中国软组织肉瘤诊治策略

软组织肉瘤是指发生在问叶组织如纤维组织、脂肪组织、肌肉组织、滑膜组织、血管及淋巴管等的恶性肿瘤,较常见的依次是恶性纤维组织细胞瘤、滑膜肉瘤、脂肪肉瘤等[1].     

软组织肉瘤的治疗进展

软组织肉瘤的治疗进展庄承海关键词软组织肉瘤综合治疗中图号Ｒ７３０．５软组织肉瘤是来源于间叶组织和与其交织生长的外胚层神经组织的恶性肿瘤。它占成人恶性肿瘤的１％，在儿童期肿瘤中占１５％〔１，２〕列第四位。过去由于其来源广泛，形态学多样化，故给诊断和治疗...     

软组织肉瘤研究进展

软组织肉瘤研究进展师英强沈镇宙（上海医科大学附属肿瘤医院，上海２０００３２）软组织肉瘤生物学特征是指导临床诊断及治疗的重要内容。随着肿瘤基础研究的不断深入，尤其近年来分子生物学突飞猛进的发展，促使众多学者关注各自研究领域的致癌机理和过程以及诊断、治疗...     

软组织肉瘤的诊断与综合治疗

软组织肉瘤(STS)是一种来源广泛、组织学各异、罕见的恶性肿瘤.其诊断的基础依赖于光镜下的形态表现,特殊染色、免疫组化及电镜观察是其病理诊断的有益补充,结合临床如年龄、肿瘤大小、部位、生长方式等,以综合判断从而能做出正确的诊断.外科手术是治疗软组织肉瘤的主要方式,辅助放疗能控制肿瘤的局部复发,现代治疗软组织肉瘤,尤其病灶位于四肢者,崇尚综合治疗.辅助化疗的作用仍有争议,但有Meta分析证实辅助化疗能提高无病生存和总生存率,特别是位于四肢者.化疗对晚期STS有一定作用,以ADM、IFO为主的强化治疗能产生较好的疗效,但选择标准更为严格.开发新的靶向治疗药物是改善STS预后的关键.     

软组织肉瘤诊断和治疗中值得关注的几个问题

各级医生应提高对软组织肉瘤及其特性的认识，使有软组织肿块的病人能得到及时而恰如其分的评估和理想的治疗。外科手术是临床局部软组织肉瘤最主要的治疗方法，治愈的机会在第一次手术。软组织肉瘤广泛切除后，建议对大多数恶性程度高者进行放疗。     

软组织肉瘤综合治疗进展

软组织肉瘤（soft tissue sarcoma，STS）是来源于间叶组织和周围神经组织的异质性很高的实体恶性肿瘤，临床并不多见，好发于青少年和45～55岁的中年人，占全身恶性肿瘤的1％^[1]。30年前，软组织肉瘤的局部治疗仅靠外科手术，截肢率极高，但由于软组织肉瘤的一个重要的生物学特征是局部复发和晚期远处转移，大多数患者因肉瘤发生远处转移而死亡。近年来，随着对STS生物学行为认识的不断提高，以手术为主的综合治疗逐步应用于临床，并取得一定进展，表现为截肢率和复发率的降低，并在不影响生存率的情况下，提高了生活质量。     

软组织肉瘤外科治疗进展

摘 要：软组织肉瘤是发生于骨以外间叶组织的肿瘤,其亚型超过50种,可以发生在身体许多部位。软组织肉瘤的解剖位置非常重要,因为它与疾病的治疗及疗效相关。手术切除是软组织肉瘤的主要治疗方式。近几十年人们对不同亚型软组织肉瘤的自然进程有了更好的了解,软组织肉瘤的外科治疗也发生了重要的变化。全文旨在综述近年来四肢软组织肉瘤、腹膜后软组织肉瘤、胃肠间质瘤和其他软组织肉瘤的外科治疗进展。     

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。     

原发性256例软组织肉瘤手术治疗的临床分析

目的:探讨软组织肉瘤的诊断、手术治疗方法及其疗效。方法:对256例原发性软组织肉瘤患者的治疗情况进行回顾性分析。行局部广泛切除及根治切除术,对侵犯骨组织的软组织肉瘤则按微波原位灭活保肢手术处理。切除肿瘤后,行血管修复重建、带血管蒂游离皮瓣转移、局部皮瓣转移、肌腱移位、肌皮瓣移位。结果:发病年龄为20-70岁,占62.11%(159/256),常见的病理类型为滑膜肉瘤、恶性纤维组织细胞瘤、脂肪肉瘤、横纹肌肉瘤、纤维肉瘤,占65.23%(167/256)。Kaplan-Meier法计算5年生存率为63.28%。结论:诊断采用CT、MRI为主的影像学,治疗以手术为主,辅助放疗和化疗。     

软组织肉瘤治疗进展

肉瘤是一组少见的具有不同临床和病理特征的间叶来源的肿瘤。整体上肉瘤可分为两大类,软组织来源的肉瘤和骨肉瘤。肉瘤大约占成人恶性肿瘤的1%,占儿童恶性肿瘤的15%。软组织肉瘤包含50多种不同的组织学亚型,最常见的亚型包括未分化多形性肉瘤、胃肠间质瘤、脂肪肉瘤、平滑肌肉瘤、滑膜肉瘤和恶性外周神经鞘瘤等。手术是软组织肉瘤最主要的治疗方法,但术后复发率高,预后差,化疗疗效仍不理想。随着人们对其生物学行为认识的加深,近些年涌现的一系列新型靶向药物取得了不错的疗效。总之,软组织肉瘤的治疗需根据疾病的组织学亚型、分子遗传学特点、分期及预后因素采取包括手术、放疗、化疗以及分子靶向治疗在内的个体化治疗模式。      

Pazopanib in the treatment of soft tissue sarcoma

Patients with advanced metastatic soft tissue sarcoma (STS) have a poor prognosis, and in the last two decades of the 20th century their overall survival has remained unchanged. Improved treatments are needed for these patients and for preventing metastases in earlier stages of disease. Numerous novel agents and new combination regimens are undergoing clinical testing in STS. Some of these agents show promising activity. Pazopanib is one such agent that has undergone Phase II and III evaluations in advanced STS. Pazopanib is a multi-tyrosine kinase inhibitor, blocking various signaling pathways, thereby preventing angiogenesis and metastasis, and inhibiting tumor cell growth and survival. In a Phase II study, pazopanib demonstrated activity in patients with advanced leiomyosarcomas, synovial sarcomas and other eligible STSs. This activity was confirmed in a Phase III trial, where pazopanib significantly extended the median progression-free survival versus placebo in a variety of STS subtypes.     

Future directions in soft tissue sarcoma treatment

Sarcoma is a broad term for mesenchymal malignancies that arise from soft tissue or bone. Despite classification by histologic subtype, clinical behavior and response to therapy have great variability. Modern genetic sequencing techniques have been able to identify additional genetic variability and subsequently new targeted therapies. In this review, we discuss the current state of STS diagnostics and treatment and explore some of the more promising areas in which progress is being made. We discuss therapies targeting PDGFRα/KIT, β-Catenin/APC/NOTCH, IDH-1/2 mutations, MDM2 amplifications, EZH2/INI1 expression loss, ALK fusion, and ASPSCR1-TFE3 fusion. We also discuss the progress that has been made within immunotherapies. While soft tissue sarcomas still portend a poor prognosis, these targeted therapies and immunotherapies provide treatment with less toxic side effects.     

软组织透明细胞肉瘤的研究进展

透明细胞肉瘤(clear cell sarcoma of soft tissue, CCS)是一种较少见的软组织肿瘤,多发于青少年及中年,以四肢远端的深部软组织多见,常与肌腱和腱膜相毗邻,易复发和转移.组织来源尚未明确.起病隐匿,肿瘤较大时可引起疼痛和压痛.大体为无明显包膜,呈分叶状或多结节状切面灰白色的肿块.组织学特点为细胞多角形或梭形,成巢状排列其间有纤维组织分隔.超微结构显示,胞质内可见黑色素颗粒;免疫组化S-100、HMB-45、Vimentin及MITF阳性.CCS中特异表达的EWS/ATF1融合基因在血管瘤样纤维组织肉瘤(angiomatoid fibrous histiocytom, AFH)中也表达.RT-PCR检测MITF可鉴别CCS和AFH两种软组织肉瘤.BREF基因是否发生突变对CCS与原发部位不明确的恶性黑色素瘤的鉴别诊断有很大意义.治疗仍以手术切除为主,预后较差.     

Olaratumab for the treatment of advanced soft tissue sarcoma

Introduction: Olaratumab, a human monoclonal antibody against platelet derived growth factor receptor alpha (PDGFR- α), is the first drug that in combination with doxorubicin for the treatment of patients with advanced/metastatic soft tissue sarcoma (STS) that has showed an improved overall survival compared to doxorubicin alone. These initial results are exciting and have the potential to change the landscape of treatment for patients with STS.

Areas covered: This article reviews the development of olaratumab for oncology use by reviewing articles in PubMed for ‘platelet derived growth factor’ and ‘receptor’ and ‘soft tissue sarcoma’. We provide an overview of the published studies to date for olaratumab and specifically the use in soft tissue sarcoma.

Expert commentary: Olaratumab is a well-tolerated drug that, when combined with doxorubicin, has shown an improved overall survival compared to doxorubicin alone and the phase III confirmatory study is eagerly awaited.     

Surgical and preoperative treatment of soft tissue sarcoma

Preoperative therapy effects, resected margin and local radicality were investigated in 40 cases of soft tissue sarcoma in which preoperative therapy (mainly radiation therapy) had been given. The results indicated that there was no effect upon prognosis due to postponement of surgery in order to perform preoperative treatment. In cases in which radiation therapy was used for preoperative treatment, even when a surgical margin resulted with in a tumor, no recurrence was found. However, histologically there was concern that some portion of the living tumor cell in marginal area of the tumor might have remained. Thus, at the present stage in cases having undergone initial treatment, radiation limited to the specific area of the resected margin causing non-curative margin should be given. If combined with preoperative radiation therapy, surgical intervention involving "wide margin" can be considered radical. On the other hand, cases having undergone surgery before and receiving preoperative therapy that show good response nevertheless show numerous recurrences. These recurrences, however, invariably occur outside of the irradiated area, and may be attributed to the fact that tumor cell dissemination from the earlier surgery was not within the radiation field. Hence, it was considered that the area for radiation in the case of a recurrence should extend well beyond the scar area.     

Experimental approaches to treatment of soft tissue sarcoma

The experimental approaches described in this article represent potential new approaches for targeted therapy. Thus far, none of the preclinical data have demonstrated a cure for sarcomas; however, the antitumor effects of many of these new agents seem to be enhanced when the agents are combined with chemotherapeutic agents. The combination of novel therapeutics with conventional chemotherapy may be the most effective strategy in terms of maximization of tumor killing and minimization of toxicity and the risk of drug resistance. Not only are new drugs being developed for treatment of sarcomas but new ways of delivering drugs are also being investigated. The angiogenic, or metronomic, schedule of drug delivery may be preferable to conventional schedules in achieving optimal tumor inhibition. In addition, isolated limb perfusion is a unique approach to delivery of drugs, such as TNF and melphalan, for sarcomas and melanomas [137, 138]. The advantages of this method of drug delivery include the ability to administer therapeutic agents in high concentrations to a specific region of the body without systemic toxicity. Further advances in the understanding of the biology of sarcomas along with novel approaches to delivery of drugs are crucial to the development of new and effective therapies.     

Surgical treatment for bone and soft tissue sarcoma

There are many kinds of wide excision or wide resection, which are methods to remove the tumor with surrounding tissues. The curability of wide resection depends on the range and characteristics of the normal surrounding tissues. The fascia, periosteum and perivascular sheath act as barriers against invasion of tumors. Therefore, evaluation of the surgical margin is essential in surgery for malignancy. Some sarcomas characteristically show invasive growth patterns while others have a discrete border. Causes of the local recurrence are 1) insufficient surgical margin, 2) skip metastasis, 3) tumor thrombus, and 4) lymph node metastasis. The so-called "Safety surgical margin" is the margin that prevents local recurrence due to insufficient surgical treatment. Local recurrence due to other causes can not be treated by surgery alone as chemotherapy is also required. For example, the infiltrative type of malignant fibrous histiocytoma requires a curative procedure. On the other hand, non-infiltrative types of sarcoma or high-grade sarcoma, which are good responders to preoperative treatment, are locally controlled by an adequate wide margin procedure. When the tumor is close to the bone, main vessels and/or nerves, it is sometimes very difficult to preoperatively decide whether or not to sacrifice these important organs. A new surgical method, "In Situ Preparation (ISP)," is a useful method to solve such problems. ISP makes it possible to evaluate the surgical margin without contamination. And additional procedures including alcohol soaking or pasteurization can be achieved according to the surgical margin. Because ISP can prevent overtreatment, the number of our cases that require resection of the nerves or vessels have decreased. After a wide resection, there have been many possible complications, including infection, deep venous thrombosis, loosening of prosthesis, skin necrosis, and arterial occlusion. Once postoperative complications occur, patients must remain in the hospital for a long time. To prevent this, the preservation of normal tissue, meaning reduction of surgical margin, is important.     

Retroperitoneal soft tissue sarcoma

The objective of the current study was to define the optimal treatment for patients with retroperitoneal soft tissue sarcomas (RPS). The authors conducted a review of the pertinent literature and found that the majority of patients had locally advanced RPS at the time of diagnosis. Surgery was the mainstay of treatment, and macroscopic total excision was feasible in approximately 50-67% of patients. The 5-year probability of local control was approximately 50%, and the likelihood of developing distant metastasis was approximately 20-30%. The 5-year survival rate was approximately 50%, and deaths due to recurrent RPS continued to occur after 5 years. Postoperative radiotherapy (RT) decreased the likelihood of local recurrence, although it demonstrated no impact on survival. Adjuvant chemotherapy had no proven efficacy. The factor that was found to have the greatest impact on the prognosis for patients with RPS was the ability to achieve a macroscopic total resection. The authors concluded that RPS usually is advanced at the time of diagnosis. The optimal treatment was complete resection. Most patients experienced recurrent disease after surgery, and the most common site of failure was local. Adjuvant RT reduced the risk of local recurrence, but its impact on survival was questionable.     

The treatment of distant metastases in soft tissue sarcoma

This article reviews the current standard approaches to the treatment of metastatic soft tissue sarcoma (STS) and evaluates new chemotherapy agents and novel approaches. A computerized search strategy was used to identify articles examining the role of chemotherapy and surgery in metastatic STS, which were published between January 1992 and December 1998. This search was supplemented by key articles from our files published before 1992. In selecting articles for inclusion in this review, emphasis was placed on randomized data and novel approaches. Only three agents-doxorubicin, ifosfamide, and dacarbazine-have shown significant activity in metastatic STS. Numerous studies have examined the efficacy and toxicity of combining the known active agents in standard doses or in high doses with cytokine support. Promising results, in terms of increased response rates, often have not been reproduced in randomized trials, and there is no convincing evidence of enhanced overall survival. New regimens should be evaluated in randomized trials incorporating quality-of-life endpoints. High-dose chemotherapy with bone marrow/stem cell rescue remains an investigational procedure of uncertain efficacy. Pilot studies have established the feasibility of intraperitoneal chemotherapy, after cytoreductive surgery, in patients with peritoneal sarcomatosis. To date, the efficacy of this approach has not been validated in phase II or III trials. The role of surgery in the treatment of isolated pulmonary metastases is well established. Results of small series raise the possibility that resection of hepatic metastases is beneficial in selected patients. Current chemotherapy options for patients with STS are limited. There is reason to hope that the situation will change with the further development of new agents that have novel and specific mechanisms of action.