58 / 220
the CWU staging. Three (1.2%) patients were classified
as no impact because the PET/CT results were ignored
in the management decision making.
Patients in whom PET/CT had a high impact on the
management plan had significantly worse PFS and OS
than those in whom PET/CT had low/no impact (both
P
<
0.001;
Fig. 2
).
3.2. Secondary outcome
The Kaplan
e
Meier estimates of 3-year PFS and OS
rates in all patients were 72.8% and 83.0%, respectively.
Univariate analyses for PFS showed that CWU stage,
PET/CT stage, and SPC associated significantly with
lower PFS (all
P
<
0.05). Multivariate analysis revealed
that PET/CT stage III
e
IV (HR
Z
2.05, 95%
CI
Z
1.25
e
3.44;
P
Z
0.007) and SPCs (HR
Z
2.30,
95% CI
Z
1.16
e
4.54;
P
Z
0.016) independently pre-
dicted PFS. Univariate analyses for OS showed that
CWU stage, PET/CT stage, and SPC associated signif-
icantly with lower OS (all
P
<
0.05). Multivariate
analysis demonstrated that PET/CT stage III
e
IV
(HR
Z
4.70, 95% CI
Z
2.08
e
10.60;
P
<
0.001) and
SPCs (HR
Z
3.07, 95% CI
Z
1.51
e
6.23;
P
Z
0.002)
independently predicted reduced OS (
Table 3
).
Subset analyses showed that the 3-year OS of the 122
patients with CWU stages I
e
II disease was 92.3% and
the patients with CWU stages I and II did not differ in
terms of OS (
P
Z
0.317,
Fig. 3
A). However, after PET/
CT, 98, 13, 7, and 4 of these 122 patients were re-staged
as stage I, II, III, and IV, respectively. This PET/CT re-
staging was of prognostic significance as the 3-year OS
rates of these four groups were 94.8%, 92.3%, 85.7%,
and 50.0%, respectively (
P
Z
0.002,
Fig. 3
B).
4. Discussion
The current study evaluated the impact of incorporating
PET/CT findings into the initial staging process on the
management and prognostic stratification of patients
with newly diagnosed HNSCC. A few prospective
studies have investigated the management impact of
PET alone or PET/CT in a subset of patients
(17
e
40%) and assessed only specific focus
[10,11,18,19]
.
Moreover, there was no research to present relevant
follow-up data for patients with HNSCC in regard to
the prognostic stratification of PET/CT staging. To our
knowledge, the current study is the first to prospectively
evaluate the incremental clinical impact of PET/CT for
the above topic.
PET/CT altered the management of 15.7% of our
patients. This is slightly higher than the rate reported
previously: Lonneux et al. showed that PET altered the
management of 13.7% of 233 patients
[10]
. This differ-
ence may be associated with superiority of PET/CT in
detecting regional or distant metastases and SPCs that
are critical for selecting treatment
[14
e
16]
. Further, in
terms of the primary tumour, hybrid imaging using
PET/CT has been shown to improve both anatomic
localisation and extent of
18
F-FDG-avid lesions
compared with PET alone
[23,24]
. All our patients un-
derwent PET/CT scan, while 83% of patients were
assessed by PET in the latter report
[10]
. However, two
other prospective studies found that PET/CT had a
much greater impact on the management of HNSCC:
PET/CT changed the management of 26
e
33.8% of the
patients, including those with only stage III
e
IV or
considerable proportion of cervical metastasis of an
unknown primary (CUP). And they regarded major
impact on management in whom PET/CT detected the
primary tumour in CUP
[11,18]
. The possible explana-
tion for different impact rates is that we included the
patients at all stage of HNSCC with known primary site.
Further, the result of Cacicedo et al.
[18]
are similar with
those of our patients staged as III
e
IV by CWU. Our
recent study already demonstrated that PET/CT lead to
improved therapeutic planning in CUP
[25]
.
The main finding of the present study was that PET/
CT staging has a prognostic role in HNSCC. PET/CT
staging separated the HRs for both PFS and OS better
than CWU staging, regardless of which treatment was
employed. Multivariate analysis revealed that PET/CT
staging independently predicted worse PFS and OS. In
addition, patients whose CWU-determined disease was
upstaged by PET/CT had significantly poorer PFS and
OS than those whose clinical stage was unchanged.
Thus, PET/CT staging can reveal disease extent better
than CWU staging. Our results are in line with findings
Table 2
Comparison of diagnostic accuracy of staging by conventional workups with and without
18
F-FDG PET/CT in discordant cases.
Imaging
TP FP FN TN Sensitivity (%)
Specificity (%)
Accuracy (%)
PPV (%)
NPV (%)
TNM staging
a
(
n
Z
71)
CWU
16 12 31 12 34.0 (22.9
e
45.0) 50.0 (38.3
e
61.6) 39.4 (28.0
e
50.7) 57.1 (45.5
e
68.6) 27.9 (17.4
e
38.3)
CWU
þ
PET/CT 29 14 17 11 63.0 (51.7
e
74.2) 44.0 (32.4
e
55.5) 56.3 (44.7
e
67.8) 67.4 (56.5
e
78.3) 39.2 (27.8
e
50.5)
P
value
b
<
0.001
0.500
<
0.001
Abbreviations: CWU, conventional work-ups;
18
F-FDG, fluorine 18-fluorodeoxyglucose; FN, false negative; FP, false positive; NPV, negative
predictive value; PET, positron emission tomography; PPV, positive predictive value; TN, true negative; TP, true positive.
a
TNM staging represented as T
þ
N
þ
M, according to discrepancies.
b
P values were determined by McNemar’s test. Values in bold indicate
P
<
0.05.
I.S. Ryu et al. / European Journal of Cancer 63 (2016) 88
e
96
38