Koos Boeve

189 General discussion and future perspectives patients (T1-4, N0) reported promising sensitivity and NPVs which were at least as high as for 99mTc-nannocolloid [101], however a clear validation with both tracers in one study and only early stage OSCC is not available yet. Detection of local recurrences In up to 30% of the OSCC, local recurrences or second primary tumours are detected during follow-up [103,104]. As described in chapter 1 , early detection of local recurrences or second primary tumours is challenging, but essential to improve prognosis. A promising technique to prevent patients for local recurrences is the intra-operative use of image- guided surgery [105] with fluorescently labelled antibodies [106]. Image-guided surgery technique is based on tumour tissue visualisation using a fluorescence tracer conjugated to an antibody [105]. This conjugated antibody binds to an antigen which is upregulated in cancer tissue, resulting in a higher fluorescence signal of tumour tissue compared to surrounding tissues. Using a multispectral fluorescence camera in the operation theatre, this difference in fluorescence can be visualised and used to define surgical resection margins or to visualize residual tumour tissue after initial surgical resection. Currently, clinical trials reported the feasibility and safety of the fluorescently labelled antibodies Panitumumab- IRDye800CW and Cetuximab-IRDye800CW in HNSCC [106,107]. Further studies are needed to confirm that this technique contributes to clear surgical resection margins to prevent patients for re-resections and lower local recurrence rates. As this method is very useful for guiding surgery, this assay might be to insensitive to detect single cells in clear surgical margins. Clear surgical margins are most often defined as tumour cell free margins of at least 5 mm. However, even in patients with clear surgical resection margins, local recurrences are reported in up to 11% of these cases [108,109]. In these particular cases, additional methods might be investigated. Various molecular methods are available that are able to detect tumour specificmutations at very low levels in a background of normal cells. E.g. the detection of minimal residual cancer with p53 mutations in surgical margins has been reported with promising sensitivities (75% and 85%) but still missed high specificities (67% and 58%) [110]. In chapter 8 we selected OSCC specific methylation markers with a genome wide approach. Important advantages of hypermethylation markers are the binary state (hypermethylated or not) and DNA hypermethylation appears more often and earlier compared to mutations [77]. These methylation markers might also be useful to detect minimal residual cancer in surgical resection margins that are microscopically tumour cell free. Another option is to use these methylation markers to detect and monitor circulating tumour cells (CTCs) or circulating tumour DNA (ctDNA) in saliva or plasma of OSCC patients after initial treatment. This might be a useful and non-invasive method tomonitor treatment