Aim: Radiotherapy has been shown to improve local control in combination with limb-sparing or conservative surgery in the management of localised soft tissue sarcoma. Our Centre's treatment protocol is to offer preoperative external beam radiotherapy (50.4 Gy in 28 fractions) followed by surgery four to six weeks later. The aim of this study is to review the treatment outcome and toxicity of patients treated with this protocol.Methods: Consecutive patients with localised extremity or truncal soft tissue sarcoma who presented between January 1996 and December 2000 and treated with preoperative radiotherapy followed by limb-sparing surgery were reviewed. Patients with recurrent disease or metastatic disease at diagnosis and patients below the age of 16 years were excluded. Local and distant recurrence, overall survival and treatment toxicity were analyzed.Results: Sixty-seven cases were identified (41 males and 26 females). The median age was 52 years (range 17 to 82). The majority (79%) had tumours located in the lower limb. The most common histological diagnoses were malignant fibrous histiocytoma and liposarcoma. The median follow-up was 4.1 years (range 0.6 to 6.9). There were six local recurrences, two of which were successfully salvaged. Twenty patients developed distant metastases. The estimated 5-year actuarial local recurrence free, distant recurrence free and overall survival were 93%, 68% and 73% respectively. Acute radiotherapy toxicity and wound complications were acceptable and late toxicity was uncommon.Conclusion: Preoperative radiotherapy followed by surgery provides effective local control in the management of soft tissue sarcoma. (c) 2006 Elsevier Ltd. All rights reserved.

Giant cell tumor of bone (GCT) is a generally benign, osteolytic neoplasm comprising stromal cells and osteoclast-like giant cells. The osteoclastic cells, which cause bony destruction, are thought to be recruited from normal monocytic pre-osteoclasts by stromal cell expression of the ligand for receptor activator of nuclear factor KB (RANKL). This model forms the foundation for clinical trials in GCTs of novel cancer therapeutics targeting RANKL. Using expression profiling, we identified both osteoblast and osteoclast signatures within GCTs, including key regulators of osteoclast differentiation and function such as RANKL, a C-type lectin, osteoprotegerin, and the wnt inhibitor SFRP4. After ex vivo generation of stromaland osteoclast-enriched cultures, we unexpectedly found that RANKL mRNA and protein were more highly expressed in osteoclasts than in stromal. cells, as determined by expression profiling, flow cytometry, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. The expression patterns of molecules implicated in signaling between stromal. cells and monocytic osteoclast precursors were analyzed in both primary and fractionated GCTs. Finally, using array-based comparative genomic hybridization, neither GCTs nor the derived stromal. cells demonstrated significant genomic gains or losses. These data raise questions regarding the role of RANKL in GCTs that may be relevant to the development of molecularly targeted therapeutics for this disease.

Aim: Thallium-201 (TI-201) scintigraphy in patients with malignant soft tissue tumours was evaluated to determine whether the images correlated with histological response to preoperative radiotherapy.Methods: We studied 54 patients, median age 32 (range 17-84) years, with non-metastatic, malignant soft tissue tumours diagnosed between 1996 and 2001. Thirty-eight patients had unoperated tumours and 16 patients had previous incomplete excisions. All patients received preoperative radiotherapy followed by surgery. No patient received chemotherapy as part of their initial management. Qualitative analyses of early phase (30 min) and late phase (4 h) TI-201 scintigraphic images before and after preoperative radiotherapy were compared with the degree of tumour necrosis determined histologically.Results: In the previously unoperated group, all 38 patients had increased TL-201 uptake in the late phase of scanning prior to radiotherapy suggesting metabolically active tissue. In the previously excised group II patients had increased TI-201 uptake in the late phase of scanning prior to radiotherapy. Following radiotherapy, patients with TI-201 retention on late phase scans had a lower rate of necrosis than patients with minimal retention, p < 0.0001. Following radiotherapy, 28 of 29 patients with minimal uptake on the late phase had 80% or more necrosis, while 24 of 25 patients with increased uptake on the late phase had less than 80% necrosis (p < 0.0001). Patients with previously excised turnours who had thallium retention following radiotherapy demonstrated evidence of residual disease at surgery. All patients with incompletely excised turnours who had no thallium retention on late phase scanning after radiotherapy demonstrated no evidence of residual disease at surgery.Conclusion: Thallium scintigraphy is a readily available investigative tool, which when used in conjunction with other imaging modalities in the assessment of primary and incompletely excised malignant soft tissue tumours, may predict histological tumour response to preoperative radiotherapy. (C) 2003 Elsevier Ltd. All rights reserved.

AIMSWe analysed wound complications in 43 patients with soft tissue sarcoma who were treated with combined pre-operative radiotherapy and surgery.METHODSAll patients received the same protocol of pre-operative radiotherapy at our institution.RESULTSThirty-six (84%) patients developed acute skin toxicity following radiotherapy. After wide local excision, 15 patients required primary soft tissue reconstruction with vascularized muscle transfer and four patients underwent free skin flap to enable wound closure as part of their primary surgery. Nineteen patients (44%) developed post-operative wound complications including 10 (23%) patients who required an additional surgical procedure. Four (27%) patients developed flap necrosis in a group of 15 who underwent primary vascularized soft tissue transfer. All required a second vascularized muscular flap. One elderly patient, who had grade 3 acute radiation skin toxicity, had an arterial graft and total hip arthroplasty for a femoral artery aneurysm and an avascular necrosis of the hip, respectively. In our series, age (> or = 40 years) was the only impact factor influencing wound complication after surgery following radiotherapy (P=0.06).CONCLUSIONSSite of tumour, radiation field size, surgical resection volume, grade of acute radiation toxicity, co-morbidity, and smoking were not demonstrated to have predictive value in wound complication following pre-operative radiotherapy. Although previous papers suggested that vascularized soft tissue transfer could be useful reducing wound morbidity, our results could not confirm this.