Craig Gerrand

Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence

We considered whether a positive margin occurring after resection of a soft-tissue sarcoma of a limb would affect the incidence of local recurrence. Patients with low-grade liposarcomas were expected to be a low-risk group as were those who had positive margins planned before surgery to preserve critical structures. Two groups, however, were expected to be at a higher risk, namely, patients who had undergone unplanned excision elsewhere with a positive margin on re-excision and those with unplanned positive margins occurring during primary resection. Of 566 patients in a prospective database, 87 with positive margins after limb-sparing surgery and adjuvant radiotherapy were grouped according to the clinical scenario by an observer blinded to the outcome. The rate of local recurrence differed significantly between the two low- (4.2% and 3.6%) and the two high-risk groups (31.6% and 37.5%). This classification therefore provides useful information about the incidence of local recurrence after positive-margin resection.

UK Guidelines for the Management of Bone Sarcomas.

These guidelines have been developed in order to provide an overview and a set of broad-based key recommendations for the management of patients with bone sarcomas in the UK. They have taken into consideration the most up-to-date scientific literature along with the recent recommendations by the European Society of Medical Oncology. The principles of the NICE guidance on both “improving outcomes for patients with sarcomas” and “improving outcomes with children and young people with cancer” have been incorporated. As care evolves, it is acknowledged that these guidelines will need updating. The key recommendations are that bone pain or a palpable mass should always lead to further investigation and patients with clinicoradiological findings suggestive of a primary bone tumour should be sent to a reference centre. Patients should then have their care managed at such a specialist centre by a fully accredited multidisciplinary team.

The Influence of Anatomic Location on Functional Outcome in Lower-Extremity Soft-Tissue Sarcoma

Background: The purpose of this study was to explore the relationship between the anatomical location of lower-extremity soft-tissue sarcoma and functional outcome.Methods: Function was evaluated with the Musculoskeletal Tumor Society (MSTS 1993) score and Toronto Extremity Salvage Score (TESS); 207 patients (median age, 54 years) were eligible. The median maximum tumor diameter was 8.0 cm; 58 tumors were superficial and 149 were deep. Nine locations based on anatomical compartments were defined: 6 tumors were in the groin/femoral triangle; 8, the buttock; 52, the anterior thigh; 22, the medial thigh; 20, the posterior thigh; 10, the popliteal fossa; 13, the posterior calf; 11, the anterolateral leg; and 7, the foot or ankle.Results: Treatment of superficial tumors did not lead to significant changes in MSTS score (mean, 90.6% preoperatively vs. 93.0% postoperatively; P = .566) or TESS (mean, 86.4% preoperatively vs. 90.9% postoperatively; P = .059). Treatment of deep tumors lead to significant reductions in MSTS score and TESS (mean MSTS, 86.9% preoperatively vs. 83.0% postoperatively; P = .001; and mean TESS, 83.0% preoperatively vs. 79.4% postoperatively; P = .015). Anatomical location was not a significant predictor of aggregated MSTS and TESS evaluations. Exploratory analysis showed variation in MSTS pain and gait handicap or limp items and TESS dressing, sitting, bending, and bathing items by anatomical location.Conclusions: The treatment of superficial tumors does not lead to significant changes in MSTS score or TESS. Anatomical location is not a significant predictor of aggregated MSTS and TESS evaluations. However, there is variation in MSTS and TESS item scores across anatomical locations.

Of dogs and men: comparative biology as a tool for the discovery of novel biomarkers and drug development targets in osteosarcoma.

The similarities between human and canine osteosarcoma with regard to histology, biological behavior and molecular genetic alterations suggest that the dog provides a supplementary model for the development and preclinical testing of novel therapeutics. Counter intuitively, careful examination of the differences between OS in the two species may also be rewarding in terms of increasing our understanding of the pathogenesis of this cancer. This review will discuss the arguments in favor of the “dog model” and outline how the evaluation of treatment strategies in dogs has indicated avenues for improvement of protocols for human patients. Pediatr Blood Cancer 2012; 58: 327–333.

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

The anatomic location of an extremity soft tissue sarcoma may influence the patients 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.

Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study.

BACKGROUND Mesenchymal chondrosarcoma (MCS) is a distinct, very rare sarcoma with little evidence supporting treatment recommendations. PATIENTS AND METHODS Specialist centres collaborated to report prognostic factors and outcome for 113 patients. RESULTS Median age was 30 years (range: 11-80), male/female ratio 1.1. Primary sites were extremities (40%), trunk (47%) and head and neck (13%), 41 arising primarily in soft tissue. Seventeen patients had metastases at diagnosis. Mean follow-up was 14.9 years (range: 1-34), median overall survival (OS) 17 years (95% confidence interval (CI): 10.3-28.6). Ninety-five of 96 patients with localised disease underwent surgery, 54 additionally received combination chemotherapy. Sixty-five of 95 patients are alive and 45 progression-free (5 local recurrence, 34 distant metastases, 11 combined). Median progression-free survival (PFS) and OS were 7 (95% CI: 3.03-10.96) and 20 (95% CI: 12.63-27.36) years respectively. Chemotherapy administration in patients with localised disease was associated with reduced risk of recurrence (P=0.046; hazard ratio (HR)=0.482 95% CI: 0.213-0.996) and death (P=0.004; HR=0.445 95% CI: 0.256-0.774). Clear resection margins predicted less frequent local recurrence (2% versus 27%; P=0.002). Primary site and origin did not influence survival. The absence of metastases at diagnosis was associated with a significantly better outcome (P<0.0001). Data on radiotherapy indications, dose and fractionation were insufficiently complete, to allow comment of its impact on outcomes. Median OS for patients with metastases at presentation was 3 years (95% CI: 0-4.25). CONCLUSIONS Prognosis in MCS varies considerably. Metastatic disease at diagnosis has the strongest impact on survival. Complete resection and adjuvant chemotherapy should be considered as standard of care for localised disease.

UK guidelines for the management of soft tissue sarcomas

Soft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues, and can occur almost anywhere in the body. Their rarity, and the heterogeneity of subtype and location means that developing evidence-based guidelines is complicated by the limitations of the data available. However, this makes it more important that STS are managed by teams, expert in such cases, to ensure consistent and optimal treatment, as well as recruitment to clinical trials, and the ongoing accumulation of further data and knowledge. The development of appropriate guidance, by an experienced panel referring to the evidence available, is therefore a useful foundation on which to build progress in the field. These guidelines are an update of the previous version published in 2010 (Grimer et al. in Sarcoma 2010:506182, 2010). The original guidelines were drawn up following a consensus meeting of UK sarcoma specialists convened under the auspices of the British Sarcoma Group (BSG) and were intended to provide a framework for the multidisciplinary care of patients with soft tissue sarcomas. This current version has been updated and amended with reference to other European and US guidance. There are specific recommendations for the management of selected subtypes of disease including retroperitoneal and uterine sarcomas, as well as aggressive fibromatosis (desmoid tumours) and other borderline tumours commonly managed by sarcoma services. An important aim in sarcoma management is early diagnosis and prompt referral. In the UK, any patient with a suspected soft tissue sarcoma should be referred to one of the specialist regional soft tissues sarcoma services, to be managed by a specialist sarcoma multidisciplinary team. Once the diagnosis has been confirmed using appropriate imaging, plus a biopsy, the main modality of management is usually surgical excision performed by a specialist surgeon. In tumours at higher risk of recurrence or metastasis pre- or post-operative radiotherapy should be considered. Systemic anti-cancer therapy (SACT) may be utilized in some cases where the histological subtype is considered more sensitive to systemic treatment. Regular follow-up is recommended to assess local control, development of metastatic disease, and any late-effects of treatment. For local recurrence, and more rarely in selected cases of metastatic disease, surgical resection would be considered. Treatment for metastases may include radiotherapy, or systemic therapy guided by the sarcoma subtype. In some cases, symptom control and palliative care support alone will be appropriate.

Influence of body mass index (BMI) on functional improvements at 3 years following total knee replacement: a retrospective cohort study

Background The number of patients presenting for total knee replacement who are classified as obese is increasing. The functional benefits of performing TKR in these patients are unclear. Aim To assess the influence pre-operative body mass index has upon knee specific function, general health status and patient satisfaction at 3 years following total knee replacement. Design Retrospective comparative cohort study using prospectively collected data from an institutional arthroplasty register. Methods 1367 patients were assessed using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Medical Outcomes Trust Short Form-36 (SF-36) scores supplemented by a validated measure of satisfaction pre-operatively and subsequently at 1,2 and 3 year post-operatively. Comparisons were made by dividing the cohort into 4 groups based on body mass index (BMI) 18.5–25.0 kg/m2 (n = 253);>25.0–30.0 kg/m2 (n = 559);>30.0−35.0 kg/m2 (n = 373);>35.0 kg/m2 (n = 182). Results Despite lower pre-operative, 1 and 3 year WOMAC and SF-36 scores patients with the highest BMIs >35.0 kg/m2 experienced similar improvements to patients with a ‘normal‘ BMI (18.5–25.0 kg/m2) at 1 year (Difference in WOMAC improvement = 0.0 (95%CI −5.2 to 5.2), p = 1.00) and this improvement was sustained at up to 3 years (Difference in 1 year to 3 year improvement = 2.2 (95%CI: −2.1 to 6.5), p = 1.00). This effect was also observed for the SF-36 mental and physical component scores. Despite equivalent functional improvements levels of satisfaction in the >35.0 kg/m2 group were lower than for any other BMI group (>35.0 kg/m2 = 84.6% satisfied versus 18.5–5.0 kg/m2 = 93.3% satisfied,p = 0.01) as was the proportion of patients who stated they would have the operation again (>35.0 kg/m2 = 69.6% versus 18.5–25.0 kg/m2 = 82.2%,p = 0.01). Conclusion Obese and morbidly obese patients gain as much functional benefit from total knee replacement as patients with lesser body mass indexes. This benefit is maintained for up to 3 years following surgery. However, these patients are less satisfied with their knee replacement and almost a third would not have the operation again.

Physical functioning, pain and quality of life after amputation for musculoskeletal tumours: a national survey

Patients who have limb amputation for musculoskeletal tumours are a rare group of cancer survivors. This was a prospective cross-sectional survey of patients from five specialist centres for sarcoma surgery in England. Physical function, pain and quality of life (QOL) outcomes were collected after lower extremity amputation for bone or soft-tissue tumours to evaluate the survivorship experience and inform service provision. Of 250 patients, 105 (42%) responded between September 2012 and June 2013. From these, completed questionnaires were received from 100 patients with a mean age of 53.6 years (19 to 91). In total 60 (62%) were male and 37 (38%) were female (three not specified). The diagnosis was primary bone sarcoma in 63 and soft-tissue tumour in 37. A total of 20 tumours were located in the hip or pelvis, 31 above the knee, 32 between the knee and ankle and 17 in the ankle or foot. In total 22 had hemipelvectomy, nine hip disarticulation, 35 transfemoral amputation, one knee disarticulation, 30 transtibial amputation, two toe amputations and one rotationplasty. The Toronto Extremity Salvage Score (TESS) differed by amputation level, with poorer scores at higher levels (p < 0.001). Many reported significant pain. In addition, TESS was negatively associated with increasing age, and pain interference scores. QOL for Cancer Survivors was significantly correlated with TESS (p < 0.001). This relationship appeared driven by pain interference scores. This unprecedented national survey confirms amputation level is linked to physical function, but not QOL or pain measures. Pain and physical function significantly impact on QOL. These results are helpful in managing the expectations of patients about treatment and addressing their complex needs.

UK guidelines for the management of bone sarcomas

This document is an update of the British Sarcoma Group guidelines published in 2010. The aim is to provide a reference standard for the clinical care of patients in the UK with bone sarcomas. Recent recommendations by the European Society of Medical Oncology, The National Comprehensive Cancer Network and The National Institute for Health and Care Excellence have been incorporated, and the literature since 2010 reviewed. The standards represent a consensus amongst British Sarcoma Group members in 2015. It is acknowledged that these guidelines will need further updates as care evolves. The key recommendations are that bone pain or a palpable mass should always lead to further investigation and that patients with clinico-radiological findings suggestive of a primary bone tumour at any site in the skeleton should be referred to a specialist centre and managed by a fully accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow up schedules are suggested.