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

10012 Poster Discussion Session (Board #4), Sat, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
18f-FDG-PET imaging as an early survival predictor in patients with
high-grade soft tissue sarcomas undergoing neoadjuvant therapy. Presenting
Author: Ken Herrmann, UCLA, Los Angeles, CA
Background: Neoadjuvant therapy is associated with considerable toxicity
and limited survival benefits in patients with soft tissue sarcoma (STS). We
prospectively evaluated whether 18F-FDG PET/CT (PET) imaging after the
initial cycle and after end of neoadjuvant therapy could predict overall
survival in these patients. Methods: 76 patients (primary STS: n�57;
metastatic disease: n�19) with high grade STS were included in this study.
PET was performed prior to (n�76), after one cycle (n�52) and after the
end of neoadjuvant therapy (n�74). Overall survival was correlated with
changes of SUVpeak, RECIST, histopathological response and other
parameters predictive of STS survival. Results: One-, two- and five- year
survival rates were 95�3.0%, 86�4.6% and 68�6.6% for primary STS.
Corresponding one- and two- year survival rates for recurrent/metastatic
STS were 77�10.0% and 47�12.1%. Optimal cut-off for early decreases
in SUV peak were significant predictors of survival in log-rank test
(p�0.027 and p�0.043). However, late decreases in SUV peak were only
predictive in primary STS (SUV peak decrease 57%; p�0.035) but not in
recurrent/metastatic STS (SUV peak decrease 52%; p�0.057). In primary
STS, 7/15 early PET non-responders but only 4/24 early PET responders
died during follow up (p�0.068). Conclusions: 18F-FDG-PET seems feasible
to predict survival after the initial cycle of neoadjuvant chemotherapy
in both patients with primary STS and recurrent/metastatic STS and can
potentially serve as an intermediate endpoint biomarker in clinical research
and patient care.
10014 Poster Discussion Session (Board #6), Sat, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Growth modulation index and RECIST-based STBSG-EORTC criteria for the
assessment of drug activity in advanced soft tissue sarcoma (ASTS)
patients (pts). Presenting Author: Sophie Cousin, Centre Oscar Lambret,
Lille, France
Background: Despite promising phase II trial results, most of new drugs
failed to improve the overall survival (OS) in ASTS pts. The choice of the
endpoint in early trials remains crucial. We have evaluated the Growth
Modulation Index (GMI) as potential endpoint. The GMI is defined as the
Time To Progression with the second (or n�1) line of chemotherapy (TTP2)
divided by the TTP with the first (or n) line (TTP1). Methods: We have
carried out a retrospective multicenter study in pts receiving second-line
chemotherapy after failure/intolerance to doxorubicin-based regimens.
Data collected included best response(s), TTP1 & TTP2 and OS. Treatments
have been classified as �active� treatment according to the EORTC-
STBSG criteria (3-month Progression-free rate �40% or 6-month
PFR�14%: including trabectedin, ifosfamide, gemcitabine�docetaxel for
all subtypes and weekly paclitaxel for angiosarcoma) versus non-active
drugs. Comparisons used chi-2 tests and Log-rank tests. We performed a
logistic regression analysis for identifying factors associated with longer
GMI. Results: The study population consisted in 106 men and 121 women,
the median age was 57 years. 110 pts (48.4%) have received �active
drugs�. The median TTP1, TTP2 and GMI were 197 days, 134 days and
0.75, respectively. The median OS was 446 days. 70 pts experienced
GMI�1.33 (30.6%). There was a strong relation between best objective
response and GMI (p�0.0001). The treatment with �active drug� was not
associated with an improvement of the OS: 490 days 407 versus days
(p�0.524). The median OS of pts with GMI�1, GMI�[1.00-1.33] and
GMI�1.33 were 324, 302 and 710 days, respectively (p�0.0001). None
of the following factors were associated with GMI�1.33 in logistic
regression analysis: age, gender, histological subtypes, grade, metastasis
locations, interval between diagnosis & metastasis, association with ifosfamide
or dacarbazine in 1st-line regimen or treatment with �active drug� in
second-line. Conclusions: GMI seems to be an interesting endpoint providing
additional information compared to classical criteria. GMI�1.33 is
associated with significant improvement of the OS.
Sarcoma
633s
10013 Poster Discussion Session (Board #5), Sat, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Growth modulation index (GMI) as a metric of clinical benefit assessment
among advanced soft tissue sarcoma (ASTS) patients receiving trabectedin
as salvage therapy. Presenting Author: Nicolas Penel, Centre Oscar
Lambret, Lille, France
Background: Von Hoff has proposed GMI �1.33 in cancer clinical trials as a
sign of drug activity. GMI is the ratio between time to progression (TTP)
with the nth line (TTPn) of therapy divided by the TTPn-1 with the n-1th line
of therapy. With this endpoint, each patient is his/her own control. Methods:
We have carried out a retrospective analysis of 279 pretreated ASTS
patients treated in four consecutive phase II trials with trabectedin 1.5
mg/m², given as a 24-hour infusion every 3 weeks. Results: The study
population consisted of 170 women and 109 men with a median age of 52.
The two most common histologies were leiomyosarcoma (145 patients,
52%) and liposarcoma (59, 21%). 142 (51%) patients received one prior
line and 137 (49%) �2 lines. The median TTPn was 2.8 months (range:
0.2-26.8), whereas the median TTPn-1 was 4.0 months (range: 0.3-79.5).
The Spearman correlation coefficient between TTPn-1 and TTPn was 0.07
(p�0.23). The median GMI was 0.6 (range: 0.0-14.4). 177 patients
(63%) had a GMI �1, 21 (8%) a GMI � 1-1.33 and 81 (29%) a GMI
�1.33. The median overall survival (OS) strongly correlated with GMI
groups: OS was 9.1, 13.9 and 23.8 months, respectively (p�0.0005,
log-rank test). There were also a strong correlations between response rate
and GMI (p�0.0001, Fisher exact test), and between GMI and progressionfree
survival (�0.0001, log-rank test). The logistic regression analysis
retained only performance status (PS) [OR�1.76 if PS�0; p�0.04]
associated with GMI�1.33. Sarcoma grade (p�0.21), histological subtype
(p�0.16), and number of prior chemotherapy lines (p�0.95) were not
associated with GMI�1.33. Conclusions: Overall,�30% of patients experienced
GMI�1.33 regardless of histological subtype or grade, and number
of prior lines of chemotherapy. Patients with PS�0 benefit more from
trabectedin. GMI�1.33 is associated with longer OS (median �24
months). GMI is better defined than previously described parameter such
as �Tumor Growth Rate� (Lopez-Martin, Abstract 3293, ASCO 2003). GMI
as an indicator of drug activity merits further exploration in this setting.
10015 Poster Discussion Session (Board #7), Sat, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
A prognostic nomogram for prediction of recurrence following surgical resection
of desmoid tumors. Presenting Author: Aimee Marie Crago, Department of
Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Desmoid tumors can respond to novel chemotherapeutics (e.g.,
sorafenib). We sought to construct a postoperative nomogram identifying
desmoid patients who are at high-risk for local recurrence and potential
candidates for systemic therapy. Methods: Desmoid patients undergoing resection
from 1982-2011 were identified from a single-institution prospective
database. Cox regression analysis was used to create a desmoid-specific
recurrence nomogram integrating clinical risk factors. Results: Desmoids were
treated surgically in 495 patients (median follow-up 60 months). Of 439
patients undergoing complete gross resection, 100 recurred (92 within 5 years
of operation). Five-year recurrence-free survival (RFS) was 71%. Only 8 patients
died of disease, all after R2 resection (6 with intraabdominal desmoids).
Radiation was associated with worse RFS (p�0.001). Multivariate analysis
suggested associations between recurrence and extremity location, young age,
and large tumors, but not margin (Table). Abdominal wall tumors had the best
outcome (5-year RFS 92% vs. 34% in patients �25y.o. with large, extremity
tumors). Age, site and size were used to construct an internally-validated
nomogram (concordance index 0.703). Integration of margin, gender, depth,
and presentation status (primary vs. recurrent disease) did not improve concordance
significantly (0.707). Conclusions: A postoperative nomogram including
only size, site and age predicts local recurrence and aids in counseling patients.
Systemic therapies may be tested in young patients with large, extremity
desmoids, but surgery alone is curative for most abdominal wall lesions.
Multivariate analysis
factor Hazard ratio (95% C.I.) P value
Margin status (R1 vs. R0) 0.99 (0.65, 1.52) 0.97
Presentation (recurrent vs. primary) 1.16 (0.70, 1.90) 0.57
Depth (deep vs. superficial) 1.37 (0.54, 3.45) 0.51
Gender (female vs. male) 1.32 (0.82, 2.10) 0.25
Site (vs. abdominal wall)
Extremity 5.02 (2.14, 8.42) �0.001
Chest wall 3.12 (1.20, 8.42) 0.020
Intraabdominal 2.73 (0.98, 7.59) 0.054
Other 1.54 (0.31, 7.63) 0.60
Size (>10 cm vs. 65y.o.)