Annual Meeting Proceedings Part 1 - American Society of Clinical ...

366s Head and Neck Cancer
5540 General Poster Session (Board #21H), Sat, 1:15 PM-5:15 PM
Prevalence, trends, and survival impact of human papillomavirus on
oropharyngeal cancer in Indian population. Presenting Author: Ankur Bahl,
Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of
Medical Sciences, New Delhi, India
Background: Among oropharyngeal squamous cell carcinoma (OSCC), the
true prevalence of HPV remains variable and studies have estimated that up
to 60% may be HPV positive. Patients with HPV positive tumor are
usuallyyounger in age, less likely to have history of tobacco or alcohol
consumption and associated with a better prognosis but this information for
Indian patients is largely unknown. Methods: 105 newly diagnosed patients
of OSCC were enrolled. HPV genotyping was done on the biopsy specimen
by consensus polymerase chain reaction and reverse line-blot hybridization
assay. HPV prevalence was studied according to gender, age, tobacco and
alcohol use and high risk sexual behavior. Results: Overall HPV prevalence
was 22.8%. HPV positive patients were younger by 8 years as compared to
negative patients (P�0.003). No significant correlation between tobacco
consumption, alcoholic habits, and HPV status was observed. The mean
number of life time sexual partners in HPV positive patients was 1.66
while, it was 1.33 in HPV negative patients (P�0.049). Incidence of high
risk sexual behaviors was more in HPV positive patients (P�0.001). There
were no significant associations between the two groups with respect to
tumor size, nodal stage and the overall stage of the tumor. 16% of the base
of tongue cancers and 40% of tonsillar carcinoma were positive (P � 0.02).
Among positive samples, HPV 16 was the commonest (79%) followed by
HPV 18 (12%). 96% of patients received treatment. At 18.8 months there
was no significant difference in OS, EFS between HPV positive and negative
OSCC (P � 0.97 and P� 0.51 respectively). Conclusions: The current study
reconfirms that HPV positive OSCC patients are younger with high risk
sexual behavior. Impact of smoking and alcohol consumption on HPV
status was not found in this study. HPV positive rates were significantly
higher for tonsillar cancer. Contrary to literature, we did not find any
differences in OS or EFS between two groups. Small numbers of patients in
the study group, short follow up period and significant tobacco smoking in
HPV group may be the one of the reason for this.
5542 General Poster Session (Board #22B), Sat, 1:15 PM-5:15 PM
Phase II trial of chemoradiotherapy concurrent with S-1 plus cisplatin in
patients with unresectable, locally advanced squamous cell carcinoma of
the head and neck (SCCHN): Results of the Japan Clinical Oncology Group
study, JCOG 0706. Presenting Author: Makoto Tahara, National Cancer
Center Hospital East, Kashiwa, Japan
Background: To evaluate the efficacy and safety of chemoradiotherapy
(CRT) concurrent with S-1 plus cisplatin in patients with unresectable
locally advanced SCCHN. Methods: Eligibility criteria included histologically
proven SCCHN with unresectable locally advanced lesions, PS 0-1,
aged 20 to 75 years old, adequate organ function, and no prior treatment.
Chemotherapy consisted of administration of S-1 twice daily on days 1-14
at 60 mg/m2 /day, and cisplatin at 20 mg/m2 /day on days 8-11, repeated
twice at a 5-week interval. Single daily radiation of 70 Gy in 35 fractions
was given concurrently startingon day 1. For patients achieving an objective
response after CRT, two additional cycles of chemotherapy wereadministered.
The primary endpoint was clinical complete response rate (%CR),
which was the proportion of complete response (CR) and good partial
response (good PR). Good PR was defined as remaining tissue with tumor
shrinkage, which was not regarded as residual tumor but rather as scar
material.The planned sample size was 45 patients, which was calculated
by SWOG’s two-stage attained design based on an expected %CR of 60%
and a threshold of 45%, with a one-sided alpha of 0.1 and a power of 0.9.
Results: From July 2008 to July 2010, 45 eligible subjects were accrued,
including 43 males, with median age 63 years, ECOG PS 0/1 (36/9),
oropharynx/ hypopharynx/larynx (26/15/4), T1/T2/T3/T4a/T4b (1/11/7/
17/9) and N0/N2a/N2b/N2c/N3 (2/3/10/24/6). %CR was 64.4% (8 CR,
21 good PR) on central review. After a median follow-up of 1.56 years,
1-year local progression-free survival was 77.8%, with 1-year progressionfree
survival of 70.9%, 1-year overall survival of 93.3% and 1-year time to
treatment failure of 57.6%. Grade 3 or 4 toxicity included mucositis
(46.7%), dysphagia (46.7%), anorexia (42.2%), radiation dermatitis
(26.7%), neutropenia (26.7%) and febrile neutropenia (4.4%). No treatment-related
deaths were observed. Conclusions: This combination showed
promising efficacy with acceptable toxicities. Further investigation in a
phase III trial is planned.
5541 General Poster Session (Board #22A), Sat, 1:15 PM-5:15 PM
Phase II trial of everolimus in patients with previously treated recurrent or
metastatic squamous cell carcinoma of the head and neck (SCCHN).
Presenting Author: Prakash Varadarajan, University of Texas Health Science
Center at San Antonio, San Antonio, TX
Background: The PI3K/Akt/mTOR pathway plays an important role in
SCCHN pathogenesis and resistance to treatment. We conducted a phase II
study of everolimus, an oral inhibitor of mTOR, in patients with refractory
SCCHN. Methods: Patients with recurrent or metastatic SCCHN treated
with at least 1 prior regimen, performance status (PS) 0-2, and adequate
organ function, received everolimus 10 mg once daily orally. The primary
endpoint was the disease control rate (DCR) defined as the proportion of
patients with a complete response, a partial response, or stable disease. A
two-stage design was followed. Cytokines were measured in plasma and
serum at baseline and post treatment. Results: 9 patients were enrolled.
Median age 63 years (range 51 - 82), Male/Female, 6/3, performance
status 0/1/2, 2/5/1. Primary site: oropharynx (2), oral cavity (4), larynx (1),
others (2). Median number of palliative therapies in the recurrent/
metastatic setting prior to study was 1 (range 1- 4). Median number of
cycles of everolimus delivered was 1 (range 1-5). No objective responses
were seen. One patient had stable disease that lasted 6 months but all
other patients had progression as best response. DCR was 11%. Median
progression-free survival was 40 days. Four patients have died due to
disease progression. Grade 3 adverse events were infrequent: pain (2
patients), anemia (2 patients), and 1 patient each with pruritus, hypertransaminasemia,
hyponatremia, lymphopenia, and fatigue. No Grade 4
toxicities were reported. Biomarker analysis in 2 patients with available
post treatment samples showed reduced plasma levels of VEGF-A, Gro-�,
and IL-17, after everolimus treatment, but no reduction was observed in
the plasma levels of IL-6 and IL-8, two cytokines often associated with
SCCHN disease progression. Conclusions: Everolimus as monotherapy was
well tolerated but did not have sufficient activity in this setting. This phase
II study did not meet the predefined primary endpoint in the first stage of
accrual.
5543 General Poster Session (Board #22C), Sat, 1:15 PM-5:15 PM
Validation for a novel diagnostic standard in HPV-positive oropharyngeal
squamous cell carcinoma. Presenting Author: Xiao-Jun Ma, Advanced Cell
Diagnostics Inc, Hayward, CA
Background: HPV testing is now widely advocated in the work up of
oropharyngeal squamous cell carcinoma (OPSCC). The �gold standard� for
oncogenic HPV detection is the demonstration of transcriptionally active
high-risk HPV in fresh tumour tissue. For clinical utility, testing strategies
have necessarily focused on formalin-fixed paraffin-embedded (FFPE)
tissue, but this has been at the expense of reduced sensitivity and
specificity for oncogenic HPV. This study evaluates a novel RNA-based in
situ hybridisation test against the analytical gold standard; detection of
high-risk HPV mRNA, derived from fresh frozen tissue samples, by
quantitative reverse transcriptase polymerase chain reaction (qPCR).
Methods: A tissue-microarray comprising FFPE cores from 79 OPSCC was
tested using High Risk HPV RNAscope (Advanced Cell Diagnostics, USA)
for HPV16, 18, 31, 33, 35, 52, and 58. Analytical accuracy and capacity
for prognostic discrimination was determined by comparison with HPV RNA
qPCR for HPV16, 18 and 33. Demographic and tumour parameters were
compared by Chi-squared and Kruskal-Wallis tests. Test sensitivity and
specificity were calculated against the standard. Kaplan–Meier survival
estimates were constructed to assess prognostication. Results: High risk
HPV RNAscope had sensitivity and specificity of 97% and 93% respectively
(PPV 91%, NPV 98%) by comparison to the gold standard. Kaplan-
Meier estimates of disease specific survival (DSS, p�0.002) and overall
survival (OS, p�0.001) by RNAscope were similar to the gold standard
(DSS, p�0.006, OS, p�0.002) and superior to p16 immunohistochemistry
(IHC) or the combination of p16 IHC and DNA qPCR. Conclusions: We
demonstrated that High Risk HPV RNAscope can be used to detect
oncogenic HPV in FFPE OPSCC samples and has both excellent analytical
and prognostic performance against the gold standard test for oncogenic
HPV. These results raise the possibility that High Risk HPV RNAscope
could be adopted as an ‘international standard’ test for OPSCC in clinical
practice. As the oncology community approaches therapeutic de-escalation
based on HPV status, such a reliable and efficacious test may have
immediate application.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.