These guidelines were drawn up following a consensus meeting of UK sarcoma specialists convened under the auspices of the British Sarcoma Group and are intended to provide a framework for the multidisciplinary care of patients with soft tissue sarcomas. The guidelines published by the European Society of Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) were used as the basis for discussion and adapted according to UK clinical practice and local requirements. Note was also taken of the National Institute for Health and Clinical Excellence (NICE) improving outcomes guidance (IOG) for people with sarcoma and existing technology appraisals. The guidelines are not intended to challenge NICE guidance but discrepancies may exist where current guidance does not reflect an international standard of care owing to the ever-evolving nature of cancer treatment. It is acknowledged that these guidelines will require updating on a regular basis. An appendix lists the key recommendations which are summarised below. Any patient with a suspected soft tissue sarcoma should be referred to a diagnostic centre and managed by a specialist sarcoma multidisciplinary team. Surgical excision followed by post operative radiotherapy is the standard management of high grade limb sarcomas although occasionally amputation remains the only option. Pre-operative treatment with chemotherapy or radiotherapy should be considered for patients with borderline resectable tumours. Isolated limb perfusion may permit limb salvage in some cases where amputation is the only other option. Adjuvant chemotherapy is not routinely recommended but may be considered in certain specific situations. Regular follow up is recommended to assess local control and the development of metastatic disease. Single agent doxorubicin is the standard first line therapy for metastatic disease. Ifosfamide is an alternative if anthracyclines are contraindicated. Combination therapy may be considered in individual patients. Second line agents include ifosfamide, dacarbazine, trabectedin and the combination of gemcitabine + docetaxel. Surgical resection of local recurrence and pulmonary metastases should be considered in individual patients. There is specific guidance on the management of retroperitoneal and uterine 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.

SummaryBackgroundFor many years, first-line treatment for locally advanced or metastatic soft-tissue sarcoma has been doxorubicin. This study compared gemcitabine and docetaxel versus doxorubicin as first-line treatment for advanced or metastatic soft-tissue sarcoma.MethodsThe GeDDiS trial was a randomised controlled phase 3 trial done in 24 UK hospitals and one Swiss Group for Clinical Cancer Research (SAKK) hospital. Eligible patients had histologically confirmed locally advanced or metastatic soft-tissue sarcoma of Trojani grade 2 or 3, disease progression before enrolment, and no previous chemotherapy for sarcoma or previous doxorubicin for any cancer. Patients were randomly assigned 1:1 to receive six cycles of intravenous doxorubicin 75 mg/m2 on day 1 every 3 weeks, or intravenous gemcitabine 675 mg/m2 on days 1 and 8 and intravenous docetaxel 75 mg/m2 on day 8 every 3 weeks. Treatment was assigned using a minimisation algorithm incorporating a random element. Randomisation was stratified by age (≤18 years vs >18 years) and histological subtype. The primary endpoint was the proportion of patients alive and progression free at 24 weeks in the intention-to-treat population. Adherence to treatment and toxicity were analysed in the safety population, consisting of all patients who received at least one dose of their randomised treatment. The trial was registered with the European Clinical Trials (EudraCT) database (no 2009–014907–29) and with the International Standard Randomised Controlled Trial registry (ISRCTN07742377), and is now closed to patient entry.FindingsBetween Dec 3, 2010, and Jan 20, 2014, 257 patients were enrolled and randomly assigned to the two treatment groups (129 to doxorubicin and 128 to gemcitabine and docetaxel). Median follow-up was 22 months (IQR 15·7–29·3). The proportion of patients alive and progression free at 24 weeks did not differ between those who received doxorubicin versus those who received gemcitabine and docetaxel (46·3% [95% CI 37·5–54·6] vs 46·4% [37·5–54·8]); median progression-free survival (23·3 weeks [95% CI 19·6–30·4] vs 23·7 weeks [18·1–20·0]; hazard ratio [HR] for progression-free survival 1·28, 95% CI 0·99–1·65, p=0·06). The most common grade 3 and 4 adverse events were neutropenia (32 [25%] of 128 patients who received doxorubicin and 25 [20%] of 126 patients who received gemcitabine and docetaxel), febrile neutropenia (26 [20%] and 15 [12%]), fatigue (eight [6%] and 17 [14%]), oral mucositis (18 [14%] and two [2%]), and pain (ten [8%] and 13 [10%]). The three most common serious adverse events, representing 111 (39%) of all 285 serious adverse events recorded, were febrile neutropenia (27 [17%] of 155 serious adverse events in patients who received doxorubicin and 15 [12%] of 130 serious adverse events in patients who received gemcitabine and docetaxel, fever (18 [12%] and 19 [15%]), and neutropenia (22 [14%] and ten [8%]). 154 (60%) of 257 patients died in the intention-to-treat population: 74 (57%) of 129 patients in the doxorubicin group and 80 (63%) of 128 ...

PurposeEURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy.Patients and MethodsAt diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary).ResultsGood response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model.ConclusionAt the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.

BACKGROUND: Pigmented villonodular synovitis (PVNS) (also known as diffuse‐type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor‐1 (CSF1). CSF1 is expressed by a minority of tumor cells, which, in turn attract non‐neoplastic inflammatory cells that express CSF1 receptor (CSF1R) through a paracrine effect. METHODS: Imatinib mesylate (IM) blocks CSF1R, and previous case reports indicated that it also exerts antitumor activity in PVNS. The authors conducted a multi‐institutional retrospective study to assess the activity of IM in patients with locally advanced/metastatic PVNS/TGCT. RESULTS: Twenty‐nine patients from 12 institutions in Europe, Australia, and the United States were included. There were 13 men, the median age was 41 years, and the most common site of disease was the knee (n = 17; 59%). Two patients had metastatic disease to the lung and/or bone. Five of 27 evaluable patients had Response Evaluation in Solid Tumor (RECIST) responses (overall response rate, 19%; 1 complete response and 4 partial responses), and 20 of 27 patients (74%) had stable disease. Symptomatic improvement was noted in 16 of 22 patients (73%) who were assessable for symptoms. Despite a high rate of symptomatic improvement and a favorable safety profile, 6 patients discontinued because of toxicity, and 4 patients decided to discontinue IM for no clear medical reason. CONCLUSIONS: IM displayed interesting activity in patients with PVNS/TGCT, providing proof of concept for targeting CSF1R in this disease. The authors concluded that the benefits of alleviating morbidity in patients with localized PVNS/TGCT must be balanced against the potential toxicity of chronic drug therapy. Cancer 2011;. © 2011 American Cancer Society.

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.

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In the majority of histologically suspected GISTs a combination of CD117 and DOG1 immunostaining is sufficient to confirm the histological diagnosis.