Weight development and neuroendocrine deficits following proton beam therapy in children with craniopharyngioma

Martin Bischoff; Julia Beckhaus; Khalil Dalia Ahmad; Frisch Sabine; Benjamin Koska; Cordula Kiewert; Rolf-Dieter Kortmann; Brigitte Bison; Carsten Friedrich; Müller Hermann L.; Beate Timmermann

P2-101

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ESPE Abstracts (2024) 98 P2-101

ESPE2024 Poster Category 2 Fat, Metabolism and Obesity (39 abstracts)

Weight development and neuroendocrine deficits following proton beam therapy in children with craniopharyngioma

Martin Bischoff ^1,2 , Julia Beckhaus ³ , Dalia Ahmad Khalil ¹ , Frisch Sabine ¹ , Benjamin Koska ¹ , Cordula Kiewert ⁴ , Rolf-Dieter Kortmann ⁵ , Brigitte Bison ⁶ , Carsten Friedrich ³ , Hermann L. Müller ³ & Beate Timmermann ^1,7

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¹Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen (WPE), West German Cancer Center (WTZ), Essen, Germany. ²Department of Radiation Oncology, Ruhr-University Bochum, Medical Faculty, Marien Hospital, Herne, Germany. ³Department of Pediatrics and Pediatric Hematology/Oncology, University Children’s Hospital, Carl von Ossietzky Universität Oldenburg, Klinikum Oldenburg AöR, Oldenburg, Germany. ⁴Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. ⁵5 Department of Radiation Oncology, University of Leipzig, Leipzig, Germany. ⁶Diagnostic and Interventional Neuroradiology, Faculty of Medicine, University of Augsburg, Augsburg, Germany. ⁷German Cancer Consortium (DKTK), Heidelberg, Germany

Background and aims: Craniopharyngiomas (CPs) are rare, non-malignant tumors near the pituitary and hypothalamus. Besides surgery, radiotherapy plays an important role in the treatment strategy. Both tumor-related factors and treatment can cause severe obesity and neuroendocrine disorders. Clinical studies have shown that endocrine deficits can occur at a dose level of 18Gy and risk increases with higher doses. Proton therapy (PT) is increasingly used in order to better spare normal tissue. This study aims at analyzing the impact of surgery and PT on weight development and endocrinopathies in patients with CP.

Patients and Methods: A total of 65 patients (38 girls and 27 boys) enrolled in the "KiProReg" study (DRKS0000536) were eligible for this analysis. The median age at diagnosis was 8.1 years (range, 0.01-17.4 years). Age- and sex-adjusted BMI standard deviation scores (BMI SDS) were determined and weight classification was performed according to the European Childhood Obesity Group guidelines. Additionally, number and time until occurrence of pituitary hormone deficiencies after PT were evaluated.

Results: The median FU time after PT was 3.2 years (range, 1.0-9.6 years). At baseline (pre-PT), 26 patient were classified as obese (BMI percentile >97) compared to 29 at last FU, with 86.2% categorized as severely obese (BMI percentile >99.5). Patients with higher BMI-SDS before PT had higher BMI-SDS at last visit (P <0.001). Timing of PT was associated with BMI-SDS levels at the start of PT. Patients irradiated due to tumor progression or as salvage therapy had higher BMI-SDS values (P = 0.023) than those irradiated primarily. Additionally, tumor volume and involvement of the hypothalamus were associated with relevant weight gain. Except for diabetes insipidus (P = 0.030), no other endocrinopathy showed a relation to BMI development. The mean dose to the pituitary and hypothalamus was 54.34 Gy (range, 52.5-55.4 Gy) and 53.9 Gy (range, 47.9-55.4 Gy), respectively. Before PT, 20 patients (31%) already suffered from panhypopituitarism. Among the other 45 children, 20 (44%) did not experience any additional hormone deficiency. Of the remaining 25 patients, growth hormone deficiency was most common after PT completion (in 68.1%), followed by thyroid-stimulating-hormone deficiency (in 45.4%), adrenocorticotropic-hormone deficiency (in 28.6%), and luteinizing-hormone-/ follicle-stimulating hormone deficiency (in 19.0%).

Conclusion: Obesity and other hypothalamic-pituitary hormone deficiencies are common in patients with CP. Early post-PT results show only slight increases in BMI compared to pre-PT levels. Panhypopituitarism is frequent before PT, with an additional dose-dependent risk of development of endocrinopathies following therapy. Close monitoring is essential.