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

5090 General Poster Session (Board #24B), Sun, 8:00 AM-12:00 PM
External validation of a nomogram predicting overall survival (OS) of women
with uterine leiomyosarcoma (ULMS). Presenting Author: Alexia Iasonos,
Memorial Sloan-Kettering Cancer Center, New York, NY
Background: A nomogram for predicting OS of women with ULMS was
developed , given the poor prognostic performance of FIGO and AJCC
staging systems. We aimed to determine the validity of the ULMS
nomogram using independent, external cohorts. Methods: The ULMS
nomogram incorporates 7 clinical characteristics: age at diagnosis, tumor
size, grade, involvement of cervix, locoregional metastases (direct extrauterine
spread, locoregional lymph node), distant metastases, and mitotic
index (per 10 HPF) to predict OS following primary surgery. Two independent
cohorts from sarcoma centers (1 US, 1 Europe) were included.
Eligible women were treated at the institutions (1994-2010) and had
undergone hysterectomy. Women with locally advanced or metastatic
disease who underwent more extensive surgery were included if the primary
tumor (uterus) was resected. Women who previously underwent resection of
the primary tumor or recurrences at other institutions were included if they
received followup care at 1 of the centers. Women who presented with
unresectable disease who never underwent surgery and those with insufficient
information on any of the nomogram variables were excluded. Results:
187 women with ULMS were identified who met the above criteria (median
age 51 yrs, median tumor size 9 cm, median mitotic index 20). Tumors
were generally high grade (88%), FIGO stage I-II (61%) without cervical
involvement (93%) and without locoregional (77%) or distant metastases
(83%). Median and 5-yr OS rates were 4.5 (95% CI 3.2-5.3) yrs and 46%,
respectively; 65 women (35%) were alive at last follow up. The nomogram
concordance index was 0.67(SE�0.02) which was as high as the concordance
index from the initial cohort used for nomogram development. The
concordance between actual OS and nomogram predictions suggests
excellent calibration of the nomogram in the validation cohort. Predictions
were within 1% of actual 5-yr OS rates, except for the patients with a 5-yr
OS rate of greater than 0.68. Conclusions: The ULMS nomogram was
externally validated and can be generalized to independent cohorts. The
nomogram provides a more individualized and accurate estimation of OS of
women diagnosed with ULMS following primary surgery.
5092 General Poster Session (Board #24D), Sun, 8:00 AM-12:00 PM
Prognosic value of lower uterine segment involvement in high-grade
endometrial cancers. Presenting Author: Paola A. Gehrig, Lineberger
Comprehensive Cancer Center, University of North Carolina at Chapel Hill,
Chapel Hill, NC
Background: To determine the relationship of lower uterine segment (LUS)
involvement and clinical-pathologic outcomes in high grade endometrial
cancers (EC). Although LUS and prognosis has been previously reported in
the literature, the results have been conflicting and limited to early stage
cases without focus upon the highest risk histologies. Methods: A singleinstitution
retrospective cohort analysis of all grade 3 EC from Jan 2005-
Sept 2010 was performed. Clinical-pathologic data were abstracted. LUS
status was determined based on permanent-section pathology. Statistical
analyses were performed using univariate and bivariate analyses with
t-tests, X2, and log-rank tests. Multivariate regressions were performed by
cox modeling. Two sided p-values�0.05 were considered significant.
Results: Of 329 cases, 52% were LUS�. Mean age was 66.1(SD 10.8) and
BMI 31.7(SD 8.3). The majority were Caucasian (63.2%) and 30.1% were
African-American (AA). Most women (80.2%) were overweight or obese,
58.7% had hypertension, and 22.5% were diabetic. Most women had stage
I disease (54.8%), but 8.6% had stage II disease, and 36.6% had stage
III-IV disease. Histologic subtypes included 32.2% endometrioid, 47.4%
serous/clear cell, and 17% carcinosarcoma. Thirty-nine percent had �
50% myometrial invasion (MI) and 43.2% had LVSI. Most of the women
(80.8%) underwent retroperitoneal node dissection (77.9% pelvic, 70.0%
periaortic). Mean follow-up time was 24.5 months (range 0.13, 73.3). Age,
HTN, and DM did not differ by LUS status. Statistically significant factors
associated with LUS positivity included race AA (38.3 v 26.5%), obesity
(57.5 v 46.7%), serous/clear cell (65.7 v 53.8%), LVSI (56.2 v 30.5%),
deep MI (52.1 v 25.3%), and positive nodes (42.4 v 12.7%). LUS� was
significantly associated with an increased rate of recurrence (HR 2.3, CI
1.16-4.47, p �0.02) after adjusting for obesity, deep MI, LVSI, nodal
status, stage, serous/clear cell histology, and adjuvant therapy. Conclusions:
Lower uterine segment was independently associated with an increased
rate of recurrence in high grade EC. This should be confirmed in
prospective endometrial trials to see if this remains an independent
predictor of recurrence.
Gynecologic Cancer
349s
5091 General Poster Session (Board #24C), Sun, 8:00 AM-12:00 PM
Pair box (PAX8) protein to predict disease recurrence and its association
with outcome in women with endometrial cancer: A retrospective study of
229 patients. Presenting Author: Damanzoopinder Samrao, USC, Los
Angeles, CA
Background: Pax-8 is a member of the pair-box (PAX) family of transcription
factor genes and it has been found to be overexpressed in numerous cancer
cell lines including ovarian and endometrial. Possibly, inhibition of Pax8
activity may even have an impact on cancer treatment. However the role of
Pax8 in human endometrial cancer has not yet been explored. Thus, the
aim of this study is to determine its predictive value in disease outcome of
endometrial cancer. Methods: 229 patients with available clinical data and
paraffin-embedded tissue were available for review and analysis. The
clinical parameters used for modeling were age, histologic subtypes,
myometrial depth of invasion, lympho-vascular invasion (LVI), FIGO grade,
lymph nodes positive, recurrence, disease status, recurrence time and
survival time. To test the association between Pax8 and the clinical
parameters, Fisher’s exact test was performed. For survival analysis,
Kaplan-Meier method was performed. Results: We found a strong association
between PAX8� and high tumor grade (p�0.002), LVI � (p�0.018),
and type II tumor subtype. Patients with tumor expressing Pax8 were more
likely to present with shorter OS and DFS p� 0.00096 and p�0.018
respectively. There was an association of PAX8 with OS (p�0.01486) with
5-years OS probability of 80.04% for patients with Pax8- and 55.9% for
patients with Pax8�. There was also an association of PAX8 and DFS
probability (p�0.02028) with 5-years DFS probability was of 72.12% for
patients with Pax8- versus 49.88% for patients with Pax8� expression.
Conclusions: Pax8 is a reliable marker in endometrial cancer and its
overexpression can predict poor outcome.
5093 General Poster Session (Board #24E), Sun, 8:00 AM-12:00 PM
Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy
in locally advanced cervical cancer. Presenting Author: Roberto Angioli,
Department of Obstetrics and Gynecology, Campus Bio-Medico University
of Rome, Rome, Italy
Background: The aim of this study is to evaluate the efficacy, in terms of
overall survival and progression free survival, and safety of adjuvant
chemotherapy after neoadjuvant chemotherapy followed by radical surgery
both in patients with and without node metastases. Methods: Between June
2000 to May 2007, all patients with diagnosis of locally advanced cervical
cancer referred to the Division of Gynecologic Oncology of the University
Campus Bio-Medico of Rome were elegible for this protocol.All enrolled
patients received 3 cycles of platinum-based chemotherapy every 3 weeks
according to the scheme cisplatin 100 mg/mq and paclitaxel 175 mg/mq.
After neoadjuvant chemotherapy all patients with stable or progression to
treatment were excluded from the protocol, all other were submitted
classical radical hysterectomy and bilateral systematic pelvic lymph node
dissection, and after to adjuvant treatment with 6 cycles of platinum based
chemotherapy with cisplatin 100 mg/mq and paclitaxel 175 mg/mq.
Results: 110 patients with local advanced cervical cancer received the
treatment with neoadjuvant chemotherapy followed by radical surgery and
adjuvant chemotherapy.Our study focused on clinical and operative data ,
in terms of overall survival and disease free survival at 5 and 3 years. 5-year
OS of our series was 78% at five years and 86% at 3-years, with
encouraging results also in subgroup with and without node mestastases.
Conclusions: The adjuvant chemotherapy regimen after neoadjuvant chemotherapy
and radical surgery rappresents a valid treatment option for
patients with locally advanced cervical cancer without lymph node involvement,
both in terms of overall survival than in terms of disease-free interval,
the results have also confirmed the validity of this approach in lymph node
metastases, with a complication rate lower than the standard radiochemotherapy
regime.
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