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

314s Genitourinary Cancer
4650 General Poster Session (Board #11A), Sun, 8:00 AM-12:00 PM
Correlation of increased eosinophil count following sipuleucel-T treatment
with outcome in patients (pts) with metastatic castrate-resistant prostate
cancer (mCRPC). Presenting Author: Douglas G. McNeel, University of
Wisconsin-Madison, Madison, WI
Background: Sipuleucel-T is the first autologous cellular immunotherapy
approved for asymptomatic or minimally symptomatic mCRPC. In the
IMPACT trial, pts treated with sipuleucel-T had transient increases in
eosinophil counts compared with control. In this retrospective analysis, we
assess potential correlations between eosinophilia, overall survival (OS),
prostate cancer-specific survival (PCSS) and immune response following
sipuleucel-T. Methods: Data from three phase III trials (D9901, D9902A,
and IMPACT) were pooled. The analysis included CBCs performed at
baseline and wks 2–34. Eosinophilia was defined as either �ULN (with
normal baseline), or a max change from baseline within the top quartile, at
any time between wks 2–16. Results: Increased eosinophil counts were
seen in sipuleucel-T pts by wk 6, decreasing to near baseline by wk 14;
eosinophil counts in control pts were stable. Of 377 sipuleucel-T pts
eligible for analysis, 105 (27.9%) had eosinophilia. Baseline disease
characteristics associated with eosinophilia were indicative of better
prognosis (i.e., longer Halabi predicted survival [p�0.007], lower PSA
[P�0.033], higher Hgb [p�0.001], and no prior docetaxel [p�0.012]). In
univariate analyses, eosinophilia correlated with improved OS (HR�0.75;
95%CI: 0.56–1.01; p�0.057) and PCSS (HR�0.71; 95%CI: 0.53–
0.97; p�0.031); trends persisted after adjusting for Halabi. The magnitude
of eosinophilia positively correlated with antigen-specific humoral
responses (p �0.039 for wks 6, 14 and 26) and elevations in the cytokines
at wk 6 (IL2 [p�0.011], IL5 [p�0.038] and TARC [p�0.001]). AEs
occurring more frequently (p�0.05) in pts with eosinophilia were infusionrelated:
pyrexia (33.3 v 21.3%) and nausea (19.0 v 10.7%). No cases of
hypereosinophilic syndrome were reported. Conclusions: Increases in eosinophils
after sipuleucel-T correlated with improved OS and PCSS. Large
increases in eosinophil counts were associated with humoral responses and
Th2-type cytokine production. Further studies of eosinophilia as a biomarker
for sipuleucel-T response, particularly in earlier disease settings,
are of interest.
4652 General Poster Session (Board #11C), Sun, 8:00 AM-12:00 PM
Comparing the ability of clinicians and a nomogram model at predicting
future 99mTc-bone scan (BS) positivity in patients (pts) with rising prostatespecific
antigen (PSA) following radical prostatectomy (RP) for prostate
cancer (PCa). Presenting Author: Michael W. Kattan, Department of
Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
Background: Nomograms that assist clinicians in predicting which PCa pts
have a high risk of developing M1 disease have been developed, but
clinicians still tend to use their own judgment of risk when managing
individual pts. This is the first study to compare the ability of clinicians vs a
nomogram at predicting future BS positivity in pts with PCa. Only androgen
deprivation therapy- (ADT-) naive post-RP pts were considered, as there are
currently no nomograms for predicting M1 disease in pts receiving ADT.
The Slovin nomogram (Slovin et al. Clin Cancer Res 2005; 11: 8669-
8673) was chosen based on considerations of the numbers of pts analyzed
and the follow-up intervals used in its development. Methods: During an
advisory board in June 2011, 24 PCa experts were given details of 25
ADT-naive post-RP PCa pts with biochemical recurrence who were randomly
selected from the Cleveland Clinic Database of 759 pts. The
predicted 1-yr from today probability of freedom from metastasis was
generated using the Slovin nomogram and estimated by the clinicians. The
predictive accuracy was quantified using the concordance index (C-index).
Results: All pts were Caucasian and median age was 62 yrs. Median PSA
level at biochemical recurrence was 1.2 ng/mL and PSADT varied between
1.3 and 11.7 months. The data used for each of the pts was acquired
between 4 and 133 months after the RP procedure. Eight pts had a positive
BS within 1 yr. Considerable variation between the clinicians’ predictions
for each pt was observed. The nomogram gave a higher C-index compared to
the clinicians (0.812 and 0.628, respectively; p�0.003). The clinicians
typically overestimated the risk of developing M1 disease. The nomogram
outperformed all of the clinicians (C-index range: 0.47 to 0.75). Urologists
predictions were superior to those of oncologists (p�0.048). Conclusions:
The Slovin nomogram was more accurate than expert clinicians in predicting
1-yr BS positivity. We suggest nomograms should become an integral
part of the clinical decision process in the PCa setting.
4651 General Poster Session (Board #11B), Sun, 8:00 AM-12:00 PM
Proton radiotherapy for prostate cancer in the Medicare population:
Patterns of care and comparison of early toxicity with IMRT. Presenting
Author: James B. Yu, Yale University School of Medicine, New Haven, CT
Background: Proton radiotherapy (PRT) is a costly treatment used for
prostate cancer despite little evidence supporting its use. We examined
patterns of PRT use in the Medicare program and assessed the short-term
toxicity of PRT vs. intensity modulated radiation therapy (IMRT). Methods:
Using national Medicare claims from 2008-2009, we identified a sample
of prostate cancer patients ages 66-94 who had received PRT or IMRT. We
used multivariable logistic regression to identify patient and regional
factors associated with receipt of PRT. We searched claims for procedure
and diagnosis codes indicative of treatment-related complications and
grouped the complications into genitourinary (GU), gastrointestinal (GI),
and other complications. To compare the effect of PRT and IMRT on
short-term toxicity, we used a Mahalanobis distance approach to match
each PRT patient to two IMRT patients, achieving balanced distribution of
clinical and sociodemographic characteristics. We compared six-month
and one-year outcomes between the two treatment groups using conditional
logistic regression. Results: We identified 27,647 men; 421 (2%)
received PRT and 27,226 (98%) received IMRT. Patients who received
PRT were widely geographically distributed, with some patients traveling
�500 miles for treatment. PRT patients were younger, healthier, and of
higher socioeconomic status. Although PRT was associated with a significant
reduction in GU complications at six-months compared with IMRT
(6.1% vs. 12.0%, OR 0.60 [95% CI 0.38-0.96], p�0.03), at one-year
post-treatment there was no longer any difference in cumulative complication
rates (18.9% vs. 21.9%, OR 0.96 [95% CI 0.61-1.53], p�0.88).
There was no significant difference in GI or other complications at
six-months or one-year post-treatment. Conclusions: Although PRT remains
a scarcely used treatment, some prostate cancer patients traveled great
distances for treatment. While PRT was associated with a reduction in
six-month GU toxicity, there were no differences in toxicity at one-year.
Further study on longer-term effects and other clinical and patient-reported
outcomes is needed to inform the widespread application of PRT.
4653 General Poster Session (Board #11D), Sun, 8:00 AM-12:00 PM
Detecting prostate cancer in BRCA1 and BRCA2 mutation carriers: A role
for EN2? Presenting Author: Emma Killick, Institute of Cancer Research,
Sutton, United Kingdom
Background: EN2 is part of the HOX gene family and plays a role in foetal
development. More recently a potential oncogenic role for the protein has
been postulated and its utility as a cancer biomarker has been explored in
prostate cancer (PrCa) and breast cancer. Carriers of mutations in the
BRCA1 and BRCA2 genes have an increased risk of PrCa (1.8-fold and
5-fold respectively) and their tumours tend to be more aggressive and
advanced than sporadic cases. Currently there is no national screening
program for BRCA mutation carriers in the UK, and the IMPACT study was
set up to evaluate PSA screening in this particular group. Here we analyse
the efficacy of the urinary EN2 protein as a marker of early cancer detection
within this higher risk group. Methods: First pass urine (without preceding
digital rectal examination) was collected as part of the IMPACT screening
study which enrolled individuals aged between 40 and 69 who were
unaffected by PrCa at time of enrolment into the study (n� 418). All
participants were from families harbouring a BRCA1 or BRCA2 mutation
and were either BRCA mutation carriers themselves or controls with a
negative predictive BRCA genetic test. They underwent annual PSA test
with a PSA of � 3.0 ng/ml triggering a diagnostic biopsy. EN2 protein was
measured in the urine using an ELISA; (positive ��42.5ng/ml). Results:
Our initial results demonstrated urinary EN2 had a sensitivity of 66.67%
and a specificity of 89.29% when discriminating which men had been
diagnosed with PrCa; the ROC AUC was 0.816. The difference in EN2 level
between those diagnosed with cancer and those who were not was
significant (p ��0.001). There was trend towards higher EN2 levels in
those with more aggressive tumours (median EN2 84.5ng/mL in Gleason
�3�4 vs 111ng/mL in Gleason �4�3), however this was not statistically
significant. In one PrCa case EN2 rise preceded PSA rise by 2 years.
Further samples are in the process of being analysed, results from these will
be included. Conclusions: Urinary EN2 protein measurement warrants
further investigation as a PrCa biomarker in this higher risk group with
genetic predisposition to PrCa.
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