Koos Boeve

179 General discussion and future perspectives The recommendations in the surgical consensus guidelines include the imaging modalities for the clinical neck staging (at least CTI, MRI or US), sentinel lymph node definition, optical tracers, lymphatic drainage patterns, tumour infiltration depth, size of a positive SLN and follow-up (frequently examination in the first two year) [16]. During surgery, the sentinel lymph nodes are defined as the lymph nodes with an at least 10 times higher count compared to the background and at least a 10% count of the hottest harvested lymph node measured using a hand-held gamma probe [16,23]. The gamma count is not associated with metastasis, or in other words, the metastasis is not always located in the lymph node with the highest count [16]. In general, 2-3 SLNs per patient are detected and removed [16,23-25]. Although the pathological procedure consensus is not reported yet, many centres use step-serial-sectioning and additional IHC nowadays [17,26], after this method was already successfully implemented inother cancer types such as breast, melanoma andendometrium cancer [27-29]. For example, in breast cancer it was reported that up to 40%of themetastases were missed with the conventional single level haematoxylin and eosin (HE) staining [28]. In OSCC, a study showed detection of metastases in 16% of 80 SLNs of OSCC patients using routine HE staining, 23% with the addition of step-serial-sectioning and in 25% with both step-serial-sectioning and additional cytokeratin immunohistochemistry [30]. Especially, isolated tumour cells (defined as metastasis <0.2 mm) were only found with the addition of step-serial-sectioning [30]. In that study the two metastases with the lowest number of isolated tumour cells were only found by using combined step-serial-sectioning and keratin staining. The SLNB protocol used in chapters 3, 4 and 5 met the recommendations of the consensus meeting about preoperative imaging (cN0 by CT, MRI or USgFNAC and SLN detection by lymphoscintigraphy and SPECT-CT), intraoperative detection using a hand- held gamma probe, postoperative pathological assessment (step-serial-sectioning and additional IHC) and clinical follow-up as reference standard for negative SLNs. Moreover, a median of 3 SLNs per patient was reported comparable with the number in the consensus guidelines. Therefore, the results in chapter 3 are in accordance with current evidence and recommended guidelines [11]. As described, the SLNB procedure is superior to the END regarding the extend of surgery, morbidity rate and complication rate [7,9,10]. However, also the cost-effectiveness of the SLNB compared to an END or watchful waiting strategy is important. Two studies reported a cost-effectiveness analysis of the SLNB procedure [31,32]. These analyses were based on measurements of costs and quality of life related to early stage OSCC combined with follow- up data of regional recurrences andmortality. Although in one study the SLNB baseline costs were similar compared to the END (€9180,- versus €9241,-) [32], both studies reported that the SLNB procedure was more effective represented by a small increase in quality-adjusted