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.     

Identification of predictors for wound complications following preoperative or postoperative radiotherapy in extremity soft tissue sarcoma

Introduction

In extremity soft tissue sarcoma (ESTS), external beam radiotherapy (EBRT) has been used in addition to limb-sparing surgery (LSS). This study aims to identify predictors for major wound complication (MWC) development following EBRT and LSS in ESTS.

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.     

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     

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).     

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.     

Radiation therapy technique in soft tissue sarcomas of the extremity—policies of treatment at the national cancer institute

We have formulated certain treatment techniques for soft tissue sarcomas of the extremities in adults, based on the experience of treating 75 patients at the National Cancer Institute. Attaining a high likelihood of tumor control is heavily dependent on a variety of factors. These factors include a knowledge of the biological characteristics of the tumor, of the normal tissue anatomy and its relationship to the tumor and of the surgical techniques available and the details of the surgery already performed. Obtaining good long term function in the irradiated extremity is dependent on sparing a strip of soft tissue and using sophisticated radiation therapy techniques. These techniques include casting of the extremity for immobilization, using a variety of gantry and collimator angulations, using treatment planning for determining the necessity for wedges or compensating filters in the radiation field and utilizing secondary collimation. With this highly individualized approach to treatment of patients with soft tissue sarcomas, optimal results can be obtained.     

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。     

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.     

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.     

间室切除在四肢软组织肿瘤治疗中的应用

目的：探讨间室切除术在四肢软组织肿瘤治疗中方法及临床价值。方法：12例四肢软组织肿瘤，上肢2例，下肢lO例，首次治疗者8例，复发者4例。行股前间室切除术3例，股后间室切除术7例，前臂外侧间室切除l例，三角肌全切除l例。伴神经部分切除术2例。功能重建包括肌腱替代和皮瓣转位等。结果：本组均保留患肢，随访10～60个月，无瘤生存10例，复发和死亡各1例。结论：对于四肢软组织肿瘤，以控制肿瘤和保存肢体为治疗核心，间室切除术系目前较理想的方法。     

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.     

Treatment and outcome of radiation-induced soft-tissue sarcomas at a specialist institution

Background

Radiation-induced sarcoma (RIS) is a rare late complication of therapeutic irradiation with a reputation for aggressive pathology and poor outcome.

Methods

We retrospectively reviewed histopathological features, surgery and outcome in 67 patients with RIS treated between 1990 and 2005 at a single tertiary referral center.

Results

Previous breast cancer was the most common indication for radiotherapy. The median interval from irradiation to development of RIS of was 11 years (3–36 years). Median tumour size was 7 cm with 56% classified as high grade, 31% intermediate grade and 13% low grade. The commonest histology was leiomyosarcoma. The only relationship for histology with site was for angiosarcoma (n = 9), all of which developed on the chest wall/breast after irradiation for breast cancer. Of 67 patients, 34 underwent potentially curative surgery, and microscopically clear margins were achieved in 75% of cases. Pedicled or free tissue transfer was required in 12 patients and abdominal or chest wall mesh reconstructions were required in 8 patients. No patient received adjuvant radiotherapy but 7 received adjuvant/neoadjuvant chemotherapy. Median follow up is 53 months. Median sarcoma specific survival was 54 months (2- & 5-year survival: 75% & 45%). The local relapse rate was 65%. Negative histopathological margins were a significant predictor of sarcoma specific survival (HR 3.0 95% CI 1.1–8.6 p = 0.04). Grade and size of tumour approached, but did not attain significance.

Conclusion

RIS is a biologically aggressive tumour with high rates of local relapse despite aggressive attempts at curative surgery.     

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。