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Clinical Significance of the Radiological Relationship between the Tumor and the main blood vessels in Enneking IIB Osteosarcoma of the extremities.
四肢 Enneking IIB 骨肉瘤肿瘤与主要血管放射学关系的临床意义。
- 影响因子:3.09
- DOI:10.7150/jca.42341
- 作者列表:"Jin Q","Xie X","Yao H","Wen L","Li H","Lv D","Zeng Z","Wang Y","Zou C","Yin J","Huang G","Wang B","Shen J
- 发表时间:2020-03-05
Abstract
:Aim: Osteosarcoma is one of the most prevalent primary bone malignancies in children and adolescents. Magnetic resonance imaging (MRI) has been considered a very critical tool to provide anatomical information of tumor and surrounding main blood vessels. To evaluate the prognostic significance of the radiological vascular involvement according to the pre-treatment MRI in patients with Enneking IIB osteosarcoma. Methods: In this retrospective study, we included 482 patients younger than 50 years old with Enneking IIB primary osteosarcoma of the extremities with complete clinical records from 2005 to 2015.Univariate and multivariable analyses were conducted to identify the risk factors for OS (Overall survival) and EFS (Event-free survival). The correlations between the risk factors was performed using Spearman analysis. The Kaplan-Meier method was used to calculate survival curves. Based on the radiological relationship between the tumor lesion and the surrounding reactive area with the main blood vessels as shown on pretreatment MRI findings. Results: Radiological vascular involvement assessed via pretreatment MRI is an important risk factor for Enneking IIB primary patients with osteosarcoma (HROS=2.32/HREFS=1.81 P<0.01) according to the univariate and multivariable analyses. Enneking IIB patients with osteosarcoma were assigned to three subtypes based on the radiological relationship between the main blood vessels and the lesion or reactive area. The 5-year cumulative OS of patients classified by the three types were 81.6% (type I), 67.1% (type II) and 44.8% (type III)(P<0.01). The 5-year cumulative EFS of the three types were 60.2% (type I), 46.7% (type II) and 30.2% (type III)(P<0.05). The total 5-year cumulative OS and EFS for all patients were 68.3% and 48.3%, respectively. Conclusion: Vascular involvement according to radiological findings from pretreatment MRI is an independent risk factor for cumulative OS and EFS in patients with Enneking IIB primary osteosarcoma of the extremities. The new subtyping based on the relationship between the tumors and surrounding reactive area with the main blood vessels based on pretreatment MRI can predict the prognosis of patients with osteosarcoma and provide certain directive information for selecting the appropriate surgical procedure for individual patients.
摘要
目的:骨肉瘤是儿童青少年最常见的原发性骨恶性肿瘤之一。磁共振成像(MRI)被认为是提供肿瘤及其周围主要血管解剖信息的重要手段。根据治疗前MRI对Enneking-IIB骨肉瘤患者的影像学血管受累评估其预后意义。方法:回顾性分析2005-2015年482例50岁以下四肢Enneking-IIB原发性骨肉瘤患者的临床资料,采用单变量和多变量分析方法,分析其OS(总生存率)和EFS(无事件生存率)的危险因素。采用Spearman分析法进行相关分析。用Kaplan-Meier法计算生存曲线。根据肿瘤病变与周围主要血管反应区的影像学关系,如预处理MRI所示。结果:根据单变量和多变量分析,MRI预处理对IIB原发性骨肉瘤患者(HROS=2.32/HREFS=1.81,P<0.01)的影像学血管受累是一个重要的危险因素。根据主要血管与病变或反应区的影像学关系,将Enneking-IIB骨肉瘤分为三个亚型。按三种类型划分的5年累计OS分别为81.6%(Ⅰ型)、67.1%(Ⅱ型)和44.8%(Ⅲ型)(P<0.01)。三种类型5年累计EFS分别为60.2%(Ⅰ型)、46.7%(Ⅱ型)和30.2%(Ⅲ型)(P<0.05)。5年累计OS和EFS分别为68.3%和48.3%。结论:根据MRI预处理的影像学表现,血管受累是四肢Enneking-IIB原发性骨肉瘤患者累积OS和EFS的独立危险因素。基于MRI预处理的肿瘤与周围主要血管反应区关系的新亚型可以预测骨肉瘤患者的预后,为个体化选择合适的手术方式提供一定的指导信息。
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METHODS:BACKGROUND:Osteosarcoma is the most common primary bone malignancy in children and adolescents. In order to find factors related to its recurrence, and thus improve recovery prospects, a powerful clinical signature is needed. Long noncoding RNAs (lncRNAs) are essential in osteosarcoma processes and development, and here we report significant lncRNAs to aid in earlier diagnosis of osteosarcoma. METHODS:A univariate Cox proportional hazards regression analysis and a multivariate Cox regression analysis were used to analyze osteosarcoma patients' lncRNA expression data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET), a public database. RESULTS:A lncRNA signature consisting of three lncRNAs (RP1-261G23.7, RP11-69E11.4 and SATB2-AS1) was selected. The signature was used to sort patients into high-risk and low-risk groups with meaningful recurrence rates (median recurrence time 16.80 vs. >128.22 months, log-rank test, P143.80 months, log-rank test, P=0.006). A multivariate Cox regression analysis showed that the significant lncRNA was an independent prognostic factor for osteosarcoma patients. Functional analysis suggests that these lncRNAs were related to the PI3K-Akt signaling pathway, the Wnt signaling pathway, and the G-protein coupled receptor signaling pathway, all of which have various, important roles in osteosarcoma development. The significant 3-lncRNA set could be a novel prediction biomarker that could aid in treatment and also predict the likelihood of recurrence of osteosarcoma in patients.
METHODS::Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.
METHODS:PURPOSE:The objective of this study was to investigate potential correlations between pathologic fractures (PFs) and prognosis of patients with primary central high-grade osteosarcoma of the extremities. METHODS:We retrospectively analyzed 2,847 patients registered in the Consecutive Cooperative Osteosarcoma Study Group database with primary central high-grade osteosarcoma of the extremities, treated between 1980 and 2010. Intended treatment included pre- and postoperative chemotherapy and surgery. Univariable and multivariable survival analyses were performed for all patients and then differentiated for adult and pediatric (≤ 18 years at time of diagnosis) patients. RESULTS:A total of 2,193 patients were ≤ 18 years of age; 11.3% of all patients had PFs. In the overall cohort, presence of PF correlated significantly with tumor site, histologic subtype, relative tumor size, and primary metastases, but not with body mass index or local surgical remission. In univariable analysis, 5-year overall survival (OAS) of patients with and without PF was 63% versus 71%, respectively (P = .007), and 5-year event-free survival (EFS) was 51% versus 58% (P = .026). In pediatric patients, OAS and EFS did not differ significantly between patients with and without PF. In adults, 5-year OAS in patients with and without PF was 46% versus 69% (P < .001), and 5-year EFS was 36% versus 56% (P < .001). In multivariable analysis, PF was not a statistically significant factor for OAS or EFS in the total cohort or in pediatric patients. In adult patients, PF remained an independent prognostic factor for OAS (P = .013; hazard ratio [HR], 1.893). It was not a significant prognostic factor for EFS (P = .263; HR, 1.312). CONCLUSION:In this largest study to date with extremity osteosarcomas, we observed the occurrence of PF to correlate with inferior OAS expectancies in adult but not in pediatric patients.