单中心高度恶性软组织肉瘤的诊疗经验

背景与目的：高度恶性软组织肉瘤是一类转移率高、预后差的恶性肿瘤。该研究总结单中心高度恶性软组织肉瘤的治疗经验,以指导制定这类肿瘤患者的个体化治疗方案。方法：对2000年7月—2014年7月在北京大学人民医院骨与软组织治疗中心接受手术及辅助治疗的473例高度恶性软组织肉瘤患者的临床资料进行回顾性分析,随访这些患者复发、转移及生存情况,分析影响预后的因素。结果：共有400例（84.6%）患者接受了保肢治疗。103例患者出现局部复发,148例患者出现肺、骨等远处转移,419例（88.6%）患者接受广泛性切除。370例患者接受术后化疗,153例患者接受局部放疗。平均随访时间为46.9个月（8.0~127.0个月）。随访期间114例患者死亡。3、5及10年总生存率分别为82.6%、69.0%及58.7%。统计学分析显示,肿瘤的组织学类型、辅助化疗及转移情况是影响患者预后的危险因素。结论：对高风险的肿瘤患者应进行积极的辅助治疗,包括通过化疗降低转移风险和局部放疗降低复发率,以期提高这些患者的生存率。     

184例软组织肉瘤患者不同治疗方法分析

目的 探讨软组织肉瘤适当的治疗方法。方法 总结184例软组织肉瘤患者的临床资料,分析单纯手术(94例)、手术后加辅助放疗(62例)、手术后加辅助化疗(28例)的长期生存率和影响预后的因素。结果 单纯手术、手术后加辅助放疗和手术后加辅助化疗患者的5年生存率分别为39.4％、48.4％和28.6％。综合治疗是提高患者牛仔率与改善乍活质量的关键。临床分期、病理类型及治疗方法足影响长期生存的重要因素。结论 软组织肉瘤术后辅助放疗可以提高患者5年生存率。     

Gemcitabine in soft tissue or bone sarcoma resistant to standard chemotherapy: a phase II study

Purpose: To assess the efficacy of gemcitabine in patients with a variety of sarcomas that have failed to respond or escaped Adriamycin- and ifosfamide-based chemotherapy. Patients and methods: A group of 18 symptomatic heavily pretreated patients with sarcomas of bone or soft tissue received one induction course of gemcitabine at a dose of 1000 mg/m² per week for 7 consecutive weeks, followed by 1 week rest. Response to the induction course was assessed by interview and by repeated ancillary tests. If no progression was observed, maintenance by gemcitabine 1000 mg/m² per week for 3 weeks every 28 days was given until failure was clinically or radiologically evident. Results: A total of 51 cycles of gemcitabine were given including 18 cycles of induction. A mean of 3.6 postinduction cycles were given to nine patients. The treatment was well tolerated by the patients. One partial response (leiomyosarcoma) and one minimal response (angiosarcoma) were observed, yielding a true objective response rate of 5.5%. An additional six patients achieved stabilization of disease (chondrosarcoma and osteosarcoma), yielding an overall progression-free rate of 44%. The median time to progression was more than 27 weeks. Clinical benefit response was observed only in those who also achieved a progression-free state. Conclusion: Gemcitabine was found to be effective in achieving stabilization and even a minimal response of soft tissue or bone sarcoma refractory to standard chemotherapy. Received: 10 June 1999 / Accepted: 7 September 1999     

90例软组织肉瘤术后放疗临床分析

目的回顾分析软组织肉瘤术后放射治疗的疗效。方法１９８８年５月～１９９５年５月间收治９０例软组织肉瘤（多次术后复发４０例,首次术后复发５０例）,全部用６０Ｃｏ或加深层Ｘ线外照射,常规照射４５～５０Ｇｙ／５ｗ,然后缩野再用６０Ｃｏ或改用深层Ｘ线照射,总剂量低度恶性肉瘤６０Ｇｙ／６ｗ,中度恶性６５Ｇｙ／６．５ｗ,高度恶性７０Ｇｙ／７ｗ。结果３、５年生存率分别为８３．３％（７０／９０）和６１．３％（３８／６２）。局部复发率为５．６％（５／９０）,远处转移率为１１．１％（１０／９０）。影响软组织肉瘤的预后因素包括肿瘤大小、恶性程度、临床分期、术后放疗间隔时间。结论放射治疗能大幅度降低软组织肉瘤术后局部复发率。     

聚乙二醇化脂质体多柔比星联合异环磷酰胺治疗晚期转移性软组织肉瘤

背景与目的：软组织肉瘤一旦出现远处转移,预后极差,中位生存时间不到1年。多柔比星联合异环磷酰胺(ifosfamide,IFO)(AI方案)是晚期软组织肉瘤常用的一线联合治疗方案。聚乙二醇脂质体多柔比星(pegylated liposomal doxorubicin,PLD)活性成分为盐酸多柔比星,药物包裹在脂质体中,可减少多柔比星的临床毒性反应。该研究探讨PLD联合IFO治疗晚期转移性软组织肉瘤的临床疗效和安全性。方法：选取晚期转移性软组织肉瘤患者25例,使用PLD联合IFO方案,PLD剂量30 mg/m²,静脉滴注,第1天;IFO剂量1.8 g/m²,静脉滴注,第1~5天;美司钠360 mg/m²,用IFO时0、4和8 h,21 d为1个周期。结果：所有患者化疗1~8个周期,中位周期数4。25例患者中部分缓解9例(36%),疾病稳定12例(48%),疾病进展4例(16%),疾病控制率(完全缓解+部分缓解+疾病稳定)为84%(21/25)。中位无进展生存时间为7.3个月(95%CI：4.6~10.0个月)。由于失访病例较多,中位总生存时间未随访到。化疗后3/4级不良反应包括白细胞下降(20%)、粒细胞下降(28%)、贫血(4%)和呕吐(4%)。只有1例患者治疗过程中予以减量。结论：临床应用PLD联合IFO方案治疗晚期转移性软组织肉瘤疗效确切,且毒性反应较轻,值得进一步深入研究。     

Post-metastasis survival in extremity soft tissue sarcoma: A recursive partitioning analysis of prognostic factors

BackgroundRecursive partitioning analysis (RPA) enables grouping of patients into homogeneous prognostic groups in a visually intuitive form and has the capacity to account for complex interactions among prognostic variables. In this study, we employed RPA to generate a prognostic model for extremity soft tissue sarcoma (STS) patients with metastatic disease.MethodsA retrospective review was conducted on 135 patients with metastatic STS who had undergone surgical removal of their primary tumours. Patient and tumour variables along with the performance of metastasectomy were analysed for possible prognostic effect on post-metastatic survival. Significant prognostic factors on multivariate analysis were incorporated into RPA to build regression trees for the prediction of post-metastatic survival.ResultsRPA identified six terminal nodes based on histological grade, performance of metastasectomy and disease-free interval (DFI). Based on the median survival time of the terminal nodes, four prognostic groups with significantly different post-metastatic survival were generated: (1) group A: low grade/metastasectomy; (2) group B: low grade/no metastasectomy/DFI ⩾ 12 months or high grade/metastasectomy; (3) group C: low grade/no metastasectomy/DFI < 12 months or high grade/no metastasectomy/DFI ⩾ 12 months; and (4) group D: high grade/no metastasectomy/DFI < 12 months. The 3-year survival rates for each group were: group A, 76.1 ± 9.6%; group B, 42.3 ± 10.3%; group C, 18.8 ± 8.0%; and group D, 0.0 ± 0.0%.ConclusionOur prognostic model using RPA successfully divides STS patients with metastasis into groups that can be easily implemented using standard clinical parameters.     

术后放射治疗在原发肢体软组织肉瘤治疗中的作用

分析本院收治的原发于肢体的软组织肉瘤的治疗情况 ,评价术后放射治疗的作用。方法　本院共收治 15 1例 ,可供分析的 139例 ,分析影响生存和局控的因素及术后放射治疗的意义。生存率和局控率用Kaplan Meier方法计算 ,单因素分析用Logrank检验 ,多因素分析用Cox回归方法。结果　全组 5年生存率为 70 .2 % ,10年为 5 0 .4% ;5年无瘤生存率为 5 2 .9% ,10年为41.2 %。单因素分析对全组病例生存率有影响的因素 :肿瘤大小、年龄和治疗方式 (P值分别为0 .0 0 8,0 .0 0 7和 0 .0 40 )。多因素分析只有治疗方式对生存有影响 (P =0 .0 40 )。首次治疗方式对局控影响差异有极显著性 (P <0 .0 1)。手术方式对单纯手术组局控影响差异有极显著性 (P <0 .0 1) ;肿瘤 <5cm时 ,射野大小对术后放射治疗组局控影响差异有极显著性 (P <0 .0 1)。结论　术后放射治疗能提高局部控制率 ,初始射野应相对大 ,并采用缩野技术。对恶性度低、肿瘤 <5cm、手术切缘阴性患者第 1次术后可不做放射治疗。     

23例软组织肉瘤非计划切除的原因及对策分析*

目的：分析导致软组织肉瘤非计划切除的原因并探讨避免软组织肉瘤非计划切除的策略。方法：自2009年10月至2012年12月新疆医科大学第一附属医院骨科中心骨病骨肿瘤科收治的105 例软组织肉瘤患者资料,其中男性65例,女性40例,平均年龄52岁;接受计划性软组织肉瘤切除术患者82例（计划手术组）,曾于外院接受非计划切除术的软组织肉瘤患者23例（非计划手术组）。 计划手术组患者行广泛切除及根治切除术,非计划手术组患者行扩大切除术。统计分析两组患者一般情况、病灶位置及大小、手术边界、肿瘤复发转移情况,并比较两组患者生存期。结果：非计划手术组达到广泛切除边界的比例明显低于计划手术组（P<0.05）。 非计划手术组患者3 年生存率明显低于计划手术组（P=0.001）。 非计划手术组平均随访18个月（3～36个月）,12例死亡（52.2%）,其中9 例（39.1%）死于肿瘤转移,3 例死于其他疾病;计划手术组平均随访23个月（5～36个月）,15例（18.3%）死亡,其中12例（14.6%）死于肿瘤转移,3 例死于其他疾病。结论：与计划手术相比,软组织肉瘤非计划切除常导致手术范围不足、肿瘤复发转移的风险,可能增高肿瘤所致的死亡率。临床医生应尽量避免非计划切除手术的发生。     

Significance of local treatment in patients with metastatic soft tissue sarcoma

Metastatic soft tissue sarcomas (STS) represent enormous challenges to improve the low survival rate, which is almost the same as past 2 decades ago, although surgery, radiotherapy and radiofrequency ablation has been accepted in the treatment of metastatic STS. Moreover, STS varies between elderly and younger victims in the aspect of diagnoses, prognosis, and treatment strategies. In order to evaluate the role of local treatment in improving prognosis for patients with metastatic STS and select the proper candidates who will benefit from local therapy, a single-institution nearly 50-year experience were collected and reviewed. Finally, we found that local treatments could improve treatment response and survival, but overall survival advantage could not be seen in elderly patients. This conclusion from a single institution could serve as a basis for future prospective multi-institutional large-scale studies.     

Retroperitoneal soft tissue sarcoma: an analysis of radiation and surgical treatment

PURPOSE: To evaluate the clinical outcomes of patients with localized retroperitoneal soft tissue sarcoma (STS) treated with complete surgical resection and radiation. METHODS AND MATERIALS: The medical records of 83 patients were reviewed retrospectively. Sixty patients presented with primary disease and the remaining 23 had recurrence after previous surgical resection. RESULTS: With a median follow-up of 47 months, the actuarial overall disease-specific survival (DSS), distant metastasis-free survival, and local control (LC) rates were 44%, 67%, and 40%, respectively. Of the 38 patients dying of disease, local disease progression was the sole site of recurrence for 16 patients and was a component of progression for another 11 patients. Multivariate analysis indicated that histologic grade was associated with the 5-year rates of DSS (low-grade, 92%; intermediate-grade, 51%; and high-grade, 41%, p = 0.006). Multivariate analysis also indicated an inferior 5-year LC rate for patients presenting with recurrent disease, positive or uncertain resection margins, and age greater than 65 years. The data did not suggest an improved local control with higher doses of external-beam radiation (EBRT) or with the specific use of intraoperative radiotherapy (IORT). Radiation-related complications (10% at 5 years) developed in 5 patients; all had received their EBRT postoperatively. CONCLUSIONS: Although preoperative radiation therapy and aggressive surgical resection is well tolerated in patients, local disease progression continues to be a significant component of disease death. In this small cohort of patients, the use of higher doses of EBRT or IORT did not result in clinically apparent improvements in outcomes.     

THE CLINIC－PATHOLOGIC ANALYSIS OF 66 CASES WITH SOFT TISSUE SARCOMA OF ABDOMEN

ＴＨＥＣＬＩＮＩＣ－ＰＡＴＨＯＬＯＧＩＣＡＮＡＬＹＳＩＳＯＦ６６ＣＡＳＥＳＷＩＴＨＳＯＦＴＴＩＳＳＵＥＳＡＲＣＯＭＡＯＦＡＢＤＯＭＥＮＺｈｅｎｇＴｉａｎｒｏｎｇ郑天荣；ＬｉｕＸｉｕｙｉｎｇ刘秀英；ＬｉＪｉａｎｃｈｅｎｇ李建成；ＺｈａｏＣｈｕｎｌｉ赵春...     

软组织肉瘤术后放射治疗及其预后分析

目的：分析软组织肉瘤术后放射治疗的疗效和预后因素。方法：64例软组织肉瘤经部分切除,完整切除和扩大切除术后接受体外放射治疗,其中常规分割放射治疗48例（1．8－2．0Gy/次,5次／周,DT40-72Gy,中位剂量60Gy),超分割放射治疗16例（1．2－1．5Gy/次,2次／d,间隔6h,DT64.8-85.0Gy,中位剂量66．5Gy),采用Kaplan-Meier法计算5年生存率并经Logrank检验,采用Cox回归分析预后因素的统计学意义。结果：全组5年生存率,局部控制率分别为60．2％、57．9％,其中常规分割组与超分割组分别为54．3％、61．9％、42．9％。多因素 回归分析显示组织学分级,病变大小,病变部位,分割方式是影响生存率的独立预后因素。结论：软组织肉瘤经完整或扩大切除术加术后放射治疗可以获得良好疗效,组织学分级,病变大小,病变部位,分割方式是影响生存率的因素。     

抗血管生成药在软组织肉瘤应用的研究进展

软组织肉瘤（STS）是少见的、具有不同临床病理学特征的、间叶组织来源的恶性肿瘤。晚期STS患者预后极差,化疗效果不理想,因此迫切需要新的治疗策略以提高疗效。随着人们对STS生物学行为认识的加深,近年来一系列新型靶向抗血管生成药不断应用于STS治疗,并获得一定疗效,这可能会跨越STS的治疗瓶颈,为STS的治疗和预后带来新的突破。本文将对抗血管生成药在STS的临床研究进展作一综述。     

软组织肉瘤补充广泛切除术的疗效分析

目的探讨补充广泛切除术在软组织肉瘤外科治疗中的意义。方法回顾性分析1998年1月至2005年10月收治的外院误诊为良性肿瘤而行局部切除的软组织肉瘤患者58例，均行补充广泛切除手术治疗。结果术后病理标本切除缘评价5cm者14例；3cm者32例；3cm以下者12例。首次术后肿瘤残存26例，占45％。补充广泛切除术后有28例需要行软组织修复重建。补充广泛切除手术后随诊10～94个月，8例复发，12例转移，死亡9例。均为高度恶性软组织肉瘤。Kaplan—Meier法计算5年生存率为84．5％，局部复发率为14％。切除缘的5年生存率3cm以上组和3cm以下组之间无显著性差异。局部复发率3cm以上组和3cm以下组有显著性差异（P〈0．05）。结论补充广泛切除术是误诊软组织肉瘤最主要的治疗手段，补充广泛切除的标准切除缘的制定是今后的研究课题。缩小切除缘，可以改善预后，减少组织缺损所造成的修复重建。     

Flap reconstruction does not increase complication rates following surgical resection of extremity soft tissue sarcoma

Background

Flap reconstruction plays an essential role in the surgical management of extremity soft tissue sarcoma (ESTS) for many patients. But flaps increase the duration and complexity of the surgery and their contribution to overall morbidity is unclear. This study directly compares the complication rates in patients with ESTS undergoing either flap reconstruction or primary wound closure and explores contributing factors.

Bone invasion in soft tissue sarcomas of the extremities: An underappreciated prognostic factor. Bone invasion in soft tissue sarcomas

BackgroundBone invasion is unfrequently reported in soft tissue sarcomas of the extremities (eSTS), it is difficult to assess preoperatively and its prognostic impact has not been extensively studied. The objective of this paper was to analyze the incidence and the clinical impact of histologically proven bone invasion in individuals with eSTS.MethodsA retrospective analysis was performed using the medical files patients who had eSTS and were treated between 2012 and 2016. A 5 years survival was estimated using the Kaplan-Meier method and a Cox proportional risk assessment. The outcomes of patients with and without bone invasion were compared.Results370 patients were included in the analysis. The median follow up was 25 months, the median age was 45 years (IQR 31–58). Bone invasion was found in 41 (11.08%). Median tumor size was 11.8 cm. The majority of individuals were diagnosed at stage IV (n = 116, 31.4%), followed by stage IIIB (n = 87, 23.5%). High histological grade was associated with worse OS (HR 2.23, CI 95% 1.36–3.65, p = 0.001). Absence of bone invasion was associated with better prognosis (HR 0.541, CI 95% 0.34–0.86, p = 0.009). OS was 27.3 vs 49.28 months. The disease-free survival (DFS) was 25.1 in bone invasion vs 45.23 without bone invasion.ConclusionBone invasion in individuals with eSTS is an independent adverse prognostic factor associated with lower OS and DFS; although infrequently reported, bone invasion might be considered as part of the staging in the future     

软组织肉瘤动脉灌注新辅助化疗后的保肢治疗

目的探讨术前动脉内灌注化疗对软组织肉瘤的疗效及在保肢治疗中的意义。方法28例肢体软组织肉瘤,其中恶性纤维组织细胞瘤18例,滑膜肉瘤3例,脂肪肉瘤6例,原始神经外胚层肿瘤（PNET）1例。术前均给予选择性肿瘤供血动脉灌注化疗2-3周期,化疗药物为阿霉素／顺铂和异环磷酰胺。化疗后均行保肢手术治疗。结果28例术前化疗后均有疼痛缓解、皮温降低、肿胀减轻、瘤体不同程度缩小、边缘变清楚及关节活动度增加。化疗后均行肿瘤广泛切除术,术中获得良好的外科切除界限。随访6-46个月,平均25个月。2例死亡,1例局部复发行截肢术。术后12个月后采用MSTS93评分系统评分为24-29分,平均为27分。28例3年生存率为92.9％,初次保肢率100％,最终保肢率89.3％。结论肢体软组织肉瘤术前动脉灌注新辅助化疗是一种有效的保肢治疗方法。     

85例软组织肉瘤回顾分析及软组织肉瘤诊治进展

目的通过近5年85例软组织肉瘤回顾分析以探索本地区软组织肉瘤的临床特点及诊治进展。方法采用经病理证实的软组织肉瘤的调查统计，对此临床资料进行回顾性发析。结果好发年龄段为30～70岁，占78-8％（67／85）；发病部位依次为下肢、躯干、腹腔、后腹膜、上肢及头颈，前3位占65．8％（56／85）；前6位病理类型为纤维肉瘤、平滑肌肉瘤、恶性纤维组织细胞瘤、皮肤隆突性纤维肉瘤、横纹肌及滑膜肉瘤，占69．4％（59／85）。常见转移部位为肺、肝、淋巴结和多发转移，远处转移占58-8％，大多属Ⅲ及Ⅳ期期局部复发近30％；预后与肿瘤大小、部位、深度、分期、分级、复发几率及转移灶数目有关。结论本组软组织肉瘤病种复杂，分布广泛，异质性明显；病期晚，肿块大且转移多见。诊断采用CT、MRI为主的影像学、病理形态学及免疫组织化学（IHC），必要时加电镜检查；治疗以手术为主，手术加放疗为基础模式，据分期、分级和生物学特性加高活性联合方案等综合治疗，软组织肉瘤靶向治疗为目前研究热点。     

大剂量异环磷酰胺治疗常规方案失效的软组织肉瘤

背景与目的:阿霉素(ADM)、氮烯咪氨(DTIC)、异环磷酰胺(IFO)为治疗进展期软组织肉瘤常用的化疗药物,但对ADM或常规剂量的IFO治疗失效的软组织肉瘤再化疗的有效方案甚少。本文探讨大剂量IFO治疗常规方案失效的软组织肉瘤的疗效及不良反应。方法:对15例常规ADM及IFO治疗失效的软组织肉瘤患者(10例进展期,5例术后化疗)采用IFO总量14g/m2持续静滴6天治疗。结果:进展期10例患者CR2例,PR2例,总有效率40%。随访4～48个月,中位生存期(21.00±3.29)个月,中位缓解时间(6.00±1.45)个月。主要不良反应为骨髓抑制,Ⅲ～Ⅳ度中性粒细胞减少占45.9%。结论:大剂量IFO治疗软组织肉瘤有效率较高,为常规ADM及IFO治疗失效后较好的挽救治疗方法。     

Feasibility of metronomic oral cyclophosphamide plus prednisolone in elderly patients with inoperable or metastatic soft tissue sarcoma

Background

The number of elderly people with soft tissue sarcoma (STS) is increasing. A sizeable population of elderly patients with STS is unfit for conventional doxorubicin- or ifosfamide-based chemotherapy. We assessed the feasibility of metronomic oral cyclophosphamide (CPM) in this population.

Patients and methods

Patients aged 65 years or older with unresectable STS received CPM 100 mg twice daily plus prednisolone 20 mg daily, the first week of a 2-week cycle in the outpatient setting. Main evaluation criterion was safety. Secondary evaluation criteria were objective response rate and progression-free survival.

Results

Twenty-six patients (median age: 72, range 66-88) received a total of 330 cycles (median per patient: 10, range 2-41) as first (n = 19) or second-line chemotherapy (n = 7). The most frequent histological subtypes were poorly differenciated sarcoma (n = 8), leiomyosarcoma and liposarcoma (n = 5 each) and angiosarcoma (n = 3). Grade ?3 lymphopenia was observed in 81% of pts but no opportunist infection occurred. Grade 3 anaemia and thrombocytopenia occurred in 2 pts (8%) each. No other grade 3-4 toxicity was seen. The response rate was 26.9% (95%CI: 9.9-44.0) and the disease control rate (responses and stable disease >12 weeks) was 69.2% (95%CI: 51.5-87.0). One complete (hepatic epithelioid haemangio-endothelioma) and 6 partial responses (including 5 pts with radiation-induced sarcomas) were seen. Progression-free survival ranged from 0 to 20.6 months (median: 6.8 months) and was significantly longer in patients with radiation-induced sarcomas (median: 7.8 versus 5.2 months, p = 0.02).

Conclusion

Metronomic CPM showed good safety results for this frail population, with promising activity in patients with radiation-induced sarcoma. Toxicity profile was favourable, allowing prolonged home staying and rare treatment discontinuations. A larger prospective study is warranted to confirm these encouraging results in elderly with STS.