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

10052 General Poster Session (Board #48E), Sun, 8:00 AM-12:00 PM
Phase II study of neoadjuvant high-dose ifosfamide with concurrent
radiotherapy followed by surgical resection in high-risk soft tissue sarcoma:
A Spanish Group for Research on Sarcomas (GEIS) study. Presenting
Author: Xavier Garcia del Muro, Instituto Catalan Oncologia, Barcelona,
Spain
Background: High-dose ifosfamide (HDI) has shown promising activity as
single agent in first-line chemotherapy for advanced soft tissue sarcoma
(STS). The purpose of this study was to assess the activity and toxicity of a
preoperative doxorubicin-free regimen of HDI given concurrently with
radiotherapy (RT) and followed by surgery in patients (pts) with localized
high-risk STS. Methods: Pts with localized � 5 cm grade 2-3 and deep STS
of the extremities and trunk wall, �65 years, no prior chemotherapy and
ECOG PS 0-1 were enrolled in this multicenter phase II study. Pts received
3 cycles of preoperative HDI at a dose of 12 gr/m2 by continuous infusion
over 5 days every 3 weeks, with mesna and prophylactic GCSF support, and
concomitant external beam RT to a total dose of 50 Gy, followed by surgical
resection. Postoperatively, pts with pathological response received 2 cycles
of HDI and those with positive surgical margins 16 Gy of RT. The primary
study endpoint was pathologic response (� 95% pathologic necrosis). A
Simon 2-stage design (response rate P0�15%, P1�35%, ��0.10,
��0.10) required at least 2 responses in the first 17 pts to expand to a
second cohort, and 7/32 responses to be considered of positive. Results:
From March 08 to December 10, 34 pts were included. Two pts were
ineligible. Median age was 54 (18-65). Tumor location was extremity (28
pts) and trunk wall (4). Preoperative planned treatment was completed in
87.5% pts. HDI was completed in 87.5% pts while RT in 94% pts. Grade
3-4 toxicities included neutropenic fever (3 pts), anemia (4), asthenia (2),
infection (2) and radiation dermatitis (2). 31 pts underwent surgery: 27
were R0 resections, of which 2 were amputations, and 4 were R1
resections. Pathologic response was � 95% necrosis in 9 pts (28%) and
50%-94% necrosis in 12 pts. After a median follow-up of 21 months,
estimated 2-year rates for disease-free survival and overall survival were
58% (95%CI, 40%-77%) and 77% (95%CI, 61%-93%), respectively.
Conclusions: Preoperative treatment with HDI given concurrently with RT in
pts with high-risk STS is feasible and safe, yielding promising pathologic
response rates.
10054 General Poster Session (Board #48G), Sun, 8:00 AM-12:00 PM
Early response to neoadjuvant chemotherapy (NAC) in combination with
regional hyperthermia (RHT) to predict long-term survival for adult-type
high-risk soft tissue sarcoma (HR-STS): Results of the EORTC-ESHO
intergroup phase III study. Presenting Author: Rolf D. Issels, Universitaet
München, Grosshadern, Munich, Germany
Background: A randomized phase III completed trial showed that RHT
added to NAC was beneficial in terms of local progression-free (LPFS), and
disease-free (DFS) survival. Overall survival (OS) was improved in patients
(pts) who completed the preoperative induction therapy with RHT (Lancet
Oncol 2010). Here we analyzed both the radiographic (RR) and histopathologic
(HR) response as early predictors for survival. Methods: 341 pts were
randomized to receive 4 cycles of NAC � RHT (169 pts) or NAC alone (172
pts) as induction therapy. RR (CR/PR vs NC/PD) and HR (�75% vs �75%
necrosis) were used to define responder vs non-responder. Predictive
impact of response on LPFS, DFS, DDFS (distant disease-free survival) and
OS was evaluated by intention-to-treat using Kaplan-Meier estimates and
the log-rank test. Stratified (surgery before study entry yes/no; extremity vs
non-extremity tumors) multivariate analyses were carried out by Cox
regression. Results: Early response in pts with measurable disease was
performed in 238 pts (103 pts not evaluable because of surgery before
study entry). In the NAC�RHT group (114 pts) response rate was 49.1%
(56 responders: RR: 18; HR: 22; RR � HR: 16) and substantially higher
(p�0.001) compared to the NAC alone group (124 pts) which was 26,6%
(33 responders: RR: 7; HR: 17; RR � HR: 9). In the NAC � RHT group,
tumor response was associated with improved DFS (HR 0.58 CI 0.36-0.95;
p�0.031) and OS (HR 0.50 CI 0.27-0.90; p�0.020) but not LPFS (HR
0.91 CI 0.49-1.71; p�0.78). For responders, OS median time was � 120
months vs 33 months for non-responders. For the entire NAC � RHT group
(169 pts, including pts with surgery before study entry) response remained
predictive for better OS (HR 0.54 CI 0.32-0.94; p�0.028) and was also
associated with better DDFS (HR 0.47 CI 0.27-0.83; p�0.009).
Conclusions: Adding RHT to NAC as induction therapy compared to NAC
alone leads to significantly higher early response in almost half of the pts
classified as responders which translates in better OS and prevention of
distant metastases.
Sarcoma
643s
10053 General Poster Session (Board #48F), Sun, 8:00 AM-12:00 PM
The Italian Rare Cancer Network. Presenting Author: Roberta Sanfilippo,
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Background: Rare cancers (RC) are a challenge in terms of quality of care,
access to health resources and clinical research. The Italian Rare Cancer
Network (RTR: “Rete Tumori Rari”) is a clinical collaborative effort to
improve quality of care in adult rare solid cancers in Italy. RTR enables
institutions to share clinical cases and to rationalize access to distant
reference centers minimizing patient migration. It indirectly promotes
collaborative clinical research by encouraging accrual into clinical trials
and supporting observational studies. Methods: RTR includes 150 oncology
institutions across Italy. Clinical cases are shared asynchronously over a
secure Web resource. Data, images and transactions are stored in an online
clinical record. Patients are shared: 1. �logically”, when they are dealt with
following common clinical practice guidelines; 2. �virtually”, when they are
discussed over the network between two or more centers; 3: �physically�,
when they are referred to an excellence center for a specific treatment
modality. Pathology review is arranged through transferal of paraffinembedded
specimens and upload of consultations. While it was chosen not
to implement telepathology facilities, a teleradiology resource is now
available. Results: From 2003 to 2011, more than 5,000 rare cancers
cases (mostly sarcomas) have been uploaded. More than 1,300 teleconsultations
have been delivered, while more than 1,000 patients moved across
the network during their experience of disease. 700 cases were reviewed
pathologically: amongst 365 cases originally diagnosed as soft tissues
sarcomas up to 2010, treatment-relevant discordances were recorded in
more than one third. An observational prospective study on gastrointestinal
stromal tumors was done, enrolling 800 patients. An original paper
documenting the activity of a drug in a highly specific sarcoma subgroup
was published. Conclusions: Clinical asynchronous online collaboration on
RC is feasible through a Web-based secure environment and proved the
most practical way of clinical distant sharing. Pathologic review was a
crucial network service, with a special added value in RC. Retrospective
and prospective observational studies, and unplanned observations in very
rare cases, were an interesting by-product.
10055 General Poster Session (Board #48H), Sun, 8:00 AM-12:00 PM
Delay in diagnosis and treatment of soft tissue sarcomas (STS): Causes of
late intervention and their role in prognosis—A prospective, multidisciplinary
group study. Presenting Author: Alessandro Comandone, Piedmontese
Group for Sarcomas/Italian Sarcoma Group, Torino, Italy
Background: STS are 1% of malignant tumors in adults. Rarity, heterogeneity
in presentation, low expertise in primary care physicians (PCP) or in
general hospitals, organisation problems in specialized centers may cause
a delay in both diagnosis and treatment. Aim of this study is to acknowledge
the barriers to optimal care and the consequences of the delay on
prognosis. Methods: Patients with STS of the extremities, trunk, retroperitoneum
treated and followed from 1999 to 2011 by the same multidisciplinary
group were included. Time and pattern of symptoms onset,
anatomic site, tumor volume, patients’ age, gender and home, interval
between diagnosis and surgical treatment or neoadjuvant chemotherapy;
time to start adjuvant RT or CT were considered in a univariate -
multivariate analysis. Results: 449 adult patient (53% F, 47% M, median
age 55 years) were followed for a median time of 116.38 months. 65.7% of
STS were at the extremities, 17.6% retroperitoneal, 16.7% at the trunk
wall. Median volume at diagnosis was 8 cm for trunk and extremities; 15
cm for retroperitoneum. Commonest histologies: liposarcoma. 18.2%;
leiomyo 16.8%; mixofibro 13.6%. Increasing mass, pain, and abdominal
disconfort were the main revealing signs of diseases. Median time of delay
were: from onset of symptom to first medical visit 68 days for trunk and
extremities, 82 for retroperitoneum; 104 days from symptoms to histological
diagnosis; 129 days from symptoms to start of therapy. Time to surgery
after definitive diagnosis was 12 days in extremities and 21 in abdomen.
Adjuvant CT started 22 days after surgery for extremities, 25 in trunk, 35 in
retroperitoneum. RT initiated after 78 days. Longer delay in treatment lead
to worse prognosis: MS 89.95 months if delay was � 3 months; 190.40
months if wait was � 3 months (p 0.007). Conclusions: Low self
consciousness of the patient; misdiagnosis or inadequate approach in
general hospitals; late referral to specialized centres are 75% of the cause
of wasted time. Organization problems at the referral Centre concur for
25% of delay. Guidelines implementation and educational programme
among general population and PCP are necessary.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.