Local Tumor Recurrence and Escape from Suppression of Bone Resorption With Denosumab Treatment in Two Adolescents With Giant Cell Tumors of Bone

Akel, Umar; Robinson, Marie-Ève; Werier, Joel; Rampersaud, Raja; Rakhra, Kawan; Johnston, Donna L.; Konji, Victor N.; Page, Marika; Matzinger, Mary Ann; Ward, Leanne M.

doi:10.1002/jbm4.10196

Cited by 9 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Observed side effects were similar as previously described, including hypocalcemia during treatment and rebound hypercalcemia with discontinuation (17,(20)(21)(22)(23)(24)(25)(26)(27). Namely, three of the four patients experienced hypocalcemia with the initiation of denosumab, noted within 1 week after medication administration, which was corrected with calcium supplementation.…”

Section: Discussionsupporting

confidence: 80%

“…Given the unknown and unstudied effects of denosumab on growing bones, the use of denosumab in children has been limited. To date, we have found reports of 17 children and adolescents in the literature who have been treated with denosumab for various indications, including osteogenesis imperfecta type VI (20), juvenile Paget's disease (21), giant cell tumors (22)(23)(24)(25)(26), fibrous dysplasia (27), osteoglyphonic dysplasia (28), cherubism (17), and non-syndromic giant cell lesions of the jaw (17,26). The use of denosumab in NL/MGCL has been reported in one adult (17).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Case Report: Safety and Efficacy of Denosumab in Four Children With Noonan Syndrome With Multiple Giant Cell Lesions of the Jaw

et al. 2020

View full text Add to dashboard Cite

Noonan syndrome is a genetic disorder caused by mutations in the RAS/MAPK pathway. Multiple giant cell lesions are a rare sequelae of disruptions in this pathway, termed Noonan-like multiple giant cell lesions (NL/MGCLs). Medical management of these tumors rather than surgical intervention is preferential as the lesions are benign but locally destructive and recurring. This case series describes four male pediatric patients with Noonan syndrome and multiple giant cell lesions of the jaw treated with denosumab, a monoclonal antibody to receptor activator of nuclear factor kappa B ligand (RANKL), which has been approved for the treatment of malignant giant cell tumors in adults but not evaluated for safety or efficacy in children. All four pediatric patients responded clinically and radiographically to the treatment. Adverse events occurred in a predictable pattern and included hypocalcemia and joint pain during the initiation of treatment and symptomatic hypercalcemia after the cessation of treatment. Growth was not significantly impaired in these skeletally immature patients. This case series demonstrates how a weight-adjusted denosumab dose can effectively treat NL/MGCLs and provides laboratory data for consideration of the timing of monitoring for known side effects.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Case Report: Safety and Efficacy of Denosumab in Four Children With Noonan Syndrome With Multiple Giant Cell Lesions of the Jaw

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A critical review of these published studies identified 60 studies that met the inclusion criteria for the present meta-analysis ( Table 1 ). 11 , 12 , 44 , 60 - 116 The www.clinicaltrials.gov website showed 7 ongoing studies of denosumab in the treatment of GCTB. The majority of the studies examined for this meta-analysis were case reports, case series studies, and nonrandomized, uncontrolled, open-label phase II studies ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

Denosumab for Effective Tumor Size Reduction in Patients With Giant Cell Tumors of the Bone: A Systematic Review and Meta-Analysis

Yayan

2020

Cancer Control

View full text Add to dashboard Cite

Background: Denosumab is a human monoclonal antibody that has been used successfully in the treatment of giant cell tumors of bone. These tumors are rare and, in principle, benign, but they are highly aggressive, locally advanced, osteolytic bone tumors that can metastasize to the lungs. Denosumab is an effective treatment when these tumors cannot be surgically removed or when surgical resection is likely to lead to severe morbidity (eg, loss of limbs or joints). The aim of this systematic review and meta-analysis was to investigate patients with giant cell tumors of bone who experienced tumor progression during treatment with denosumab and to compare them with patients who experienced reduction of their giant cell tumors of bone during treatment with denosumab. Methods: Embase, Cochrane Library, and MEDLINE/PubMed databases were searched for trials submitted by January 7, 2020, that reported the efficacy and safety of denosumab in patients with giant cell tumors of bone. Results: Sixty studies were reviewed, involving a total of 1074 patients who had giant cell tumors of bone and were treated with denosumab. Of the 60 studies, 58% of the patients were from case series studies, 39% from open-label phase II studies, and 3% from case reports. The response rate for denosumab as a treatment for giant cell tumors of bone was 97.5%, with statistical significance ( P < .0001). Pain in the limbs was statistically the most common adverse event for denosumab treatment in case series studies ( P < .0001). No treatment-related deaths occurred in the reviewed studies. Conclusion: Cumulative evidence supports the addition of surgery to optimal medical therapy with denosumab to reduce tumor size, clinical symptoms, and mortality among patients with giant cell tumors of bone.

show abstract

“…14 Several studies have reported denosumab to be an effective treatment option for aggressive and difficult cases of GCTB. 15 –20 However, despite the reported benefits, adjuvant treatment using denosumab has recently been shown to be associated with a risk of recurrence in curettage treatment of GCTB. 12,21 A phase 3 trial of adjuvant treatment using denosumab in surgical settings has been running in Japan since 2017; however, the study is still ongoing due to difficulty of collecting entries.…”

Section: Brief Introductionmentioning

confidence: 99%

Preoperative denosumab treatment with curettage may be a risk factor for recurrence of giant cell tumor of bone

Sano

Suehara

Okubo

et al. 2020

J Orthop Surg (Hong Kong)

View full text Add to dashboard Cite

Purpose: Giant cell tumor of bone (GCTB) is a local aggressive bone tumor, histologically classified as intermediate malignancy. Recently, the RANKL inhibitor, denosumab, was developed as a novel and effective treatment option for GCTB. Since the risk of preoperative use of denosumab with curettage had been previously reported, this study aimed to investigate the relationship between recurrences and clinicopathological features associated with adjuvant denosumab treatment in GCTB. Methods: A total of 87 GCTB cases were treated at our institution. We reviewed 66 patients with conventional-type GCTB occurring in the extremities and analyzed 78 surgical treatments, including curettages and resections, with clinicopathological features and denosumab treatment. Results: GCTB lesions, including 66 primary and 12 recurring, underwent surgical treatment like curettage and resection. Recurrence-free survivals in 78 GCTB surgeries were 78.7% in 3 years and 71.9% in 5 years. In the resected cases of GCTBs, there was no recurrence either with or without denosumab. In curettage cases, 3-year recurrence-free survivals were 0.0% ( n = 3) in preoperative treatment of denosumab, 66.7% ( n = 6) in postoperative treatment, and 76.6% ( n = 43) in no treatment. Interestingly, three preoperative treatment cases demonstrated low MIB-1 index despite 100% recurrence. The other clinicopathological factors did not contribute much to the risk of recurrence in curettage cases. Conclusion: Our findings revealed the use of denosumab in GCTB, prior to curettage, to possibly increase the risk of local recurrence. Together with previous reports, our finding might provide information for beneficial treatment of GCTB.

show abstract

Local Tumor Recurrence and Escape from Suppression of Bone Resorption With Denosumab Treatment in Two Adolescents With Giant Cell Tumors of Bone

Cited by 9 publications

References 14 publications

Case Report: Safety and Efficacy of Denosumab in Four Children With Noonan Syndrome With Multiple Giant Cell Lesions of the Jaw

Case Report: Safety and Efficacy of Denosumab in Four Children With Noonan Syndrome With Multiple Giant Cell Lesions of the Jaw

Denosumab for Effective Tumor Size Reduction in Patients With Giant Cell Tumors of the Bone: A Systematic Review and Meta-Analysis

Preoperative denosumab treatment with curettage may be a risk factor for recurrence of giant cell tumor of bone

Contact Info

Product

Resources

About