Purpose of reviewAneurysmal bone cysts are rare, locally aggressive bone tumors. Optimal treatment of ABCs is still matter of debate as therapies including sclerotherapy, selective arterial... Show morePurpose of reviewAneurysmal bone cysts are rare, locally aggressive bone tumors. Optimal treatment of ABCs is still matter of debate as therapies including sclerotherapy, selective arterial embolization and systemic treatment with denosumab are increasingly utilized, in addition to or instead of traditional curettage. The purpose of this review is to discuss current concepts and difficulties in diagnosing and treating primary ABCs, based on latest available literature.Recent findingsIn diagnostics, multiple new fusion partners of USP-6 have been described on next-generation sequencing specifically for primary ABCs. In a recent systematic review, failure rates of percutaneous injections and surgery were comparable. In a literature review, the use of denosumab seemed effective but resulted in multiple cases of severe hypercalcemia in children.Accurately diagnosing primary ABC is crucial for treatment decisions. Curettage remains a valid treatment option, especially with adjuvant burring, autogenous bone grafting and phenolization. Percutaneous sclerotherapy represents a solid alternative to surgery, with polidocanol showing good results in larger studies. Systematic therapy with denosumab exhibits favorable results but should be reserved in the pediatric population for unresectable lesions, as it may result in severe hypercalcemia in children. When selecting a treatment option, localization, stability and safety should be considered. Show less
Heijden, L. van der; Lipplaa, A.; Langevelde, K. van; Bovee, J.V.M.G.; Sande, M.A.J. van de; Gelderblom, H. 2022
Purpose of review Giant cell tumors of bone (GCTB) are intermediate, locally aggressive primary bone tumors. For conventional GCTB, surgery remains treatment of choice. For advanced GCTB, a more... Show morePurpose of review Giant cell tumors of bone (GCTB) are intermediate, locally aggressive primary bone tumors. For conventional GCTB, surgery remains treatment of choice. For advanced GCTB, a more important role came into play for systemic therapy including denosumab and bisphosphonates over the last decade. Recent findings In diagnostics, focus has been on H3F3A (G34) driver mutations present in GCTB. The most frequent mutation (G34W) can be detected using immunohistochemistry and is highly specific in differentiating GCTB from other giant cell containing tumors. PD-L1 expression can be used as biological marker to predict higher recurrence risks in GCTB patients. The use of bisphosphonate-loaded bone cement is under investigation in a randomized controlled trial. A new technique consisting of percutaneous microwave ablation and bisphosphonate-loaded polymethylmethacrylate cementoplasty was proposed for unresectable (pelvic) GCTB. Increased experience with use of denosumab raised concern on elevated recurrence rates. However, conclusions of meta-analyses should be interpreted with risk of indication bias in mind. Several small studies are published with short-course denosumab (varying from 3 to 6 doses). One small trial directly compared denosumab and zoledronic acid, with no statistical differences in radiological and clinical outcome, and nonsignificantly higher recurrence rate after denosumab. As bisphosphonates directly target neoplastic stromal cells in GCTB, larger directly comparative trials are still warranted. Neoadjuvant denosumab is highly effective for advanced GCTB, and a short-course is advised to facilitate surgery, whereas increased recurrence rates remain of concern. Randomized controlled trials are conducted on bisphosphonate-loaded bone cement and on optimal dose and duration of neoadjuvant denosumab. PD-L1 could be a potential new therapy target in GCTB. Show less
Heijden, L. van der; Bindt, S.; Scorianz, M.; Ng, C.; Gibbons, M.C.L.H.; Sande, M.J. van de; Campanacci, D.A. 2022
AimsGiant cell tumour of bone (GCTB) treatment changed since the introduction of denosumab from purely surgical towards a multidisciplinary approach, with recent concerns of higher recurrence rates... Show moreAimsGiant cell tumour of bone (GCTB) treatment changed since the introduction of denosumab from purely surgical towards a multidisciplinary approach, with recent concerns of higher recurrence rates after denosumab. We evaluated oncological, surgical, and functional outcomes for distal radius GCTB, with a critically appraised systematic literature review.MethodsWe included 76 patients with distal radius GCTB in three sarcoma centres (1990 to 2019). Median follow-up was 8.8 years (2 to 23). Seven patients underwent curettage, 38 curettage with adjuvants, and 31 resection; 20 had denosumab.ResultsRecurrence rate was 71% (5/7) after curettage, 32% (12/38) after curettage with adjuvants, and 6% (2/31) after resection. Median time to recurrence was 17 months (4 to 77). Recurrences were treated with curettage with adjuvants (11), resection (six), or curettage (two). Overall, 84% (38/45) was cured after one to thee intralesional procedures. Seven patients had 12 months neoadjuvant denosumab (5 to 15) and sixmonths adjuvant denosumab; two recurred (29%). Twelve patients had six months neoadjuvant denosumab (4 to 10); five recurred (42%). Two had pulmonary metastases (2.6%), both stable after denosumab. Complication rate was 18% (14/76, with 11 requiring surgery). At follow-up, median Musculo-Skeletal Tumour Society score was 28 (18 to 30), median Short Form-36 Health Survey was 86 (41 to 95), and median Disability of Arm, Shoulder, and Hand was 7.8 (0 to 58).ConclusionDistal radius GCTB treatment might deviate from general GCTB treatment because of complexity of wrist anatomy and function. Novel insights on surgical treatment are presented in this multicentre study and systematic review. Intralesional surgery resulted in high recurrence-rate for distal radius GCTB, also with additional denosumab. The large majority of patients however, were cured after repeated curettage. Show less
Heijden, L. van der; Dijkstra, S.; Sande, M. van de; Gelderblom, H. 2020
Purpose of review Giant cell tumour of bone (GCTB) is an intermediate, locally aggressive primary bone tumour. In addition to local therapy, new drugs became available for this disease. Denosumab,... Show morePurpose of review Giant cell tumour of bone (GCTB) is an intermediate, locally aggressive primary bone tumour. In addition to local therapy, new drugs became available for this disease. Denosumab, a receptor activator of nuclear factor kappa-B-ligand inhibitor, was introduced as systemic targeted therapy for advanced or inoperable and metastatic GCTB. Also, the bisphosphonate zoledronic acid has activity in GCTB by directly targeting the neoplastic stromal cells. Recent findings In a small RCT, bisphosphonates were successful in controlling tumour growth and a higher apoptotic index of tumour cells was seen after zoledronic acid versus controls. Although bisphosphonate-loaded bone cement has not been studied to a large extent, it does not seem harmful and may constitute a logical local adjuvant. From the largest clinical trial to date, the risk-to-benefit ratio for denosumab in patients with advanced GCTB remains favourable, also in facilitating less morbid surgery. Concerns have arisen that recurrence rates would be higher than after conventional treatment, ranging from 20 to 100% in a systematic review, although this may be because of bias. H3F3A (G34W) driver mutations are helpful in the differentiation between GCTB and other giant cell-containing malignancies. H3.3-G34W proved sufficient to drive tumourigenesis. The cumulative incidence of malignancy in GCTB is estimated at 4%, of which primary malignancy 1.6% and secondary malignancy 2.4%, the latter mainly after radiation. To date, a potential causal relationship between denosumab and pulmonary metastases has not been confirmed; if they do not behave indolently, it would be advised to reassess diagnosis and consider malignancy. Denosumab remains a highly effective treatment option for patients with advanced GCTB. A short duration of 2-4 months neoadjuvant denosumab is advised to facilitate less morbid surgery and prevent incomplete curettage by macroscopic tumour alterations. Reduced dose intensity is being studied to reduce long term side-effects. Further research on bisphosphonates and other targets including H3.3-G34W remains warranted. Show less
