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Bone Joint J ; 102-B(2): 177-185, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009426


AIMS: To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). METHODS: This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). RESULTS: There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. CONCLUSION: Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177-185.

Antineoplásicos/uso terapêutico , Neoplasias Ósseas/cirurgia , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/cirurgia , Sacro/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/tratamento farmacológico , Criança , Terapia Combinada , Curetagem/métodos , Feminino , Tumor de Células Gigantes do Osso/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
J Immunother ; 42(9): 321-330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31219973


The aim of this study was to provide a basis for the theory that the combination of conventional chemotherapy and immunotherapy would be an effective treatment for osteosarcoma. Here, the expression of programmed death ligand 1 (PD-L1) in 26 clinical osteosarcoma tissue samples collected before and after chemotherapy was analyzed. The effects of osteosarcoma cells treated with doxorubicin, a conventional chemotherapeutic agent, on the proliferation and apoptosis of CD8 T lymphocytes were investigated in vitro. Thereafter, the effectiveness of doxorubicin combined with an anti-PD-L1 antibody as an osteosarcoma therapy was tested in 24 subcutaneous tumor mouse models. The results showed that the expression of PD-L1 was upregulated by chemotherapy in both the clinical osteosarcoma tissue samples and the osteosarcoma cell lines. The proliferation of CD8 T lymphocytes was inhibited, and apoptosis in CD8 T lymphocytes was enhanced by the doxorubicin-pretreated osteosarcoma cells, whereas this effect was reversed by the anti-PD-L1 antibody. A more effective result was observed when doxorubicin was combined with the anti-PD-L1 antibody in vivo. In short, the combination of conventional chemotherapy and an anti-PD-L1 antibody might be an effective option for osteosarcoma treatment, as anti-PD-L1 antibody can reverse the immunosuppression induced by chemotherapy.

J Orthop Res ; 37(1): 258-264, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30255519


The method used to evaluate the response of osteosarcoma to preoperative chemotherapy before specimen resection is still unclear. The purpose of this study was to identify factors that contribute to overall survival (OS) and to discuss their roles in making a decision regarding Enneking surgical margins. Patients (109) with pathologically confirmed Enneking stage IIB osteosarcoma were retrospectively analyzed. Univariate and multivariate survival analyses were performed. Patient characteristics and chemotherapy-induced contrast-enhanced MRI changes were considered as potential factors. Changes in the tumor volume and the relative necrosis ratio measured by MRI were independent risk factors predicting the OS of patients who underwent limb-salvage surgery. For those in whom the tumor volume had decreased (VolRatio <1) or the relative necrosis ratio had increased by at least 10% (NecRatioInc ≥0.1), there was no significant difference in OS between Enneking wide and marginal margins. Variables measured by contrast-enhanced MRI could be used to evaluate chemotherapy response and increase the limb-salvage rate. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Neoplasias Ósseas/diagnóstico por imagem , Gadolínio DTPA , Imagem por Ressonância Magnética , Margens de Excisão , Osteossarcoma/diagnóstico por imagem , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Terapia Neoadjuvante , Osteossarcoma/tratamento farmacológico , Osteossarcoma/mortalidade , Osteossarcoma/cirurgia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
Knee ; 25(5): 952-958, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30108009


BACKGROUND: The proximal tibia is the second most common site of aggressive bone tumors. In proximal tibia resection, the patellar tendon is sectioned one to two centimeters from its insertion on the tibial tubercle, which makes it technically challenging to achieve an appropriate patellar height and firm fixation of the patellar tendon. The purpose of this study was to determine whether the patellar height influences knee function after proximal tibia endoprosthetic reconstruction (EPR). METHODS: Twenty-nine patients with pathologically confirmed aggressive bone tumors in the proximal tibia were retrospectively analyzed. We used the Insall-Salvati ratio (ISR) and the Blackburne-Peel index (BPI) to radiographically analyze the patellar height. Functional outcomes were retrospectively assessed using the Musculoskeletal Tumor Society (MSTS) score, the Oxford Knee Score (OKS) and the range of motion (ROM) which was evaluated through extensor lag and active flexion. Univariate analysis with Pearson's correlation and a multivariate linear regression of patient characteristics and surgery-related changes were performed. RESULTS: The postoperative ISRs were negatively correlated with the functionality domain of the MSTS score (function, gait, walking) and the OKS. Pearson's correlation analysis showed a significant correlation between the postoperative ISR and extensor lag. The change in patellar height had no impact on the active flexion of the knee. CONCLUSIONS: Patellar height is an independent factor contributing to knee function after proximal tibia EPR. The quality of patellar tendon reconstruction is a key point in proximal tibia EPR after tumor resection.

Neoplasias Ósseas/cirurgia , Articulação do Joelho/cirurgia , Prótese do Joelho , Osteotomia/métodos , Patela/diagnóstico por imagem , Procedimentos Cirúrgicos Reconstrutivos/métodos , Tíbia , Adolescente , Adulto , Idoso , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/fisiopatologia , Feminino , Marcha/fisiologia , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteossarcoma/diagnóstico , Osteossarcoma/fisiopatologia , Osteossarcoma/cirurgia , Patela/cirurgia , Ligamento Patelar/cirurgia , Amplitude de Movimento Articular , Estudos Retrospectivos , Adulto Jovem
Int J Surg ; 36(Pt A): 283-292, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27840310


PURPOSE: There are conflicting findings about the effect of resection margins on local recurrence in osteosarcoma after surgery. In this meta-analysis, we examined the association between local recurrence and resection margins for osteosarcoma in extremity and pelvis. METHODS: EMBASE, PubMed and Cochrane CENTRAL were searched from January 1980 to July 2016. The quality of included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale. The odds ratio and 95% confidence interval of local recurrence were estimated, respectively, for inadequate vs adequate margins and marginal vs wide margins using a random-effect model. Chi-square test was performed to comparing the local recurrence rate between extremity and pelvic osteosarcomas with an identical surgical margin. RESULTS: Thirteen articles involving 1559 patients (175 with and 1384 without local recurrence) were included in this study. The meta-analysis showed that the osteosarcoma resected with inadequate and marginal margins, whether in extremity or in pelvis, were associated with a significantly higher local recurrence rate than the osteosarcoma resected with adequate and wide margins, respectively. Chi-square test showed that, when pelvic and extremity osteosarcomas were removed with an identical resection margin, the local recurrence was significantly more frequent in pelvis osteosarcoma than in extremity osteosarcoma. CONCLUSION: This study provides level IIa evidence to support that the surgery with adequate or wide resection margin has positive effect on reducing the risk of local recurrence in osteosarcoma. In addition, the factors independent of resection margin are more likely to increase the risk of local recurrence in pelvic osteosarcoma. LEVEL OF EVIDENCE: Level IIa, Therapeutic study.

Neoplasias Ósseas/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia , Osteossarcoma/cirurgia , Ossos Pélvicos/cirurgia , Extremidades , Humanos