6th ICHNO Abstract Book

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page 52 6th ICHNO
6 th ICHNO Conference
International Conference on innovative approaches in Head and Neck Oncology
16 – 18 March 2017
Barcelona, Spain
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Material and Methods
We performed a retrospective analysis of patients with
non-nasopharyngeal, non-OPSCC and known HPV status
identified in the NCDB. Patient characteristics and
survival data were analyzed by univariate and multivariate
analyses using Cox proportional hazards regression and the
log-rank test within Kaplan-Meier analysis.
Results
A total of 27,160 patients with known HPV status were
identified of which 8,672 (32%) were HPV-
positive. Patients with HPV-positive disease were more
likely to be male, younger, and present with an oral cavity
primary, greater nodal burden and higher overall clinical
stage than HPV-negative patients (p < 0.01). On
multivariate analysis, factors predictive of worse overall
survival included age ≥ 65 years (HR: 1.45; 95% C.I. 1.34-
1.57; p < 0.001), Charlson/deyo comorbidity score of 1
(HR: 1.10; 95% C.I. 1.01-1.20; p < 0.05) and ≥ 2 (HR: 1.78;
95% C.I. 1.57-2.02; p < 0.001), non-private/unknown
insurance (HR: 1.41; 95% C.I. 1.30-1.54; p < 0.001),
hypopharynx subsite (HR: 1.23; 95% C.I. 1.09-1.38; p <
0.01), tumor size (HR: 1.19; 95% C.I. 1.16-1.22; p < 0.001),
increasing nodal stage (N1 = HR: 1.19; 95% C.I. 1.06-1.33;
p < 0.01), (N2 = HR: 1.16; 95% C.I. 1.05-1.29; p < 0.01),
(N3 = HR: 1.66; 95% C.I. 1.20-2.28; p < 0.01), and HPV-
negative status (HR: 2.01; 95% C.I. 1.83-2.21; p <
0.001). Unadjusted 2-year overall survival for patients
with HPV-positive and HPV-negative disease according to
stage was: Stage I 92% vs. 88%, Stage II 86% vs. 75%, Stage
III 88% vs. 68%, Stage IVA 85% vs 60%, and Stage IVB 68% vs
46%.
Conclusion
Patients with HPV-positive non-OPSCC exhibit similar
patient and disease characteristics as those previously
described for patients with HPV-positive OPSCC. Overall
survival was significantly influenced by HPV status. As
such patients with HPV-positive non-OPSCC disease
represent are favorable cohort that warrant further
investigation.
PO-108 TLR induced PDL-1 expression in HNSCC as a
potential tool of immunomodulation
B. Wollenberg1, R. Pries1, M. Drenckhahn1, K. Ploetze-
Martin 1, B. Wollmann1
1University of Lübeck, Otorhinolaryngology- Head and
neck surgery, Lubeck, Germany
Purpose or Objective
Head and neck squamous cell carcinoma (HNSCC) is one of
the most common solid neoplasms worldwide. Its
occurrence is being associated with exposure to smoking
and alcohol consumption. Even though enormous progress
concerning the treatment of HNSCC has been made, the
mortality rates are still high due to local tumor invasion,
development of metastases and failure of chemo- and
radiation therapies.
In Neuroblastoma it has been shown that specific antibody
targeting of PD-L1 leads to increased anti-tumor functions
of T-lymphocytes, whereas triggering with the TLR3 ligand
Poly I:C leads to a strong up regulation of PD-L1. We
therefore asked whether Toll-like receptors act as PD/PD-
L1 regulators in HNSCC and which consequence this finally
has for the immuno-activity of natural killer (NK-) cells.
Material and Methods
Different established HNSCC cell lines were treated with
the TLR3 ligand Polyinosinic:polycytidylic acid (PolyI:C)
and TLR4 ligand LPS through both extracellular and
intracellular ways. PD-L1 expression was analyzed on the
mRNA- as well as on the protein level using RT-PCR and
Western hybridization experiments. NK cells were
analyzed for cytolytic activity using the CytoTox-96 Non-
Radioactive Cytotoxicity Assay (Promega). This
colorimetric assay quantitatively measures lactate
dehydrogenase (LDH), a stable cytosolic enzyme that is
released upon cell lysis. Released LDH in culture
supernatants were measured using a coupled enzymatic
assay, which resulted in the conversion of a tetrazolium
salt (INT) into a red formazan product.
Results
We observed that TLR3 as well as TLR4 agonists resulted
in significantly increased expression levels of PD-L1 in
permanent HNSCC cell lines. These data could be
corroborated by immunohistochemical analyzes of the
sub-cellular PD-L1 expression in response to TLR
stimulation. Increased expression of PD-L1 correlated with
modulated NK-cell activities and strongly affected
cytolysis of the analyzed target cells.
Conclusion
When considering innovative antibody-based
immunotherapy approaches, check-point regulators such
as the PD-1/PD-L1 pathway have recently shown very
promising results. Our data underline the requirement of
combined therapeutic strategies, namely to inhibit the
PD1 function on the immune cell side as well as to block
the TLR dependent up-regulation of check point inhibitors
on the tumor side.
Poster: Imaging and radiomics
PO-109 The added value of SPECT-CT for identification
of sentinel lymph nodes in early stage oral cancer
I. Den Toom1,2, A. Van Schie3, S. Van Weert 2, O.
Hoekstra 3, H. Karagozoglu4, E. Bloemena4,5, R. De Bree1,2
1UMC Utrecht, Head and Neck Surgical Oncology,
Utrecht, The Netherlands
2VU University Medical Center, Otolaryngology-Head and
Neck Surgery, Amsterdam, The Netherlands
3VU University Medical Center, Radiology and Nuclear
Medicine, Amsterdam, The Netherlands
4VU University Medical Centre/Academic Center for
Dentistry, Oral and Maxillofacial Surgery / Oral
Pathology, Amsterdam, The Netherlands
5VU University Medical Center, Pathology, Amsterdam,
The Netherlands
Purpose or Objective
To assess the role of Single Photon Emission Computed
Tomography with Computed Tomography (SPECT-CT) for
the identification of sentinel lymph nodes (SLNs) in
patients with early stage (T1-T2) oral cancer and a
clinically negative neck (cN0).
Material and Methods
In addition to planar lymphoscintigraphy SPECT-CT was
performed in 66 consecutive patients with early stage oral
cancer and a clinically negative neck. The addition of
SPECT-CT to planar images was retrospectively analysed
for the number of additional SLNs, more precise
localisation of SLNs and importance of anatomical
information by a team consisting of a nuclear physician,
surgeon and investigator.
Results
Identification rate for both imaging modalities combined
was 98% (65/66). SPECT-CT identified 15 additional SLNs
in 14 patients (22%). In 2/15 (13%) of these additional SLNs
the only metastasis was found, resulting in an upstaging
rate of 3% (2/65). Figure 1 shows an example of an
additional SLN level II on the left side (arrow) on SPECT-
CT. In 20% of the patients with at least one positive SLN
the only positive SLN was detected due to the addition of
SPECT-CT. SPECT-CT was considered to add important
anatomical information in 2 patients (3%). In 5/65 (8%) of
the patients initially scored SLNs on planar