Intra-muscular location in soft tissue sarcomas: Impact on oncologic outcome

Background

Soft tissue sarcoma (STS) of intra-muscular location is confined within well-defined barrier, amenable to easier surgical resection. It is generally assumed that STS of intra-muscular location would have favorable outcomes compared to those of inter-muscular location. However, no clear evidence on this assumption can be found. This study examined if intra-muscular location of STS would have favorable effect on oncologic outcomes.

Methods

Among the 161 patients treated for previously untreated, non-metastatic and deep-seated STS, extra-compartmental tumors (65) or tumors that spread beyond the muscle of origin (23) were excluded. Remaining 73 patients were classified into two groups according to tumor location; intra-muscular group (confined within muscle of origin, n = 32) and inter-muscular group (located between muscles, n = 41).

Results

Two patients (6.3%) in intra-muscular group developed local recurrence whereas 10 patients (24.3%) developed local recurrence in inter-muscular group (p = 0.056). Patients in intra-muscular group showed significantly better local recurrence-free survival than those in inter-muscular group (p = 0.029). However, there was no significant difference in development of metastasis (p = 0.143) nor disease-specific survival (p = 0.106).

Conclusions

Our study indicates that STS of intra-muscular location is associated with better local control. Whether this advantage is due to its biological property or surgical resectability remains to be elucidated.     

Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults.

Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 Mg/M² day 1, Adriamycin (ADR) 60 mg/M² day 2, and DTIC 400 Mg/M² days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M². Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000–5000 rad by megavoltage photons in 5 weeks, and in selected cases, an additional 1500–2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy.The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8–41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment.     

Wound complications are a predictor of worse oncologic outcome in extremity soft tissue sarcomas

BackgroundIn various oncological conditions, complications correlate with diminished prognosis, however literature on soft tissue sarcomas is limited and inconclusive. The aim of this study was to assess risk factors and the oncologic impact of wound complications in primary extremity soft-tissue sarcomas.MethodsPatients with primary extremity soft tissue sarcomas without dissemination and with clear surgical margins (R0) were analyzed. Groups with and without wound complications were compared by univariate and multivariable analysis to identify risk factors. Uni- and multivariable analysis of factors associated with local recurrence free survival (LRFS), metastasis free survival (MFS) and disease specific survival (DSS) were performed.Results682 patients were included in the study, wound complications occurred in 94 patients (13.7%) within 90 days. Age, ASA-stage, high tumor size and grade, tumor location in the foot, neoadjuvant radiation therapy and operation time represented independent risk factors for wound complications. Patients with wound complications had a significantly worse estimated 5-year LRFS of 49.4 ± 6% versus 78.3 ± 2.1% and 5-year DSS of 77.9 ± 5.4% versus 89.1 ± 1.6%. Wound complications could be identified as an independent risk factor for worse LRFS (HR 2.68[CI 1.83–3.93], p < 0.001) and DSS (HR 1.79[CI 1.01–3.16], p = 0.046).ConclusionWound complications after soft tissue sarcomas of the extremities are associated with worse local oncological outcome and survival. Patients with high risk of wound complications should be identified and strategies implemented to reduce surgical complications and possibly improve oncologic prognosis.     

Pediatric nonrhabdomyosarcoma soft tissue sarcomas

The nonrhabdomyosarcoma soft tissue sarcomas (NRSTSs) are a heterogeneous group of mesenchymal cell neoplasms that account for about 4% of childhood cancers. Because each histologic subtype of NRSTS is rare, they have been poorly studied and little is known about their biology, natural history, or optimal treatment. Data from adults with soft tissue sarcomas provide some helpful insight, but adult and childhood NRSTSs differ considerably in the distribution of their histologic subtypes, and certain entities are known to behave differently in young children. The greater risks posed to children by treatment, particularly by radiotherapy, also must be considered in treatment planning for children. This article summarizes what is known to date about childhood NRSTS, including the epidemiology, pathogenesis, and clinical approach to diagnosis and treatment of these tumors.     

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     

Chemotherapy of soft tissue sarcomas in the extremities.

A retrospective study on chemotherapy against soft-tissue sarcomas in the extremities was carried out on 98 patients. The local recurrence rate was 10.3% with intensive chemotherapy in post-1980 patients with high-grade sarcomas but 46.7% without chemotherapy--a fairly significant difference (P less than 0.01). The survival rate was significantly higher with intensive chemotherapy in post-1980 patients with high-grade sarcomas. Thus, intensive chemotherapy based on a new protocol should be given in cases of high-grade sarcoma. Considering surgical margin, the local recurrence rate was 33.3% in post-1980 cases inadequately operated upon but 8.6% in those adequately operated upon, which shows a significant difference (P less than 0.05).     

International expert opinion on patient-tailored management of soft tissue sarcomas

BackgroundSoft tissue sarcomas (STS) are a heterogeneous group of cancers comprising over 50 histological subtypes. Current treatment strategies for sarcomas are increasingly adapted to histological and molecular subtype, and several patient- and tumour-related factors influence treatment decision.MethodsSeven oncologists specialising in the management of STS, from Europe, the United States of America and Japan, met to develop a practical model to identify parameters guiding treatment decision-making in advanced STS. Literature searches were carried out to identify key published evidence, in particular phase II and III randomised trials, to validate the model, and extensive clinical experience was used as expert evidence. A document was developed to provide a logical approach to advanced STS management and was analysed critically by a second group of STS specialists.ResultsBroad consensus was reached during this exercise and the following parameters were identified as key factors influencing treatment decision: chemosensitivity of histological subtype, natural history of the diagnosis, tumour burden, tumour site, locally advanced primary and/or metastases, patient’s general condition, relevant comorbidities, previous chemotherapy, treatment goal and patient acceptance. These parameters, judged useful for treatment selection, were based on published literature, the selection process within clinical trials and expert opinion (some factors have not been formerly defined in published literature).ConclusionA model describing factors affecting treatment decisions in sarcoma was established. The model requires validation and several of its parameters require standardisation.     

Multidisiciplinary “limb salvage” treatment of soft tissue and skeletal sarcomas

Sixty-five patients with soft tissue sarcomas and 40 patients with skeletal sarcomas were treated pre-operatively with infra-arterial Doxorubicin and radiation therapy (3500 rad in 10 fractions). The tumors were widely excised and in the case of skeletal sarcomas, the bone was replaced with a cadaver allograft or metal endoprosthesis in an attempt to achieve limb salvage. Chemotherapy consisting of Adriamycin and Methotrexate was administered post-operatively. These patients have been followed from 6 to 70 months with a median follow-up for soft tissue and skeletal tumors of 24 and 30 months respectively. In the soft tissue sarcoma group there have been 2 local recurrences; actuarial overall and disease-free survival at 3 years was 64 and 61%, respectively. In the skeletal sarcoma group there have been only 2 recurrences and the actuarial survival and disease-free survival of 75 and 55% at 2 years, respectively. In the soft tissue sarcoma group there have been 33 thigh lesions, 13 of which have required periosteal stripping. Five of the patients with thigh lesions have developed femoral fractures. All of these patients had post-operative chemotherapy and four of the five patients had periosteal stripping. In the skeletal sarcoma group, eleven of the twenty-one cadaver allografts have either fractured or become unstable requiring replacement with metallic endoprostheses that have been used exclusively for the past two years. Ninty-seven of the total group of 105 patients achieved limb salvage to the last follow-up or time of death with an acceptable complication rate. Longer follow-up is mandatory to determine the late effects of this combined modality regimen.     

Angiogenesis inhibition in non-GIST soft tissue sarcomas

Because angiogenesis is of crucial importance in the pathogenesis of cancer, blocking the function of proangiogenic factors has been shown to improve the outcomes of patients with several cancer types. Given the poor survival durations of patients with advanced soft-tissue sarcomas (STSs), which has remained stable at a median of 12 months over the last 20 year, there is an unmet need for novel agents active against these tumors. Like in other tumors, accumulating evidence points at an important role for angiogenic factors in STSs, rendering these factors attractive treatment targets. This review discusses the currently available evidence supporting a role for angiogenic factors in the pathogenesis of STSs and the first preliminary study results obtained with angiogenesis inhibitors.     

53例屈窝软组织肉瘤治疗经验

目的 探讨屈窝软组织肉瘤的治疗及预后。方法 53例屈窝软组织肉瘤，52例手术，其中4例以皮瓣覆盖血管、神经及修复皮肤缺损，放疗30例，化疗33例。结果伤口并发症8例，复发19例，转移21例，死亡22例。放疗、初治患者局部控制率明显优于未放疗、转诊患者，肿瘤大小及组织学级别与预后相关。结论 放疗可以提高屈窝软组织肉瘤局部控制率，肿瘤大小及组织学级别在其预后判断上有价值，使用皮瓣可以提高屈窝软组织肉瘤保肢率，减少并发症。     

Limb salvage surgery in combination with brachytherapy and external beam radiation for high-grade soft tissue sarcomas

While combined treatment of high-grade soft tissue sarcoma with resection and radiotherapy has become an accepted standard, outlines of treatment algorithms remain a matter of debate. Our institutional practice foresees wide surgical resection with adjuvant brachytherapy and external beam radiation. It was the purpose of this study to determine long-term outcome, prognostic factors for local and systemic recurrence and morbidity in patients with high-grade soft tissue sarcomas of the extremities, who were subjected to this regimen.     

21例软组织肉瘤局部复发的治疗

目的探讨复发软组织肉瘤的治疗方案。方法分析宁德市医院放疗科1999至2007年收治的局部复发软组织肉瘤患者21例的治疗情况并复习有关文献。结果 21例复发患者再次行扩大切除术,术后辅以放疗,放疗剂量DT66～70Gy,预后良好,随访无复发。结论复发软组织肉瘤患者行再次扩大切除后辅以术后放疗是较好的治疗方法。     

软组织肉瘤手术加术中放疗的临床研究

目的：探讨软组织肉瘤术中放疗的意义。方法：对39例软组织肉瘤患者行根治或姑息性手术，术中放疗在术中放疗手术室进行，术中根据肿瘤大小，选择不同术中放疗限光筒及6～12MeV电子线1次照射15～25Gy，姑息手术者剂量加大至36Gy。术后辅以外照射治疗，常规设野，5／周，2Gy／次，总量40～50Gy。初发病灶10例，术后复发29例。结果：39例患者随访12～64个月，3、5年局控率分别为71．8％和64．1％。3年生存率为82．0％。结论：术中放疗具有较高的局控率，比之其他治疗具有许多优点，将获得较高的生存率。     

软组织肉瘤手术加术中放疗的临床研究

目的:探讨软组织肉瘤术中放疗的意义。方法:对39例软组织肉瘤患者行根治或姑息性手术,术中放疗在术中放疗手术室进行,术中根据肿瘤大小,选择不同术中放疗限光筒及6～12MeV电子线1次照射15～25Gy,姑息手术者剂量加大至36Gy。术后辅以外照射治疗,常规设野,5/周,2Gy/次,总量40～50Gy。初发病灶10例,术后复发29例。结果:39例患者随访12～64个月,3、5年局控率分别为71.8%和64.1%。3年生存率为82.0%。结论:术中放疗具有较高的局控率,比之其他治疗具有许多优点,将获得较高的生存率。     

Histological factors contributing to favorable prognoses of soft tissue sarcomas in premenopausal patients

The correlations of sex with various histologic factors in soft tissue sarcomas (STS) were studied in 142 adult patients over the age of 20 years. They included 63 with malignant fibrous histiocytomas, 20 with liposarcomas, 20 with synovial sarcomas, 11 with malignant Schwannomas and 28 with other forms of STS. These were divided into four groups, according to age (20-49 years and greater than or equal to 50 years) and sex. Survival rates in female patients were better than those in male patients, and the difference was significant between the 20-49 year groups (p less than 0.01). The relative frequencies in distribution of each histologic type were similar among male and female patients in both age groups. Among histological factors, mitotic counts showed a significant correlation (P less than 0.04) with sex, followed by cellularity. STS in female patients aged 20-49 years had lower mitotic counts than in patients in other groups, where it occurred with a higher frequency of low and intermediate grade tumors. The findings suggested estrogen, either directly to indirectly, to have a favorable effect on STS prognosis in premenopausal female patients.     

Radiotherapy vs. radiotherapy and razoxane in the treatment of soft tissue sarcomas: Final results of a randomized study

The effect of the sensitizer razoxane on soft tissue sarcomas (STS) was prospectively evaluated in a randomized, controlled trial. The main purpose of the study was to determine the response rates and local control under the combined treatment compared to irradiation alone.

Between 1978 and 1988, 144 patients entered the study; 130 were evaluable for response, toxicity, or survival. The patients were randomized to receive with gross disease (unresectable primaries, recurrent disease, or metastatic disease). The median radiation dose was 60 Gy postoperatively, and 56–58 Gy in patients with gross disease. The dose difference has palliative reasons. Razoxane was given orally at a daily dose of 150 mg/m² during the time of the radiotherapy, starting 5 days before the first irradiation. In general, the groups were comparables as to their prognostic factors. There was some imbalance, however, in favor of the postoperative group reveiving radiotherapy alone.

Between the patient groups treated postoperatively in an adjuvant form, there were no substantial differences in local control and survival. Among 82 patients with gross disease, the treatment with radiotherapy and razoxane led to an increased response rate compared to photon irradiation alone (74 vs. 49%). The local control rate was likewise improved (64 vs. 30%; p = 0.05). The acute toxicity was somewhat higher in the sensitizer arm, but there was no difference in the occurrence of late complications.

Radiotherapy combined with razoxane seems to improve the local control in inoperable, residual, or recurrent STS compared to radiotherapy alone. The combined treatment is a fairly well tolerated procedure at low costs. It can be recommended for inoperable primary STS or gross disease after incomplete resection, conditions which are still associated with limited local control and a grave prognosis.     

Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas

BackgroundThe primary treatment of soft tissue sarcomas (STS) is a radical resection of the tumor with adjuvant radiotherapy. Conventional fractionation of preoperative radiotherapy is 50 Gy in fraction of 2 Gy a day. The purpose of the conducted study was to assess the efficacy and safety of hypofractionated radiotherapy in preoperative setting in STS patients.Methods272 patients participated in this prospective study conducted from 2006 till 2011. Tumors were localized on the extremities or trunk wall. Median tumor size was 8.5 cm, 42% of the patients had tumor larger than10 cm, whereas 170 patients (64.6%) had high grade (G3) tumors. 167 patients (61.4%) had primary tumors. Patients were treated with preoperative radiotherapy for five consecutive days in 5 Gy per fraction, with an immediate surgery. Median follow up is 35 months.Results79 patients died at the time of the analysis, the 3-year overall survival was 72%. Local recurrences were observed in 19.1 % of the patients. Factors that had a significant adverse impact on local recurrence were tumor size of10 cm or more and G3 grade. 114 patients (42%) had any kind of treatment toxicity, vast majority with tumors located on lower limbs. 7% (21) of the patients required surgery for treatment of the complications.ConclusionIn this non-selected group of locally advanced STS use of hypofractionated preoperative radiotherapy was associated with similar local control (81%) when compared to previously published studies. The early toxicity is tolerable, with small rate of late complications. Presented results warrant further evaluation.     

软组织肉瘤的放射治疗

放疗是软组织肉瘤重要治疗手段之一,术前或术后放疗可降低肿瘤局部复发风险,局部扩大切除结合术前或术后放疗能达到与截肢术同等的长期生存率并且保存肢体功能,近些年来随着放疗技术的进步,软组织肉瘤放疗的正常组织损伤风险正在减少。     

侵犯关节周围骨组织的软组织肉瘤外科治疗策略

目的探索侵犯关节周围骨组织的肢体软组织肉瘤的外科手术方法,并分析术后并发症、肢体功能和患者的生存状况。方法回顾性分析2004年5月至2011年10月期间,我中心所收治的30例局部侵犯关节周围骨组织的软组织肉瘤患者的临床资料。其中男14例,女16例,平均年龄51岁（17～75岁）。恶性纤维组织细胞瘤12例,脂肪肉瘤8例,原始神经外胚层肿瘤（PNET）4例,滑膜肉瘤、腺泡状软组织肉瘤和恶性神经鞘瘤2例。其中10例发病位于股骨近端,9例股骨远端,8例肱骨近端,2例胫骨近端,1例累及整个股骨。所有患者均采取了肿瘤连同受累骨组织一起广泛切除、以肿瘤型假体重建骨缺损的手术方式。术后定期复查患肢功能、x线片、肺CT等,并且密切随访,内容包括术后并发症的发生情况、肢体功能恢复情况及肿瘤学与生存状况等。结果平均随访25个月（3—84个月）,1例暂时性腓总神经麻痹;3例术后伤口愈合不良行清创手术,其中1例因深部感染不愈而截肢;2例假体断裂行翻修手术;4例肿瘤复发,局部复发率13．3％,其中1例接受截肢手术。总的肺转移为15例,且11例死亡患者中均为肺转移,其中3例合并骨转移。至最后一次随访时14例无瘤生存,5例带瘤生存,平均MSTS评分股骨近端90％,股骨远端82％,胫骨近端73％,肱骨近端71％,全股骨为60％。2年和5年生存率分别为61．6％和30．8％。结论将受累骨组织和肿瘤一起广泛切除可获得无瘤边界,降低复发率,骨缺损采用肿瘤型假体重建可恢复良好的肢体功能。巨大肢体软组织肉瘤侵犯骨组织可能是患者预后不良的因素。