2017 Section 7 Green Book

C. Schilling et al. / European Journal of Cancer 51 (2015) 2777 e 2784

concurrent END. The end-points of this study were SN identification rate, false-negative rate (FNR) and disease- free survival (DFS) at 3 years post-recruitment. Because of the lack of contemporaneous SNB data, we have used comparable data from patients treated by conventional END as well as SNB data in similar tumour groups who routinely use SNB in management of the neck to con- textualise the results. The aim of this investigation was to assess whether SNB is a safe and reliable therapeutic technique in T1 e T2 oral squamous cell carcinoma. A European multicentre prospective study (October 2005 e October 2010) was approved by the European Organisation for Research and Treatment of Cancer and local ethics committee, with patients providing informed consent. Eligible patients had 0.5- to 4-cm squamous cell carcinoma with an N0 neck on CT and/or MRI ( < 1.1 cm or up to 1.5 cm in level II and no atypical features) ultrasound-guided fine needle aspiration cytology. SENT was principally designed for oral squamous cell carcinoma; however, tumour-bordering structures of the oropharynx which were transorally accessible and resectable (without mandibular split or robotic techniques) were also included. Tumour location was recorded according to Systematized Nomenclature of Medicine (SNOMED) topography code [14] apart from ‘oral tongue posterior 1/3’ which related to tu- mours of the posterior part of the oral tongue and not tongue base tumours. Patients with a previous malignant neoplasm of the head and neck or any disease that might have altered lymphatic drainage were excluded. Patients had to be fit enough to tolerate a completion neck dissection if the SNB proved positive. A total of 480 cases were recruited prospectively from 14 European centres. The criterion for unit participation was completion of at least 10 successful training SNB procedures (validated against neck dissection) prior to 2. Patients and methods

recruiting to SENT. Sixty-five patients (14%) were excluded from the final analysis ( Table 1 ). When adjuvant treatment (radiotherapy [RT] or chemoradiotherapy) was given during the follow-up period for close margins or a metachronous primary tumour (N Z 17), patients were excluded on the premise that radiation fields extended into the upper neck and could theoretically extinguish missed metastases, thereby erroneously reducing the SNB FNR. Pre-operative lymphoscintigraphy was performed within 24 hours of surgery after Tc-99m nanocolloid (Nanocoll/Nanocis ) was injected using a standardised technique [15] at four points around the tumour (median dose 57 MBq e interquartile range 60 MBq). The position of the SNs was marked on the neck. At surgery, the SNs were detected by a hand-held gamma probe and in 164 of 415 patients (39%), peritumoural injection of blue dye was given (SN recorded by colour, radiation count and site in neck). Lymph nodes with radiation count more than three times the background activity were considered SNs. If a radiation hot spot was in more than one neck level (SN versus second or third echelon nodes), then the primary SN was decided by maximum radiation count. The SNs were fixed in 10% neutral-buffered formalin and a validated protocol for analysis was followed [16] . Five serial sections were cut every 150 m m through the block and one from the centre of each series was stained with haematoxylin and eosin (H&E). If metastasis was still not detected, an adjacent section at each level was stained with anti-pan cytokeratin antibody AE1/3. If cytokeratin was detected but the viability of the cells was in question, the adjacent serial sections were examined stained with H&E. One center (67 in 415: 16% of pa- tients) cut a single frozen section (FS) from the midline of the node, with remaining specimen examined as above. This allowed on-table diagnosis [17] and imme- diate neck dissection if the FS was positive. SENT recorded metastasis as viable or non-viable deposits sized in terms of percentage of the total node. For the purposes of this report, SNB þ nodes were retrieved where possible (75 in 94 cases, 80%) and re- graded according to the Union for International Cancer Control (UICC) Seventh Edition guidelines [18] . Deposits were re-classified as isolated tumour cells (ITC, < 200 cells or < 0.2 mm deposit with no stromal reac- tion), micrometastasis (0.2 e 2 mm), and macrometa- stasis ( > 2 mm). In the SENT cohort, ITC was treated as a positive neck (completion neck dissection performed within 3 weeks). Tumours were excised aiming for pathological clear margin of > 4 mm, and all defects were closed without free flap reconstruction. Neck specimens were pinned out maintaining alignment and fixed in neutral-buffered formalin. They were examined macroscopically and by routine H&E with cervical metastasis mapped by neck

Table 1 Cases excluded from SENT trial. Reason for exclusion

Cases

% Total recruited (n Z 481)

N Z 1 0.5 N Z 5 1

Failed lymphoscintigraphy Failed identification of SN at surgery Obvious nodal disease at surgery Breach of protocol (neck dissection despite negative SNB (n Z 5), or no neck dissection after positive SNB (n Z 20)

N Z 1 0.5 N Z 25 5

N Z 16 3.5 N Z 17 4.5

Lost to follow-up

Radiotherapy for close margin or second primary tumour

N Z 66 14

Total

SENT, Sentinel European Node Trial; SN, sentinel node; SNB, sentinel node biopsy.

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