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.     

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     

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.     

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.     

Planned combined onco-plastic (COP) surgical approach improves oncologic outcomes in soft tissue sarcomas

BackgroundCombined modality of radiotherapy and surgery is the standard of treatment of soft tissue sarcomas (STS). The goal of this study was to assess whether a Combined Onco-Plastic (COP) surgical approach in the setting of neo-adjuvant radiotherapy can improve the oncologic outcomes of STS and reduce the rate of wound complications.MethodsWe performed a retrospective review of all patients with STS treated at a single sarcoma centre (St Vincent’s Hospital, Melbourne) between 2007 and 2018. Patients were stratified into two groups based on whether they have received the COP approach or were closed primarily by the orthopaedic surgeon. We analysed oncological outcomes and rate of wound complications.ResultsA total of 546 patients with comparable demographics and tumor characteristics were included. The COP approach was performed in 75.6% of the patients. Wide margins were obtained in 97.4% of the cases, and this was significantly higher in the COP group (p < 0.001). The cumulative rate of local recurrence was 4.9%, with a 52% risk reduction in the COP approach, although this reduction was not significant (HR = 0.48; 95% CI 0.21–1.06; p = 0.070). The COP approach had better disease free survival (DFS) (aHR 1.86, 95% CI 1.45–2.37; p < 0.001) and Overall survival (risk of death aHR 0.49; 95% CI 0.30–0.79; p = 0.004). The overall wound complication rate was 18.6% with no difference between the two groups.ConclusionA planned collaboration between the orthopaedic oncologist and the plastic surgeon is beneficial in the treatment of STS after neo-adjuvant radiotherapy, allowing remarkably good oncological outcomes and a low rate of wound complications.     

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).     

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。     

Microvessel density does not predict outcome in high grade soft tissue sarcoma

The induction of new blood vessel growth into tumours from a pre-existing vascular bed (angiogenesis) is a characteristic of virtually all malignant tumours studied. Previous studies have demonstrated a consistent correlation between the extent of angiogenesis and disease prognosis for a wide range of carcinomas, but not for sarcomas. AIMS: To investigate the most appropriate method for assessment of microvessel density (MVD) using a cohort of patients with large (>5 cm), deep (intramuscular), high grade soft tissue sarcoma and investigate any relationship between MVD, vascular endothelial growth factor (VEGF) expression and prognosis. METHODS: Forty-two patients were included in the study. MVD was evaluated in peripheral, central, necrotic and hotspot areas within the tumour by either Chalkley count or total count of immunostained vessels in five high power (x 200) visual fields. RESULTS: Hot spots of angiogenesis were only present in 33% of specimens. There was a strong correlation p<0.001 between the two methods of quantification with Chalkey method being recommended. VEGF expression evaluated by immunohistochemistry was seen in all but one tumour with strong diffuse cytoplasmic staining within tumour cells, which was not correlated with microvessel density, metastasis or survival. There was a positive correlation between MVD and histological subtype (p<0.01), and primary tumour size and the development of metastasis (p=0.049) but MVD was not predictive of metastasis or overall survival. CONCLUSIONS: Unlike the majority of previous studies involving various types of carcinoma, there was no correlation between microvessel density and metastasis or survival in a group of patients with large (>5 cm), deep, high grade soft tissue sarcoma.     

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.     

Pelvic soft tissue sarcomas

Pelvic soft tissue sarcomas (PSTS) are a rare, heterogeneous group of tumors. They have been usually analyzed with retroperitoneal sarcomas (RPS), but actually have key differences. Due to their unique anatomic location, symptomatic presentation of PSTS may be more common than RPS. Adequate imaging approach is paramount for guiding differential diagnosis, while preoperative biopsy is mandatory, especially when preoperative treatment may be considered as initial approach. The most frequent histologic subtype is leiomyosarcoma, which is different as expected in the retroperitoneum where liposarcoma is the commonest histology. Also solitary fibrous tumor is commonly diagnosed in the pelvis. Surgical approach for PSTS differs from that for RPS mainly due to anatomic relations. Similarly, in the lack of definite evidence from specific trials about neoadjuvant and adjuvant treatments, the anatomic constraints to obtain wide margins in the pelvis as well as the expected functional outcome in case of organ resections should be factored into decision for individualized treatment offer. Vascular and genitourinary involvement are frequent, as well as herniation through pelvic foramina. For these reasons a multidisciplinary surgical team should always be considered. Early referral of these patients to high-volume centers is critical and may impact on survival, given that optimal initial resection is a major predictor of curative treatment. International consensus on PSTS treatment is advocated, similarly to the recent efforts realized for RPS.     

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.     

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。     

Isolated limb perfusion of soft tissue sarcomas: A comprehensive review of literature

Patients with primary irresectable, locally advanced soft tissue sarcomas of the limbs form a challenging group for the treating physician. Multimodality treatment is necessary to guarantee optimal limb salvage and survival rates. Since the introduction of isolated limb perfusion in the late fifties, several treatment regimens have been proposed. Isolated perfusion with melphalan and TNF-α, as part of a multimodality treatment, is regarded as the current best treatment option today. Ongoing studies are investigating potential benefit of other doses, new chemotherapeutic agents and new techniques in perfusion and radiotherapy. This article provides a historical overview of published literature and insight in upcoming treatment techniques.     

Image guided surgery: new technology for surgery of soft tissue and bone sarcomas.

AIM: Providing the surgical oncologist with a new means of performing safe and radical sarcoma surgery with the help of image guidance technology. METHOD: Two patients with pelvic sarcomas were operated upon with the help of an intra-operative navigation system. The technology of image guided surgery is described in one patient with a retroperitoneal sarcoma invading the bony pelvis and another patient with a chondrosarcoma of the iliac crest. RESULTS: We show that this new procedure enables optimal radical surgical resection with minimal treatment related morbidity or loss of function. CONCLUSION: Image guided surgery is a new technical tool in sarcoma surgery.     

Current pathology work-up of extremity soft tissue sarcomas,evaluation of the validity of different techniques

Objective

In patients with extremity soft tissue sarcomas (STSs) a correct histopathological diagnosis is considered important before surgical treatment. We evaluated the preoperative use and sensitivity of the various pathology techniques.

Methods

In a population-based study in patients operated for a newly diagnosed extremity STS between January 2000 and December 2003 the preoperative pathology work-up was evaluated. Data were retrieved from a national pathology database (PALGA). The sensitivity of the three techniques was assessed considering an examination affirmative when the conclusion of the pathology report stated the presence of mesenchymal malignancy.

Results

The pathology reports of 573 patients were identified in the database. In 177 patients (31%) no pathology examination was done before resection of the tumour. In the remaining 396 patients the pathology procedure of first choice had been an incisional biopsy (IB) in 195 patients (49%), a core-needle biopsy (CNB) in 90 patients (23%) and a fine needle aspiration (FNA) in 111 patients (28%). An affirmative diagnosis was established in 95% of the patients following an IB, in 78% after a CNB and in 38% following FNA. After an initial CNB an additional IB was performed in 18 of the 90 patients improving the yield to 89%. After an initial FNA a subsequent histological biopsy was done in 53 of the 111 patients, increasing the sensitivity to 71%.

Conclusions

In this population-based study in patients treated for extremity STS, the proportion of patients operated without preoperative pathology evaluation was high. In the remaining patients an incisional biopsy was still the most commonly performed technique with the highest yield.     

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.     

Gemcitabine at fixed dose-rate in patients with advanced soft tissue sarcomas: a mono-institutional phase II study

Purpose  To explore the clinical activity and toxicity of gemcitabine infused at the fixed dose of 10 mg/m²/min over 100 min in patients with soft tissue sarcomas (STSs). Patients and methods  Fourteen patients with advanced locally unresectable and/or metastatic, pretreated STSs (seven leiomyosarcoma, three malignant schwannoma, one synovialsarcoma, one malignant fibrous histiocytoma, one endometrial stromal cell sarcoma, one undifferentiated) were treated with gemcitabine 10 mg/m²/min/week over 100 min given for 3 weeks out of 4. The median age was 52 years (range 27–77), male/female ratio was 3/11, and the median WHO performance status was 0 (range 0–1). The median number of previous medical treatments for advanced disease was 1 (range 1–2). Results  A median number of three cycles (range 1–10 cycles) and a total of 151 weekly administrations (median 9, range 3–27) of gemcitabine were administered. Treatment was well tolerated and the main causes of dose-reduction or omission/delay were hematological and liver toxicities. One patient (7%; 95% confidence interval: 0.2–33.9%) with a metastatic uterine leiomyosarcoma obtained a partial response that lasted for 6.5 months. Three patients (two leiomyosarcoma and one schwannoma) (21%) obtained a stabilization of disease. The median time to progression was 3.1 months (range 1.0–9.5). The median overall survival was 11.8 months (range 1.0–54.5+). Conclusions  Gemcitabine infused at the fixed dose of 10 mg/m²/min over 100 min shows a good tolerability but an overall modest activity in unselected STSs histotypes. Nevertheless, an interesting tumor growth control rate was observed in specific histological variants (i.e., leiomyosarcoma), thus confirming data from recent controlled clinical trials.