Denosumab for central giant cell granuloma in an Australian tertiary paediatric centre

Vanderniet, Joel A.; Wall, Christie-Lee; Mullins, Anna; London, Kevin; Lim, Lydia; Hibbert, Sally; Briody, Julie; Padhye, Bhavna; Poon, Myra; Biggin, Andrew; Dalla-Pozza, Luciano; Munns, Craig F.

Affiliations

¹Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Sydney, NSW, Australia

²Cancer Centre for Children, The Children’s Hospital at Westmead, Sydney, NSW, Australia

³Department of Nuclear Medicine, The Children’s Hospital at Westmead, Sydney, NSW, Australia

⁴Department of Oral and Maxillofacial Surgery, Westmead Hospital, Sydney, NSW, Australia

⁵Department of Paediatric Dentistry and Oral and Maxillofacial Surgery, The Children’s Hospital at Westmead, Sydney, NSW, Australia

⁶Department of Paediatric Dentistry, Westmead Centre for Oral Health, Sydney, NSW, Australia

⁷Discipline of Paediatrics and Child Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

⁸Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia

⁹Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia

¹⁰Department of Endocrinology and Diabetes, Queensland Children’s Hospital, Brisbane, QLD, Australia

Abstract and keywords

Background: Central giant cell granulomas (CGCG) are rare osteolytic, benign but often locally aggressive tumours of bone. Surgical curettage may not be possible in extensive lesions and resection carries high morbidity, especially in growing children, and previous medical therapies have had variable efficacy and high recurrence rates. Interruption of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling holds promise as an effective therapeutic strategy for these tumours.

Aims: To evaluate the efficacy and safety of our protocol for denosumab treatment of CGCG in children.

Methods: Retrospective review of 4 patients treated with denosumab using a standardised protocol for CGCG in a tertiary paediatric centre. Denosumab 70 mg/m2 was given 4-weekly, followed by 2 doses of zoledronate 0.025 mg/kg, aimed at preventing rebound hypercalcaemia.

Results: Treatment of CGCG resulted in metabolic remission in all patients, but recurrence, detected by positron emission tomography (PET), occurred at 6 months in three patients and 12 months in one patient. Three patients developed symptomatic hypercalcaemia 4–5 months and one patient asymptomatic hypercalcaemia 7 months after cessation of denosumab, with 3 requiring additional bisphosphonate treatment.

Conclusions: Denosumab produced a radiological and metabolic response in our patients, but metabolic recurrence occurred in all patients. PET imaging was effective for monitoring treatment response and early detection of recurrence. Incidence of rebound hypercalcaemia in this paediatric cohort was high. We present proposed changes to our protocol with the aim of producing sustained remission and preventing rebound hypercalcaemia.

Keywords: Hypercalcemia; Hypocalcemia; Recurrence; PET CT

Links

DOI: 10.1016/j.bone.2022.116395

PubMed: 35331976

WoS: 000783974800001

History

Received: 2021-12-28

Revised: 2022-02-26

Accepted: 2022-03-17

Online: 2022-03-21