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

5576 General Poster Session (Board #28C), Sat, 1:15 PM-5:15 PM
Predictors for response to cetuximab in a prospective clinical trial (E2303)
of patients with head and neck squamous cell carcinoma (HNSCC).
Presenting Author: Amanda Psyrri, University of Athens, Athens, Greece
Background: Theidentification of resistance mechanisms to Epidermal
Growth Factor Receptor (EGFR) inhibitors remains critical lack in the
management of HNSCC. We sought to determine predictors for response to
cetuximab in a phase II clinical trial. Methods: 63 patients (pts) with
operable stage III/IV HNSCC participated in E2303, an Eastern Cooperative
Oncology Group (ECOG) phase II trial of induction chemotherapy with
weekly cetuximab, paclitaxel and carboplatin x 6 followed by chemoradiotherapy
with the same regimen. A tissue microarray was constructed and
EGFR, ERK1/2, Met, pAkt and STAT protein expression levels were
assessed using AQUA. The objectives of analysis were to determine
association of biomarkers with E2303 efficacy outcomes (best objective
response (OR), overall survival (OS), progression-free survival (PFS), and
event-free survival (EFS)). The logistic regression model was used to
examine relationship between marker measurements (on a continuous
scale) and OR. The univariate and multivariate Cox proportional hazards
models were used to evaluate the relationship between markers and
event-time distributions. Fisher’s exact test was used to evaluate differences
in response rate between groups (high vs. low AQUA scores).
Event-time distributions were estimated by the Kaplan-Meier method and
compared by the log-rank test. Results: Cytoplasmic ERK1/2 levels weresignificantly
associated with PFS and OS (p�0.03 and 0.01, respectively).
Nuclear ERK1/2 levels were significantly associated with OS (p�0.02) and
tended towards significance for PFS (p�0.09). The multivariate Cox
regression analysis shows that cytoplasmic and nuclear ERK1/2 are
significantly associated with OS and PFS after controlling for primary site
and disease stage, respectively There was no significant association
between cytoplasmic or nuclear ERK1/2 status and OR (p-values 0.98 and
0.41, respectively).No association was found between expression of any of
other biomarkers and outcome measures. Our data analysis was based on
35 pts with marker data available. Conclusions: Ras/MAPK/ERKpathway
may be associated with resistance to cetuximab in HNSCC.
5578 General Poster Session (Board #29B), Sat, 1:15 PM-5:15 PM
A combined evaluation strategy of FDG PET/CT and contrast-enhanced diagnostic
CT (ceCT) for lymph nodes in the neck. Presenting Author: Neetha Gandikota,
Department of Nuclear Medicine, Mount Sinai Medical Center, New York, NY
Background: Accurate assessment of cervical lymph nodes (LNs) for determination
of metastatic involvement is of prime importance for management. Our
objective was to determine the incremental value of combining metabolic and
morphologic information in the differentiation between benign and malignant
LNs. Methods: A total of101 pts with head and neck squamous cell (n�91) or
thyroid cancer (n�6) or lymphoma (n�4) were included in the study. PET/CT
and neck ceCT were acquired simultaneously or sequentially at staging (n�48)
or restaging (n�53). In 131 LNs, variables evaluated includes SUVmax, size,
shape (elliptical vs non-elliptical), presence of extracapsular extension (Ecextirregular
margins), necrosis, and fatty hilum. Histopathology (n�96) and 12 mo
follow-up (n�35) were used for confirmation of the findings. ROC analyses
determined the SUVmax cut-off. Results: Of131 LNs, malignancy wasconfirmed
in 49 (37%).Results are shown in table. In the detection of malignancy, SUVmax
of 4.5 yielded the best balance between the sensitivity and specificity,
performing better than all CT variables alone. Combination analysis improved
results only when SUVmax (4.5) was added to Ecext. However, best combination
results were obtained at a SUV cut-off of 3.7. Higher SUV cut-off did not
significantly improve overall performance of SUVmax alone (Table). Conclusions:
In the differentiation of malignant from benign LNs, SUVmax (4.5) yields better
results than CT variables alone. However combining a lower SUVmax (3.7) with
Ecext produced the best results. Increasing SUVmax cut-off only produced a gain
in specificity at a significant cost of sensitivity.
Univariate variables Sen Spec Odds ratio 95% CI P value
SUVmax 82% 79% 16 5 – 54.6 � 0.01
�/- ecext 41% 93% 10 3.4 – 28.8 � 0.01
�/- necrosis 44% 88% 5.9 2.4 – 14.5 � 0.01
Shape 54% 83% 5.8 2.5 - 13 � 0.01
�/- fatty hilum 90% 15% 0.6 0.2 - 2 0.4
Size (1.2 cm) 70% 58% - - 0.11
Combined analyses SUV max
and ecext
SUV max
and necrosis
SUV max
and elliptical
shape
Sen Spec Sen Spec Sen Spec
SUVmax cut 3.7 95% 80% 100% 22% 100% 23%
SUVmax cut 4.5 86% 80% 91% 44% 89% 23%
SUVmax cut 5.3 76% 100% 82% 78% 73% 62%
P value 0.005 0.007 0.03
Head and Neck Cancer
375s
5577 General Poster Session (Board #29A), Sat, 1:15 PM-5:15 PM
The impact of advanced age on outcomes in squamous cell carcinoma of
the head and neck. Presenting Author: Virginia Ann Moye, University of
North Carolina School of Medicine, Chapel Hill, NC
Background: Limited data are available regarding outcomes in elderly head
and neck cancer patients. This retrospective study was designed to
characterize head and neck cancer in geriatric patients in the UNC Tumor
Registry. Methods: Of 1,598 patients identified from the registry, 1,291
patients were �70 years old (young group, YG) and 307 patients were � 70
(elderly group, EG) at diagnosis. Both overall survival (OS), calculated from
diagnosis to death or the last follow up, and relapse free survival (RFS) were
censored at 60 months. Log-rank test was used to compare survival
difference. Cox proportional hazard model was used to estimate hazard
ratio, adjusting for potential confounding factors. All tests were performed
in R 2.13.1. Results: EG patients were more likely to present at an early
stage with 25% presenting at stage I and 37% presenting at stage IV
compared to 17% and 51% respectively in YG. EG had a median OS of 35
months (95% CI: 28-41 months) compared to approximately 60 months in
YG (p � 0.0001 log rank test). The median RFS for EG and YG are 25 (95%
CI: 20-32 months) and 44 (95% CI: 38-52 months) months respectively (p
� 0.0001 log rank test). When controlling for possible confounders, EG
patients were nearly twice as likely to die (HR 1.94, 95% CI 1.635-2.302,
p�0.0001) and 70% more likely to relapse in 5 years compared to YG (HR
1.704, 95% CI 1.449-2.004, p�0.05). The median life expectancy for
elderly patients in our study was nearly 5 years for stage I/II and �2 years
for stage III/IV. Conclusions: Poor OS and RFS in elderly patients compared
to younger patients in this study indicate a need for further investigation
considering comorbidities and aggressiveness of treatment. Significant
differences in life expectancy in elderly patients with early versus late
disease may help guide patients and clinicians in determining how
aggressively to treat.
5579 General Poster Session (Board #29C), Sat, 1:15 PM-5:15 PM
A phase I/II study of concurrent nab-paclitaxel, carboplatin, and IMRT for
locally advanced squamous cancer of the head and neck (LASCCHN).
Presenting Author: Roy B. Tishler, Department of Radiation Oncology,
Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Boston, MA
Background: We studied escalating doses of weekly nab-paclitaxel (Abraxane,
AB) combined with weekly carboplatin (CP) and daily IMRT in patients
with LASCCHN to determine the safety and optimal dosing of AB. The
favorable biodistribution of AB, an albumin bound formulation of paclitaxel,
may allow for intensified locoregional treatment without increasing
normal tissue toxicity. Methods: An AB dose escalation was performed,
initially using concurrent weekly CP (AUC � 1.5), Erbitux (ER) and daily
IMRT to 70 Gy. After ER was dropped, dose escalation of AB from 20
mg/m2 to 50 mg/m2 was performed in 10 mg/m2 increments using a 3 � 3
study design. Results: A total of 28 patients have enrolled and all have
completed treatment. Patients ranged in age from 42 to 72 years old
(median � 59), with follow up from 3 to 48 months (median � 25). Most
patient had oropharyngeal primaries (n�22) and stage III (n�8) or IV
(n�20) disease; 18 were HPV�, 6 HPV- and 4 unknown. Initially 6
patients received weekly AB (20 mg/m2 ), ER and CP, but ER was dropped
due to greater than anticipated mucositis and dysphagia. Subsequently, 3
patients each received CP with AB at 20, 30 and 40 mg/m2 weekly and a
total of 13 received CP with AB at 50 mg/m2 . The median radiation dose is
70 Gy and the median number of weekly chemotherapy cycles is 7. The
primary toxicities were Grade 3 dysphagia, mucositis and dermatitis in 24
of 28 patients. Only 3 (of 28) PEG tubes remain at 4, 6 and 14 months. No
DLTs were observed at any dose level. There have been 5 recurrences, with
4 being local-regional. Two patients have died of disease and 26 are alive.
Conclusions: Concurrent AB, CP, and IMRT is a safe chemoradiotherapy
combination in LASCCHN with early data demonstrating feasibility and
efficacy.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.