TY - JOUR
T1 - RANKL inhibition for giant cell lesions of the jaw
T2 - A retrospective cohort analysis
AU - Schreuder, Willem H.
AU - Lipplaa, Astrid
AU - Cleven, Arjen H.G.
AU - van den Berg, Henk
AU - Bisschop, Peter H.
AU - de Jongh, Renate T.
AU - Witjes, Max J.H.
AU - Kessler, Peter A.W.H.
AU - Merkx, Matthias A.W.
AU - Edelenbos, Esther
AU - Klop, Cornelis
AU - Schreurs, Ruud
AU - Westermann, Anneke M.
AU - Tromp, Jacqueline M.
AU - Levenga, Henriette
AU - Gelderblom, Hans
AU - de Lange, Jan
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/11
Y1 - 2022/11
N2 - Background: In all giant-cell-rich lesions (GCRL) occurring in bone, a common underlying excessive RANKL expression is held responsible for the osteolytic activity. Apart from giant cell tumour of bone (GCTB), systematic outcome analysis of RANKL inhibition in other GCRL is unavailable. The aim of this study is to assess the efficacy and safety of a 1-year denosumab protocol in giant cell lesions of the jaw (GCLJ). Methods: A retrospective cohort study was conducted compromising patients treated with a 1-year protocol of monthly subcutaneously administered 120 mg denosumab. Objective tumour response based on histology and imaging was used to calculate objective tumour response rate, progression-free survival (PFS) and time to progression. Type, severity and frequency of adverse events were recorded in a standardised way to assess safety. Results: Twenty patients, predominantly female (90%), were included. Fifty-five per cent of lesions were located in the mandible; most classified as aggressive lesions (90%). Thirty-five per cent (7/20) of cases were either recurrent after prior treatment or progressive, while on other drug treatment. Objective tumour response rate was 100% after 12 months of treatment. Median PFS was 50.4 months (95% CI 38.0–62.8) with a cumulative PFS rate of 22.6% (95% CI 1.8–43.4) at 5 years follow-up. Median time to progression was 38.4 months (95% CI 26.0–50.8). Treatment was well tolerated, and none of the patients had to interrupt therapy for toxicity. Conclusion: High-dose denosumab is effective and safe in achieving a complete response in GCLJ within 12 months. The high long-term relapse rate after treatment cessation is the main obstacle for denosumab to become standard treatment for GCLJ.
AB - Background: In all giant-cell-rich lesions (GCRL) occurring in bone, a common underlying excessive RANKL expression is held responsible for the osteolytic activity. Apart from giant cell tumour of bone (GCTB), systematic outcome analysis of RANKL inhibition in other GCRL is unavailable. The aim of this study is to assess the efficacy and safety of a 1-year denosumab protocol in giant cell lesions of the jaw (GCLJ). Methods: A retrospective cohort study was conducted compromising patients treated with a 1-year protocol of monthly subcutaneously administered 120 mg denosumab. Objective tumour response based on histology and imaging was used to calculate objective tumour response rate, progression-free survival (PFS) and time to progression. Type, severity and frequency of adverse events were recorded in a standardised way to assess safety. Results: Twenty patients, predominantly female (90%), were included. Fifty-five per cent of lesions were located in the mandible; most classified as aggressive lesions (90%). Thirty-five per cent (7/20) of cases were either recurrent after prior treatment or progressive, while on other drug treatment. Objective tumour response rate was 100% after 12 months of treatment. Median PFS was 50.4 months (95% CI 38.0–62.8) with a cumulative PFS rate of 22.6% (95% CI 1.8–43.4) at 5 years follow-up. Median time to progression was 38.4 months (95% CI 26.0–50.8). Treatment was well tolerated, and none of the patients had to interrupt therapy for toxicity. Conclusion: High-dose denosumab is effective and safe in achieving a complete response in GCLJ within 12 months. The high long-term relapse rate after treatment cessation is the main obstacle for denosumab to become standard treatment for GCLJ.
KW - Denosumab
KW - Giant cell lesions of the jaw (GCLJ)
KW - RANKL
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U2 - 10.1016/j.ejca.2022.08.011
DO - 10.1016/j.ejca.2022.08.011
M3 - Article
C2 - 36174298
AN - SCOPUS:85139178032
SN - 0959-8049
VL - 175
SP - 263
EP - 273
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -