A high proportion of bone marrow T cells with regulatory phenotype (CD4+CD25hiFoxP3+) in Ewing sarcoma patients is associated with metastatic disease

Immunosuppressive CD4+CD25^hiFoxP3+ T cells (T_reg cells) have been found at increased densities within the tumor microenvironment in many malignancies and interfere with protective antitumor immune responses. Osseous Ewing sarcomas (ESs) are thought to derive from a bone marrow (BM) mesenchymal cell of origin, and microscopic marrow involvement defines a subpopulation of patients at a high risk of relapse. We hypothesized that BM‐resident T cells may contribute to a permissive milieu for immune escape of ESs. Using 6‐color‐flow cytometry, we investigated the pattern of immune cell subset distribution including NK cells, γδ T cells, central and effector memory CD8+ and CD4+ T cells as well as T cells with regulatory phenotype (T_reg cells) in BM obtained at diagnosis from 45 primary or relapsed ES patients treated within standardized protocols. Although patients at relapse had an inverted CD4:CD8 T‐cell ratio, neither CD8+ effector/memory T‐cell subsets nor T_reg cells significantly differed from patients at diagnosis. No significant associations of innate and effector/memory T‐cell subpopulations with known risk factors were found, including age, gender, tumor site, primary metastases and histological tumor response. By contrast, T_reg cells were found at significantly higher frequencies in patients with primary metastatic disease compared with localized ESs (5.0 vs. 3.3%, p = 0.01). Thus, increased BM T_reg cells in patients with metastasized ES may reflect an immune escape mechanism that contributes to the development of metastatic disease. Immunotherapeutic strategies will have to adequately consider the regulatory milieu within areas of Ewing tumor‐immune interactions. © 2009 UICC     

Outcomes after limb sparing resection in primary malignant pelvic tumors

Aim

To evaluate morbidity, oncologic results and functional outcome in patients with malignant tumors of pelvis treated with limb sparing resection.

Methods

Between March 2002 and November 2010, 106 cases of non metastatic malignant pelvic tumors were treated with limb sparing resections of pelvis. Diagnosis included chondrosarcoma (65), Ewing's sarcoma (25), osteogenic sarcoma (10), synovial sarcoma (3) and malignant fibrous histiocytoma, high grade sarcoma, epitheloid hemangiothelioma (1 each). Three patients had intralesional surgery because of erroneous pre-operative diagnosis of benign tumor and were excluded from final analysis. Remaining 103 patients underwent limb sparing resections with intent to achieve tumor free margins. In 1 case, an intraoperative cardiac event lead to the surgery being abandoned. Reconstruction was done in 2 of 38 cases that did not include resection of acetabulum. For 64 resections involving acetabulum various reconstruction modalities were used.

Results

Surgical margins were involved in 20 patients. Forty five patients had complications. 91 patients were available for follow up. Follow up of survivors ranged from 24 to 122 months (mean 55 months).Twenty one patients (23%) had local recurrence. Sixty patients are currently alive, 46 being continuously disease free. Overall survival was 67% at 5 years. Patients in whom acetabulum was retained had better function (mean MSTS score 27) compared to patients in whom acetabulum was resected (mean MSTS score 22).

Conclusions

Though complex and challenging, limb sparing surgery in non metastatic malignant tumors is oncologically safe and has better functional outcomes than after an amputation surgery.     

Malignant round cell tumours of bone: atypical clinical and imaging features

Objective.To describe the clinical, radiological and MRI features of six atypical cases of histologically proven appendicular Ewing sarcoma/ primitive neuroectodermal tumour (PNET). Design. Retrospective review of case notes and available imaging was carried out. Patients. Six patients (4 male, 2 female; mean age 27years, range 19–44 years), presenting over a 77-month period, were identified from the Bone Tumour Register. All had unusual clinical and imaging features for Ewing sarcoma/PNET. Results and conclusions. Four tumours were centred on the distal femoral metaphysis, one in the proximal tibial metaphysis and one in the distal tibial metaphysis. Plain radiographs were available in four cases and showed minor cortical changes. MRI demonstrated a relatively small, eccentrically located intraosseous component with a large, eccentric extraosseous component. Extension into the epiphysis was seen in three cases and into the adjacent joint in two cases. Intraosseous ”skip” metastases were present in three cases. The clinical and imaging features were atypical for conventional intraosseous Ewing sarcoma/PNET and the exact site of origin (intraosseous, periosteal or soft-tissue) was unclear. Received: 6 December 1999 Revision requested: 7 February 2000 Revision received: 20 July 2000 Accepted: 4 August 2000     

躯干中轴部位局限期尤文氏肉瘤家族肿瘤的综合治疗效果分析#br#

目的探讨躯干中轴部位尤文氏肉瘤家族肿瘤（ESFT）的临床特点及治疗策略。 方法从新疆医科大学附属肿瘤医院2008年1月至2017年5月收治的发生于躯干中轴部位的79例局限期ESFT患者中,筛选出有完整随访资料者67例;根据治疗方式分为综合治疗组39例（化疗+手术+放疗15例、化疗+手术12例及化疗+放疗12例）和单一治疗组28例（化疗10例、手术12例及放疗6例）,采用RECIST 11版标准评价近期疗效,根据随访资料分析远期生存情况。 结果综合治疗组的有效率为769％（30／39）,高于单一治疗组的500％（14／28）,差异有统计学意义（P＜005）;综合治疗组的中位总生存期（OS）和无事件生存期（EFS）分别为570个月和360个月,优于单一治疗组的190个月和80个月,差异有统计学意义（P＜005）。39例综合治疗者中27例接受手术+放疗+化疗或手术+放疗的有效率、中位OS和EFS分别为815％（22／27）、480个月和320个月,优于12例接受化疗+放疗的667％（8／12）、380个月和235个月,差异有统计学意义（P＜005）。39例综合治疗者中24例接受阿霉素联合异环磷酰胺（ADM+IFO）方案的有效率为625％（15／24）,与其余15例（非ADM+IFO方案）的733％（11／15）相比,差异无统计学意义（P＞005）;24例接受ADM+IFO方案的中位OS和EFS均＞640个月,与其余15例（非ADM+IFO方案）的580个月和340个月相比,差异亦无统计学意义（P＞005）。 结论综合治疗能改善发生在躯干中轴部位局限期ESFT患者的疗效和生存。化疗、手术联合放疗的治疗模式在疗效和生存方面优于化疗联合放疗模式。     

Ewing’s肉瘤细胞X-射线照射后TNF-α和TGF-β mRNA表达的研究

 目的　研究Ewing’s肉瘤细胞系 (RM 82 )X 射线外照射后肿瘤坏死因子 (TNF α)和转化生长因子 (TGF β)mRNA表达水平的变化 ,探讨X 射线诱导内源性TNF α和TGF β产生的可能性及意义。 方法　应用实时荧光RT PCR ,检测接受不同剂量X 线照射 (2Gy ,5Gy ,10Gy ,2 0Gy ,30Gy ,4 0Gy)和受照后不同时间 (1h ,3h ,6h ,12h ,2 4h ,4 8h ,72h)。TNF α和TGF βmRNA表达水平的变化。 结果　RM 82细胞TNF αmRNA表达水平较外照射前显著升高。一方面受照后TNF αmRNA表达逐渐升高 ,照射剂量达 4 0Gy时TNF αmRNA表达水平达高峰 ,为正常对照组的 10 8倍 ;另一方面 ,照射后 3h后TNF αmRNA表达逐渐升高 ,6h达高峰 ,为正常对照组的 18倍。相反 ,TGF βmRNA表达水平X 射线照射前后无显著变化。结论　Ewing’s肉瘤细胞系 (RM 82 )接受X 线照射后TNF αmRNA表达明显升高 ,且呈现时间、剂量依赖性。放射治疗可诱导Ewing’s肉瘤细胞系 (RM 82...     

Clinical features and outcomes in patients with extraskeletal Ewing sarcoma

BACKGROUND:

Ewing sarcoma can arise in either bone or soft tissue. The purpose of this study was to investigate whether patient characteristics, treatment strategies, and outcomes differ between skeletal Ewing sarcoma and extraskeletal Ewing sarcoma (EES).

METHODS:

Patients <40 years of age with Ewing sarcoma or peripheral primitive neuroectodermal tumor reported to the United States Surveillance, Epidemiology, and End Results Program database from 1973 to 2007 were evaluated based on skeletal (n = 1519) versus extraskeletal (n = 683) site of origin. Patient characteristics were compared using Fisher exact tests. Overall survival was estimated via the Kaplan‐Meier method and compared using log‐rank tests and Cox proportional hazard models.

RESULTS:

Patients with EES had a higher mean age (19.5 vs 16.3 years; P < .001) and were less likely to be male (53.4% vs 63.3%; P < .001) or white (84.8% vs 92.5%; P < .001) compared with patients with skeletal tumors. Extraskeletal tumors were more likely to arise in axial locations (72.9% vs 54.2%; P = .001) but were less likely to arise specifically in the pelvis (19.8% vs 26.6%; P < .001). Metastatic status or tumor size did not differ by group. Five‐year overall survival was superior for localized EES compared with localized skeletal tumors (69.7% vs 62.6%; P = .02). The hazard ratio for death in patients with localized skeletal tumors compared with localized EES was 2.36 (95% confidence interval, 1.61‐3.44) beyond 24 months from initial diagnosis.

CONCLUSIONS:

Patient characteristics and outcomes differ among patients with EES compared with patients with skeletal Ewing sarcoma. These findings may have important implications for patient care. Cancer 2011. © 2011 American Cancer Society.