ANTI-TUMOUR TREATMENTThe value of FDG-PET in the detection, grading and response to therapy of soft tissue and bone sarcomas; a systematic review and meta-analysis
Introduction
Sarcomas comprise approximately 1% of malignant tumours and represent a significant diagnostic and therapeutic challenge.1 The incidence in The Netherlands of new soft tissue and bone sarcomas is 4.9 per 100,000 giving approximately 800 new cases per year.2 Soft-tissue sarcomas are a heterogeneous group of tumours that arise from tissue of mesenchymal origin and are characterised by infiltrative local growth.3 Malignant primary bone tumours such as Ewing’s sarcoma typically occur in children and adolescents, although osteosarcoma can also occur in the elderly. Soft tissue sarcomas occur in both children and the elderly. The metastatic spread of sarcomas is mainly haematogenous to the lungs, although lymphatic spread may occur.4 Soft tissue sarcomas can occur at any site throughout the body. Almost 45% of all soft tissue sarcomas are found in the extremities, especially in the lower limb, and 20% intra-abdominal.[5], [6] The presence or absence of metastases and the tumour histology and grade mainly influence the treatment of choice. Because sarcomas may be very heterogenous in composition, noninvasive assessment of the parts with the highest grade of malignancy would be helpful for clinical practice. A total body impression of metastatic spread could potentially be useful. In addition, assessment of response to treatment following local or systemic administration of anti-cancer drugs would be a valuable use of FDG-PET.
Optimal management of sarcomas depends on the site, size and grade of the tumour and accurate staging of the disease when first diagnosed. The site and size of the primary tumour can be determined using magnetic resonance imaging (MRI) and conventional computed tomography (CT) but benign soft tissue masses and soft tissue sarcomas may appear to be very similar on clinical and radiological examination. Besides that, sarcomas are well known for their heterogeneous character. Biopsy of the mass is the most specific method for diagnosis and grading and this is usually directed by anatomical imaging.7 A practical problem is that biopsy of a small portion of the tumour does not always represents the overall character of the tumour and may miss clinically significant high-grade areas.8 This implies potential errors in the diagnosis and grading of the tumour and consequently in the treatment of the disease.
Approximately 10% to 15% of patients with a sarcoma develop a local recurrence and 35% to 45% develops a distant recurrence, even after adequate therapy.[9], [10] Detection of local recurrence is often difficult because of disturbance of the normal anatomy by previous surgery and any subsequent radiotherapy.11 In contrast to other imaging techniques such as MRI and CT, which are more suitable for visualisation of anatomy, positron emission tomography (PET) depicts the increased metabolism associated with abnormal tissues, enabling visualisation and quantification in vivo. 18F fluorodeoxyglucose (FDG), which accumulates in tumour cells in proportion to the rate of glucose metabolism, is currently the most commonly used radiopharmaceutical for PET.12
The objective of this study was to assess the diagnostic and therapeutic value of FDG-PET in the detection, grading and therapy response of soft tissue and bone sarcomas, through a systematic review of relevant literature and a meta-analysis.
Section snippets
Methods
A comprehensive computer-aided search of the databases PubMed/Medline, Embase and Cochrane, of the medical literature published after 1990, was conducted in June 2002 using the search terms “positron emission tomography” (text word or medical subject heading (MeSH)) and “sarcoma” (text word or MeSH). We used several search strategies to optimise our search.[13], [14], [15] We augmented our computerised literature search by manually reviewing the reference lists of identified studies and
Literature search
A total of 128 studies were found. After reviewing the title and the abstract 95 studies were excluded. Of the remaining 33 studies, 4 were excluded after reviewing the full article. Twenty-nine studies met the inclusion criteria: 11 focusing on soft tissue sarcomas only, 6 focusing on bone sarcomas and in the remaining 12 studies soft tissue and bone sarcomas could not be separated (mixed sarcomas). The characteristics of the included studies are shown in Table 1. The total number of patients
Discussion
This systematic review included 29 studies concerning the value of FDG-PET in the detection, grading and therapy response of soft tissue and bone sarcomas. The studies had limited methodological quality. Pooled sensitivity and specificity for the detection of sarcomas were 0.91 and 0.85. Moreover, pooled analysis of the mean SUV in sarcomas and benign tumours in the studies of mixed sarcomas was statistically significant, as was the difference between low and high grade mixed sarcomas (studies
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