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

642s Sarcoma
10048 General Poster Session (Board #48A), Sun, 8:00 AM-12:00 PM
Differential gene expression in liposarcoma: Insight into pathways for
dedifferentiation? Presenting Author: Dale Han, H. Lee Moffitt Cancer
Canter & Research Institute, Tampa, FL
Background: Liposarcoma (LPS) dedifferentiation signifies conversion to a
clinically aggressive phenotype, but the biologic processes required for this
change have not been determined. We describe differential gene expression
patterns between well-differentiated (WD) and dedifferentiated (DD)
tumors to determine pathways involved in LPS dedifferentiation. Methods:
From 1999 to 2006, 121 fatty tumors were resected at a single institution.
Twenty tumors, consisting of atypical lipomatous tumors (ALT), WD LPS or
DD LPS, were randomly selected and clinicopathologic characteristics were
retrospectively reviewed. Gene expression profiling was performed on
extracted RNA using the Affymetrix GeneChip platform. Differentially
expressed genes were obtained and gene network analysis was done using
GeneGO by MetaCore. Results: Median age was 59 years and 70% of cases
were male. WD tumors, consisting of 3 ALT and 6 WD LPS, were compared
with 11 DD LPS. After a median follow-up of 64 months, 7 patients had
died of whom 6 had DD LPS. DD histology was associated with lower overall
survival (p�0.05). Significance Analysis of Microarrays for WD tumors vs.
DD LPS using a 0% false discovery rate showed differential expression of
188 genes. Network analysis of genes from WD tumors vs. DD LPS showed
significant (p�0.001) differential regulation of glucose-activated transcription
factor ChREBP (carbohydrate response element binding protein), a key
element involved in lipogenesis, gluconeogenesis and glycolysis. There was
also significant differential regulation of insulin signaling, PI3K-dependent
and PKA signal transduction pathways and of amino acid, fatty acid and
glucose metabolism pathways (p�0.05). These pathways, based on Gene
Ontology cellular processes, mapped to gene networks primarily involved in
lipid metabolism (p�0.05). Conclusions: Differential expression of genes
involved in lipid metabolism networks is seen in DD LPS and changes in
lipid metabolism may be associated with dedifferentiation. These differential
gene expression patterns may help identify fatty tumors potentially at
risk for progressing to a malignant or DD state and provide prognostic
factors and therapeutic targets for patients with LPS.
10050 General Poster Session (Board #48C), Sun, 8:00 AM-12:00 PM
Does combined dose intensification radiotherapy improve disease control
in resectable retroperitoneal sarcoma? Long-term results of a phase I/II
trial. Presenting Author: Myles J. F. Smith, Department of Surgical
Oncology , Toronto, ON, Canada
Background: Late failure is a challenging problem in retroperitoneal
sarcoma (RPS) and reported 10 yr overall survival (OS) rates range from
20-30%. Use of preoperative external beam radiotherapy (XRT) in the
management of RPS remains controversial. No RCT and very few prospective
trials of any type have been completed. We investigated the effects of
preop XRT plus dose escalation with early postop brachytherapy (BT) on
long term survival and recurrence in RPS. Methods: From 06/96 to 10/00,
40 patients (25 female) with resectable RPS were entered onto a phase I/II
trial of preop XRT (50 Gy) plus postop BT (20-25 Gy). As previously
reported, BT to the upper abdomen was associated with significant grade
III-V postop toxicity, and from 12/98 on, BT was applied only to cases
where the “field at risk” excluded the upper abdomen. Kaplan Meier
survival curves were constructed; OS and recurrence free survival (RFS)
were compared by log rank (SPSS 19.0). Results: Median age at study entry
was 58 (38-70) yrs. Twenty nine patients presented to our center with
primary disease (73%), and 22 (55%) had high grade tumors. All patients
had preop XRT and total gross resection, while half (n�19) received BT. As
of 12/2011, median follow-up time is 108 mos. For the entire study cohort,
OS at 5 and 10 yrs were 70% and 65%, respectively; RFS at 5 and 10 yrs
were 65% and 58%, respectively. RFS at 5 yrs was reduced in high vs. low
grade RPS (50% vs. 83%, p�0.028), but by 10 yrs. was similar in high and
low grade tumors (50% vs. 67%, p�ns). RFS was reduced in patients who
presented with recurrent vs. primary disease (27% vs. 69% at 10 yrs.,
p�0.018), as was OS (36% vs. 76% at 10 yrs., p�0.034). Neither OS nor
RFS was improved in the cohort of patients who received BT compared to
the cohort who did not: at 10 yrs. RFS was 53% �BT and 62% -BT, while
OS was 53% and 76%, respectively, p�ns. Conclusions: In this prospective
study with mature follow-up, long term OS and RFS in patients who
underwent combined preop XRT plus resection of RPS compare favorably
with those reported in retrospective institutional and population-based
series. Postoperative BT did not contribute to disease control.
10049 General Poster Session (Board #48B), Sun, 8:00 AM-12:00 PM
Interest of tumor to liver ratio 18F-FDG uptake in positron emission
tomography for detection of neurofibrosarcoma in neurofibromatosis 1
patients. Presenting Author: Patrick Combemale, Centre Leon Berard,
Lyon, France
Background: Malignant peripheral nerve sheath tumors (MPNSTs) are
difficult to detect in neurofibromatosis 1 (NF1) individuals. The 18F FDG
positron emission tomoscintigraphy (FDG PET) is a useful tool. The
Standard Uptake Value (SUV) is the gold standard but it is subject to
individual variation among patients and medical centers. So we assessed
the interest of FDG PET based on a specific tumor to liver uptake ratio (T/L)
instead of SUV to find a reproducible and constant cut-off for detecting
malignant tumors. Methods: From 2000 to 2010, we conduct a multi
centric study: all patients with NF1 and presenting clinical signs of MPNST
suspicion (increased tumor size, induration or pain) underwent a FDG PET.
Preliminary study estimated a T/L ratio of 1.5 as cut-off for malignity.
Based on semi-quantitative analysis of FDG PET images, patients were
compared with this cut-off value. Results: 98 patients with 125 tumors
were included. FDG PET evaluation identified 42/125 suspected lesions
with T/L � 1.5; among these 30 MPNST and 12 benign lesions were found.
83/125 tumors were classified as non-suspicious and 82 were actually
benign according to histology or long term follow up. The 1.5 T/L cut off
corresponds to 99 % Negative Predictive Value (NPV) and 71% Positive
(PPV). The positive likelihood ratio (LR) was thus equal to 7, 69 and the
Negative LR to 0, with 97% sensitivity and 87% specificity. When T/L ratio
is � 1.5, MPNST is eliminated with 99% NPV, thus avoiding useless
surgery. When T/L ratio is above 1.5, there is a strong suspicion of
malignancy. But there is a risk of false positivity, which requires discussion
before any therapeutic decision. On the over hand we found no significant
correlation between SUVmax and malignancy. Conclusions: This study
confirms the FDG PET in the detection of NF1-associated MPNST. The
tumor/liver ratio with a cut off 1.5 has a very sensitive and specific value to
sort out malignant from benign tumors and thus provides adequate surgery.
More this semi-quantitative analysis method is just as easy as SUV, more
sensitive and more reproducible.
10051 General Poster Session (Board #48D), Sun, 8:00 AM-12:00 PM
Geriatric high-grade soft tissue sarcoma (G-HG STS): An analysis of 116
patients (pts) evaluating prognostic factors and clinical outcomes stratified
by histology. Presenting Author: Richard Hong Hui Quek, National Cancer
Centre, Singapore
Background: STS in geriatric pts is not well studied. We evaluated
prognostic factors and clinical outcomes in elderly pts with HG STS.
Methods: Single centre retrospective study. G-HG STS pts defined as age
� 65 yrs seen in our centre from 2002 - 2011 with complete medical
records were identified. Charlson age-comorbidity score was assessed for
each pt. Results: 116 pts from 4 most common HG STS histo-types
representing 69% of pts in the geriatric STS cohort were analysed;
leiomyosarcoma (LMS, 14%), non well-differentiated liposarcoma (nWD-
LPS, 9%), angiosarcoma (AS, 30%), and undifferentiated pleomorphic
sarcoma (UPS, 47%). Median age was 72 yrs, 81% presented with
localised disease; of 78% of these localised pts who had curative surgery,
49% received adjuvant therapy, of whom 92% had radiotherapy (RT) only.
AS arises more commonly from the head/neck region (p�0.001) and fewer
receive curative surgery (p�0.006). In 43 pts who had metastases either at
diagnosis or relapse, 33% received first-line palliative chemotherapy with a
response rate of 27% in evaluable pts. At a median follow-up of 15.8 mths,
overall survival (OS) for the entire cohort was 25.1 mths, 30.5 vs 3.9 mths
in pts presenting with localised vs metastatic disease respectively
(p�0.0001). In pts who had curative surgery for localised disease, overall
relapse-free survival (RFS) was 17.7mths; 26.8 mths vs 16.0 mths vs 7.3
mths vs 12.5 mths in LMS, nWD-LPS, AS and UPS respectively. In
univariate analysis, adjuvant RT, non-head/neck primary and sarcoma
subtype were associated with improved RFS. In multivariate analysis,
adjuvant RT (p�0.001), sarcoma subtypes AS (p�0.011) and UPS
(0.012) vs LMS remained significant. In pts with metastatic HG STS either
at diagnosis or relapse, overall median OS was 5.9 mths; 5.9 mths (LMS),
30.5 mths (nWD-LPS), 6.4 mths (AS) and 4.3 mths (UPS). In univariate
analysis, presence of bone metastases was significantly associated with
inferior OS (p�0.0029). Charlson score did not correlate with RFS or OS.
Conclusions: Prognosis of G-HG STS appears poor particularly in AS and
UPS. Adjuvant RT improves outcomes in this group of pts and should not be
omitted based on age alone.
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