebsregister.de

Referenties:
1. Müller HL. Childhood Craniopharyngioma – Recent advances in diagnosis, treatment and follow-up. 2008, Horm Res, 69(4):193-202
2. Roth CL, Hunneman DH, Gebhardt U, Stoffel-Wagner B, Reinehr T, Müller HL. Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma. 2007. Pediatr Res. 61(4):496-501
3. Müller HL, Gebhardt U, Pohl F, Flentje M, Emser A, Warmuth-Metz M, Kolb R, Calaminus G, Sörensen N. Relapse patterns after complete resection and early progression after incomplete resection of childhood craniopharyngioma. 2006 Klin Pädiatr, 218: 315-321
4. Müller HL, Gebhardt U, Faldum A, Emser A, Etavard-Gorris N, Kolb R, Sörensen N. Functional capacity and body mass index in patients with sellar masses – Cross-sectional study on 403 patients diagnosed during childhood and adolescence. 2005 Childs Nerv Syst, 21: 539-545
5. Müller HL, Bruhnken G, Emser A, Faldum A, Etavard-Gorris N, Gebhardt U, Kolb R, Sörensen N. Longitudinal study on quality of life in 102 survivors of childhood craniopharyngioma. 2005 Childs Nerv Syst, 21: 975-980
6. Müller HL, Emser A, Faldum A, Bruhnken G, Etavard-Gorris N, Gebhardt U, Oeverink R, Kolb R, Sörensen N. Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma. 2004 J Clin Endocrinol Metab 89: 3298-3305
7. Harz KJ, Müller HL, Waldeck E, Pudel V, Roth C. Obesity in patients with craniopharyngioma: Assessment of physical activity and food intake. 2003. J Clin Endocrinol Metab 88:5227–5231
8. Müller HL, Handwerker G, Wollny B, Faldum A, Sörensen N. Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients. 2002. J Clin Endocrinol Metab 87:3993-3996

Recent Publications:

• Müller HL. Childhood cranioharyngioma. Pituitary. 2012 Jun 8. [Epub ahead of print]
• A.Bereket, W.Kiess, R.H.Lustig, H.L.Müller, A.P.Goldstone, R.Weiss, Y.Yavuz, Z.Hochberg. Hypothalamic obesity. Obes Rev. 2012 May 11. doi: 10.1111/j.1467-789X.2012.01004.x.
• Müller HL. Childhood craniopharyngioma - Current concepts in diagnosis, therapy and follow-up. 2010. Nature Rev Endocrinol 6: 609-618.
• Müller HL et al. Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up. 2011 Eur J Endocr 165: 17-24
• Müller HL. Consequences after craniopharyngioma surgery in children. 2011. J Clin Endocrinol Metab 96: 1981-1991.
• Müller HL et al. Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up. 2011. Eur J Endocrinol 165: 17-24.
• Roth C, Gebhardt U, Müller HL. Appetite-regulating hormone changes in patients with craniopharyngioma. 2011. Obesity 19: 36-42.
• Müller HL. Increased daytime sleepiness in patients with childhood craniopharyngioma and hypothalamic tumor involvement: review of the literature and perspectives. 2010 Int J Endocrinol Epub 2010 Dec 16.
• Müller HL. Childhood craniopharyngioma: current controversies on management in diagnostics, treatment and follow-up. 2010. Expert Rev Neurother 10: 515-524.
• Müller HL et al. Analyses of treatment variables for patients with childhood craniopharyngioma - results of the multicenter prospective trial KRANIO-PHARYNGEOM 2000 after three years of follow-up. 2010. Horm Res Paediatr. 73: 175-180.
• Roth C, Müller HL et al. Changes of peripheral alpha-melanocyte-stimulating hormone in childhood obesity. 2010. Metabolism 59: 186-194.

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