PET monitoring of therapy response in head and neck squamous cell carcinoma

In the Western world, more than 90% of head and neck cancers are head and neck squamous cell carcinomas (HNSCCs). The most appropriate treatment approach for HNSCC varies with the disease stage and disease site in the head and neck. Concurrent chemoradiotherapy has become a widely used means for the definitive treatment of locoregionally advanced HNSCC. Although this multimodality treatment provides higher response rates than radiotherapy alone, the detection of residual viable tumor after the end of therapy remains an important issue and is one of the major applications of (18)F-FDG PET. Studies have shown that negative (18)F-FDG PET or PET/CT results after concurrent chemoradiotherapy have a high negative predictive value (>95%), whereas the positive predictive value is only about 50%. However, when applied properly, FDG PET/CT can exclude residual disease in most patients, particularly patients with residual enlarged lymph nodes who would otherwise undergo neck dissection. In contrast to other malignancies, data are limited on the utility of (18)F-FDG PET for monitoring the response to induction chemotherapy in HNSCC or for assessing treatment response early during the course of definitive chemoradiotherapy. The proliferation marker (18)F-3'-deoxy-3'fluorothymidine is currently under study for this purpose. Beyond standard chemotherapy, newer treatment regimens in HNSCC take advantage of our improved understanding of tumor biology. Two molecules important in the progression of HNSCC are the epidermal growth factor receptor and the vascular endothelial growth factor (VEGF) and its receptor VEGF-R. Drugs attacking these molecules are now under study for HNSCC. PET probes have been developed for imaging the presence of these molecules in HNSCC and their inhibition by specific drug interaction; the relevance of these probes for response assessment in HNSCC will be discussed. Hypoxia is a common phenomenon in HNSCC and renders cancers resistant to chemo- and radiotherapy. Imaging and quantification of hypoxia with PET probes is under study and may become a prerequisite for overcoming chemo- and radioresistance using radiosensitizing drugs or hypoxia-directed irradiation techniques and for monitoring the response to these techniques in selected groups of patients. Although (18)F-FDG PET/CT will remain the major clinical tool for monitoring treatment in HNSCC, other PET probes may have a role in identifying patients who are likely to benefit from treatment strategies that include biologic agents such as epidermal growth factor receptor inhibitors or VEGF inhibitors.