Denosumab-treated Giant Cell Tumors of Bone: A Clinicopathologic Analysis of 35 Cases From the French Group of Bone Pathology.
Denosumab治疗的骨巨细胞瘤: 法国骨病理学组 35 例临床病理分析。
- 作者列表："Treffel M","Lardenois E","Larousserie F","Karanian M","Gomez-Brouchet A","Bouvier C","Le Loarer F","Aubert S","de Pinieux G","Audard V","Rios M","Sirveaux F","Vignaud JM","Gauchotte G","Marie B
:Denosumab, an antibody directed against receptor activator of nuclear factor-κB ligand (RANKL), has recently been introduced in the treatment strategy of giant cell tumor of bone. In this study, we assessed the tumor changes induced by denosumab in a national multicentric series of 35 cases (French Bone Pathology Group network-ResOs). Tissue specimens collected before and after denosumab treatment were investigated for RANKL, H3.3 G34W, p63, and Ki-67 expression, and for H3F3A mutation. These parameters were put in correspondance with clinical and radiologic presentation to identify prognostic factors, and more specifically, predictive markers of an optimal histologic response to denosumab, identified as a ≥50% loss in giant cells with fibrosis and ossification. The main changes in posttreatment specimens showed an induction of ossification (P=2.10), an increased fibrosis (P=3.10), and a major decrease in giant cells (P=6.10). No significant change in mononuclear tumor cell density and in patterns of expression of RANKL (P=0.061) and H3.3 G34W was observed (P=0.061). An optimal histologic response to denosumab treatment was associated with an enhanced progression-free survival (P=0.010 in univariate analyses; P=0.040 in multivariate analyses). The initial number of giant cells was predictive of the histologic response to treatment (P=0.016). In summary, denosumab treatment induced radical changes in the tumor. The histologic response, despite the absence of objective regression of the mononuclear cells, was associated with an enhanced progression-free survival. Greater numbers of giant cells represented the only predictive indication of an optimal histologic response to denosumab treatment.
: Denosumab是一种针对核因子-κ b受体活化因子配体 (RANKL) 的抗体，最近被引入骨巨细胞瘤的治疗策略。在这项研究中，我们评估了denosumab在 35 例国家多中心系列 (法国骨病理学组网络-ResOs) 中诱导的肿瘤变化。研究denosumab治疗前后收集的组织标本RANKL、H3.3 G34W、p63 和Ki-67 表达以及H3F3A突变。这些参数与临床和放射学表现相对应，以确定预后因素，更具体地说，是denosumab最佳组织学反应的预测标志物。确定为纤维化和骨化的巨细胞丢失 ≥ 50%。治疗后标本的主要变化显示诱导骨化 (P = 2.10)，纤维化增加 (P = 3.10)，巨细胞大量减少 (P = 6.10)。未观察到单核肿瘤细胞密度和RANKL (P = 0.061) 和H3.3 G34W (P = 0.061) 表达模式的显著变化。Denosumab治疗的最佳组织学反应与无进展生存期增强相关 (单变量分析P = 0.010; 多变量分析P = 0.040)。巨细胞的初始数量可预测治疗的组织学反应 (P = 0.016)。总之，denosumab治疗诱导了肿瘤的根治性变化。尽管没有单核细胞的客观消退，但组织学反应与无进展生存期增强相关。更多数量的巨细胞代表了denosumab治疗最佳组织学反应的唯一预测指标。
METHODS:OBJECTIVE:Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: :Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: :Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION:Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: :This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.
METHODS:PURPOSE:Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS:The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS:The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS:Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.