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

634s Sarcoma
10016 Poster Discussion Session (Board #8), Sat, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Is CTNNB1 mutational analysis predictive for progression in patients with
sporadic desmoid tumors primarily observed? Presenting Author: Chiara
Colombo, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
Background: Recently, a wait and see (W&S) approach has been proposed
for patients affected by desmoid tumor (DT). Specific CTNNB1 mutation
has been correlated with higher risk of recurrence after surgical resection.
Aim of this study was to evaluate the correlation between CTNNB1
mutation type and time to progression in patients primarily observed (TTP).
Methods: We included all consecutive patients:(1) primarily observed at the
Fondazione IRCSS Istituto Nazionale Tumori (Milano, Italy) or Institut
Gustave Roussy (Paris, France) for primary sporadic DTs (2) with available
FFPE preserved tissue for CTNNB1 mutational analysis, (3) with measurable
disease and adequate follow-up. TTP from date of diagnosis to date of
radiological (PRO-R) or symptomatic (PRO-S) progression were conducted
by Kaplan-Meier method and log-rank test to compare strata. Results: A
total of 79 patients (August 2002- July 2011) were included (81% female,
19% male); median age was 34 (IQ, 10-77); sites distribution: abdominal/
chest wall (75%), extremity (21%), intra-abdominal (4%). CTNNB1
mutations were observed in 76% of DT samples: 41A (48%), 45F (25%),
45P (2%); 24% were WT. Median follow-up was 19 mo (IQ, 11-28).
Thirty-six patients experienced progression (86% PRO-R, 14% PRO-S):
41A (47%), 45F (55%), 45P (100%), WT (26%). An inferior TTP at 36
months was observed in mutated patients vs WT, while no difference was
detected for specific subtype mutated patients (WT 68%, 45F 24%,
41/45P 35%, p� 0.045). A variety of different treatments including
surgery, hormonal therapy, chemotherapy, antiCOX2 or persistent W&S
approach were proposed at progression. Forty-two patients did not receive
any treatment. Conclusions: A clear trend towards a lower risk of progression
was observed in WT patients, but no difference between specific mutated
patients (45F vs 41/45P) was observed. Prospective studies to eventually
clarify the potential role of CTNNB1 as prognostic tool in tailoring desmoids
treatment are presently underway.
10018 Poster Discussion Session (Board #10), Sat, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Localized angiosarcomas (AS): Identification of prognostic factors (PF) and
analysis of treatment impact—Series from the French Sarcoma Group
(GSF/GETO). Presenting Author: Clothilde Lindet, Centre Oscar Lambret,
Lille, France
Background: AS represents less than 2% of all adult soft tissue sarcoma. PF
and role of respective (neo)-adjuvant treatments in management of localized
AS remain badly established. Methods: We have conducted a retrospective
multicentre study (June 1980-October 2009) of 107 patients with
localized AS. All cases have been centrally reviewed by pathologist expert.
Univariate and multivariate analysis were conducted to identify independent
PF. Overall survival (OS) and Local Recurrence Free Survival (LRFS)
were estimated using the Kaplan-Meier method. Impact of treatments had
been explored with Cox Model after adjustment to the PF. Results: The sex
ratio was 18/89 (0.2). Median age was 71 years. 22% (24/107) and 62%
(67/107) of patients developed AS in preexisting lymphoedema and in
irradiated field, respectively. 71 cases (66%) were superficial. The most
frequent primary locations were: limbs (35, 33%), chest wall (32, 29%)
and breast (22, 20%). Grade was 1 in 21/103 (20%), 2 in 35/103 (34%)
and 3 in 47/103 cases (46%). Treatments consisted in surgery, adjuvant
radiotherapy and (neo)-adjuvant chemotherapy in, respectively, 95, 27 and
27 cases. R0 margin was obtained in 49 cases. The median OS and LRFS
were, respectively, 38.8 months and 27 months. In multivariate analysis,
the following PF influenced the OS: lymphedema (HR�2.02 [1.15-3.55])
and size�5cm(HR�1.48 [1.01-2.45]). After adjustment to these PF, R0
margins was the sole treatment parameter improving the OS (HR�0.19
[0.05-0.73]). In multivariate analysis, the following PF influence the
LRFS: Age�70 (HR�1.68 [1.02-2.76]) and pre-existing lymphedema
(HR�2.07 [1.15-3.75]). After adjustment to these prognostic factors, R0
margins (HR�0.48 [0.38-0.69]) and adjuvant radiotherapy (HR�0.29
[0.10-0.83]) improved the LRFS. Conclusions: Pre-existing lymphedema,
tumour size and age�70 are the major PF in patients with localized AS.
The achievement of R0 margins is of major importance for improving the
outcome whatever the endpoint (OS, LRFS) Adjuvant radiotherapy decreased
the local recurrence. (Neo)-adjuvant chemotherapy does not
influence survivals.
10017 Poster Discussion Session (Board #9), Sat, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Desmoid fibromatosis and pregnancy: A multi-institutional analysis of recurrence
and obstetric risk. Presenting Author: Marco Fiore, Fondazione IRCCS
Istituto Nazionale dei Tumori, Milan, Italy
Background: Desmoid fibromatosis (DF) may be diagnosed during or after
pregnancy (P). However, the risk of progression during P, or in women of
child-bearing age with DF prior to P, is unknown. Furthermore, obstetric risks
have not been well described. Methods: Institutional databases were reviewed at
3 sarcoma referral centers in Europe and US for women with sporadic DF from
1985 to 2011. Pregnancy and treatment data, outcomes, and obstetric
complications were recorded. Results: Overall 75 women were identified. DF was
diagnosed during P in 17 women (Group A) or within 6 mo after P in 10 (Group
B), was in situ at the time of P in 29 women (Group C), or had been resected prior
to P in 19 (Group D). Anatomic site, outcomes, and treatment for each group are
in the Table. Among patients operated at diagnosis, 2/11 (18%) recurred (Group
A�B). Among the entire cohort, 15 women (20%) recurred after definitive
treatment and only 6 (8%) needed multiple treatments after P. Ten spontaneous
regressions occurred after P (13%). Twelve women had further P following the
DF-related one, and 3 (25%) needed treatment after the subsequent P. At a
median follow up of 35 mo from P, 17 women did not receive any treatment
(23%), and 39 remain disease-free (52%). Caesarean section was needed in 14
cases (19%), but only in 1 expressly due to DF. DF-related P was associated with
abortion in 6 cases (4 spontaneous, 2 voluntary); in no case was it caused by the
presence of DF. Conclusions: DF developing prior to or during P may progress
during the course of P or thereafter. Spontaneous regression after P was also
observed. When resected, P-related DF rarely recurs. Wait & see is an option as
well. DF history is not an indication for therapeutic abortion nor a contraindication
against subsequent P.
A B C D
Total number 17 10 29 19
Abdominal wall 11 (64%) 6 (60%) 14 (48%) 14 (73%)
Limbs 1 (6%) 2 (20%) 11 (38%) 2 (11%)
Visceral 4 (24%) 2 (20%) 1 (4%) 2 (11%)
Other 1 (6%) 0 3 (10%) 1 (5%)
Primary / recurrent 17/0 10/0 19/10 17/2
DF progression during or after P 12 (70%) - 16 (55%) 4 (21%)
Treatment after progression 9 (53%) - 8 (28%) 3 (16%)
Surgery (*1 ILP) 5 - 6* 2
Medical therapy 4 - 2 1
DF progression after definitive treatment 3 (18%) 1 (10%) 8 (28%) 3 (16%)
Spontaneous regression 1 (5%) 1 (10%) 7 (24%) 1 (5%)
10019 Poster Discussion Session (Board #11), Sat, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Activity of sorafenib in radiation-associated breast angiosarcomas harboring
MYC and FLT4 amplifications. Presenting Author: Sandra P. D’Angelo,
Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Angiosarcomas (ASs) are rare, aggressive vascular malignancies
of endothelial cell differentiation which arise de novo or secondary to
radiation therapy (RAS.) A subset of patients(pts) with AS harbor mutations
in KDR (VEGFR-2) or overexpression of MYC and/or FLT4(VEGFR-3). MYC
& FLT4 gene amplifications occur almost exclusively in RAS. These
alterations provide a rationale for investigating agents that target angiogenesis
in RAS. In a phase II trial of sorafenib, AS pts had a partial response
(PR) of 14%; targeting the appropriate pt population may be essential. We
hypothesize that co-amplification of MYC & FLT4 may be predictive of
response to sorafenib. Methods: Using our institutional sarcoma database &
data query system, we identified AS patients treated with sorafenib at
Memorial Sloan-Kettering Cancer Center between 1992-2011. Molecular
analysis performed on available tissue. With IRB approval, clinical information
was collected. Results: We identified 10 women with RAS that received
sorafenib. Average age 68 (range 51-84.) 7 pts had distant metastatic
disease. Median lines of systemic therapy prior to sorafenib: 2 (range 1-4.)
Sorafenib was first line in 60% of pts, administered at 400mg daily and
adjusted for toxicity. Best responses included: complete response (CR)
2/9(22%), PR 1/9(11%), stable disease (SD) 5/9(56%) range 5-23m,
progressive disease 1/9(11%) for a clinical benefit rate of (CR�PR�SD)
89%. Responses were seen in patients with lung metastases (n�2) and
locally advanced disease (n�1) and were durable for 17, 42 and 26
months. Median duration on therapy was 15 months (range 0-42 months.)
7 pts underwent molecular analysis: co-amplification of MYC & FLT4 3 pts
(30%); MYC amplification 4 pts (40%); KDR mutation 0 patients. Of the 3
responders, MYC & FLT4 co-amplification were observed in 2 patients and
not evaluated in one. Conclusions: Sorafenib is active against RAS of the
breast. In this small series, complete and partial responses were seen in
patients with co-amplification of MYC & FLT4. This observation requires
further study. Performing molecular studies on all AS pts will help define
the pathophysiology of this deadly disease to guide rationale clinical trials.
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