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

5560 General Poster Session (Board #24D), Sat, 1:15 PM-5:15 PM
Acetylated tubulin and risk of nodal metastases in squamous cell carcinoma
of the head and neck (SCCHN). Presenting Author: Nabil F. Saba,
Winship Cancer Institute, Emory University, Atlanta, GA
Background: We previously established that AT expression predicts for
response to chemotherapy in SCCHN (Saba et al, AACR 2010 meeting
abstr 3744). We wanted to further examine the relation of AT expression
and nodal metastases in SCCHN. Methods: We assessed AT expression in
archival tissue specimens from primary SCCHN cases with (50 cases) and
without (53 cases) lymph node metastases (NM) using standard immunohistochemistry
(IHC). Clinical characteristics of patients were retrieved
from the department of pathology under the guidelines of the institutional
review board (IRB). IHC staining for AT was scored based on intensity and
percentage of tumor cells stained: 0 � no staining, 1� �weak, 2� �
moderate, 3� �moderate to high, 4� �high and a weighted index (WI)
was calculated as percent stain x stain intensity. Wilcoxon two-sample test
and Kruskal-Wallis test were used to estimate the relationships of the WI
with nodal metastasis, node status, primary tumor location, grade, and
stage. Log-rank test was used to examine the difference in OS and DFS
among four groups based on quartiles of the WI. A Cox proportional hazard
model was employed to estimate the adjusted effect of WI on OS and DFS.
Results: A higher AT expression was associated with nodal metastasis
(p�0.0155) and higher stage (p�0.0311). A lower AT expression was
associated with oral cavity primary (p�0.0107). After adjusting for age,
gender, race, and smoking status, a lower AT expression was significantly
associated with better DFS in the subset of patients with NM by multivariate
analysis (HR�1.008; 95% CI�1.002- 1.014; p�0.0123). Among
patients with no NM there was a marginally significant difference in OS
among four different groups based on quartiles of AT expression
(p�0.0765). Conclusions: High AT expression is associated with nodal
metastases in SCCHN and may be a marker of poor prognosis in patients
with node positive disease. The value of AT as a prognostic marker in
SCCHN needs to be better defined. This work is supported by a SPORE CDP
Grant P50 CA128613-03 to NFS.
5562 General Poster Session (Board #24F), Sat, 1:15 PM-5:15 PM
Nomogram for prediction of prognosis in patients treated for oral cavity
squamous cell carcinoma. Presenting Author: Pablo H. Montero, Head and
Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer
Center, New York, NY
Background: TNM staging is an effective tool for prognostic prediction in
patients with oral cavity cancer, but it disregards variables such as the
anatomic subsite, medical comorbidity, lifestyle, etc. A nomogram has the
ability to take into account many factors predictive of outcome for an
individual patient, beyond the traditional TNM. We have developed a
nomogram to accurately predict overall mortality (OM) and disease specific
mortality (DSM) in individual patients treated for oral cancer. Methods:
Demographic, host, and tumor characteristics of 1,617 oral cancer
patients treated with surgery and adjuvant treatment between 1985 and
2009 were available from a preexisting database. Recurrent disease was
recorded in 509 patients, 328 died of cancer-related causes and 542 died
of other causes. The median follow-up was 42 months (range 1-300
months). Cox proportional hazards regression model was used for OM and
competing risk regression was used for DSM. Death from other causes was
treated as competing risk for DSM. Missing values in the predictors were
multiply imputed before analysis. Variables analyzed as prognosis predictors
included age, gender, race, alcohol/tobacco use, anatomic subsite,
comorbidity, tumor size/thickness, bone/deep muscle invasion, nodal
status/level, grade, vascular/perineural invasion, margin status and adjuvant
therapy. Step-down method was used to select the statistically most
powerful predictors for inclusion in the final nomogram for each outcome.
Results: Age, severe comorbidity, subsite, tumor size, bone/deep muscle
invasion, margin status, vascular and perineural invasion, nodal status and
level, and adjuvant therapy were the variables with highest predictive value
for OM. The most influential predictors of DSM were gender, tumor size,
nodal status and location, subsite, margin status, grade and vascular
invasion. Nomograms were generated for prediction of OM and DSM. The
nomograms were internally validated with correction for over-fitting; biascorrected
concordance index for OM was 75% and DSM 76%. Conclusions:
We have developed nomograms that can accurately estimate OM and DSM
based on tumor and host characteristics of an individual patient treated for
oral cancer.
Head and Neck Cancer
371s
5561 General Poster Session (Board #24E), Sat, 1:15 PM-5:15 PM
Patient-reported symptoms following IMRT alone for oropharynx cancer: A
survivorship study. Presenting Author: Gary Brandon Gunn, University of
Texas M. D. Anderson Cancer Center, Houston, TX
Background: Patients (pts) with favorable oropharynx cancer (OPC) are
often treated with single modality RT with excellent disease control. We
present the pattern of pt-reported symptoms in OPC survivors treated with
IMRT alone. This will represent a benchmark for later comparison to pts
treated with other modalities (e.g., proton therapy, transoral surgery).
Methods: Pts eligible for this cross-sectional questionnaire-based study had
OPC treated with IMRT (no systemic therapy), in remission �18 mos,
completed the MD Anderson Symptom Inventory – Head and Neck Module
(MDASI-HN). Clinical data were tabulated and analyzed using nonparametric
statistics. Results: 89 pts participated. OPC sub-site was tonsil
in 58, base of tongue (BOT) in 30, and soft palate in 1 pt. 65% were TX/1,
28% T2, and 7% T3/4, while 53% were NX/1 with 47% N2. Mean RT dose
was 66 Gy (SD�2.5). Median age was 54 years (SD�11). Mean follow-up
at MDASI-HN was 74 months (SD�15). Mean MDASI-HN symptom rating
(0 to 10 scale) was 1.3 (95% CI 0.97-1.6), with no significant difference
by OPC sub-site. No single MDASI-HN items showed significant difference
in the percentage of pts with moderate to severe (M/S) reports by OPC site,
thou dry mouth approached significance (p�0.054), 53% in BOT vs. 32%
for tonsil. Overall, 14% of pts were entirely symptom free (i.e. “0” across all
22 symptom items), 33% reported only mild symptoms, 23% only
moderate symptoms, and 31% reported any symptom as severe . The top 7
symptoms were dry mouth, swallowing, sleep, taste, fatigue, distress, and
teeth and these were reported at M/S levels by 39%, 24%, 19%, 17%,
16%, 14%, and 10% of pts, respectively. For those with any M/S symptom,
the median number of symptoms reported at M/S levels was 3. 1/89 pts had
a feeding tube at the time of MDASI-HN completion. Conclusions: The late
symptom burden for long-term OPC survivors following IMRT alone was low,
with nearly half of pts with only minimal symptoms across all items.
Considering other endpoints (e.g. disease control, acute toxicity, second
malignancies, and functional measures), future treatment strategies should
seek to match or exceed these results. Future RT symptom prevention/
reduction strategies should focus on the top symptoms identified here.
5563 General Poster Session (Board #24G), Sat, 1:15 PM-5:15 PM
Head and neck cancer in Fanconi anemia and dyskeratosis congenita.
Presenting Author: Blanche P. Alter, National Cancer Institute , Bethesda,
MD
Background: Fanconi Anemia (FA) and dyskeratosis congenita (DC) are
inherited bone marrow failure syndromes (IBMFS) with extraordinarily high
risks of cancer, particularly head and neck squamous cell carcinoma
(HNSCC). The standardized incidence ratios (SIR) for solid tumors are 40
in FA and 10 in DC, and for HNSCC 700 and 900 respectively. In the
general population, cancers of the oropharynx may be associated with
human papilloma virus (HPV) more than the oral cavity. The specific
locations of HNSCC in FA and DC have not been reviewed, and thus the
hypothetical role of HPV in these cancers is unknown. Methods: Literature
cases were reviewed through PubMed searches using the terms “Fanconi
anemia” and “dyskeratosis congenita”. All papers were reviewed, and
details of the specific cancers recorded. FA literature included reports from
1927 through 2011, and DC literature from 1910 through 2011. Participants
in the National Cancer Institute (NCI) IBMFS retrospective/
prospective protocol (NCI 02-C-0052, opened in 2002) were also analyzed
for cancer. The HPV vaccine was not available during most of the time
frame of this study. Results: There were 411 cases of cancer among 2190
(19%) cases of FA described individually in the literature, and 21 cancer
cases out of 116 (18%) FA patients in the NCI cohort. HNSCC were
reported in 112 FA literature cases (5%), and 9 (8%) in the cohort. The
oropharynx was the initial site for HNSCC in 31/112 literature cases (28%)
and 3/9 NCI cases (33%). With regard to DC, 51/647 (8%) cases in the
literature had cancer, as did 9 of 94 (10%) NCI participants. HNSCC were
reported in 21/647 (3%) DC literature cases, and in 5/94 (5%) from the
NCI cohort. Four of the 21 HNSCC (19%) in the literature were oropharyngeal,
and 2/5 (40%) in the NCI cohort. The cumulative incidences of any
HNSCC in the NCI FA and DC cohorts were 50% and 21% by 40 years of
age (censored at death from other causes). Conclusions: Patients with FA
and DC have extremely high risks of HNSCC at substantially younger ages
than the general population. Approximately 30% of these cancers occur in
the oropharynx. The HPV vaccine could be important in prevention of these
cancers. Future studies of the HPV status of oral cavity and oropharynx
HNSCC tumors from patients with FA and DC will be informative.
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