Recurrence of giant cell tumour of bone: role of p53, cyclin D1, β-catenin and Ki67

Lujic, Nenad; Sopta, Jelena; Kovacevic, Relja; Stevanovic, Vladan; Davidović, Radoslav

doi:10.1007/s00264-016-3292-2

Cited by 15 publications

(13 citation statements)

References 29 publications

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“…Histologically, osteoclast-like multinuclear giant cells and mononuclear neoplastic stroma cells influence tumor activity [1, 28], but histological classification of GCT was not reliable in predicting prognosis [5, 15, 29]. We also evaluated mitosis rate of the mononuclear cell population and found that higher mitosis rate was associated with significantly lower recurrence-free survival and higher hazard ratio in multivariate analysis, which is compatible with another report [21].…”

Section: Discussionsupporting

confidence: 80%

Retrospective analysis of 51 intralesionally treated cases with progressed giant cell tumor of the bone: local adjuvant use of hydrogen peroxide reduces the risk for tumor recurrence

et al. 2019

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Background Giant cell tumor of the bone (GCT) has high local recurrence rates and the prognosis is hard to predict. We therefore retrospectively analyzed clinical outcome and recurrences of 51 GCT cases focusing on the effects of adjuvant local use of hydrogen peroxide. Methods The series enclosed 51 advanced GCT cases of the upper and lower extremities ( n = 27 Campanacci grade III; n = 24 grade II; n = 39 surgery at our institution, n = 12 elsewhere). Mean follow-up was 88.3 (± 62.0) months. Surgical details, histology, metastases, recurrences, and interview-based data on satisfaction and function including the Musculoskeletal Tumor Society (MSTS) score were evaluated. It was investigated whether hydrogen peroxide was additionally used or not to clean the tumor cavity after curettage as we hypothesized influence on recurrences. To analyze the underlying mechanisms, GCT-derived stromal cell lines were cultured in vitro and tested for cell viability and apoptosis after treatment with hydrogen peroxide. Statistical analysis was performed with Student’s t tests, analysis of variance (ANOVA) with post hoc testing, Mann-Whitney U tests, chi-square tests, Kaplan-Meier analysis, and multivariate Cox regression analysis. Results The whole series had 21 recurrences (41%). Eleven recurrences were found (28%) after surgery at our institution. Kaplan-Meier analysis of cumulative recurrence-free survival revealed at 2 years follow-up 69% (72%, only our institution) and at 10 years follow-up 54% (68%, only our institution). Intralesional resection was performed by vigorous curettage, burring, and defect filling with either polymethylmethacrylate bone cement ( n = 45) or cancellous bone from the iliac crest ( n = 6). Univariate chi-square analysis showed significantly lower recurrence rate after bone cement filling (2.3-fold, p = 0.024). Cleaning of the lesion cavity with hydrogen peroxide significantly reduced recurrence rate (whole collective 2.9-fold, p = 0.004; our institution 2.8-fold, p = 0.04) and significantly increased cumulative recurrence-free survival rate (whole collective at 10 years follow-up 74% versus 31%, p = 0.002; our institution 79% versus 48%, p = 0.02) compared to cases without hydrogen peroxide treatment. In multivariate analysis, significant risk factors for recurrence were pathological fracture (hazard ratio 3.7; p = 0.04), high mitosis rate (hazard ratio 15.6; p = 0.01), and lack of hydrogen peroxide use (hazard ratio 6.0; p = 0.02). In vitro cell culture analyses found apoptotic nature of hydrogen pe...

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Section: Discussionsupporting

confidence: 80%

Retrospective analysis of 51 intralesionally treated cases with progressed giant cell tumor of the bone: local adjuvant use of hydrogen peroxide reduces the risk for tumor recurrence

et al. 2019

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“…23 Other research groups had also reported various immunostaining factors (p53, cyclin D1, b-catenin, and Ki67 (MIB-1)) useful for predicting the recurrence of GCTB. 24,25 Therefore, to determine the utility of adjuvant therapy using denosumab in GCTB, the current study retrospectively analyzed the associations between recurrence status and clinicopathological factors, including denosumab and immunostaining factors, using 66 GCTB cases that occurred in the extremities, excluding the malignant ones.…”

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)

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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.

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“…13,14,17,18 Recently, some researchers have identified some immunostaining factors (MIB-1, GPX-1, cyclin D1 and b-catenin) that are associated with predilection for GCTB recurrence. [19][20][21] This is all still experimental and has the potential for clinical use to determine cases that are more likely to recur. GCTB is different from Giant Cell Rich Malignancies where there is presence of giant cells in the malignant tumours.…”

Section: What Is Giant Cell Tumour Of the Bone (Gctb)mentioning

confidence: 99%

The current standing on the use of denosumab in giant cell tumour of the bone

Singh¹,

Puri

2020

J Orthop Surg (Hong Kong)

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Giant cell tumour of the bone (GCTB) has been classically treated surgically. With the advent of denosumab, there is potential to use it as a targeted therapy to downstage the tumour and control its progression. Like all new therapies, the dosage, duration, and long-term effects of treatment can only be determined over the time through numerous trials and errors. The current recommendation of use of the monoclonal antibody is 3–4 months of neoadjuvant denosumab in patients with advanced GCTB for cases who were not candidates for primary curettage initially, and prolonged use for surgically unsalvageable GCTB. The use of Denosumab in the adjuvant setting to prevent recurrence is not established.

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Recurrence of giant cell tumour of bone: role of p53, cyclin D1, β-catenin and Ki67

Cited by 15 publications

References 29 publications

Retrospective analysis of 51 intralesionally treated cases with progressed giant cell tumor of the bone: local adjuvant use of hydrogen peroxide reduces the risk for tumor recurrence

Retrospective analysis of 51 intralesionally treated cases with progressed giant cell tumor of the bone: local adjuvant use of hydrogen peroxide reduces the risk for tumor recurrence

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

The current standing on the use of denosumab in giant cell tumour of the bone

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