儿童尤文肉瘤类肿瘤14例临床分析

目的 提高对儿童尤文肉瘤类肿瘤的认识及疗效,评价应用上海儿童医学中心横纹肌肉瘤-2002方案化疗(简称RS-2002方案)的有效性及安全性.方法 制定并实施以个体因素相关的诊断治疗方案,对1997年9月至2006年9月上海儿童医学中心收治的初治尤文肉瘤类肿瘤患儿进行分析.连续病例总数为19例,家长放弃治疗5例,其余14例进入治疗方案,男9例,女5例;中位年龄7.04岁(范围:1.58～11.67岁),<10岁9例;就诊时为局限性疾病9例,伴远处转移性病变5例.所有病例均经外科手术获得病理学明确诊断,分型为尤文肉瘤9例,原始神经外胚层肿瘤5例.采用多学科联合综合治疗模式,根据疾病的扩散程度进行临床分组,不同组别接受不同强度的化疗方案.肿瘤局部控制方法为手术切除及(或)局部放疗.对患儿治疗前后、治疗过程中及停药随访中进行影像学跟踪评估.运用SPSS 11.0统计软件对患儿临床数据进行统计分析,生存率分析采用Kaplan-Meier法.结果 随访至2007年4月30日,13例患儿存活.11例处于无复发状态,中位随访期为41个月(7～115个月);3例复发,疾病复发距诊断的中位时间为23个月(16～30个月).10年总生存率(OS)为88.9%±10.5%,10年无疾病复发率(DFS)为72.2%±13.8%.1例患儿发生第二肿瘤.无治疗相关死亡发生.结论 多学科联合的综合治疗模式及RS-2002化疗方案能有效并安全地治疗儿童尤文肉瘤类肿瘤.     

尤文肉瘤家族治疗进展

尤文肉瘤家族(Ewing's sarcoma family tumor,ESFT)是儿童常见的恶性骨肿瘤,具有侵袭性、溶骨性和明显传播倾向.目前多学科综合治疗方法使患儿预后得到了显著改善.但即使积极治疗,仍有20％ ～40％的原发肿瘤患儿和近80％的转移肿瘤患儿难获显著疗效.随着生物靶向治疗的研究进展,一些晚期尤文肉瘤...     

儿童及青少年女性实体肿瘤患者卵巢功能评估及其研究进展

儿童及青少年常见的实体肿瘤包括儿童期特有的母细胞瘤类,例如神经母细胞瘤、视网膜母细胞瘤、肾母细胞瘤、肝母细胞瘤等;与成人共患的肉瘤类,例如横纹肌肉瘤、非横纹肌肉瘤类软组织肿瘤、尤文肉瘤、骨肉瘤等,以及中枢神经系统肿瘤、生殖细胞瘤等.这些肿瘤的治疗多半采取手术、化疗、放疗、干细胞移植等在内的综合治疗.其中腹部和盆腔区域原...     

左颞部婴儿型纤维肉瘤1例报道并文献复习

目的了解婴儿型纤维肉瘤(IFS)的临床特点、病理、诊断、治疗及预后。方法对2015年12月我科病房收治的1例左颞部婴儿型纤维肉瘤病例进行回顾性分析,观察患儿进行规范化治疗后的症状、体征、实验室指标的变化,并进行文献复习。结果经6周期规范化疗后,患儿原发部位稳定,无复发,远处无转移,随诊无肿瘤复发。结论婴儿型纤维肉瘤是一种相对少见的、仅发生于婴幼儿的一类软组织肉瘤,缺乏特异性,最终需病理确诊;术后化疗可有效控制病情,防止复发。     

儿童非横纹肌软组织肉瘤临床预后因素及治疗对策

目的 分析18岁以下儿童和青少年的非横纹肌肉瘤的生存率,并探讨常见肿瘤的治疗策略。方法 对1989年1月到2002年12月治疗并随访的67例非横纹肌肉瘤病例的资料进行分析,其中滑膜肉瘤16例,恶性纤维组织细胞瘤9例,纤维肉瘤9例,脂肪肉瘤7例,骨外尤文氏肉瘤/原始神经外胚叶瘤7例,腺泡状软组织肉瘤6例,平滑肌肉瘤4例,恶性外周神经鞘瘤、透明细胞软组织肉瘤、血管肉瘤各2例,上皮性软组织肉瘤、促纤维增生性小圆细胞肿瘤、恶性肾外横纹肌样肿瘤各1例。引入年龄、性别、肿瘤大小、外科病理分期、是否接受化疗和放疗等因素,应用SPSS10.0统计软件,采用COX回归和χ^2检验进行统计学分析。结果 影响非横纹肌肉瘤生存率的唯一临床因素是外科病理分期。手术完全切除比肿瘤残留或转移者的生存率更高,Ⅰ、Ⅱ期和Ⅲ、Ⅳ期的2年EFS分别为89.74%和17.86%,差异有统计学意义。无肿瘤残留者生存率高于肿瘤残留或不能切除者。结论 儿童和青少年非横纹肌软组织肉瘤罕见,各肿瘤的临床特征不同,尚无统一治疗方法。治疗原则仍以达到无肿瘤残留为目标的外科手术治疗为主;除尤文氏瘤/原始神经外胚叶瘤和滑膜肉瘤已经证实化疗有效外,其他肿瘤的术后辅助化疗和放疗尚存在争议。新辅助化疗对于部分不能切除的肿瘤可以提高手术切除率。成立全国性的协作组可以尽快积累病例,增加治疗经验,制定规范的治疗方案,是改善儿童非横纹肌软组织肉瘤疗效的有效途径。     

神经母细胞瘤的治疗进展

神经母细胞瘤是儿童期比较常见的恶性实体肿瘤,发病时临床表现多种多样,初期诊断具有一定困难性,且易发生早期转移,是引起儿童期死亡的主要疾病之一,高危神经母细胞瘤患儿的临床治疗效果仍具有很大挑战性.目前神经母细胞瘤的治疗方法主要集中在手术治疗、系统化疗、放射治疗、移植技术等.近年来更着重于靶向治疗及分子生物学(即基因学)治疗上的研究.靶向治疗是靶向性地与肿瘤的不同特异性位点发生作用,从而杀死肿瘤细胞,减少对正常组织的影响,为神经母细胞瘤患儿提供更加安全有效的治疗方案.     

儿童输尿管肿瘤的诊治分析

目的 总结儿童输尿管肿瘤的病理类型、临床表现、诊断、治疗和预后,提高对该病的认识.方法 回顾性分析2011年1月至2015年10月我院收治的5例输尿管肿瘤患儿的临床资料,结合文献总结儿童输尿管肿瘤的病理类型、临床表现、诊断、治疗及预后.5例患儿均为男性,输尿管炎性肌纤维母细胞瘤3例,2例以腹痛就诊,分别为6岁和10岁,肿瘤位于输尿管下段,均行输尿管下段肿物切除+输尿管端端(输尿管膀胱)吻合,1例以尿痛并血尿就诊,年龄1岁9月龄,肿物来源于下段输尿管,经输尿管膀胱连接部长入膀胱,继发膀胱输尿管积水,经输尿管和膀胱联合切除肿物+输尿管膀胱再植术.结果 术后随访5~48个月,未见肿瘤复发及转移.恶性横纹肌样瘤1例6岁,以左下腹痛2周就诊,输尿管肿瘤边界不清与腰大肌肉和后腹膜粘连,切除肿物行输尿管端端吻合,术后ICE方案化疗一疗程后局部复发,放弃治疗,术后233d死亡.尤文/原始神经外胚层瘤1例12岁,以右侧腰痛10d就诊,肿瘤位于输尿管髂血管水平,行输尿管肿瘤切除术+输尿管端端吻合术,术后予CAV+IE化疗12个月,随访56个月,未见转移及复发.结论 输尿管肿瘤在儿童发病率极低,文献曾报道的病理类型包括炎性肌纤维母细胞瘤、恶性横纹肌样瘤、尤文/原始神经外胚层瘤、横纹肌肉瘤,术前无特异方法诊断,手术完整切除肿瘤并重建输尿管是治疗的主要方法,确诊需要结合病理检查,根据病理类型决定是否化疗,治疗后均需要长期随访.     

复发肝母细胞瘤的治疗进展

复发肝母细胞瘤依然是治疗的难点.本文介绍了肝母细胞瘤复发时的特点,包括复发部位、复发率、肿瘤复发相关的危险因素.同时重点介绍复发肿瘤的治疗方法,包括不同复发部位的肿瘤再手术、化疗、放疗、靶向治疗等,综述了这些治疗措施的临床应用或实验室研究进展,并分别比较了各种治疗方法的有效率.     

缩短疗程化疗治疗儿童青少年局限期尤文氏肉瘤家族肿瘤的研究

目的局限型尤文氏肉瘤家族肿瘤(ESFT)合适的化疗疗程数尚未确定。本研究探讨8个疗程化疗联合局部治疗对儿童青少年局限期ESFT的疗效,并分析局部治疗方式对预后的影响。方法 2002年3月至2010年3月在中山大学肿瘤防治中心收治的46例儿童、青少年局限期ESFT入组。所有患者均接受CDV/IE交替方案8个疗程的化疗,每3周重复。CDV化疗包括环磷酰胺(1000 mg/m~2,d1)、长春新碱(1.5 mg/m~2,d1)、阿霉素(50 mg/m~2,d1);IE化疗包括异环磷酰胺(1.5 g/m~2,d1-5)、足叶乙甙(100 mg/m~2,d1-5)。局部治疗采用手术和(或)放疗。结果 46例患者中位年龄11岁(8个月~19岁)。男34例,女12例。肿瘤位于躯干17例,头颈15例,四肢12例,腹膜后2例。骨尤文氏肉瘤24例,骨外尤文氏肉瘤22例。35例局部晚期患者接受术前化疗,化疗客观有效率为88.6%。11例先行手术完整切除后化疗。局部治疗方式为手术加放疗19例,单纯手术13例和单纯放疗14例。中位随访64个月,全组5年无事件生存率(EFS)和总生存率(OS)分别为67.0%±7.0%和73.6%±6.5%。局部治疗采用手术加放疗、单纯手术和单纯放疗的患者的5年EFS分别为73.7%±10.1%、61.5%±13.5%和62.5%±13.5%(P>0.05)。局部早期和局部晚期患者5年EFS分别为79.5%±13.1%和62.9%±8.2%(P>0.05)。随访结束时,无心脏毒性或第二肿瘤发生。结论 8个疗程化疗联合有效的局部治疗对于局限期儿童青少年ESFT患者可获得较好的生存率。     

RNA聚合酶Ⅰ转录抑制剂治疗白血病及肿瘤性疾病的研究进展

<正>近10余年来,靶向治疗因其基于特定的作用靶点而发挥抗肿瘤作用,由于具有特异性强、对正常组织毒副作用小,而一直成为白血病及肿瘤领域的研究热点,也成为化疗的重要辅助手段。目前靶向药物作用靶点主要为细胞表面分子、细胞内激酶、抗凋亡分子及通过表观遗传学机制为靶点,虽然临床取得一定疗效,但仍未明显延长患者的生存期。目前亟待发现新的靶向药物,提高白血病及肿瘤患者的     

Nonmetastatic pelvic Ewing sarcoma: report of the French society of pediatric oncology.

BACKGROUND: Since January, 1984, 59 children with histologically confirmed Ewing sarcoma of the pelvic bone have been treated with three successive chemotherapy protocols recommended by the French Society of Pediatric Oncology. The purpose of the current study was to evaluate the role of surgery and/or radiotherapy in local progression-free, disease-free, and overall survivals (LPFS, DFS, and OS, respectively). PROCEDURE: We retrospectively examined 59 children treated for nonmetastatic, pelvic Ewing sarcoma over the last 12 years. All were first treated with chemotherapy according to the current French protocol. Six patients developed progressive disease before local treatment and were excluded for local control and survival analysis. Local treatment was surgery alone in 17 cases, radiation therapy in 27 cases, and surgery plus radiation therapy in 9 cases. RESULTS: With a median of follow-up of 6.5 years, no significant differences in local control or survival were observed with the three chemotherapeutic protocols. Of the 53 patients evaluable for local control, 6 relapsed locally only, 8 had local and distant relapses, and 9 had distant metastases only. The 5-year OS rate was worst for patients with radiotherapy alone compared to those with surgery or combined modality treatment (44 % vs. 72 %, P = 0.043). The 5-year LPFS and DFS rates were worst in the radiotherapy-alone group but not significantly (63% vs. 79%, P = 0. 22 and 42% vs 71%, P =0.07, respectively). The importance of surgery to OS and DFS was confirmed by multivariate analysis (P = 0.026 and P = 0.048, respectively). One surviving patient was diagnosed with in-field fibrosarcoma, which was presumably radiation induced. CONCLUSIONS: Despite intensive, multiagent chemotherapy, survival from pelvic Ewing sarcoma has not improved over the past decade; however, the survival rate does not seem to be worse than that from Ewing sarcoma at other locations, insofar as at least 50% of the patients were cured. Surgery or a combination of surgery and radiation therapy are the best local treatment; exclusive radiation therapy should be reserved for patients with inoperable lesions or partially or nonchemosensitive tumors or when surgery would be an amputation.     

Cutaneous Ewing sarcoma: report of 2 cases and literature review of presentation, treatment, and outcome of 76 other reported cases

Cutaneous Ewing sarcoma is a rare variant that has been poorly characterized and has no standard therapy. We report 2 patients with cutaneous Ewing sarcoma and review 76 other cases reported in the literature for demographics, presentation, treatment, and outcome. Only 2 patients presented with metastatic disease, and only 8 patients developed metastatic disease. Ninety-one percent of all patients are alive despite wide variations in treatment regimens. On the basis of this summary, treatment consisting of local control with surgery and/or radiation and abbreviated chemotherapy is proposed as a treatment option for this less aggressive Ewing sarcoma.     

Reactivation of TWIST1 contributes to Ewing sarcoma metastasis

1 Background

Ewing sarcoma is a cancer of bone and soft tissue. Despite aggressive treatment, survival remains poor, particularly in patients with metastatic disease. Failure to treat Ewing sarcoma is due to the lack of understanding of the molecular pathways that regulate metastasis. In addition, no molecular prognostic markers have been identified for Ewing sarcoma to risk stratify patients.

2 Procedure

Ewing sarcoma patients were divided into high or low Twist1 gene expression and survival curves were generated using the R2 microarray‐based Genomic Analysis platform ( http://r2.amc.nl ). Tumors from Ewing sarcoma patients were also evaluated for TWIST1 expression by immunohistochemistry. Ewing sarcoma xenografts were established to evaluate the role of TWIST1 in metastasis. The effects of Twist1 on migration and invasion were evaluated using migration and invasion assays in A673 and RDES cells.

3 Results

Twist1 expression was a negative prognostic marker for overall survival in a public Ewing sarcoma patient data set based on Twist1 mRNA levels and in patient tumor samples based on Twist1 immunohistochemistry. TWIST1 is detected in significantly higher percentage of patients with metastatic diseases than localized disease. Using Ewing sarcoma tumor xenografts in mice, we found that suppressing TWIST1 levels suppressed metastasis without affecting primary tumor development. Knockdown of Twist1 inhibited the migration and invasion capability, while overexpression of Twist1 promoted migration and invasion in Ewing sarcoma cells.

4 Conclusion

These results suggest that TWIST1 promotes metastasis in Ewing sarcoma and could be used as a prognostic marker for treatment stratification; however, further validation is required in a larger cohort of patients.     

Hematometrocolpos in an adolescent female treated for pelvic Ewing sarcoma

Radiation therapy is often used to achieve local control of pelvic Ewing sarcoma in children. The effects of radiation on the female reproductive tract have been well documented in adults with gynecological malignancies, but the long-term consequences of pelvic radiation in pre-pubertal or adolescent girls are not as well described. We report a case of hematometrocolpos developing in an adolescent previously treated with chemotherapy and radiation therapy for pelvic Ewing sarcoma. We describe the clinical presentation, radiographic features, gross pathology, treatment strategies, outcome, as well as putative predisposing factors and preventative interventions.     

Impact of whole-body MRI and FDG-PET on staging and assessment of therapy response in a patient with Ewing sarcoma

In patients with Ewing sarcoma, precise staging is not only crucial for the therapeutic regimen but also for a reliable evaluation of response to therapy. We report on a 15-year-old girl with metastatic spread of a Ewing sarcoma who, apart from conventional staging by bone scan, chest X-ray and CT, was subsidiary examined by FDG-PET and whole-body MRI before and after chemotherapy. Both modalities detected more bone lesions than the bone scan, which led to an altered strategy for radiotherapy. Both examinations might be a great asset to stage-adjusted therapy regimens, ultimately influencing patient outcome.     

Immunotherapy with autologous dendritic cells and tumor antigens for children with refractory malignant solid tumors

Abstract:  Immature DCs were generated from the peripheral blood monocytes from five children with refractory solid tumors (Ewing sarcoma, synovial sarcoma, neuroblastoma) using GM-CSF and IL-4. These DCs were then pulsed with tumor-specific synthetic peptides or tumor lysates in the presence of the immunogenic protein KLH for 12 h. Pulsed DCs were administered subcutaneously every one or two weeks in an outpatient setting without any toxicity. In one patient with Ewing sarcoma, the residual tumor disappeared following autologous PBSCT and DC therapy, and a complete remission has been maintained for 77 months. In two patients with synovial sarcoma or with neuroblastoma, growth of the tumors was temporally suppressed for one and 10 months, respectively, followed by their exacerbation. A DTH response was detected against KLH in all five patients and against the tumor lysate in one patient. In the patients with a possible DC-mediated anti-tumor effect, the number of CD8⁺ HLA-DR⁺ lymphocytes and INF-γ⁺CD8⁺ lymphocytes increased and an elevation of the NK cell cytotoxic activity was observed during and/or after DC therapy. DC-based immunotherapy may therefore be a feasible, well-tolerated and promising approach in the treatment of children with refractory malignant tumors.     

Ewing sarcoma/primitive neuroectodermal tumor of the kidney treated with chemotherapy including ifosfamide

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the kidney is extremely rare, and is usually diagnosed after nephrectomy without neoadjuvant chemotherapy. Although ifosfamide and etoposide improve survival to a great extent in ES/PNET, the use of nephrotoxic agent, particularly ifosfamide, is a concern after nephrectomy. We describe the case of a 14‐year‐old female patient with abdominal mass who was diagnosed with ES/PNET of the right kidney after nephrectomy. Adjuvant chemotherapy including ifosfamide and etoposide were given. The estimated glomerular filtration rate decreased to 75% after the end of therapy. There was no evidence of recurrence 70 months after initial diagnosis.     

Outcome after relapse in an unselected cohort of children and adolescents with Ewing sarcoma

BACKGROUND: Survival after relapse in patients with Ewing sarcoma is very poor and this retrospective study attempts to identify of prognostic factors predicting survival after relapse. PROCEDURE: A total of 191 patients with localised Ewing sarcoma were registered in the ET-2 trial of the United Kingdom Children's Cancer Study Group (UKCCSG). All patients received standardised primary treatment with chemotherapy and surgery and or radiotherapy as local modality treatment. Sixty-four patients who relapsed are included in this report. Treatment at relapse was variable and included chemotherapy, surgery, radiotherapy and high dose therapy (HDT) or megatherapy with peripheral stem cell transplantation (PBSCT) or autologous bone marrow transplantation (ABMT) in various combinations. A subgroup of patients had only non-specific symptomatic treatment at relapse. Both univariate and multivariate methods were used to investigate variables affecting survival after relapse. RESULTS: The overall actuarial median survival from relapse for all patients was 14 months (95% CI 11-16 months). Univariate analysis showed that males had a longer survival (median, 16 months vs. 11 months); patients who relapsed while on treatment did worse (median, 3 months vs. 16 months) and patients who had a longer disease-free interval (DFI) prior to relapse had a better outcome (DFI <1 year, median survival = 3 months; DFI 1-2 years, survival = 8 months; DFI > 2 years, median survival = 24 months, P < 0.001). Multivariate analysis confirmed that duration of first remission was the only factor associated with longer survival after relapse. CONCLUSIONS: These data suggest that although aggressive therapy may delay disease progression after relapse for some children, the course of the disease after relapse is usually fatal. International co-operative studies are needed to evaluate new strategies.     

Second malignancy in 597 patients with ewing sarcoma of bone treated at a single institution with adjuvant and neoadjuvant chemotherapy between 1972 and 1999

The relative risk of second tumors in patients with Ewing sarcoma is controversial, and little is known about their treatment and outcome. The purpose of the current study was to define the incidence and features of second tumors among 597 long-term survivors of nonmetastatic Ewing sarcoma treated with adjuvant and neoadjuvant chemotherapy, radiotherapy, and/or surgery. The authors found that the risk of secondary malignancy after adjuvant or neoadjuvant treatment of Ewing sarcoma is higher than that after other childhood or adolescent cancers only after radiotherapy. Based on this, postoperative radiotherapy should be avoided when surgery with adequate margins is feasible.     

Panobinostat—A Potential Treatment for Metastasized Ewing Sarcoma? A Case Report

Ewing sarcoma (ES) is a form of primary bone cancer, with few treatment options for patients who develop relapse with an overall 5‐year survival of 13%. New treatment options are needed and histone deacetylase (HDAC) inhibitors show encouraging results in preclinical studies. Our patient developed inoperable progressive lung metastases and was treated with the HDAC inhibitor panobinostat. During 18 months of treatment, no new lesions appeared; the treatment was stopped due to progression. This clinical observation warrants further evaluation of HDAC inhibitors in ES. Combination with chemotherapy and biomarker studies could improve the therapeutic index of these classes of compounds.