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

5528 Poster Discussion Session (Board #19), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
A phase II trial of cetuximab in high-risk premalignant lesions of the upper
aerodigestive tract. Presenting Author: Joseph A Califano, Johns Hopkins
University School of Medicine, Baltimore, MD
Background: High risk head and neck premalignancy includes patients with
prior HNSCC and loss of heterozygosity (LOH). These patients demonstrate
30-60% rates of progression to malignancy despite conventional surgical
excision. We performed a phase II trial using short term therapy with
cetuximab, a humanized monoclonal antibody directed against EGFR, in
the treatment of high risk premalignant lesions of the UADT. Methods:
Inclusion criteria required; 1) presence of 3p, 9p21, or 17p LOH, and/or 2)
surgically unresectable high grade premalignant lesions, and/or 3) high
grade premalignancy after curative therapy for HNSCC. Patients received
cetuximab 400 mg/m2 on week one followed by 250 mg/m2 on week 2-8 or
observation, with the option for crossover to cetuximab for patients
originally randomized to the observation arm. Histologic grade (1�benign,
2�mild dysplasia, 3�moderate dysplasia, 4�severe dysplasia/carcinoma
in situ, 5�invasive cancer) and change in grade of dysplasia was evaluated.
Results: 19 patients were enrolled. Two patients discontinued therapy due
to toxicity. We noted a decrease in grade of dysplasia in the cetuximab
treated group (-1.0) vs. the observation group (-0.2), (Wilcoxon test p value
� 0.18). In the observation group, 0/5 patients (0%) underwent complete
resolution of dysplasia; while 4/12 (33.3%) treated patients had no
remaining dysplasia after therapy (p � 0.26), three of these patients had
complete resolution of dysplastic changes after cetuximab therapy alone.
Of these three patients, two have had no recurrence of leukoplakia or
dysplasia at 1.5 and 2 years. One patient treated with oral cavity dysplasia
has had no recurrence of dysplasia or lesions within the oral cavity, but
developed a hypopharyngeal cancer at 1.5 years after trial completion. Of 5
patients randomized to observation, three underwent crossover to cetuximab
therapy, and two of these three patients had complete resolution of
dysplasia. Conclusions: EGFR blockade with cetuximab alone can result in
significant, durable, and complete clinical and histological resolution of
moderate to severe dysplasia in at least a subset of high risk patients.
5530 Poster Discussion Session (Board #21), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
The influence of institutional head and neck cancer (HNC) clinical trial
accrual on overall survival (OS): An analysis of RTOG 0129. Presenting
Author: Evan John Wuthrick, Ohio State University Medical Center-James
Cancer Hospital, Columbus, OH
Background: NCCN recommends HNC patients (pts) be treated by providers
with experience in HNC management. Whether treatment by experienced
providers (measured by no. of pts treated) is associated with HNC survival
outcome is unknown. Methods: Analysis included 471 pts in RTOG 0129
with stage III-IVa HNC with known tumor HPV and smoking status
randomized to cisplatin concurrent with standard or accelerated fractionation
radiotherapy (RT). Participating centers were stratified into pt accrual
tertiles (ATs) to 21 RTOG HNC trials from 1997-2002. As a surrogate for
experience, we investigated the independent effect of AT on OS and
progression-free survival (PFS) in multivariable cox proportional hazards
models. Results: Median follow up was 4.8 yrs (range 1.1 - 6.5). In
Kaplan-Meier analysis, OS and PFS for pts at centers in the two lower AT
(low accruing centers [LAC]) were similar and compared to the upper AT
(high accruing centers [HAC]). Median accrual in LAC vs HAC was 11 vs 82
pts. Pts treated at LAC and HAC had similar age, HPV status, pack-years, N
stage, comorbidities and study arm assignment (SAA), but pts at LAC had
better performance status (PS)(Zubrod 0; 62% vs 52%; p�0.04), fewer T4
tumors (27% vs. 35%; p�0.05) and were more likely uninsured (12% vs
4%; p�0.009). Compared to HAC, LAC pts had significantly worse OS, (5
yr 51.0% vs 69.1%; p � 0.002), and PFS (5 yr 42.7% vs 61.8%; p �
0.001) and more locoregional failure (5 yr 36.4% vs 20.8%; p �0.001).
Treatment at LAC was associated with ~90% increase in risk of death (OS
HR 1.91, 95%CI 1.37-2.65) and progression (PFS HR 1.89, 95%CI
1.39-2.56) when compared to pts treated at HAC, after adjustment for age,
PS, pack-years, T and N stage, SAA and HPV status. Acute and chronic
toxicities, RT dose, fractions, and treatment duration did not differ for pts
at LAC vs HAC. RT at LAC was more likely than HAC to differ from protocol
(18% [16.8% acceptable variation {AV}, 1.2% unacceptable deviation
{UD}] vs 6% [4.7% AV, 1.3% UD]; p�0.001). Conclusions: Pts with HNC
treated at LAC in RTOG trials were associated with significantly worse
survival outcomes compared to pts treated at HAC.
Head and Neck Cancer
363s
5529 Poster Discussion Session (Board #20), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
Prognostic significance of the AJCC staging in patients with squamous cell
carcinoma of the oropharynx. Presenting Author: Carlos Rodrigo Acevedo-
Gadea, Yale University School of Medicine, New Haven, CT
Background: There have been significant changes in the epidemiology of
head and neck squamous cell carcinomas (HNSCC), with an increase in the
incidence of oropharyngeal (OP) cancer and opposite effect in other sites.
Since the rise in OP cancer incidence is attributed to human papillomavirus
(HPV), which is associated with a different biology and clinical behavior, we
evaluated whether the current AJCC system retained its prognostic impact
in this patient population. Methods: The Surveillance Epidemiology and
End Results (SEER) registry was queried for patients with HNSCC diagnosed
between 2004 and 2007. Overall survival (OS) was estimated by the
Kaplan-Meier method and the Cox model was used to compare the survival
curves for each AJCC stage. Patients were grouped into three anatomical
locations: oral cavity (OC), larynx (L) and OP. Results: There were 26,520
patients meeting eligibility criteria, including 8622 OP, 7332 OC, and
10566 L. The AJCC staging retained its prognostic significance across all
stages for patients with HNSCC of the OC and L. Patients with OP cancer,
however, had similar 4-year survival for stages I through IVA, whereas stage
IVB and IVC had a significantly decrease survival compared to IVA and IVB
respectively (Table). Conclusions: The OS for stages III and IVA OP cancer is
similar to those with stages I and II, in an effect that may be attributed to
the increased frequency of HPV in this population, rendering the tumors
more sensitive to chemotherapy and radiation. Therefore, the AJCC stage in
OP cancer may be more useful in guiding the therapy than as a prognostic
factor.
4-year OS according to tumor site and stage.
Oral cavity Larynx Oropharynx
I 72.9% 71.6% 62.4%
II 59.3% Vs I (HR 1.91, 64.0% Vs I (HR 1.51, 57.7% Vs I (HR 1.14,
p � 0.001)
p � 0.001)
p � 0.22)
III 44.5% Vs II (HR 1.51, 48.9% Vs II (HR 1.68, 67.2% Vs II (HR 0.81,
p � 0.001)
p � 0.001)
p � 0.017)
IVA 33.9% Vs III (HR 1.49, 39.3% Vs III (HR 1.29, 63.9% Vs III (HR 1.16,
p � 0.001)
p � 0.001)
p � 0.014)
IVB 27.2% Vs IVA (HR 1.46, 23.1% Vs IVA (HR 1.85, 42.6% Vs IVA (HR 1.99,
p � 0.001)
p � 0.001)
p � 0.001)
IVC 12.0% Vs IVB (HR 1.74, 16.6% Vs IVB (HR 1.28, 22.2% Vs IVB (HR 2.14,
p � 0.001)
p � 0.027)
p � 0.001)
5531 Poster Discussion Session (Board #22), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
Outcomes of HIV patients treated with chemoradiotherapy (CRT) for
squamous cell carcinoma of the head and neck (SCCHN). Presenting
Author: Waleed F Mourad, Beth Israel Medical Center, New York, NY
Background: SCCHN with HIV is a challenging clinical situation in the
medical arena due to limited data. We report our outcomes and the impact
of chemotherapy (CT) and HPV on this patient (pt) population Methods: This
is a single institution retrospective study of 71 HIV pts with SCCHN treated
from 1998-2011. The median age at RT and HIV diagnosis was 51 (32-72)
and 34 (25-50) respectively. HIV duration was 11 yrs (6-20). Stage I-II, III
and IV were 22, 27 and 51% respectively. Pts treated with RT alone were
37% and CRT 63% {CDDP 91%}. Fifty pts were on HAART during
treatment and 50% of pts with SCC of the oropharynx were HPV�. Median
dose of 70, 63 and 54 Gy were delivered at 1.8-2 Gy/fraction to gross
disease, high and low risk neck respectively. Twelve pts (17%) underwent
neck dissection for N3 Results: With a median follow up of 50 months
(12-140) the median weight loss was 20 lbs (6-40). Acute skin desquamation
and mucositis grades � 2 and 3 were 76 and 24% respectively.
Treatment breaks � 10 and 5 days were 7 and 21% respectively. One pt
died from induction CT, 1 was hospitalized for grade 4 mucositis and 1
developed osteoradionecrosis during CRT. Late dysphagia grades � 2, 3
and 4 were 74, 15 and 11%. Late xerostomia grades � 2 and 3 were 77
and 23% respectively. The median CD4 count and viral load before, during
and after treatment were 370, 135, 100 and 0, 160, 260 respectively.
Seven pts (10%) developed second primary malignancy. The 4 yr locoregional
control (LRC) and overall survival (OS) were 69% and 55%
respectively. Chi-square test shows significant relationship between LRC
and RT duration, as well as between CT and lower CD4 counts and higher
viral load (P�0.001). Positive trends were observed between (weight loss
�10% and LRC) and (absence of second malignancy and OS) (P�0.271).
There was no significant relationship between HPV �ve or CT on either LRC
or OS. Conclusions: The addition of CT to RT yielded higher morbidity and
mortality without clear benefit on LRC or OS. HIV per se seems to have a -ve
impact on HPV �ve pts outcomes. Comparing observed rates of LRC and
OS, our data show that RT�CT administered for HIV �ve pts with SCCHN
appears to be less effective than HIV-ve pts. Larger size studies are
warranted to optimize the management of this growing patient population.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.