侵袭性纤维瘤病诊治进展

侵袭性纤维瘤病不同于普通良性软组织肿瘤，表现为局部浸润生长．但未见转移。侵袭性纤维瘤病手术切除后，具有高局部复发率。放疗提高局部控制率，化疗应用于不宜手术和放疗患者是有益的。全文就侵袭性纤维瘤病的诊治作一综述。     

侵袭性纤维瘤病诊治进展

侵袭性纤维瘤病不同于普通良性软组织肿瘤，表现为局部浸润生长．但未见转移。侵袭性纤维瘤病手术切除后，具有高局部复发率。放疗提高局部控制率，化疗应用于不宜手术和放疗患者是有益的。全文就侵袭性纤维瘤病的诊治作一综述。     

侵袭性纤维瘤病的非手术治疗

侵袭性纤维瘤病（aggressive fibromatosis,AF）是介于良恶性之间的交界性肿瘤,以局部浸润和高复发率为特点。AF的治疗既往以手术切除为主,但单纯手术复发率较高,盲目的手术往往造成患者机能或外形的损伤。近年来,包括内分泌治疗、手术、放疗、化疗、非甾体抗炎药物治疗、靶向药物、干扰素等多种治疗手段得到尝试,并取得一定疗效。此外,鉴于AF的惰性特征,观察等待也是多个行业指南推荐的一线方案。在AF的治疗决策上,必须综合考虑患者需求,注重机体功能和外形的保全,将非手术手段放到与手术同等地位加以考虑。     

142例侵袭性纤维瘤病的临床特点及预后分析

目的 分析侵袭性纤维瘤病的临床特征及预后因素,为临床治疗提供依据.方法 回顾分析本院1983-2009年治疗的142例侵袭性纤维瘤病患者的临床资料,观察临床特点及治疗方式对预后影响.采用Logrank单因素分析及Cox多因素回归分析评估可能影响局部预后的危险因素.结果 随访率为93.7%,随访满5、10者分别为63例、6例.本组病例男女比例为1∶1.8,18～35岁女性为高发人群(25.4%).病变部位发生于躯干(55.6%)及四肢(31.7%)多见.5、10年局部复发率分别为24.4%、31.1%,生存率均为99.3%.单因素分析发现肿瘤大小(χ2=4.37,P=0.037)和切缘情况(χ2=12.36,P=0.002)为肿瘤复发的危险因素.多因素分析发现切缘情况为独立的复发危险因素(RR=2.129;χ2=9.47,P=0.002),放疗为侵袭性纤维瘤病的保护因素(RR=0.360;χ2=4.95,P=0.026).放疗后切缘阳性患者10年局部复发率从70.1%降至20.7%(χ2=4.22,P=0.040);而切缘阴性患者从19.8%降至10.4%(χ2=0.90,P=0.344).结论 根治性切除为侵袭性纤维瘤病的首选治疗,术后放疗可以降低切缘阳性患者的局部复发率,但对切缘阴性患者的意义尚需大样本临床研究证实.

Abstract：

Objective Aggressive fibromatosis is a rare kind of soft tissue tumor and was evaluated by few large studies. This study was to evaluate the clinical characteristics and identify the prognostic factors of this disease. Methods One hundred and forty-two patients with aggressive fibromatosis treated from January 1983 to August 2009 in Tianjin Medical University Cancer Hospital were retrospectively reviewed.The prognostic value of clinical and treatment factors was analyzed. Univariate analysis was performed with Log-rank test and Multivariate analysis was performed with Cox regression model. Results The follow-up rate is 93.7% and the median follow up time was 54 months (range,6 -208 months). Sixty-three patients had a minimum follow up time of 5 years and 6 patients had a minimum follow up time of 10 years. The male/female ratio was 1/1.84. The disease was most popular in women aged from 18 to 35 years old. The disease frequently occurred in the trunk (55.6%) and extremity (31.7%). All patients received surgery,and 46 received radiotherapy. The 5-year and 10-year local recurrence rates were 24. 4% and 31.1%,respectively. The 5-year and 10-year overall survival rates were both 99. 3%. Univariate analysis revealed that factors correlated with local recurrence were tumor size ( χ2 = 4. 37, P = 0. 037 ) and margin status (χ2 = 12. 36,P =0. 002). Multivariate analysis revealed that margin status was an independent risk factor (RR = 2. 219; χ2 = 9. 47,P = 0. 002) and radiotherapy was an independent protective factor ( RR = 0. 360;χ2 = 4. 95, P = 0. 026 ) for disease recurrence. When radiotherapy was delivered, the 10-year local recurrence rate decreased from 70. 1% to 20. 7% in patients with positive margin ( χ2 = 4. 22, P = 0. 040 )and decreased from 19.8% to 10.4% (χ2= 0.90, P= 0.344) in patients with negative margin.Conclusions Radical resection is the mainstay of treatment for aggressive fibromatosis. Postoperative radiotherapy can reduce the recurrent rate for patients with positive margin. In patients with negative margin,the role of radiotherapy should to be further evaluated in large clinical trials.     

头颈部侵袭性纤维瘤病放射治疗研究进展

侵袭性纤维瘤病（AF）为良性肿瘤,局部侵袭性强,治疗失败以局部复发为主。手术为头颈部AF的主要治疗手段,配合放疗能明显降低局部复发率。放疗适用于手术切缘阳性,手术后肉眼残留,手术近切缘,局部复发者,手术伤害大或不可手术切除者可行单纯放疗。放疗范围包括全部肿瘤或术床,外放范围依据周围解剖结构实际情况适当调整。放疗剂量为50~56 Gy。     

142例侵袭性纤维瘤病的临床特点及预后分析

Objective Aggressive fibromatosis is a rare kind of soft tissue tumor and was evaluated by few large studies. This study was to evaluate the clinical characteristics and identify the prognostic factors of this disease. Methods One hundred and forty-two patients with aggressive fibromatosis treated from January 1983 to August 2009 in Tianjin Medical University Cancer Hospital were retrospectively reviewed.The prognostic value of clinical and treatment factors was analyzed. Univariate analysis was performed with Log-rank test and Multivariate analysis was performed with Cox regression model. Results The follow-up rate is 93.7% and the median follow up time was 54 months (range,6 -208 months). Sixty-three patients had a minimum follow up time of 5 years and 6 patients had a minimum follow up time of 10 years. The male/female ratio was 1/1.84. The disease was most popular in women aged from 18 to 35 years old. The disease frequently occurred in the trunk (55.6%) and extremity (31.7%). All patients received surgery,and 46 received radiotherapy. The 5-year and 10-year local recurrence rates were 24. 4% and 31.1%,respectively. The 5-year and 10-year overall survival rates were both 99. 3%. Univariate analysis revealed that factors correlated with local recurrence were tumor size ( χ2 = 4. 37, P = 0. 037 ) and margin status (χ2 = 12. 36,P =0. 002). Multivariate analysis revealed that margin status was an independent risk factor (RR = 2. 219; χ2 = 9. 47,P = 0. 002) and radiotherapy was an independent protective factor ( RR = 0. 360;χ2 = 4. 95, P = 0. 026 ) for disease recurrence. When radiotherapy was delivered, the 10-year local recurrence rate decreased from 70. 1% to 20. 7% in patients with positive margin ( χ2 = 4. 22, P = 0. 040 )and decreased from 19.8% to 10.4% (χ2= 0.90, P= 0.344) in patients with negative margin.Conclusions Radical resection is the mainstay of treatment for aggressive fibromatosis. Postoperative radiotherapy can reduce the recurrent rate for patients with positive margin. In patients with negative margin,the role of radiotherapy should to be further evaluated in large clinical trials.     

四肢侵袭性纤维瘤病的治疗体会

目的探讨四肢侵袭性纤维瘤病的临床特点和外科手术联合放疗的临床效果。方法回顾性分析43例四肢侵袭性纤维瘤病患者的临床资料,观察疾病的临床特点并对比单纯手术（24例）与手术联合放疗（19例）的治疗效果。结果单纯手术组复发率为33.3%,手术联合放疗治疗组复发率为21.1%。2组生存率均为100.0%,四肢功能评定均为良好。结论四肢侵袭性纤维瘤病首选外科手术治疗,术后放疗可以达到良好的局部控制效果,应结合患者实际病情及术后生活质量制定个体化方案。     

小儿侵袭性纤维瘤病的病因及临床分析

小儿侵袭性纤维瘤病是一种少见的纤维组织增生,具有局部浸润生长、但不转移及恶变、术后易于复发之特点。我院近12年共收治侵袭性纤维瘤病患儿20例,手术48例次现将结果报告如下。一、临床资料1一般资料:本组男11例,女9例。初次手术年龄:1～5岁11例,5～10岁6例,10岁以上3例。肿瘤位于臀部12例,股部2例,腹部1例,颈部3例,颈及肩部2例。出生后即发现肿瘤1例,急性阑尾炎术后伤口处发现肿瘤1例,臀部注射后出现肿瘤2例,下蹲困难3例,余13例无记载。本组20例中无伴发家族性息肉及本病家族史。2术前诊断:术前伴发肢体活动受限13例,颈部肿瘤伴胸腔积液1…     

腹壁侵袭性纤维瘤病21例临床分析

目的:探讨腹壁侵袭性纤维瘤病的临床特点和治疗方法。方法:回顾研究中国医科大学附属盛京医院2000-2010年间外科收治的21例腹壁侵袭性纤维瘤病例,包括初发18例,复发3例。术前3例复发患者确诊,9例疑诊。16例患者行广泛切除,5例患者行单纯肿瘤切除或切缘不足2cm。13例因肿瘤切除后腹部缺损较大用人工补片行腹壁重建。8例患者术后行放射治疗。结果:术后获随访18例,复发4例,复发率为22.2%,其中切缘大于2cm的14例患者中复发1例,切缘不足2cm且未行放疗的3例全部复发。7例加用放疗者均未复发。补片修补患者无复发及切口疝发生。结论:侵袭性纤维瘤呈侵袭性生长,复发率高,应提高对本病的认识。切缘阴性的手术是首选的治疗方法,放疗能降低术后复发率。     

胸腔内巨大侵袭性纤维瘤病二例报告

病例1：患者女,16岁。发现右腋下胸部肿块伴隐痛2年于2010—06—24入乐清市第二人民医院,无发热、咳嗽及活动后气促。体检：浅表淋巴结未及肿大,右腋下胸壁可触及境界不清肿块,质硬,不活动,无压痛,颈静脉无怒张,右肺叩诊呈实音,呼吸音消失,心界向左移位,律齐,未闻及杂音。     

The pharmacological treatment of aggressive fibromatosis: a systematic review.

BACKGROUND: Despite the use of surgery and radiotherapy, 20-35% of patients with aggressive fibromatosis (AF) will have local recurrence. The purpose of this review was to collect and analyze all available information regarding the role of non-cytotoxic and cytotoxic chemotherapy in AF that has been accumulated over the past few decades. PATIENTS AND METHODS: A systematic review of published clinical trials, studies and case series was carried out using the Medline Express Databases and the Cochrane Collaboration Database from 1970 to October 2000. RESULTS: Most studies published in the literature are in the form of successful case reports and single-arm series with small patient numbers. Most commonly used agents include hormonal agents, non-steroidal anti-inflammatory drugs (NSAIDs), interferons and cytotoxics. The literature data support the use of hormonal agents. Several questions, however, remain unresolved, such as which is the most suitable endocrine manipulation and what is the optimal dose and duration of treatment. NSAIDs and interferons have demonstrated activity against AF either alone or in combination with hormone therapy or chemotherapy but the precise mechanism of action is still unknown. Finally, there is growing evidence in the literature that chemotherapy is effective against AF with almost one in two patients being likely to respond. CONCLUSIONS: The evidence in the literature supports the opinion that both non-cytotoxic and cytotoxic chemotherapies are effective against AF. However, the lack of sufficient patient numbers and randomized trials compromises the validity of the reported results and mandates further investigation with properly designed prospective studies including larger patient numbers, with main end points to include not only tumor response rate and survival but also quality-of-life issues.     

Identification of biological factors predictive of response to imatinib mesylate in aggressive fibromatosis

Background:

Imatinib induces responses and disease stabilisations in non-resectable patients with aggressive fibromatosis (AF). The precise target of imatinib in AF and predictive factors for response to treatment are unknown.

Methods:

We investigated factors potentially predictive of response to imatinib in a series of 40 patients with progressive AF included in a phase II trial of imatinib: we tested the presence of KIT exon 10 variant (M541L), the expression of imatinib-sensitive kinases and cell cycle proteins by immunohistochemistry (IHC), and other clinical and biological factors.

Results:

Of 10 patients for whom DNA could be extracted, 3 had a KIT exon 10 variant (30%), with no correlation with response or progression-free survival (PFS). The expression of other imatinib targets (PDGFRA/B, macrophage colony-stimulating factor receptor (M-CSFR)) and of downstream components of the cell cycle, cell proliferation and proliferation pathway (cyclin D1, ERK, MEK 1–2) did not correlate with PFS. Pre-treatment lymphopenia (<1500/μl) and tumour size >120 mm correlated with shorter PFS in univariate and multivariate analyses.

Conclusion:

Our findings show that a baseline biological characteristic of the patient is the major parameter influencing response to imatinib in aggressive fibromatosis. Tumour characteristics, including the presence of a KIT exon 10 M541L variant, may influence tumour control but this needs to be confirmed and better explained.     

盆腹腔巨大复发侵袭性纤维瘤病放疗1例

侵袭性纤维瘤病(aggressive fibromatosis,AF),又称硬纤维瘤(desmoid tumor)或韧带样纤维瘤(desmoid-type fibromatosis),是一种罕见的软组织肿瘤.它属于一种良性疾病,但具有局部浸润性生长的特性,导致其手术完全切除困难,出现反复复发的征象.现将1例巨大复发侵袭性纤维瘤病患者的治疗情况报道如下.     

Possible therapeutic role of vitamin D3 in aggressive fibromatosis

Desmoids, also known as aggressive fibromatoses, are locallyinvasive tumors that are intermediate in their biological behaviorthat lies between benign fibrous proliferations and low-gradefibrosarcomas. In this report, we present a case of a youngfemale patient with a huge tumoral mass located in the rightshoulder region that recurred after total resection and wasresistant to radio-chemo-hormonal therapy. Eventually, she respondedto 1,25-(OH)₂-vitamin D₃ treatment.     

Effective treatment of aggressive fibromatosis with celecoxib guided by genetic testing

Aggressive fibromatosis (AF) or desmoid tumors is an aggressive fibroblastic proliferation which is locally invasive but can not metastasize. The treatment of AF is challenging. Surgery was the main treatment modality for AF in the past, other strategies including radiotherapy, systemic therapies and wait-and-see policy. The use of non-steroidal anti-inflammatory drugs (NSAIDs) and targeted therapies has demonstrated good results. In the case report, a 39-year-old man presented with progressive chest wall pain. Computed tomography (CT) showed an approximately 46× 13 mm soft-tissue mass between the inside of the fifth and sixth rib on the right side. The entire mass was excised and an AF was confirmed based on histopathology. Four months after surgery, magnetic resonance imaging (MRI) showed a soft-tissue mass in surgical areas and biopsy confirmed local recurrence. Therefore, Tomotherapy was administered. However, two months later, an (18)F-fluorodeoxyglucose (FDG) Positron Emission Tomography combined with CT (PET-CT) revealed the presence of an FDG-avid mass in the area of local recurrence. Genetic testing reported the presence of a p.T41A mutations on the CTNNB1 gene, which predicted that he is sensitive to the COX-2 inhibitor celecoxib. The tumor regressed rapidly after the application of celecoxib. Within the 20-month follow-up period, the patient showed remarkable regression without any signs and symptoms. Our case report provides further evidence for the efficacy of celecoxib in AF with CTNNB1 gene mutations. To our knowledge, this is the first report of AF treated with celecoxib under the guidance of the genetic testing. However, further studies are required.     

The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors)

Background

Aggressive fibromatosis (syn. desmoid tumor) is a sporadically occurring neoplastic proliferation of fibroblasts originating from musculoaponeurotic planes, forming invasively growing masses without the capability to metastasize. The choice of treatment remains surgical resection with or without radiotherapy, and is characterized by high recurrence rates. Better understanding of the aetiology of aggressive fibromatosis is needed to be able to develop new treatment strategies to cope with the high recurrence rates.

Methods

Relevant studies were identified through a search of the electronic databases PubMed/ Medline. The following search terms were used: ‘aggressive fibromatosis’, ‘desmoid tumor’, ‘adenomatous polyposis coli’, ‘APC’, ‘beta-catenin’, ‘Wnt’, ‘Wingless’ and ‘Wnt/Wingless’. Studies were selected for review on the basis of abstract reading. A hand search was performed by checking reference lists in selected articles.

Results

The neoplastic nature of aggressive fibromatosis and the role of the adenomatous polyposis coli (APC) and β-catenin signaling cascade in driving the onset and progression of this disease are discussed.

Conclusion

Mutations in either the APC or β-catenin genes are likely to be a major driving force in the formation of these desmoid tumors. More research is needed to develop new treatment strategies.     

Tcf-3 expression and beta-catenin mediated transcriptional activation in aggressive fibromatosis (desmoid tumour).

Aggressive fibromatosis harbours mutations resulting in beta-catenin protein stabilization. Primary cell cultures demonstrate constitutive tcf activation in aggressive fibromatosis. Expression and co-immunoprecipitation studies suggest that beta-catenin binds and activates tcf-3 in this tumour. This is the first demonstration of tcf-3 activation by beta-catenin stabilization in a human neoplastic process.