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