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

350s Gynecologic Cancer
5094 General Poster Session (Board #24F), Sun, 8:00 AM-12:00 PM
The novel biomarker HE4 versus CA125 in detecting endometrial cancer: A
case control prospective study. Presenting Author: Francesco Plotti,
Campus Bio-Medico of Rome, Rome, Italy
Background: In endometrial cancer, there are no markers routinely used in
clinical practice. This study prospectively investigates the sensitivity and
specificity of new marker HE4 in detection of endometrial cancer. Methods:
Serum samples were prospectively obtained 24 hours before surgery from
25 patients with endometrial cancer and from 25 patients with uterine
benign pathology, operated from January 2011 to October 2011 at
University Campus Bio-Medico of Rome. Preoperative CA125 levels were
evaluated by a one-step “sandwich” radioimmunoassay. HE4 levels were
determined using the HE4 enzymatic immune assay. The CA125 normal
value is considered less than 35 U/mL. Two HE4 cut-off are considered:
less than 70 pmol/L and less than 150 pmol/L. The specificity analysis was
performed using the parametric T-Test for comparing the HE4 series and
the Mann-Whitney test for the CA125 series. The level of statistical
significance is set at p � 0.05. Results: The sensitivity of CA125 in
detecting endometrial cancer is 16% whereas the sensitivity of HE4 is 48%
and 28 % for 70 pmol/L and 150 pmol/L cut-off respectively. The
specificity of HE4 is 100% (positive predictive value � 100%, negative
predictive value � 65.79% and 58.14% considering the two HE4 cut-off,
respectively), whereas the CA125 specificity is 72 % (positive predictive
value � 36.36%, negative predictive value � 46.15%) in detection of
endometrial cancer. Conclusions: HE4 has a good sensitivity and a
specificity of 100% in detection of endometrial cancer and may be useful
for detecting early stage endometrial cancer. In particular the HE4 at
cut-off of 70 pmol/L yields the best sensitivity and specificity.
5096 General Poster Session (Board #24H), Sun, 8:00 AM-12:00 PM
Phase II trial on cisplatin-doxorubicin hydrochloride-paclitaxel (TAP) combination
as neoadjuvant chemotherapy (NACT) for locally advanced cervical
adenocarcinoma (LACA). Presenting Author: Francesco Raspagliesi,
National Cancer Institute of Milan, Milan, Italy
Background: NACT followed by surgery is a different therapeutic approach
to locally advanced cervical cancer that seems to offer specific advantages
over chemoradiation such as potential activity against distant micrometastases,
a debulking effect improving subsequent surgical outcome, less
toxicity, and an easier management of salvage therapy. This phase II trial
was designed to evaluate the toxicity and activity of NACT with TAP in
patients with LACA. Methods: Patients (pts) with FIGO stage IB2 (9 pts)- II
(21 pts) uterine adenocarcinoma were treated with cisplatin 70 mg/mq,
doxorubicin hydrochloride 45 mg/mq and paclitaxel 150 mg/mq day 1
every 21 days for 3 cycles. Eight pts (26.6%) presented with positive
lymphnodes ( �LY) at diagnosis (5 pelvic and 3 pelvic�paraortic). After the
last cycle of chemotherapy patients underwent radical surgery with lymphnode
dissection. Clinical responses to chemotherapy was evaluated
according to Recist criteria. Pathological response was classified as no
residual tumor (pCR), residual disease with �3 mm stromal invasion (pR1)
or residual disease with �3 mm stromal invasion (pR2). Due to the slow
accrual the trial was closed before the target population of 45 pts was
reached. Results: Between 2003 to 2010, 30 women were enrolled. Two
complete clinical responses (6.7%), 21 partial responses (70%) and 7
stabilizations of disease (23.3%) were registered. All the patients underwent
radical surgery and were assessable for pathologic responses. Five
patients (16.6%) achieved a pCR , 8 (26.6 %) a pR1 response; 17 patients
(56.7%) a pR2 response. At pathological assessment 10 pts (33.3%)
presented with �LY (7 pelvic, 1 paraortic, 2 pelvic�paraortic). At a median
follow up of 45 months progression free survival and overall survival were
37 months (95% CI 1-98) and 45 months (95% CI 9-101�) respectively.
Hematologic toxicity was the most relevant side effect with 13 pts (43 %)
reporting grade 3-4 neutropenia. Conclusions: The TAP combination seems
to be feasible with an acceptable toxicity profile and a promising response
rate for the treatment of LACA. The effect of NACT on lymphnodes status
warrant further investigation.
5095 General Poster Session (Board #24G), Sun, 8:00 AM-12:00 PM
Association of adjuvant therapy in early-stage low-risk endometrial cancer
with increased mortality: A statewide cancer registry analysis. Presenting
Author: Michael R. Milam, University of Louisville, Louisville, KY
Background: National Comprehensive Cancer Network (NCCN) guidelines
state that patients with early stage low risk endometrial cancer (defined
with 2009 criteria as stage IA endometrioid endometrial cancer) may be
managed with observation with consideration of adjuvant therapy.The
premise of this study is to review the patterns of care of those patients who
received adjuvant therapy and its impact on survival. Methods: This is a
retrospective cohort analysis of 1044 women from 2004-2008 in the
Kentucky Cancer Registry (KCR) one of the affiliates utilized in the
Surveillance, Epidemiology and End Results (SEER) Program database.
Inclusion criteria for the patients in this analysis were those women with
2009 Stage IA uterine cancer of endometrioid histology, moderate and well
differentiated tumor grade, who received definitive primary surgery. Adjuvant
therapy was defined as any postoperative radiotherapy and/or chemotherapy
after definitive surgical treatment. Patients with adjuvant therapy
after surgery (AT) were compared to those patients who underwent surgery
only (SO). Chi-square tests were used to identify associations between type
of treatment and clinical/demographic factors. K-M plots and Cox regression
models were used to examine survival between the two treatment
groups. Results: 5.3% (55/1044) of patients with early stage low risk
endometrial cancer were treated with AT compared to 94.7% (989/1044)
of SO patients.No statistical differences in mean age, race, tumor size,
smoking status, insurance status, lymph node dissection and gynecologic
oncology care were found among the AT or SO groups. Five year survival was
significantly better in the SO cohort compared to the AT cohort (92% alive
at 5 years for SO vs. 66% alive at 5 years; p�0.0001). Controlling for other
confounders in the multivariate Cox regression analysis, SO patients had
substantially less risk for death compared to the AT groups (HR: 0.21;
95%CI 0.12-0.38; p�0.0001). Conclusions: In this statewide cancer
registry analysis, adjuvant therapy after surgery in early stage low risk
endometrial cancer patients is uncommon and is associated with an
increased risk of mortality.
5097 General Poster Session (Board #25A), Sun, 8:00 AM-12:00 PM
Analysis of somatic mutation in miRNAs and miRNA regulation-related
genes in gynecological cancers: New frameshift mutation of TNRC6A found
in endometrial cancer. Presenting Author: Qi Mei, Department of Oncology,
Tongji Hospital, Tongji Medical College, Huazhong University of Science
and Technology, Wuhan, China
Background: Micro RNAs (miRNAs) are small non-coding RNAs which plays
an important role in tumorigenesis and mutation of a miRNA gene or
miRNA regulation-related gene may cause butterfly effect on alteration of
global gene expression.In order to investigate this hypothesis,high resolution
melting analysis (HRM) and denaturing high-performance liquid
chromatography (DHPLC) were used to screen 20 miRNA genes and 6
miRNA regulation-related genes for mutations in gynecologic cancers.
Methods: In this study,182 DNA samples from breast cancer tumors,42
from ovrian cancers and 28 from endometrial cancers were obtained.18
human cancer cell lines were also included.We used HRM and/or DHPLC to
screen mutations of these genes in human cancer cell lines and tumor
tissues. All samples with curves that differed in shape compared to
wild-type were directly sequenced for confirmation.Secondary structures
for the wild-type and variant primary precursor of miRNA sequences
obtained from sequencing were predicted using RNAfold software.Western
blot and immunohistochemistry were used to evaluate the related protein
change in cancer cell line and tumor tissues. Results: Polymorphisms of
these genes were very frequently observed in gynecologic cancers.Two rare
variants were found in the primary precursor sequences of mir-200c and
mir-142 gene.Moreover,a novel frameshift mutation( c.3547_3548insA)
in TNRC6A gene was found in two endometrial cacner cell lines (RL95-2
and Hec-1A) and endometrial cancers (1/28).Western blot and immunohistochemistry
showed loss of expression of TNRC6A protein in the endometrial
cacner cell lines and endometrial cancers with this mutation.
Conclusions: Two rare novel variants in 20 miRNA genes and a novel
frameshift mutation in TNRC6A gene were identified in gynecologic
cancers.Oue data indicate that mutations in TNRC6A gene may contribute
to the cancer development and might be a potential new therapeutic target
in endometrial cacner.
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