Rehabilitation and quality-of-life issues in patients with extremity soft tissue sarcoma

Opinion statement The current standard of care for soft tissue sarcoma (STS) is limb salvage surgery and adjuvant radiotherapy, with long-term survival rates of approximately 70%. However, the extensive surgical resection and subsequent reconstruction result in 50% of survivors living with chronic disability. Rehabilitation aims to optimize functional independence and quality of life, and is routinely offered to patients undergoing surgical treatment for STS. Unfortunately, there is a dearth of research related to rehabilitation in this area. We propose a model for assessing disability, for designing treatment interventions and for evaluating rehabilitative outcomes in STS. The World Health Organization’s (WHO) international classification of functioning, disability, and health (ICF) is divided into three domains: 1) impairments (related to body structure and function), 2) activity limitations (related to usual self-care activities/activities of daily living), and 3) participation restrictions (related to social roles). A literature review of STS rehabilitation reveals that most studies have focused on disability assessment, with few papers describing or evaluating rehabilitation interventions commonly employed in STS. Clinicians are forced to extrapolate findings from other patient populations in order to evaluate the effectiveness of specific rehabilitation strategies (ie, those used for particular sequelae of STS, such as lymphedema or impaired exercise tolerance). There is strongest support for complex decongestive physiotherapy (targeting lymphedema) and aerobic exercise interventions (aimed at alleviating cancerrelated fatigue and psychosocial sequelae). The most poorly researched topic is rehabilitation for genitourinary disability (both incontinence and sexual dysfunction). Most studies related to oncologic rehabilitation are restricted to the impairment level (eg, affecting range of motion, muscle strength) of the ICF, with only a small minority addressing activity limitations (eg, affecting activities of daily living) experienced by patients. A consideration of participation restrictions (eg, fulfillment of vocational roles) is almost wholly absent from the literature. Yet social role reintegration is of fundamental importance to patients. Further research is required in these two domains. The ICF provides a comprehensive framework for future research into rehabilitation interventions for STS.     

Management of recurrent soft tissue sarcoma of the retroperitoneum

Local recurrence is the determinant of tumor-related mortality in retroperitoneal sarcomas because death often occurs as a result of local progression mostly without synchronous metastasis. Complete resection of the lesion and surgical margins status are the only therapeutic factors significantly associated with local control. Further outcome improvements need multimodal therapy since prognosis of these recurrences is poor with lower rates of complete resection and higher grade of malignancy than primary. Complete resection of the recurrence often requires removal of adjacent organs to achieve negative margins. External beam radiotherapy (EBRT), eventually associated with a boost of intra-operative electron beam radiotherapy (IORT) could improve the outcome in these patients. Preoperative timing could limit its toxicity. Chemotherapy protocols may enhance local and systemic outcome and can reduce the volume of high grade tumors and therefore allow a higher rate of complete resection. Isolated pelvic perfusion with local high doses chemotherapy is under investigation. Surgical excision of lung metastases should remain the treatment of choice, if preoperative evaluation indicates that complete clearance of the metastases is possible. Intra-operative chemotherapy after cyto-reductive surgery for the treatment of sarcomatosis is disappointing and complete surgery remains the cornerstone of the treatment with best results for low grade sarcomatosis. Adequate management at the time of primary presentation is likely to afford the best chance for long-term survival.     

Technetium-99m-tetrofosmin scintigraphy in patients with metastatic soft tissue sarcoma

The lipophilic cationic compound Tc-99m-tetrofosmin has been demonstrated to be a valuable tool for the detection of a variety of tumours. Tc-99m-tetrofosmin uptake by sarcomas in vitro as well as in primary tumours has been reported. Data on the visualisation of metastatic soft tissue sarcomas using this tracer are missing so far. Ten consecutive patients with histopathologically verified metastatic soft tissue sarcoma were included in the present study. Five patients had previously received cytotoxic treatment, the other five patients were chemonaive. All patients underwent whole body planar examination after administration of 500-550 MBq Tc-99m-tetrofosmin, and in case of lung metastases on CT scan, SPECT images were carried out. Non-physiological accumulation of the tracer was considered as a positive result. Scintigraphic results were compared to conventional imaging by means of MRI/CT scanning. Visualisation of distant metastases was achieved in five patients all of whom were chemonaive, while in the chemotherapeutically pretreated patient group (n=5) false negative results were seen. Progressive disease was confirmed by follow-up in all patients. Pulmonary metastases were visualised only in SPECT acquisition and not on planar images. In one patient with diffuse bone marrow infiltration (inflammatory myofibroblastic sarcoma) Tc-99m-tetrofosmin scintigraphy was positive, while CT showed a negative result. According to our results, detection of metastatic soft tissue sarcomas by Tc-99m-tetrofosmin scintigraphy was strongly dependent on the history of previous treatment of the patient. A positive finding before initiation of chemotherapy was not indicative for subsequent therapeutic response. In the staging of chemonaive patients with metastatic soft tissue sarcoma Tc-99m-tetrofosmin may provide some additional information.     

Contemporary role of amputation for patients with extremity soft tissue sarcoma

Introductionlimb-sparing surgery is the mainstream treatment for primary extremity soft tissue sarcoma (ESTS) at referral centers, following advances in surgical reconstructions and multimodal management. However, amputation is still needed in selected patients and has not yet been described for a ESTS cohort in a contemporary scenario.Material and methodsconsecutive patients who underwent surgery for primary ESTS from 2006 to 2018 were extracted from a prospectively collected database at our reference center. Patients receiving amputation for either primary tumor or local recurrence (LR) after limb-sparing surgery were selected for analysis.ResultsAmong 1628 primary ESTS, 29 patients underwent primary amputation (1.8%), 22/1159 (1.9%) for upper limb and 7/469 (1.5%) for lower limb ESTS. Patients were mainly affected by grade III FNCLCC (89.6%) of notable dimension (median size 16 cm, IQR 10–24). 65.5% of patients received preoperative treatments (systemic or regional chemotherapy, radiotherapy or chemo-radiation). Secondary amputation for LR was performed after a median of 23 months in 16/1599 patients (1%). Median survival time was 16.2 and 29.6 months after primary or secondary amputation respectively. Factors prompting the need for a primary amputation were most often a combination of multifocal disease, bone invasion and pain or neurovascular bundle involvement and relevant comorbidities, mainly for grade III tumors in elderly patients.ConclusionContemporary rate of amputation for ESTS at a reference center is extremely low. Still, amputation is required in selected cases with advanced presentations, especially in elderly, frail patients.     

Significance of local treatment in patients with metastatic soft tissue sarcoma

Metastatic soft tissue sarcomas (STS) represent enormous challenges to improve the low survival rate, which is almost the same as past 2 decades ago, although surgery, radiotherapy and radiofrequency ablation has been accepted in the treatment of metastatic STS. Moreover, STS varies between elderly and younger victims in the aspect of diagnoses, prognosis, and treatment strategies. In order to evaluate the role of local treatment in improving prognosis for patients with metastatic STS and select the proper candidates who will benefit from local therapy, a single-institution nearly 50-year experience were collected and reviewed. Finally, we found that local treatments could improve treatment response and survival, but overall survival advantage could not be seen in elderly patients. This conclusion from a single institution could serve as a basis for future prospective multi-institutional large-scale studies.     

Perioperative irradiation in extremity soft tissue sarcoma

Adjuvant radiotherapy constitutes an important component of the treatment of soft tissue sarcomas. Extremity soft tissue sarcomas constitute a large proportion of this rare mesenchymal tumor. Questions regarding timing, techniques and toxicity come into play about optimizing adjuvant radiotherapy. This article will discuss recent trends and outcomes of perioperative, that is, preoperative and postoperative, irradiation.     

Functional outcome in extremity soft tissue sarcoma

The studies reporting functional outcome for patients undergoing limb preservation surgery for extremity soft tissue sarcoma (STS) have evaluated mainly impairments, that is, deficits at an anatomic structure level, such as joint range of motion and strength. Disability, activities of daily living, self-care, and mobility have been less frequently evaluated. Review of the literature suggests that approximately 50% of patients treated for STS have significant impairments, whereas the frequency of disability is less. Synthesis of the results is difficult because of the heterogeneity of patient samples, treatment, and the outcomes used to evaluate function. Future studies require the use of standardized definitions and reliable and valid functional outcome measures. Improved patient outcomes can be achieved only by understanding the determinants of these outcomes and by introducing interventions to improve patient functional outcome.     

Prognostic factors affecting survival in metastatic soft tissue sarcoma: an analysis of 110 patients

Background

Data on treatment outcome and prognostic factors in patients with metastatic soft tissue sarcoma (STS) are limited in the literature.

Methods

A total of 119 patients with metastatic STS treated between June 2003 and December 2012 were analyzed for treatment outcome and prognostic factors.

Results

Median age was 37 years (range 2–72 years) with a male to female ratio of 1.5:1. Most common histologic subtypes were synovial sarcoma (36 %) and leiomyosarcoma (16 %). Median tumor size was 12 cm (range 1.6–30 cm). Twenty-four (20 %) patients were treated with multimodality therapy and 80 % patients received systemic chemotherapy alone. At a median follow-up of 10 months (range 1–66 months), the 2-year EFS and OS were 10 and 19 %, respectively, with a median EFS and OS of 6 and 10 months, respectively. Univariate analysis identified albumin ≤4 g/dl (p = 0.001), histologic subtypes other than synovial sarcoma (p = 0.02), non-extremity tumors (p = 0.03) and single modality treatment (p = 0.03) as factors predicting poor EFS; however, for OS, hemoglobin ≤10 g/dl (p = 0.02), tumor size >10 cm (p = 0.01) and single modality treatment (p = 0.04) were identified as poor prognostic factors. Multivariate analysis identified only serum albumin ≤4 g/dl (p = 0.002, HR 0.47, 95 % CI 0.29–0.75) associated with poor EFS; however, for OS, hemoglobin ≤10 g/dl (p = 0.009, HR 0.49, 95 % CI 0.29–0.83), tumor size >10 cm (p = 0.003, HR 2.11, 95 % CI 1.28–3.47) and single modality treatment (p = 0.01, HR 0.47, 95 % CI 0.25–0.86) emerged as poor prognostic factors.

Conclusions

Serum albumin, tumor size, hemoglobin and treatment modality affect survival in metastatic STS.

     

Localized extremity soft tissue sarcoma: an analysis of factors affecting survival

The management of extremity soft tissue sarcoma is undergoing rapid change as new techniques of adjuvant treatment are developed. Critical assessment of these advances requires a fundamental understanding of the natural course of this disease. In an effort to define important prognostic factors, this review of 423 adults with localized extremity soft tissue sarcomas, treated at one institution (1968 to 1978), was undertaken. The effect of the following variables on survival was examined: patient factors, ie, age, sex, symptoms, and status at presentation; tumor factors, ie, site, size, depth, bone or neurovascular invasion, histogenesis, grade, and nodal status; and treatment factors, ie, biopsy technique, type of operation, surgical margins, adjuvant treatment, and subsequent local treatment failure. Patient factors with an adverse impact on survival included age greater than 53 and the presence of local symptoms. High tumor grade, positive regional nodes, histology other than liposarcoma, fibrosarcoma or malignant fibrohistiocytoma, invasion of vital structures, proximal site, deep location, and size greater than 10 cm were also poor prognosticators. Treatment factors correlating with optimal survival included limb sparing surgery, adequate margins, biopsy with delayed definitive resection, and absence of subsequent local failure. Patients treated by amputation had a greater proportion of risk factors than patients treated with limb-sparing surgery (LSS). When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of poor outcome: local symptoms, age greater than 53, high grade, proximal site, size greater than 10 cm, positive regional nodes, surgery by amputation, and inadequate margins. These factors are now to be evaluated in our prospective study based on 600 patients with soft tissue sarcoma of all sites admitted to our institution in the last 3 years. These factors should be considered as important stratifications in prospective trials.     

RETRACTED ARTICLE: New drug developments for patients with metastatic soft tissue sarcoma

For the subgroup of patients with inoperable gastrointestinal stromal tumors, progress has been made by the rapid development and approval of the targeted therapy imatinib mesylate. Small round cell sarcomas (SRCT), such as Ewing/primitive neuroectodermal tumor, desmoplastic SRCT, and rhabdomyosarcoma, are chemotherapy-sensitive and potentially curable malignancies that are treated with multimodality dose-intensive neoadjuvant protocols regardless of size or overt metastatic disease. However, the number of effective cytotoxic agents for the treatment of patients with metastatic so-called adult soft tissue sarcoma is limited, especially when patients have failed anthracycline- and ifosfamide-based chemotherapy.     

Liver metastases from extremity soft tissue sarcoma

Liver involvement by soft tissue sarcoma is an unfavorable prognostic factor for survival. Complete resection of liver metastases can bring improvement in selected patients, but chemotherapy remains the only palliative treatment option for most. Anecdotal long-term survival of patients with unresectable liver metastases treated with systemic chemotherapy has been reported, such as the patient presented here.     

Dynamic prediction of overall survival for patients with high-grade extremity soft tissue sarcoma

Purpose

There is increasing interest in personalized prediction of disease progression for soft tissue sarcoma patients. Currently, available prediction models are limited to predictions from time of surgery or diagnosis. This study updates predictions of overall survival at different times during follow-up by using the concept of dynamic prediction.

Impact of surgery in patients with metastatic soft tissue sarcoma: A monocentric retrospective analysis

Background and Objectives

The role of local surgical procedures in patients with metastatic soft tissue sarcoma is still undefined. Few retrospective studies have reported survival benefits for patients with pulmonary metastases after complete surgical resection. Treatment decisions are therefore mainly based on personal experiences rather than on reproducible knowledge.

Method

A total of 237 patients with metastatic sarcoma, treated between 1982 and 2015 at the University Hospital Tuebingen, Germany, were eligible for inclusion. Out of the 237 screened patients, 102 patients underwent at least one metastasectomy. Overall survival was defined as the primary endpoint in this study. For association of non‐linear relationship to the endpoint, significant prognostic factors were included into a recursive partitioning model. A subgroup analysis for long‐term survivors was also performed.

Results

The median overall survival was 64 months. The 3‐, 5‐, 10‐, and 20‐years overall survival rates were 70.7%, 50.3%, 24.7%, and 14.8%, respectively. The number of resections and the progression‐free intervals were independent prognostic factors in three statistical models.

Conclusion

Repeated resections of metastases from different localizations are a strong predictor for prolonged survival. We suggest that the progression‐free interval after metastasectomy should be considered as a predictive factor for benefit from further surgery.     

High-dose cisplatin for metastatic soft tissue sarcoma

Between August 1984 and January 1987, the Southwest Oncology Group (SWOG) registered 46 patients with metastatic sarcomas on SWOG 8465, a Phase II trial of high-dose cisplatin in patients with metastatic soft tissue sarcoma. Six patients were ineligible for the following reasons: poor performance status (two patients); ineligible diagnosis (three patients, two with Ewing's sarcoma of bone and one with metastatic chondrosarcoma); and evaluable but nonmeasurable disease (one patient with bone-only disease). Of the 40 fully evaluable patients, 34 had received prior chemotherapy; treatment was with cisplatin (40 mg/m2/d for 5 consecutive days). Cisplatin was mixed in 250 ml of 3% NaCl and hydrated with a normal saline solution at a rate of 250 ml/h, beginning 12 hours before the first dose of cisplatin was specified. The second treatment was given 3 weeks after the first, with all subsequent treatments given every 4 weeks. After three cycles of treatment, responding patients were treated at a cisplatin dose of 20 mg/m2/d for 5 consecutive days. Leukopenia was of Grade 3 or 4 in seven patients, whereas thrombopenia was of Grade 3 or 4 in eight patients. More severe myelosuppression was produced in patients who had received prior radiotherapy. A single case of reversible Grade 4 nephrotoxicity was produced; neurotoxicity was observed in 11 cases, but was of Grade 3 in only 2 cases. Of the 40 evaluable cases, six showed partial responses or no responses, for a major response rate of 15%. High-dose cisplatin has minor activity and major toxicity in the treatment of metastatic soft tissue sarcomas, and should be considered investigational.     

Prognostic value of monocyte and neutrophils to lymphocytes ratio in patients with metastatic soft tissue sarcoma

Metastatic soft tissue sarcomas (STS) represent enormous challenges to improve the low survival rate, which is almost the same as past 2 decades ago. Prognosis of cancer patients are based not only on tumor-related factors but also on host-related factors, particularly systemic inflammatory response. We evaluated the association among possible risk factors and survival for metastatic STS by reviewed a single-institution nearly 50-year experience. We found that both monocyte ratio and NLR ratio were significant prognostic predictors for OS and PFS of metastatic STS. And patients with monocyte ratio or NLR ratio > 1 should be screened out as candidates for more intensive or aggressive multimodality treatments and more aggressive follow-up. For this reason, this result could serve as a basis for future prospective study.     

Contemporary management of metastatic soft tissue sarcoma

Soft tissue sarcoma (STS) is a rare, heterogeneous cancer that can have high rates of distant metastases. Optimal treatment planning requires detailed knowledge of distinct sarcoma histologies as well as the wide array of therapeutic options through surgical, medical, radiation, and interventional oncology. In this review article, we discuss the contemporary management of metastatic STS and the underlying data behind these recommendations. All patients with metastatic STS should be discussed in a multidisciplinary tumor board at an experienced sarcoma center. For patients with oligometastatic disease, there should be strong consideration for definitive local therapy such as surgical resection, stereotactic body radiation therapy, or ablative procedures. In cases with widespread metastases, cytotoxic chemotherapy represents the standard treatment for STS patients with traditional chemotherapies, such as anthracyclines, gemcitabine/docetaxel, ifosfamide, and dacarbazine, still being the most commonly used drugs today. The recent approvals of trabectedin, eribulin, and pazopanib have expanded the therapeutic armamentarium for metastatic STS. Histology-directed treatment is crucial for certain subtypes of STS which are highly sensitive to targeted therapy and relatively insensitive to chemotherapy. Despite the significant progress that has been made in metastatic STS in the past decade, overall prognosis is poor and there is a critical need for novel therapeutics.     

Surgery in soft tissue sarcoma: more conservative in extremities,more extended in the retroperitoneum

Extremity soft-tissue sarcomas (ESTS) account for approximately 50% and retroperitoneal soft-tissue sarcomas (RSTS) for approximately15% of all soft-tissue sarcomas. Surgery remains the main treatment modality for all soft-tissue sarcomas. Neoadjuvant and/or adjuvant chemo-and radiation-therapy are also often used to improve the treatment outcomes. In ESTS, surgery had originally been mutilating. The introduction of principles of surgical adequacy and of complementary treatments, especially radiotherapy, led to a reduction in the amputation rate in favor of conservative treatments. The implementation of plastic, vascular and nerve reconstructions allowed for further increase in conservative procedures, with better functional and cosmetic results. Moreover, recent reports have demonstrated how preoperative treatments can offset the negative prognostic impact of marginal resection on local outcome and survival, extending the limit of limb and function preservation. In RSTS, surgery had consisted of simple excision, while the resection of surrounding organs/viscera had been considered only in cases of direct involvement/infiltration. This strategy was associated with a high rate of local recurrence, which in many cases it was the driving cause of death. In order to improve local control and subsequent overall survival, some authors have recently advocated a policy of extended surgery including surrounding organs/viscera en bloc with the tumor. In this review, the authors discuss the standard world wide accepted surgical treatment for ESTS and the new surgical approach for RSTS.     

The influence of anatomic location on outcome in patients with soft tissue sarcoma of the extremity

BACKGROUND: The anatomic location of an extremity soft tissue sarcoma may influence the patient's presentation, management, and local and systemic recurrence rates. The objective of this study was to compare the presentation, management, and outcome of patients with soft tissue sarcomas of the upper extremity and the lower extremity. METHODS: Prospectively collected data from patients who underwent limb-sparing surgery for extremity soft tissue sarcoma between January, 1986 and April, 1997 were analyzed. Local recurrence free rates and metastasis free rates were calculated using the method of Kaplan and Meier. Univariate and multivariate analyses of potential predictive factors were evaluated with the log-rank test and the Cox proportional hazards model. RESULTS: Of 480 eligible patients, 48 patients (10.0%) had a local recurrence, and 131 patients (27.3%) developed distant metastasis. The median follow-up of survivors was 4.8 years (range, 0.1-12.9 years). Patients with upper extremity tumors had smaller lesions (6.0 cm vs. 9.3 cm; P < 0.001), more often underwent unplanned excision before referral (89 patients [64.0%] vs. 160 patients [46.9%]; P < 0.001), and less often received radiotherapy (98 patients [70.5%] vs. 289 patients [84.8%]; P < 0.001). The 5-year local recurrence free rate was 82% for patients with sarcomas of the upper extremity and 93% for patients with sarcomas of the lower extremity (P = 0.002). The 5-year metastasis free rate was 82% for patients with sarcomas of the upper extremity and 69% for patients with sarcomas of the lower extremity (P = 0.013). CONCLUSIONS: Local recurrence was more frequent in patients who had sarcomas of the upper extremity compared with patients who had sarcomas of the lower extremity. Factors that contributed to this difference included histologic type, the use of radiotherapy, and local anatomy. Metastasis was more frequent among patients with sarcomas of the lower extremity, because those tumors tended to be large and deeper compared with upper extremity tumors.     

肢体软组织肉瘤保守性手术辅助放射治疗现状

辅助性放疗可以在不影响局部控制率的前提下,减少外科切除范围,提高保留器官的可能性,维持满意的生活质量,保守性手术联合辅助性放疗已经成为肢体软组织肉瘤治疗的现代治疗标准.