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Page 6 of 14 Galli et al. J Cancer Metastasis Treat 2022;8:48 https://dx.doi.org/10.20517/2394-4722.2022.19

Among the 41 patients undergoing ND at the time of STL, 4 (9.7%) had histopathological evidence of neck
node metastases (i.e., pN+). In the MRI group, two pN+ cases were not properly identified and only one out
of two metastases shown on MRI was confirmed on histopathological analysis [Figure 2A].

PET/CT correctly staged one pN+ case and missed one metastasis in another case [Figure 2B]. The rates of
occult metastases in the MRI-negative and PET/CT-negative neck node disease were 6.1% (2/33) for MRI
and 3.2% (1/31) for PET/CT. Twenty-nine patients underwent both MRI and PET/CT, and 26 of these were
staged as cN0. Occult LN metastasis was found in 3.8% of these patients (1/26). In three patients, nodal
disease was suspected on imaging, but was not confirmed on histopathological work-up [Figure 2C].
Figures 3 and 4 show radiological examples of false positive and false negative LN on PET/CT and MRI. In
the false positive PET/CT case [Figure 3A], no concrete histopathology was diagnosed within the LN.
Histopathology revealed sinus histiocytosis in the corresponding LN of the false positive MRI case
[Figure 4A].

The disease prevalence rates in the groups were 8.6% (3/35) for MRI, 5.7% (2/35) for PET/CT, and 3.4%
(1/29) for both modalities combined.

The diagnostic values of each modality in this specific disease setting are displayed in Table 3. Briefly, for
neck node re-staging, MRI and PET/CT had good specificities (96.9% and 91.0%, respectively) and NPV
(93.9% and 96.8%, respectively), but low sensitivity and PPV. Using both modalities together resulted in a
high NPV of 96.2%.

Of the four patients with neck node metastases, information about the neck levels was available only for
two: in one patient a single metastasis occurred in the ipsilateral level IIA, while in the second patient
metastases occurred in the ipsilateral level IIA and contralateral level III. At initial tumor diagnosis, only
one of these patients had clinically and radiologically positive neck nodes.

Among the five patients with initial nodal disease, only one was classified as pN+ at the time of salvage
surgery; this was an occult metastasis (i.e., rcN0).

When the distributions of the two occult metastases were examined in relation to the initial and recurrent
tumor stages, one patient initially staged as UICC I-II was found to have an occult metastasis. At
recurrence, this patient had an rcT2 rcN0 tumor (MRI and PET/CT: cN0). The second occult metastasis
occurred in a patient who had only undergone MRI imaging (MRI: cN0). The patient was initially staged as
UICC III-IV, then as rcT4 rcN0 at recurrence. We did not encounter a situation with a true positive neck
side and a false positive contralateral neck side in our cohort.

Oncological outcomes and adverse events
The median follow-up time after STL was 3.1 years (range: 0.6 months to 11.1 years). At the last follow-up,
60.9% of all patients were alive without recurrent disease, and 4.9% were with disease [Figure 5]. Nineteen
percent of patients had died because of tumor progression, and the remaining deceased patients had died of
non-cancer related causes. With respect to disease control, 10 patients (23.8%) presented with disease
recurrence within a median time of 25.9 months (range: 9 months to 8.1 years). Among these, eight patients
had regional recurrences within a median time of 9.5 months following STL + ND (range: 0.5-1.5 years).
Eight patients had parastomal recurrences and two had lung metastasis. None of the recurrences occurred
in neck lymph nodes.