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Annals of Oncology
Results: The 3 treatment groups were homogeneous for clinical pathological features.
The tumor response (necrosis in resected specimen) was comparable (P = .473)
(Table) and was correlated with myoglobin (P < .05). Locoregional toxicity was
similar in the three groups (P = .233) (Table). Surgical resection was radical in 83.2%
of cases. The 5-year LDFS was 70.2%, with no differences according to HILP
schedule (P = .475). 22.2% of patients required limb amputation, for complications
(n = 1), unresponsiveness (n = 17) or recurrence (n = 8). The amputation rate was
higher in upper LSTS (P = .049). Systemic metastases occurred in 47 patients (40.2%)
after a median of 14.6 months; their occurrence inversely correlated with post-HILP
necrosis (P = .001). Five-year OS was 48.1%. The avoidance of amputation (P = .044),
CT (P = .003) and lung as site of systemic recurrence (P = .018) were associated with
longer OS. Lung metastases were predictors for longer OS in case of systemic
progression (OR 3.81,95% CI 1.74-8.34,P < .001). Prognosis was not influenced by
CT (P = .087).
Conclusions: Doxorubicin, doxorubicin + TNFa and TNFa + L-PAM schedules are
equally active, with comparable toxicity profiles. Upper LSTS and poor post-HILP
necrosis were related with higher amputation rates. Despite preserving limb function,
40% of HILP patients develop a systemic recurrence, particularly when achieving
lower responses. Lung relapses lung have a relatively better prognosis.
Drug schedule
DOXO
n=47
TNFa + DOXO
n=30
TNFa + L-PAM
n=40
Tumor necrosis,
median %
(range)
Locoregional toxicity
according to Wieberdink
n° of pts (%)
1-2345
54 (7-91) 38 (80.9) 8 (17.0) 1 (2.1) 0
64 (10-100) 24 (80.0) 4 (13.4) 1 (3.3) 1 (3.3)
57 (4-91) 37 (92.5) 1 (2.5) 2 (5.0) 0
Disclosure: All authors have declared no conflicts of interest.
1505P COMPARISON OF TWO CHEMOTHERAPY REGIMENS (AI VS.
EIA) COMBINED WITH REGIONAL HYPERTHERMIA (RHT) IN
HIGH-RISK SOFT-TISSUE SARCOMA (HR-STS)
P.O. Aubele 1 , E. Kampmann 1 , G. Schuebbe 1 , S. Abdel-Rahman 1 , N. Dieterle 1 ,
R. Laubender 2 , R. Issels 3 , L. Lindner 1
1 Dept Internal Medicine III Hematology/Oncology, University Hospital Munich –
Grosshadern, Munich, GERMANY, 2 University of Munich, Institute of Medical
Informatics, Biostatistics, and Epidemiology, Munich, GERMANY, 3 German
Research Center for Environmental Health, Helmholtz Zentrum München,
Neuherberg/Munich, GERMANY
Introduction: A phase III study showed that RHT combined with EIA (E =
etoposide, I = ifosfamide and A= doxorubicin) is effective in HR-STS (Lancet Oncol,
2010). EIA + RHT significantly improved tumor response and prolonged local
progression-free (LPFS) and disease-free survival (DFS). Due to the mutagenic
potential of etoposide the EIA-regimen was modified thereafter. Here we report a
retrospective single center sequential analysis of EIA vs. AI both combined with
RHT.
Methods: Patients (pts) with localized HR-STS received EIA (E:125mg/m2; I:6g/m2;
A:50mg/m2) or AI (A:60mg/m2; I:9g/m2) with RHT (T max. 42°C; 60min.). Inclusion
criteria and procedures were equivalent to the protocol of the phase III study.
Response was evaluated according to RECIST and survival parameters were analysed
using cox regression models, Kaplan-Meier and chi-square test. Possible confounders
were selected by backward elimination using the likelihood ratio test.
Results: 106 Patients (median age 48 years; 19 - 70) were treated with EIA (42pts;
from 2006 – 2008) or AI (64pts; 2009 – 2012) with a median follow up of 28 months
for EIA and 10 months for AI. Best clinical response rate (CR + PR + SD) for EIA +
RHT was 89% compared with 97% for AI + RHT (p = 0,59). Risk for local disease
progression or death was not significantly different (Hazard ratio (HR) 0.896; 95% CI
0.433 -1.855; p= 0,767). 1-year rates of LPFS and DFS were 73% [95% CI 0.60 - 0.87]
and 73% [95% CI 0.60 - 0.87] for EIA and 77% [95% CI 0.65 - 0.89] and 63% [95%
CI 0.49 - 0.77] for AI. Accordingly, for DFS HR was 0.739 (95% CI 0.382 - 1.428; p
= 0.368) and for OS HR was 1.011 (95% CI 0.306 - 3.339; p = 0.958). There was also
no significant difference in HRs for LPFS, DFS or OS after adjustment for
confounders.
Conclusion: Combining both regimens with RHT, AI is an equally effective regimen
if compared to the EIA regimen. The efficacy of both regimens combined with RHT
is comparable to the published results of the phase III study. P. Aubele,
E. Kampmann, G. Schuebbe contributed equally; this work contains parts of the
doctoral thesis of G. Schuebbe.
Disclosure: All authors have declared no conflicts of interest.
1506P SUPERIORITY OF CHOI VS RECIST CRITERIA IN
EVALUATING OUTCOME OF ADVANCED SOFT TISSUE
SARCOMA (STS) PATIENTS TREATED WITH SORAFENIB
R. De Sanctis 1 , A.F. Bertuzzi 1 , P. Magnoni 2 , L. Giordano 3 , M. Gasco 1 ,
R. Lutman 2 , A. Santoro 1
1 Medical Oncology and Hematology, Humanitas Cancer Center, IRCCS,
Rozzano, ITALY, 2 Radiology, Humanitas Cancer Center, IRCCS, Rozzano Milan,
ITALY, 3 Biostatistics Unit, Humanitas Cancer Center, IRCCS, Rozzano Milan,
ITALY
Background: Objective tumor response may be underestimated by RECIST criteria,
since biological agents can cause metabolic response (necrosis) not related to tumor
size. For this reason, CHOI criteria were designed to evaluate both tumor density
and size. We compared CHOI and RECIST criteria in evaluating response to
sorafenib in patients with advanced STS, treated within a phase II trial. The objective
was to compare CHOI and RECIST criteria and to relate response to progression-free
(PFS) and overall survival (OS).
Patients and methods: Sixty one advanced STS patients received sorafenib 400 mg
twice daily for progressive or relapsed disease after anthracycline-based
chemotherapy. Treatment was continued until progression or major toxicity.
Contrast-enhanced CT was performed every 3 months. Thirty patients were
evaluable for response, according to both RECIST and CHOI criteria.
Results: A total of 30 patients were included in the analysis. According to RECIST,
we observed 1 (3%) complete response (CR), 1 (3%) partial remission (PR), 18 (60%)
stable diseases (SD) and 10 (34%) progressive diseases (PD) at 3 months. According
to CHOI, we observed 1 (3%) CR, 10 (34%) PR, 5 (16%) SD and 14 (47%) PD. The
agreement between the two techniques was low (cohen Kappa: 0.36; CI 95%,
0.17-0.55). Of the 18 pts with SD according to RECIST, a total of 13 (72%) pts were
reallocated to responder (8 PR, 44%) and non-responder (5 PD, 28%) groups, while
only in 5 cases SD was confirmed using CHOI criteria. Median PFS and OS for SD
RECIST pts were 8.3 and 22.7 months, respectively. In these 18 pts, we compared
median PFS and OS of responders (CR + PR, n= 8) vs non-responders (SD + PD, n=
10) according to CHOI criteria. PFS was 11.2 vs 7.9 (p= 0.05), and OS 23.3 vs 15
months (p= 0.21).
Conclusions: Our analysis suggests that CHOI criteria may be helpful to define
response to a biological treatment in STS. According to CHOI criteria, SD pts as
defined by RECIST could be better divided in two subgroups (responders and
non-responders) with a different outcome. Therefore, CHOI criteria may have an
early significant predictive value for PFS in STS pts treated with biological
agents.
Disclosure: All authors have declared no conflicts of interest.
1507P CORRELATION BETWEEN TUMOUR NECROSIS AND
OVERALL SURVIVAL IN ADULTS WITH OSTEOSARCOMA
TREATED WITH NEOADJUVANT CISPLATIN AND
DOXORUBICIN
G. Rivalland, D. Porter
Cancer and Blood Service, Auckland City Hospital, Auckland, NEW ZEALAND
Purpose: The degree of tumour necrosis following neoadjuvant chemotherapy has
crucial prognostic significance in methotrexate containing regimens. We examined
whether a similar relationship exists for a non methotrexate containing regimen in a
cohort of adult patients treated at the Auckland Regional Cancer Service between Feb
1996 and Feb 2011.
Methods: We retrospectively identified 35 patients with high grade osteosarcoma
using data recorded prospectively in the New Zealand Bone Tumour registry
and regional pathology laboratories. All patients received neoadjuvant cisplatin
and doxorubicin, without high dose methotrexate. Reported necrosis rates
following surgery clustered into 3 groups: >90%, 30-65% and