BACKGROUND: Craniopharyngiomas are tumorous embryogenic malformations. As the survival rate after craniopharyngioma is high (92 %), prognosis and quality of life (QoL) in survivors mainly depend on adverse late effects such as obesity. PATIENTS AND METHODS: We analyzed 214 children and adolescents with craniopharyngioma. The records of 185 patients (86 %) were available for retrospective analysis of weight profiles and risk factors for obesity. Quality of life (QoL) was measured in 145 patients by the Fertigkeitenskala Münster/Heidelberg score (FMH) and in 77 patients by PEDQOL questionnaire. RESULTS: Eighty-two of 185 patients (44 %) developed severe obesity (body mass index [BMI] > 3 SD). Obese patients were compared with 79 patients (43 %) who kept normal weight (BMI < 2 SD). No differences between obese and normal weight patients were found in terms of gender distribution, age at diagnosis and follow-up period. However, the BMI SDS at the time of diagnosis was higher (p < 0.0001) in patients who developed obesity than in those who did not. Furthermore, obese patients presented with bigger tumors (p < 0.05) and a higher rate of a hydrocephalus requiring a shunt (p < 0.05) and hypothalamic involvement (p < 0.05). The mothers of patients who developed severe obesity had a higher BMI (p < 0.001) at the time of diagnosis. Obese patients had a higher height-SDS at diagnosis (p < 0.05) and at the time of last follow-up (p < 0.05) when compared with normal weight patients. A prediction model for severe obesity after craniopharyngioma was calculated by logistic regression based on the risk factors: patient's BMI > 2 SD at diagnosis (p < 0.05; odds ratio: 16.4), hypothalamic involvement (p < 0.05; odds ratio: 3.4) and maternal BMI > 25 kg/m(2) (p < 0.05; odds ratio: 4.6). Significant increases in BMI (p < 0.001) occurred during the early post-operative period especially during the first three years after diagnosis. FMH percentiles correlated negatively with BMI SDS (Spearman r: - 0.37; p < 0.001). Children with craniopharyngioma rated their QoL more negative (p < 0.05) in regard to physical abilities, cognitive functioning and social functioning when compared with healthy children of the same age group. Severely obese patients with craniopharyngioma estimated their QoL lower (p < 0.05) for all domains except for autonomy, cognition and familial integration in comparison with non-obese patients. CONCLUSION: Hypothalamic tumor involvement and familial disposition for obesity are risk factors for the development of severe obesity in patients with craniopharyngioma. As weight gain starts early after diagnosis and severe obesity causes a reduction in QoL, early therapeutic efforts should be considered in patients at risk. To confirm our results the prospective multicenter study Kraniopharyngeom 2000 on children and adolescents with craniopharyngioma was initiated (www.kraniopharyngeom.com).

Adolescent↗

PubMedDate not supplied

Functional capacity, obesity and hypothalamic involvement: cross-sectional study on 212 patients with childhood craniopharyngioma.

The aim of this study was to analyze the impact of hypothalamic involvement of craniopharyngioma on functional capacity (FC) and obesity in 212 patients with childhood craniopharyngioma. FC could be evaluated using an ability scale (Fertigkeitenskala Münster-Heidelberg [FMH]) in 174 patients with childhood craniopharyngioma. Obesity was quantified in 212 patients at the time of diagnosis and at the time of latest evaluation by body mass index SDS [BMI]. The influence of hypothalamic tumor involvement on FC and BMI was analyzed. Patients with hypothalamic involvement (n = 125) presented with higher BMI SDS at the time of diagnosis (p = 0.001) and at latest follow-up evaluation (p < 0.001). FC as measured by FMH percentiles was lower (p < 0.001) in patients with hypothalamic involvement when compared with patients without hypothalamic involvement. FC negatively correlated (p < 0.001) with BMI SDS (Spearman's Rho = -0.40) only in patients with hypothalamic involvement whereas no correlation between FC and BMI SDS was found in patients without hypothalamic involvement. We conclude that hypothalamic involvement of childhood craniopharyngioma had major impact on FC in survivors. Obesity resulted in impaired FC of patients with hypothalamic involvement. BMI at diagnosis was a sensitive parameter to identify patients at risk of severe obesity. Further analysis on this issue is performed in the prospective, multicenter surveillance study on children and adolescents with craniopharyngioma (KRANIOPHARYNGEOM 2000).

Adolescent↗

PubMedDate not supplied

Prognosis and sequela in patients with childhood craniopharyngioma -- results of HIT-ENDO and update on KRANIOPHARYNGEOM 2000.

The overall survival rate of patients with craniopharyngioma, an embryogenic malformation, is high (0.92 +/- 0.03). However, there is considerable morbidity and impaired quality of life, even when the tumor can be completely resected. Aim of our study was to analyze risk factors for severe obesity (body mass index [BMI] > or = 7 SD) and the prognosis of severely obese survivors of childhood craniopharyngioma recruited in our cross-sectional study on 183 patients (HIT-ENDO) and in the prospective study KRANIOPHARYNGEOM 2000. Severe obesity (BMI > or = 7 SD) was present in 16 % of patients and associated with higher tumor volume (p < 0.05), more frequent neurosurgical interventions (p < 0.05) and a higher rate of hypothalamic involvement (p < 0.001). Self-assessed functional capacity (FMH) was lower (p < 0.001) in severely obese survivors (FMH: median 33, range: 4-64) when compared with normal weight patients (FMH: 50; 1-95). Overall survival (20 years) was lower (p = 0.034) in patients with severe obesity in comparison to patients with moderate obesity and normal weight. Cardiovascular morbidity and mortality was high in severely obese patients. Between 10/01 and 03/04 fifty-seven patients (27 female/30 male) were recruited in KRANIOPHARYNGEOM 2000 (www.kraniopharyngeom.com). The impact of tumor localization (3.2 % intrasellar, 22.6 % suprasellar, 74.2 % combined intra/suprasellar; 51.6 % hypothalamic involvement) and treatment (26 complete resections, 22 partial resections followed by irradiation in one case; primary irradiation after biopsy in one case) on quality of life, functional capacity and prognosis will be evaluated longitudinally and prospectively.

Adolescent↗

PubMedDate not supplied

Relapse pattern after complete resection and early progression after incomplete resection of childhood craniopharyngioma.

In HIT Endo data on therapy and prognosis of 306 patients with childhood craniopharyngioma (CP) were analyzed. The 5 years-overall survival rate was 94 +/- 4 % in irradiated patients and 93 +/- 5 % in non-irradiated patients. Aims of the prospective study KRANIOPHARYNGEOM 2000 were to collect data on the incidence and time course of relapses after complete surgery and tumour progressions after incomplete resection. Furthermore, the impact of irradiation therapy (XRT) on tumour relapse and recurrence rates was analyzed. Since 2001 ninety-eight patients with CP were recruited at a median age at diagnosis of 9.9 years ranging from 1.8 to 18.0 years. Complete resection was achieved in 44 %, incomplete resection in 54 %. XRT was performed in 24 of 98 CP patients; in 10 early after incomplete resection, in 14 of 24 after progression of residual tumour or relapse, in 3 of 14 after second surgery of relapse. XRT was performed at a median age of 12.0 years ranging from 5.0 to 18.9 years and in median after an interval of 9 months after first diagnosis. The analysis of event-free survival rates (EFS) in patients with CP showed a high rate of early events in terms of tumour progression after incomplete resection (3y-EFS: 0.22 +/- 0.09) and relapses after complete resection (3y-EFS: 0.60 +/- 0.10) during the first three years of follow-up. A high rate of early events (1y-EFS: 0.78 +/- 0.10; 2y-EFS: 0.57 +/- 0.15) was also found for patients after XRT (3 cystic progressions, 3 progressions of solid tumour; in 24 patients after XRT). We conclude that tumour progression and relapse are frequent and early events even in irradiated patients. Monitoring of cerebral imaging and clinical status is recommended in follow-up of patients with childhood CP. In order to analyze the appropriate time point of XRT after incomplete resection, QoL, EFS and overall survival in patients (age > or = 5 years) will be analyzed in KRANIOPHARYNGEOM 2007 after stratified randomization of the time point of irradiation after incomplete resection (early irradiation versus irradiation at progression of residual tumour).

Adolescent↗

PubMedDate not supplied

Preradiation chemotherapy of children and young adults with malignant brain tumors: results of the German pilot trial HIT'88/'89.

BACKGROUND: Preradiation chemotherapy could be beneficial in malignant brain tumors, because the blood-brain tumor-barrier is disrupted after surgery, bone marrow recovery--essential for intense chemotherapy--is still intact, and CNS toxicity and ototoxicity of active drugs are lower before irradiation of a child's brain. PATIENTS AND METHODS: A neoadjuvant phase 2 and a single arm pilot trial were initiated to investigate the efficacy and toxicity of an intense multidrug regimen before radiotherapy in 147 patients aged between 3 and 29; 9 years with medulloblastoma (94), malignant glioma (22), ependymoma (21), and stPNET (10). They were treated with one or two cycles consisting of procarbazine, ifosfamide/mesna with etoposide, high dose methotrexate/CF, and cisplatin with cytarabine. RESULTS: Radiation therapy was delayed for 17-30 weeks (median 23 weeks) in 112 patients who received two cycles. Chemotherapy was well tolerated. Serious infections were observed in 20 patients, with one fatal fungal septicemia. In 69 high risk patients with a residual tumor and/or solid CNS metastases an objective response (CR plus PR) was achieved in 67% medulloblastoma, 57% stPNET, 55% anaplastic ependymoma and 25% malignant glioma. Progression-free survival (PFS) at 5 years was 57% in 14 high risk patients with medulloblastoma, who achieved a complete response (CR). After a less than CR the PFS was 20% (p = 0.01). Overall survival at 5 years was 57% in medulloblastoma, 62% in ependymoma, 36% in malignant glioma and 30% in stPNET. CONCLUSION: The HIT'88/'89 regimen was well tolerated and efficacious in regard to response rates and early PSF particularly in medulloblastoma and anaplastic ependymoma. Based on these results the prospectively randomized trial HIT'91 was designed to investigate the optimal timing of chemotherapy. Preradiation chemotherapy according to the HIT'88/'89 regimen was compared with the standard regimen using CCNU, cisplatin, and vincristine after radiation therapy. Additionally, strict quality control of the three treatment modalities was instituted to help improve the survival rates in both trial arms.

Adolescent↗