Koos Boeve

13 General introduction and scope of this thesis CHALLENGE 1: DETECTION OF OCCULT METASTASIS IN EARLY STAGE (cT1-2N0) OSCC Clinical neck staging has been extended in the last decades frommere physical examination by palpation to imaging of the neck by Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and followed by Ultrasound guided Fine Needle Aspiration Cytology (USgFNAC) in case of suspicion for lymph node metastasis [17]. Despite this evolution in neck staging, still 23-37% of the early stage (cT1-2N0) OSCC patients are diagnosed with occult metastases [18-20]. Occult metastasis means that these metastases were not detected clinically, and thus defined as ‘clinically negative neck’, but postoperatively by histopathological examination or present as late metastasis after treatment of the primary tumour has been completed. Conventionally two strategies were available for patients with a clinically negative neck: frequent clinical examination of the neck (known as watchful waiting) or an elective neck dissection (END). In the eighties of the last century, neck levels I-V (Figure 1B) were dissected during an END, which was later restricted to levels I-III. A level I-III END is also known as a ‘selective neck dissection’ (SND) [12]. With the END, 63-77% of the patients are overtreated and risk postoperative morbidities such as loss of shoulder function or lymph oedema [16]. Using watchful waiting as neck strategy will result in occult metastasis detection at a more unfavourable stage [21]. Overtreatment with ENDs and late detection in case of watchful waiting are major limitations for these two conventional neck strategies and were reasons to search for individual selection for a neck dissection. Tumour infiltration depth is one of these well-studied predictive variables for lymph node status and survival and was incorporated with a 4 mm cut-off in treatment protocols to select patients for an END instead of watchful waiting [22,23]. The predictive value of tumour infiltration depth resulted in incorporation in the 8 th edition of the pTNM classification with 5 mm and 10 mm cut-offs (pT1 ≤5 mm, pT2 5-10 mm, pT3 <10 mm, Table 1). Table 1. Differences between the 7 th and 8 th AJCC pathological T-classification T category 7 th TNM: tumour diameter 8 th TNM: tumour infiltration depth added T1 ≤2 cm ≤5 mm T2 >2 and ≤4 cm >5 and ≤10 mm T3 >4 cm >10 mm T4 Moderately and very advanced Extrinsic tongue muscle infiltration is now deleted Moderately advanced local disease: tumour invades adjacent structures only. Very advanced local disease: tumour invades masticator space, pterygoid plates, or skull base or encases the internal carotid artery. Tumour diameter was the only criterion for both clinical and pathological T1-3 staged tumours in the 7 th T classification of the American Joint Committee on cancer (AJCC). In the 8 th edition pathological T classification tumour infiltration depth was added for T1-3 tumours and extrinsic tongue muscle infiltration was deleted for the T4 category. In the 8 th edition pT1-3 tumours are staged by both tumour diameter and tumour infiltration depth. [SOURCE: American Joint Committee on Cancer TNM cancer staging [24,25]]