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

4638 General Poster Session (Board #9E), Sun, 8:00 AM-12:00 PM
Epidermal growth factor receptor (EGFR) expression and KRAS mutations
in penile squamous cell carcinoma: Analysis of potential application of
anti-EGFR monoclonal antibodies. Presenting Author: Hongfeng Gou,
Department of Abdominal Cancer, Cancer Center, West China Hospital,
Sichuan University, Chengdu, China
Background: Penile squamous cell carcinoma (SCC) is a rare cancer with
poor prognosis and limited response to conventional chemotherapy. Anti-
EGFR monoclonal antibodies (mAbs) have exhibited significant anti-tumor
activities in several cancers such as colorectal carcinoma, head and neck
cancer. KRAS mutations are linked to a poor response to mAbs and may
thereby result in resistance to anti-EGFR agents. This study was aimed to
examine EGFR expression and KRAS, BRAF mutations in penile SCC and to
analyze the potential application of anti-EGFR monoclonal antibodies
(mAbs) for this disease. Methods: Totally 150 penile SCC specimens from
patients undergone surgical resection were included. EGFR expression was
evaluated by immunohistochemistry. KRAS mutations at codons 12 and
13, and the BRAF mutation at codon 600 were analyzed on DNA isolated
from formalin fixed paraffin embedded tissues by direct genomic sequencing.
Results: EGFR expression was positive in all specimens, and its
overexpression rate was 92%. We failed to observe a significant correlation
between EGFR expression and tumor grade or lymph node metastases. The
detection of KRAS and BRAF mutations analysis were performed in 94 and
83 tumor tissues, respectively. KRAS mutation was detected in only one
sample and no patient was found to harbor BRAF V600E point mutation.
Conclusions: We found the overexpression of EGFR and the absence of
KRAS and BRAF mutations in penile SCC. This suggests that anti-EGFR
mAbs may be potentially considerable therapeutic agents in penile SCC.
4640 General Poster Session (Board #9G), Sun, 8:00 AM-12:00 PM
Dynamic sentinel lymph node biopsy in patients with invasive squamous
cell carcinoma of the penis: A prospective study of the outcome of 500
inguinal basins assessed in a single institution. Presenting Author: Wayne
Lam, St. George’s Hospital, London, United Kingdom
Background: Dynamic sentinel node biopsy (DSNB) in combination with
ultrasound scan (USS) has been the technique of choice at our centre since
2004 for the assessment of non palpable inguinal lymph nodes in patients
with squamous cell carcinoma of the penis (SCCp). Sensitivity/falsenegative
rates may vary depending on whether results are reported per
patient or per node basin and with and without USS. The purpose of this
study was to determine the long-term outcome of DSNB and ultrasoundguided
fine needle aspiration cytology (FNAC) in our cohort of newly
diagnosed patients and to analyse any variation in sensitivity of the
procedure. Methods: A prospective cohort study over 6 years (2004 to
2010). Inclusion criteria: New diagnosis SCCp, T1G2 or greater definitive
histology, non-palpable nodes in inguinal basin. Exclusion: patient with
persistent/untreated local disease. Sensitivity of the procedure was calculated,
per node basin, per patient, DSNB alone, USS/DSNB combined.
Minimum follow up 12 months. Results: 500 inguinal basins in 264
patients underwent USS�/-FNAC and DSNB. 70 (14%) positive inguinal
basins in 57(22%) patients were identified. 9 (2%) inguinal basins had no
tracer uptake. 2 inguinal basins were confirmed false negative at 8 and 12
months. 2 inguinal basins had positive USS�FNAC and negative DSNB.
Overall sensitivity of the technique is reported in the table. Conclusions:
DSNB in combination with USS has excellent performance characteristics
to stage patients with clinically node-negative penile cancer with a 3%
false negative rate. USS improves performance by 4% over DSNB alone.
There is no difference in performance of the combined technique if it is
reported per node basin or per patient.
USS�/-FNAC � DSNB DSNB alone
Technical (per inguinal basin) 97% 95%
Clinical (per patient) 97% 93%
Genitourinary Cancer
311s
4639 General Poster Session (Board #9F), Sun, 8:00 AM-12:00 PM
Activity of insulin growth factor-receptor (IGF-1R) antibody cixutumumab
combined with the mTOR inhibitor temsirolimus in patients with metastatic
refractory adrenocortical carcinoma. Presenting Author: Aung Naing,
Department of Investigational Cancer Therapeutics (Phase I Program),
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Adrenocortical carcinoma (ACC) is a rare and aggressive
endocrine malignancywithout an available effective systemic chemotherapy.
IGF-R2 overexpression leading to the activation of the IGF1R/
mTOR pathway is well described in ACC. Cixutumumab, a fully human IgG1
monoclonal antibody directed at insulin growth factor-1 receptor (IGF-1R),
was combined with temsirolimus on the basis of preclinical data. Methods:
Patientsreceived cixutumumab, 3-6 mg/kg IV weekly, and temsirolimus,
25 mg-37.5 mg IV weekly (4-week cycles), with restaging after 8 weeks.
Results: Twenty-six patients were enrolled (13 [50%] men); median age, 47
years; median number of prior therapies, 4. Five patients previously
received an IGF-1R inhibitor and one, temsirolimus. The most frequent
toxicities, at least possibly drug-related, were grade 1-2 thrombocytopenia
(38%), mucositis (58%), hypercholesterolemia (31%), hypertriglyceridemia
(35%), and hyperglycemia (31%). Eleven of 26 patients (42%)
achieved stable disease (SD) � 6 months (duration range � 6to21
months) with 3 of the 11 having received a prior IGF-1R inhibitor.
Conclusions: Cixutumumab combined with temsirolimus was well tolerated
and more than 40% of patients achieved prolonged SD. This study was
supported by R21CA13763301A1 (AN), U01CA62461 (RK), and
U01CA62487 (PL).
4641 General Poster Session (Board #9H), Sun, 8:00 AM-12:00 PM
Adjuvant radiotherapy after primary surgical resection in patients with
adrenocortical carcinoma: Retrospective cohort analysis. Presenting Author:
Mouhammed Amir Habra, University of Texas M. D. Anderson Cancer
Center, Houston, TX
Background: Adrenocortical carcinoma (ACC) is a rare malignancy with high
recurrence and mortality rates. The role of adjuvant radiotherapy (RT) to
improve outcome remains unclear. Considering the rarity of ACC, we
conducted a historical cohort study to ascertain the effect of adjuvant RT
on overall survival and recurrence rates. Methods: Patients were selected
from the MD Anderson Cancer Center (MDACC) ACC registry (1998- 2011)
who had primary tumor resection with no evidence of distant metastasis at
the time of initial diagnosis and a minimum follow-up of 6-months. The
adjuvant RT group included patients who received adjuvant RT within 3
months of diagnosis. Control group included patients who did not receive
RT and matched based on resection margin status and stage at diagnosis.
Results: There were no significant differences between the adjuvant RT
group (n�15) and comparison group (n �45) in gender distribution, age,
tumor size, functional status, and use of adjuvant mitotane therapy. On
multivariate Cox proportional hazard model for overall survival, the adjuvant
RT group had hazard ratio of 1.981(95% confidence interval [CI] 0.894-
4.391, p�0.0922) compared to the control group. The differences in
median time to local recurrence, distant recurrence and of recurrence free
survival were not significant between the two groups. In subgroup analysis
including only the patients whose initial treatments were from outside of
MDACC, RT group (n�15) had hazard ratio of overall survival of 1.604
(95% CI 0.712- 3.613, p�0.2543) compared to group without adjuvant
RT (n� 32). Median times to local recurrence, distant recurrence, or of
recurrence free survival were also not significantly different between the
two groups. Conclusions: To our knowledge, this is the largest single
institution report about adjuvant RT use in ACC. In our study, RT did not
appear to cause a significant difference in overall survival, recurrence rate,
or time to recurrence. However, it is still possible that patients offered
adjuvant RT and control groups may have been inherently different. Hence,
a prospective study is needed to clarify the role of adjuvant RT in patients
with resectable ACC.
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