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

646s Sarcoma
10064 General Poster Session (Board #50A), Sun, 8:00 AM-12:00 PM
Head and neck sarcomas: A comprehensive cancer center experience. Presenting
Author: Mohamedtaki Abdulaziz Tejani, University of Rochester Medical
Center, Rochester, NY
Background: Head/neck sarcomas are rare, accounting for 1% of head/neck
malignancies and 5% of sarcomas. There are about 1000 cases/year in the U.S.
comprising of many histologic subtypes making rigorous study of these tumors
difficult. Outcomes have historically been worse in this anatomic group due to
unique obstacles encountered during their treatment. Methods: We retrospectively
analyzed cases of head/neck soft tissue sarcomas treated at Fox Chase
Cancer Center (1999–2009). Study objectives were to describe clinicopathologic
characteristics, treatment and outcomes of adult head/neck sarcoma
patients and identify prognostic factors for disease control and survival. Cox
proportional hazards regression analysis was performed to identify predictors of
DFS and OS. The HR and 95% CI for Cox model and median DFS/OS from
Kaplan-Meier curves were calculated. Results: 31 patients were identified.
Median age was 50 (range 15–91). 23 patients were male. Most tumors were
high grade (25) and almost all were localized at presentation (29). Common
histologies were synovial cell (6), rhabdomyosarcoma (5), angiosarcoma (4),
lipsarcoma (4) and leiomyosarcoma (3). 25 patients with localized stage
underwent excision: 9 had surgical resection only, 10 had surgical resection with
neo/adjuvant radiation and 6 had surgical resection as well as neo/adjuvant
chemotherapy and radiation. 7 patients required re-excision to achieve negative
margins. Median DFS was 1.1 years (95% CI: 0.7–12.1) and median OS was 3.3
years (95% CI: 2.1-5.4). Of 16 patients with recurrent disease, 12 were local.
Patients with positive margins had worse DFS (p�0.04) and OS (p�0.03).
Tumors greater than 5cm were associated with worse DFS (p�0.07). Age and
grade did not correlate with outcome. Conclusions: Head/neck sarcomas are
difficult to completely excise due to anatomic constraints and local recurrence
rates are high. Achieving a negative margin is critical in improving outcome.
Median DFS and OS are worse than those achieved with other subsites.
Head/neck sarcomas are best managed in a multi-disciplinary setting.
Univariate association
DFS OS
HR 95% CI p HR 95% CI p
Neg vs. pos margins 4.03 1.05-15.39 0.04 4.47 1.14-17.58 0.03
Size 5cm 3.00 0.91-9.91 0.07 1.66 0.55-4.99 0.37
10066 General Poster Session (Board #50C), Sun, 8:00 AM-12:00 PM
Preclinical study of trabectedin (TR) and poly(ADP-ribose)polymerase 1
(PARP-1) inhibitor combination in soft tissue sarcoma (STS). Presenting
Author: Ymera Pignochino, Institute for Cancer Research and Treatment,
Candiolo, Italy
Background: TR is an alkylating agent approved in Europe for the treatment
of advanced STS as second/third line therapy. TR binds to the minor groove
of DNA and interferes with gene transcription and nucleotide excision
repair mechanism, inducing DNA double strand breaks (DSBs), and S/G2
cell cycle arrest. There is a strong clinical interest to increase TR activity
combining it with other anti-cancer drugs. PARP-1 inhibitors disable DNA
base-excision repair mechanism causing the accumulation of DSBs and
look like a reasonable TR partner to be explored. We focused our in vitro
studies on the effects of the combination of TR with the PARP-1 inhibitor
Olaparib (OL). Methods: We explored the activity of TR-OL combination
against a panel of different histotypes of STS cell lines, evaluating cell
viability after 72h treatment with escalating doses of TR (0-2 nM), OL
(0-20 �M), and their constant combination. Following colony formation,
cell cycle, apoptosis (annexin V�/PI�) and DNA damage (phospho-histone
H2AX - Ser139) were checked. Results: The TR-OL combination strongly
affects STS cell viability, showing synergism (Combination Index � 1,
based on Chou–Talalay method) on 8 out of 13 cell lines tested. We
observed a strong synergism, as a massive reduction of colony growth
(402.91, MES-SA, and DMR-SN-8.4.98 lines) induced by the combination
if compared with each single agent (78% vs. ~27% : p�0.05). OL
potentiates the S/G2 cell-cycle arrest caused by TR at 48h (Control� 29%,
TR� 33.4%, OL� 31.5%, TR-OL� 80.9%), and induces a strong increase
of the apoptotic cells at 72h (Control� 17.4%, TR� 28.3%, OL� 33.5%,
TR-OL� 56.8%). Furthermore, the TR-OL synergism on DNA damage is
confirmed by a significant increase of the DSBs marker (Control� 8.7%,
TR� 59.5%, OL� 23.8%, TR-OL� 76.5%). Conclusions: These results
validate the biological rationale to combine TR and PARP-1 inhibitors in
STS and suggest assessing this drug combination in the clinical setting.
10065 General Poster Session (Board #50B), Sun, 8:00 AM-12:00 PM
Response to radiation therapy in solitary fibrous tumor/hemangiopericytoma.
Presenting Author: Giacomo Baldi, Fondazione IRCCS Istituto
Nazione dei Tumori, Milan, Italy
Background: To reporton the activity of radiotherapy (RT) in a retrospective
series of solitary fibrous tumors (SFT)/hemagiopericytoma (HCP), a rare soft
tissue sarcoma subtype whose sensitivity to RT is poorly known. Methods:
We retrospectively reviewed all patients with a diagnosis of SFT/HCP whom
we saw from 2005 to 2011, focusing on cases treated with RT in
neoadjuvant, adjuvant, exclusive, palliative settings. Patients who received
concomitant chemotherapy were excluded. We confirmed diagnosis by
review in all cases. We evaluated the overall response rate (RR) by RECIST.
Results: Nineteen patients were identified (males � 9, females � 10;
median age � 61 years, range 39-85; site of primary� 6 meninges, 4
pleura, 3 pelvis, 3 retroperitoneum, 2 limbs, 1 abdominal wall; site of RT�
5 bone and soft tissue, 5 pelvis, 3 soft tissue, 2 meninges, 2 retroperitoneum,
1 abdominal wall, 1 pleura; reason for RT� 3 neoadjuvant, 2
adjuvant, 2 exclusive and 12 palliative setting). Median RT dose was 42 Gy
(range 12-60). Seventeen of 19 pts are evaluable for response (2 adjuvant).
The RR was: 29% (4 pts) partial response, 65% (12 pts) stable disease
(SD), 6% (1 pt) progressive disease (PD). All patients treated with
neoadjuvant RT had a RECIST SD as best response to pre-operative
treatment with evidence of pathologic response in 2 of 3 cases. Conclusions:
Contrary to what is widely thought,this retrospective analysis suggests that
SFT/HCP is sensitive to radiation therapy. Prospective studies are needed.
10067 General Poster Session (Board #50D), Sun, 8:00 AM-12:00 PM
Global differences in chemotherapeutic regimens of soft tissue sarcoma
(STS): Results of PALETTE, an EORTC 62072/GSK VEG110727 global
network phase III trial of pazopanib versus placebo. Presenting Author:
Sandrine Marreaud, EORTC Headquarters, Brussels, Belgium
Background: The global PALETTE EORTC/GSK network study on advanced
STS patients (pts) randomized 223 European (EU), 43 American (US), 81
Asian, and 22 Australasian (AUS) pts between pazopanib and placebo.
Prior to study entry pts should have received at least one anthracycline
containing regimen, and preferably, if pts’condition allowed, all available
standard chemotherapy treatments for STS in their countries. We investigated
the differences in chemotherapy pts received prior- and post-protocol
at a global level. Methods: Pts were grouped by continent. Pre- and
post-protocol chemotherapeutic treatments (txs) were analyzed. The number
of prior lines of systemic tx for advanced STS was divided between 0-1
vs 2 or more. Chemotherapy was studied in detail between Asian and other
countries. Fisher’s exact test was used for statistical analysis. Results: Data
from all 369 pts were analyzed. (Neo-) adjuvant systemic tx was given in
21% of EU, 23% of US, 36 % of Asian and 41% of AUS pts. In advanced
STS: 2 or more lines of prior systemic txs were administered in 60% of EU,
84% of US, 42% of Asian, 22% of AUS pts before study entry. Prior to
study entry 68% of EU, 65% of US, 84% of Asian and 68% of AUS pts
received ifosfamide(or analogs); after protocol 21 % of EU, 14% of US,
13% of Asian and 5% of AU pts. There were significant differences in
chemotherapy between Asian (n�81) and other (n�288) pts: prior to
protocol trabectedin was administered in 1 vs 21%; gemcitabine 19 vs 39
%; cisplatin: 36 vs 5%; etoposide 32 vs 4% (all p�0.001), and docetaxel:
17 vs 31 % (p�0.004) of pts. Post-protocol trabectedin was given to 4 vs
34% (p�0.001), gemcitabine both in 19%; cisplatin 10 vs 4% (p�0.01);
etoposide 12 vs 6%, and docetaxel 20 vs 12 % (both, p�0.02) of pts.
Conclusions: The PALETTE study showed considerable intercontinental
differences in chemotherapeutic txs for advanced STS pre- and post study
drug. These differences might be due to availability and reimbursement of
drugs, clinical studies and the practice patterns of sarcoma specialists
world-wide. This is of particular interest for the design of future randomised
global clinical trials in advanced STS.
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