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

4532 Poster Discussion Session (Board #11), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
Serum tumor marker (STM) decline rates during high-dose chemotherapy
(HDCT) to predict outcome for germ cell tumor (GCT) patients (pts).
Presenting Author: Darren Richard Feldman, Memorial Sloan-Kettering
Cancer Center, New York, NY
Background: STM decline rates predict outcome for GCT pts during 1st-line conventional-dose chemotherapy. We investigated the importance of STM
decline rates during salvage HDCT. Methods: HDCT included an initial low
dose (LD) portion (1-2 cycles of paclitaxel plus ifosfamide [TI] � G-CSF) for
stem cell collection followed by a high-dose (HD) portion (3 cycles of
carboplatin � etoposide or TI � carboplatin). Eligible pts had elevated STM
(AFP �15 and/or HCG �2.2) at the start of LD and completed �1 HD
cycle. Slope and t1/2 were calculated for HCG and AFP for cycles 1-2 of LD
and HD starting with the peak value during days (d) 1-6 of LD and HD to
avoid interference from lysis. T1/2 for AFP �7d and HCG �3.5d were
categorized as satisfactory (SAT); normalization within 7d was also considered
SAT, regardless of t1/2. Pts with elevated AFP and HCG had to have
adequate decline in both to be considered SAT. Progression-free (PFS) and
overall survival (OS) were compared for SAT vs. unsatisfactory (UNSAT) pts
using the log-rank test. Results: Of 117 pts (115 male, 105 nonseminoma),
the most common primary sites were testis (81) and mediastinum (26). 93,
19, and 5 pts completed 3, 2, and 1 HD cycles, respectively. Overall,
19/117 had SAT decline during LD (19/77 for HCG; 7/57 for AFP). For LD,
there was no significant difference in PFS or OS for SAT vs. UNSAT decline.
For HD, 17/96 had SAT decline (11/59 for HCG; 9/47 for AFP). SAT overall
decline (HCG and AFP) during HD predicted superior PFS (p�0.0025) and
OS (p�0.0046) with 2-year (yr) PFS 0.88 (0.59, 0.97) vs. 0.37 (0.26,
0.47) and 3yr OS 0.82 (0.55, 0.94) vs. 0.37 (0.26, 0.48). SAT HCG
decline alone also predicted superior PFS (p�0.0018) and OS (p�0.004)
with 2yr PFS 0.91 (0.51, 0.99) vs. 0.32 (0.19, 0.46) and 3yr OS 0.91
(0.51, 0.99) vs. 0.35 (0.22, 0.50) whereas only a non-significant trend for
improved PFS (p�0.14) and OS (p�0.16) was seen for AFP alone.
Conclusions: STM decline rates during the HD portion of salvage HDCT
predicts favorable PFS and OS, mostly driven by HCG. However, UNSAT
STM decline does not exclude long-term PFS/OS. STM decline rates during
the initial LD portion of HDCT programs do not predict outcome; thus,
UNSAT LD decline should not prohibit subsequent HDCT.
4534 Poster Discussion Session (Board #13), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
A retrospective analysis of patients with intermediate-risk germ cell tumor
(IRGCT) treated at Indiana University from 2000 to 2010. Presenting
Author: Costantine Albany, Indiana University Melvin and Bren Simon
Cancer Center, Indianapolis, IN
Background: Based on the International Germ Cell Cancer Collaborative
Group (IGCCCG), IRGCT represents 26% of non-seminomas and 10% of
seminomas with 2 year PFS of 74% (63-85%). Most patients are treated
with 4 cycles of Bleomycin, Etoposide and Cisplatin (BEP). However, the
optimal therapy for this heterogeneous group is not well defined. Our
hypothesis was that many patients with IRGCT may not require BEPx4 as
they are clinically closer to good risk rather than to poor risk disease.
Methods: We conducted a retrospective analysis of all patients with
testicular cancer seen at Indiana University (IU) between 2000- 2010. We
identified 170 pts with IRGCT of whom 84 consecutive pts received their
therapy at IU. 2 chemotherapy categories were identified: BEP (or equivalent)
x4 or BEPx3 (�/-EPx1). Results: 45 pts received either BEPx4 (41),
VIPx4 (2) or BEPx2 followed by HDCTx2 (2). 39 pts received BEPx3 (9) or
BEPx3�EPx1 (30). Treatment decisions were based on clinical characteristics
and markers amplitude. There were 78 (93%) non-seminoma, 6 (7%)
seminoma. 27 (32%) stage II and 57 (68%) stage III. Mean AFP 3899
(range 1000-9550; n�50), mean hCG 16354 (range 5000-49000;
n�34). The overall 1 and 2 year Kaplan-Meier estimates were 93% and
87% for PFS and 98% and 92% for OS. Results are depicted below.
Conclusions: Our results for patients with IRGCT treated from 2000-2010
are superior to the IGCCCG pts treated from 1975-1990. Routine administration
of BEPx4 probably represents overtreatment in a substantial
percent of IRGCT.
BEPx3 (�/- EPx1) BEPx4 /other p value
Number 39 45
AFP mean (range) 3890 (1009- 8300) n�23 3907 (1000- 9550) n�28
hCG mean (rRange) 16074 (5000-49000) n�14 16549 (5000- 36800) n�20
Persistent GCT on post
5 2
chemo RPLND
Salvage high dose
4 6
chemotherapy (HDCT)
Death 2 2
PFS 1 yr, 2 yrs 95%, 89% 91%, 85% 0.60
OS 1 yr, 2 yrs 100%, 94% 96%, 90% 0.86
Genitourinary Cancer
285s
4533 Poster Discussion Session (Board #12), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
Phase II trial of bevacizumab (BEV)/high-dose chemotherapy (HDC) for
refractory germ-cell tumors (GCT). Presenting Author: Yago Nieto, University
of Texas M. D. Anderson Cancer Center, Houston, TX
Background: HDC is a curative therapy for relapsed GCT. However, multiple
prior relapses, cisplatin refractoriness (relapse/progression (PD) within 4
weeks) or absolute refractoriness (no prior response), or very high tumor
markers at relapse predict poor early event-free survival (EFS). The
validated Beyer model (JCO 1996;14:2638) identifies groups with poor
risk (5% EFS at 1-year post-HDC), intermediate risk (25% EFS) or good risk
(�50% EFS). Given high VEGF expression in metastatic GCT and synergy
between BEV and chemotherapy, we studied concurrent BEV/HDC in
refractory GCT. Methods: Eligibility includes � 1st relapse/PD, poor/interm
risk and no contraindications to HDC or BEV. Treatment consisted of 2
cycles of HDC with stem-cell support following BEV (5 mg/kg) 1 week
before each cycle. HDC-1 consists of a novel regimen of infusional
gemcitabine with docetaxel/melphalan/carboplatin (BBMT 2005;11:297).
HDC-2 includes ifosfamide/carboplatin/etoposide. Target accrual is 25 pts,
to distinguish a 1-yr expected EFS of 15% (median time to progression
[TTP], 9 months) from 50% 1-year EFS (median TTP, 2 years). Results: 21
pts have been treated, median age 22 (range, 19-45) poor risk (N�15) or
interm risk (N�6), cisplatin refractoriness (N�9) or absolute refr (N�12),
median 3 prior relapses (1-4), median 3 prior regimens (2-6), PD at HDC:
11 pts. Tumor sites: lungs (N�15), liver (8), bones (5), brain (5), retroperit
(15), mediast (12). Histol at Dx: embryonal ca (4), chorio (3), mixed with
teratoma (14). Prior surgery for metastases: 8 pts (6 abdomen, 1 liver, 1
brain). Prior radiation: 6 pts. Toxicity of HDC-1: grade 3 mucositis in all
pts, rash (8 G2, 2 G3) and transaminase elevation; 2 pts with marginal
baseline renal function died from early sepsis; 1 pt died from late fungal
pneumonia. After HDC-1, markers normalized in 14/17 evaluable pts. 15
pts received HDC-2 at a median 49 (38-66) days after 1st stem cell
infusion, which was well tolerated. 8 pts had residual lesions resected with
findings of either teratoma (N�2) or no viable tumor (N�6). With median
follow-up of 23 (3-43) months, 14 pts are alive in CR (67% EFS).
Conclusions: BEV with HDCx2 shows encouraging preliminary results in
heavily pretreated refractory GCT.
4535 Poster Discussion Session (Board #14), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
Large retroperitoneal lymph nodes (RPLN) as a novel risk factor for venous
thromboembolism (VTE) in germ cell tumor (GCT) patients (pts) receiving
first-line chemotherapy (chemo). Presenting Author: Ben Tran, Princess
Margaret Hospital, Toronto, ON, Canada
Background: VTE causes substantial morbidity and mortality in GCT pts.
The Khorana model is a validated predictive model that stratifies VTE risk in
cancer pts receiving chemo; Khorana score �3 (K3) identifies pts at high
risk. Many GCT pts have bulky RPLN that can cause venous stasis in the
lower limbs. This study examines the incidence of VTE in GCT pts and
assesses large RPLN as a novel predictor of VTE risk. Methods: Retrospective
data from the Princess Margaret Hospital GCT database was complemented
by review of medical records. GCT pts receiving 1st line chemo
between 2000-2010 were included. Pts diagnosed with VTE prior to chemo
and pts receiving thromboprophylaxis (TP) were excluded. Pts diagnosed
with VTE during or within 3 months of completing chemo were identified.
Large RPLN were defined as having maximal diameter �5cm. Odds ratios
for VTE risk with large RPLN and K3 were calculated. Discriminatory
accuracy (DA) of each predictor was calculated using area under the
receiver operating characteristic curves (AUROC). An external cohort from
London Regional Cancer Program, with similarly collected data, was used
to validate results. Results: In the test cohort 21 (10%) of 216 pts
developed VTE. Both large RPLN (OR 6.2, p�0.001) and K3 (OR 11.8,
p�0.001) were significantly associated with VTE. Positive predictive value
(PPV) was lower for large RPLN compared to K3 (21% v 44%, p�0.014)
but sensitivity was greater (71% v 40%, p�0.001), while DA showed no
difference (AUROC 0.73 v 0.67, p�0.46). In the validation cohort 10 (9%)
of 111 pts developed VTE. There was a non significant trend for associations
between VTE and both large RPLN (OR 2.54, p�0.16) and K3 (OR
4.5, p�0.13). When compared to K3, sensitivity was greater for large
RPLN (60% v 20%, p�0.003), but there was no difference in PPV (14% v
29%, p�0.25) or DA (AUROC 0.61 v 0.57, p�0.72). Conclusions: VTE
occurs in 1 in 10 GCT pts receiving curative chemotherapy. Large RPLN is
a novel and clinically applicable predictor of VTE risk, although prospective
validation would be beneficial. Randomized controlled trials of TP in GCT
pts should be considered in pts at high risk of VTE, identified by large RPLN
or K3.
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