Reflection and Reaction 512 www.thelancet.com/oncology Vol 11 June 2010 Improving the therapeutic ratio in head and neck cancer We read with great interest the recent review by Corry and colleagues 1 in the March, 2010, issue of The Lancet Oncology, on the possibility of improving the therapeutic ratio for patients with advanced head and neck cancer. Among the strategies discussed was the possibility of lowering treatment intensity for patients with a better prognosis, to abrogate major late tissue toxicity. In this context, it was proposed that better-prognosis subgroups of patients with human papillomavirus- related oropharyngeal cancer and Epstein-Barr-virus- related nasopharyngeal cancer are candidates for de-escalated therapy. We wish to highlight the major opportunity that exists to improve head and neck cancer treatment by identifying a range of biomarkers predictive of response to different treatments. Considerable effort has gone into identifying factors which predict response to radiotherapy and chemotherapy. For example, hypoxia-inducible factor- 1α (HIF-1α) has been identified as a poor prognostic factor in patients with head and neck squamous-cell carcinoma (HNSCC) treated with radiotherapy. 2 The negative effect of tumour hypoxia on radiotherapy outcome has been well characterised. By contrast, high HIF-1α expression has been associated with a favourable outcome following surgery. 3 If validated, these findings could be used to guide treatment choices. Newer imaging methods, such as dynamic contrast-enhanced MRI, have been shown to detect tumour hypoxia in head and neck cancer 4 and might prove useful in predicting response. For chemotherapy, multiple biomarkers including beta-3 tubulin, RR-1, and ERCC-1 5 have been used to predict outcomes with platinum-based and taxane-based chemotherapy. Parallel to the identification of potential biomarkers for treatment responses, a host of new therapeutic drugs are in development. These include drugs designed to modulate the epidermal growth factor receptor and angiogenic pathways, along with intracellular signalling mechanisms. Identification of relevant drug targets within tumours might also be used to guide the selection of systemic therapy. Therefore, the development of truly individualised therapy for HNSCC can be envisaged, based on a battery of biomarkers and new imaging techniques that guide both the choice and intensity of treatment. This might involve not only a reduction in treatment intensity for some patients, but an escalation or selection of alternative treatments for other patients, which could improve substantially the therapeutic ratio. However, incorporating the multitude of prognostic and predictive markers into clinical practice is very challenging. To allow the robust identification and validation of markers, clinical trials must be done with parallel translational research aims. Additionally, tissue biobanks and national registries Knowledge of HIF-1α expression levels could improve our understanding of head and neck tumour pathobiology as well as provide a crucial step towards stratifying therapeutic options for patients with head and neck cancer. Moreover, inhibition of HIF-1α expression could be a decisive part of future head and neck cancer treatment options. Alexander W Eckert, Johannes Schubert, Helge Taubert* Department of Oral and Maxillofacial Plastic Surgery, Martin-Luther-University Halle-Wittenberg, Halle, Germany helge.taubert@medizin.uni-halle.de The authors declared no conflicts of interest. 1 Corry J, Peters LJ, Rischin D. Optimising the therapeutic ratio in head and neck cancer. Lancet Oncol 2010; 11: 287–91. 2 Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. 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