145 / 220
positive non-sentinel nodes, 13 in 15 (87%) were located in
the same neck level as the SN or an adjacent neck level.
3.3. Outcome
In this cohort of patients, 3-year figures for OS,
DFS and DSS were 88%, 92% and 94%, respectively.
Disease recurred in 56 patients (
Table 4
).
Univariate analysis of the factors that affected
outcome (overall survival) was investigated with
Kaplan
e
Meier survival analysis for categorical vari-
ables and Cox proportional hazards for continuous
variables (such as age of patient) (
Table 5
,
Fig. 1
e
3
). A
multivariate Cox proportional hazards model was then
run with all variables that showed a univariate p value
<
0.25. The resulting multivariate Cox proportional
hazards model found that the grouped number of pos-
itive nodes (p
Z
0.0008) and SN status (p
Z
0.003) were
the only significant factors.
3.4. Complications
Morbidity of SNB was minimal. Minor complications
were seroma
[1]
, haematoma
[8]
, local infection
[3]
, and
lymphoedema
[1]
. There were two notable complica-
tions: one phrenic nerve palsy and one patient had a
cerebellar stroke secondary to surgery.
Mean hospital stay following SNB and primary
tumour resection was 5.7 d (range 0
e
30) with 161 pa-
tients discharged within 3 d of their surgery. Lengths of
stay varied considerably by country (average of 9 d in
Belgium compared to 3 d in Denmark).
3.5. Adjuvant therapy
Adjuvant therapy (RT or chemoradiotherapy) was given
to 12% (48 in 415) of patients. In the SNB-positive
group, 27% (25 in 94) received adjuvant therapy (more
than one positive node or extracapsular spread
e
ECS)
but was used more freely (80%) in the false-negative
SNB group (12 in 15) to help salvage patients. There was
no significant survival difference between those with and
without adjuvant radiotherapy (p
Z
0.67).
4. Discussion
The results of the study demonstrate clearly the value
and safety of SNB for staging the N0 neck in routine
clinical practice. The principal aim of the study was to
establish whether SNB is a safe oncological procedure.
This has been confirmed with DFS of 92% at 3 years
following treatment.
The second objective was to determine, in the context
of oral and oropharyngeal cancer, whether SNB was an
effective diagnostic test for microscopic deposits of
metastatic cancer. The study showed conclusively that
the SNB technique works effectively in the oral cavity.
The injection of radiotracer (lymphoscintigraphy) will
define an SN in the vast majority of patients (
>
99%).
In this cohort of patients with a 3:1 distribution of
T1:T2 oral squamous carcinoma and radiologically N0
neck, it transpired that 26% (109 in 415) had occult
cervical disease. The SNB technique failed to detect
occult metastasis in 14% (15 in 109) of patients, only half
of whom (53.3%: 8 in 15) were amenable to salvage.
This is somewhat counterbalanced through identifi-
cation of unexpected contralateral lymphatic drainage
by SNB. This occurred in 12% (49 in 369) of cases and in
seven instances, the contralateral SN was positive. Thus,
6% (7 in 109) of occult cervical metastasis would have
Table 3
NPV, sensitivity and FNR by tumour location where a false-negative
result is recorded as isolated neck recurrence following a negative
sentinel node biopsy.
Tumour
False-negative rate
Sensitivity NPV
Anterior tongue
14% (9/65)
85%
94%
Posterior tongue
21% (3/14)
79%
91%
Floor of mouth
13% (2/16)
87.5%
98%
Total SENT group 14% (15/109)
86%
95%
Fisher’ exact test
p
Z
1
NPV, negative predictive value; SENT, Sentinel European Node Trial.
Table 4
Recurrences at 3 years.
Total
(n
Z
415)
SNB negative
(n
Z
321)
SNB positive
(n
Z
94)
Local ( distant)
18 (4.3%)
13 (4.0%)
5 (5.3%)
Local and neck 9 (2.2%)
8 (2.5%)
1 (1.0%)
Neck ( distant)
29 (7.5%)
15 (4.7%)
14 (15%)
Distant
0
0
0
Outcome following recurrence
Dead with disease
14 (4.3%)
16 (17%)
Alive no disease
19 (5.9%)
2 (2.1%)
Dead with no disease
2 (0.6%)
2 (2.1%)
Alive with disease
2 (0.6%)
0
SNB, sentinel node biopsy.
Table 5
Univariate Kaplan
e
Meier (for categorical) or Cox PH (for contin-
uous) analysis of factors influencing overall survival following SNB
(significance levels *0.05, **0.01, ***0.001).
Factor
Overall survival
(OS) p value
Age of patient
0.003* (Cox PH)
Site of tumour (grouped per location
anterior versus posterior oral cavity)
0.755
T size (T1 versus T2)
0.465
Depth of invasion (
>
4 versus 4 mm)
0.142
Degree of differentiation (well versus
moderate, poor)
0.004*
Margin ( 1 versus
>
1 mm)
0.741
Sentinel node status (SNB
þ
versus SNB )
0.000083***
Metastasis type (ITC versus Mi, Ma)
0.032*
Total positive nodes (0, 1, 2,
>
2)
0.000016***
Extra-capsular spread (no versus yes)
0.029*
RT (no, yes)
0.93
PH, proportional hazards; SNB, sentinel node biopsy; ITC, isolated
tumour cells; Mi, micrometastasis; Ma, macrometastasis; RT,
radiotherapy.
C. Schilling et al. / European Journal of Cancer 51 (2015) 2777
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125