Predictive value of fluorodeoxyglucose uptake in head and neck cancer: importance of standardization

Abstract

In the past the majority of patients with advanced stage head and neck squamous cell carcinoma (HNSCC) were treated with a combination of surgery and radiotherapy, often at the expense of functional and cosmetic morbidity, and thus reduced quality of life. Nowadays, in an attempt to decrease the morbidity, non-surgical treatments for advanced HNSCC are increasingly applied with considerable complete remission rates. It appeared that new radiation schemes (accelerated or hyperfractionated) and combinations of chemotherapy and radiotherapy all increase remission rates. When starting an organ sparing non-surgical therapy for functionally inoperable HNSCC (i.e. too high morbidity of surgical treatment expected), salvage surgery is held in reserve for residual or recurrent disease. However, salvage surgery with curative intent is only possible in about half of such patients. Moreover, the complication rate of salvage surgery after chemoradiation is high, with wound healing problems as a well-known complication. Since non-surgical treatment itself is also associated with acute and long-term side effects, leading to compromised quality of life, patients undergoing primary non-surgical treatment (radiotherapy with or without chemotherapy) followed by salvage surgery are exposed to cumulative morbidity of all treatment modalities. Another important disadvantage of surgery for residual or recurrent tumour after radiotherapy is the fact that although it may be indicated postoperative radiotherapy is mostly no longer possible, limiting the oncological outcome of this treatment. Because salvage treatment after (chemo)radiation carries a questionable prognosis but a high incidence of complications, (chemo)radiation may not be the choice of treatment in all patients with advanced HNSCC. A reliable predictor of outcome after chemoradiation is needed to select patients who are likely to benefit from non-surgical treatment. Valuable predictive factors provide information on the outcome of therapy in an individual patient allowing avoidance of over- as well as undertreatment. In the present context, better selection may refrain a substantial number of patients from futile extensive and toxic treatment (radiation with or without chemotherapy), decrease the complication rate of surgical treatment and reserve radiotherapy for a postoperative setting if indicated. Conventional prognostic factors for locoregional control include T-stage, N-stage and tumour site, grade and volume. The predictive value of molecular biological markers is currently under investigation. Tumour metabolism is another potential prognostic factor and can be studied with positron emission tomography (PET). Up-regulation of glucose uptake through overexpression of glucose transporters is an early event in malignant transformation. 18Fluoro-2-deoxyglucose (FDG) is the most widely used PET tracer in oncologic PET studies and can be used to measure the glucose metabolism in malignant tissues. Quantification of tracer uptake can be done in several ways, from pure visual analysis to simple calculations of uptake level using a Standardized Uptake Value (SUV; ie. the ratio of measured activity in a static scan obtained e.g. 60 min after FDG injection over the injected dose and