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Volume 88 � Number 2 � Supplement 2014 Poster Presentations 511
HRZ3.51, 95% CI: 1.56-7.90, pZ0.001). Interrogation of The Cancer
Genome Atlas database for HNSCC samples with both methylation and
outcome data available (nZ305), revealed a similarly absent or low fre-
quency of methylation events for the loci investigated. However, the
presence of RUNX3 hypermethylation did not correlate with worse
outcome for patients (HR Z 1.27; 95% CI: 0.56 - 2.88; pZ0.57 and
HR Z 1.08; 95% CI: 0.65 - 1.82; p Z0.76, OTSCC and HNSCC,
respectively).
Conclusion: In OTSCC, we found little evidence of promoter hyper-
methylation of genes previously reported to be frequently methylated in
HNSCC. Whilst OTSCC may have subsite-specific methylation for the loci
examined, it is likely that previously reports have overestimated methyl-
ation events with the use of non-quantitative methodology.
Author Disclosure: A.M. Lim: None. I.L.M. Candiloro: None. N. Wong:
None. M. Collins: None. H. Do: None. C. Angel: None. J. Corry: None. D.
Rischin: None. B. Solomon: None. A. Dobrovic: None.
111Circulating HPV DNA as a Marker of Treatment Response ofHead-and-Neck Cancer Patients Treated With Radiation Therapy orChemoradiation TherapyMolecular Biology and Therapeutics
T.W. Rutkowski,1 A.M. Mazurek,2 M. �Snietura,3 A. Hajduk,1 A. Wygoda,1
and K. Składowski1; 1Department of Radiation Oncology, Maria
Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,
Gliwice, Poland, 2Center for Translational Research and Molecular
Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and
Institute of Oncology, Gliwice, Poland, 3Department of Pathology, Maria
Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,
Gliwice, Poland
Purpose/Objective(s): A casual relationship between papillomavirus
(HPV) infection and the oropharyngeal carcinoma (OPC) development
has been established. Patients with HPV-positive OPC tumors present
better prognosis than those with HPV-negative tumors so the confirma-
tion of OPC origin may be crucial for treatment decision. Despite of
favorable outcome for these patients, locoregional or distant failure still
could be observed. The assessment of circulating HPV DNA (HPV in
circulating cell-free DNA of plasma) is an attractive noninvasive method
for virus detection in the blood. If the response to treatment is reflected
in HPV detection, it may become feasible tool in monitoring of treatment
results. The study is focused on preliminary results of HPV detection as
a marker for monitoring of the response to the radiation therapy (RT) or
chemoradiation therapy (RCHT) in patients with head and neck cancer
(HNC).
Materials/Methods: The collection of blood plasma from 150 consecutive
patients before definitive RT/RTCHT due to HNC was performed. After
DNA extraction from plasma, the presence of HPV16 and HPV18 was
assessed by qPCR using E6/7 specific primer/probe sets. Sensitivity and
specificity of HPV detection in blood was established in comparison to
HPV detection in a paraffin embedded tumor specimens. For HPV-positive
patients, blood collections were carried out during RT/RTCHT and after its
completion.
Results: In this study we identified 24 HPV16-positive patients (16%), all
of them OPC cases. The sensitivity and specificity of the method has been
established on 64% and 100%, respectively. The assessment of early
treatment outcome showed total tumor regression in 91% of HPV-positive
patients (22/24) after RT/RTCHT. Serial measurement demonstrated that
HPV16 become undetectable in all cured patients and was still observed in
those with treatment failure 2/24 (9%).
Conclusions: Preliminary results indicate that detection of HPV16 in cell-
free DNA is a feasible method to confirm HPV-positive tumors. Detection
of HPV16 in blood plasma correlates also with clinically observed tumor
regression after treatment. Further observations are carried out to establish
its role in early recurrence detection.
Author Disclosure: T.W. Rutkowski: None. A.M. Mazurek: None. M.�Snietura: None. A. Hajduk: None. A. Wygoda: None. K. Składowski:
None.
113WITHDRAWN
117A Pilot Study of Cetuximab and the Hedgehog Inhibitor IPI-926 inRecurrent/Metastatic (R/M) Head-and-Neck Squamous CellCarcinomaMolecular Biology and Therapeutics
D.W. Bowles, S.B. Keysar, M.J. Glogowska, P.N. Le, M.A. Pittman,
G. Wang, C.E. Ray, P.J. Rochon, D. Raben, and A. Jimeno; University of
Colorado, Aurora, CO
Purpose/Objective(s): The combination of cetuximab (Cet) and the
hedgehog inhibitor IPI-926 is more active than either single agent in pa-
tient-derived xenograft models of head and neck squamous cell carcinoma
(HNSCC). The objectives of this study were to determine the maximal
tolerated dose (MTD) of IPI-926 combined with Cet in R/M HNSCC and
to assess biomarkers via direct tumor biopsies.
Materials/Methods: IPI-926 was orally administered daily in two esca-
lating dose levels in combination with weekly Cet following a Cet lead-in
period. Tumor biopsies were performed prior to drug therapy, after Cet
alone, and after combined therapy. Eligibility criteria included biopsiable
disease and adequate hematologic and organ function. Prior Cet was
allowed.
Results: 10 patients (pts) were screened and 9 pts (M/FZ7/2, average age
58 years) were treated a 2 dose levels (130 mg IPI-926, nZ3; 160 mg IPI-
926, nZ6). 7 pts had received prior Cet. HPV status was positive (nZ5),
negative (nZ3), or unknown (nZ1). No dose limiting toxicities were
observed. The MTD for IPI-926 in combination with cetuximab was 160
mg daily. The most common treatment-associated adverse events (AEs)
were grade (G) 1/2 acneiform rash (4/9), fatigue (2/9), nausea (2/9),
peeling skin (2/9), dry skin (2/9), and muscle cramps (2/9). The skin
toxicity is consistent with cetuximab whereas muscle cramping and nausea
are more consistent with IPI-926. One pt in the 160 mg cohort had a G3
infusion reaction to the Cet loading dose and was not evaluable for effi-
cacy. One partial response (PR) was seen in a Cet-naı̈ve, HPV+ pt and a
minor response (-25%) was seen in a Cet-naı̈ve, HPV- pt. Responses per
RECISTwere PR (1/8), stable (3/8), and progressive disease (4/8). Median
time on study for evaluable pts was 103 days (range: 40-191). 6 pts un-
derwent all 3 tumor biopsies; 2 pts underwent 2 biopsies.
Conclusions: Cet plus IPI-926 is well tolerated in pts with R/M HNSCC
with signs of anti-tumor efficacy. Serial tumor biopsies are feasible. H/E,
immunohistochemistry, and RNAseq analysis for epithelial to mesen-
chymal transition markers and tumor initiating cells will be presented. The
study has completed enrollment.
Author Disclosure: D.W. Bowles: None. S.B. Keysar: None. M.J. Glo-
gowska: None. P.N. Le: None. M.A. Pittman: None. G. Wang: None. C.E.
Ray: None. P.J. Rochon: None. D. Raben: A. Employee; University of
Colorado. A. Jimeno: E. Research Grant; Infinity Pharmaceuticals.
118Human Papillomavirus-16 Promotes Cancer Stem Cell Expansion inHNSCC Through Inactivation of p53Molecular Biology and TherapeuticsQ. Pan, M. Zhang, X. Xie, L. Piao, B. Kumar, A. Schmitt, M. Old,
A. Agrawal, E. Ozer, and T. Teknos; The Ohio State University Medical
Center, Columbus, OH
Purpose/Objective(s): Recent evidence supports the recognition that
human papillomavirus-16 (HPV16) is a major risk factor for the devel-
opment of head and neck squamous cell carcinoma (HNSCC), in particular
oropharyngeal SCC (OPSCC). Based on the differences in etiology and
prognosis, HPV16-positive and HPV-negative HNSCC are believed to be