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

2064 General Poster Session (Board #15C), Sat, 1:15 PM-5:15 PM
Impact of duration of bevacizumab (Bev) treatment in the prognosis of
adults with recurrent malignant gliomas. Presenting Author: Mohamed Ali
Hamza, University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Bev is the standard treatment for patients with recurrent
glioblastoma (GB) but is also used in treating recurrent anaplastic gliomas
(AG). Differences in outcome between these groups and optimal duration of
treatment with Bev in pts with recurrent malignant gliomas are not well
defined. We examined the relationship between the duration of Bev
treatment and the outcome in pts with GB and AG. Methods: In this
retrospective chart and data review derived from our longitudinal database,
we identified pts with recurrent AG and GB who were treated with Bev alone
or Bev-containing regimens between 2005 and 2009; the data was
analyzed to determine the overall survival (OS) and the progression free
survival (PFS). Results: A total of 261 patients with recurrent malignant
gliomas (196 with GB and 65 with AG) were identified. There was no
significant difference between the median length of treatment between AG
and GB (5.81�0.66 months vs. 6.77�0.52 months, p�0.32). PFS6 was
34.2% (95% CI, 27.8-41.3) for patients with GB and 44.2% (95% CI,
32.5-56.7) for patients with AG. Patients with GB who were treated �6
months had a significantly higher OS (29.13 months vs. 20.16 months, p�
0.001) compared to those treated �6 months, and a significantly higher
PFS compared to those treated �6months (11.33 months vs. 3.7 months,
p�0.0001). For patients with AG, although treatment �6 months had a
significantly higher PFS (13.93 months vs. 3.53 months, p�0.0001), OS
was not significantly different (months 38.6 vs. 52.5 months, p�0.6)
compared with those treated �6 months. Conclusions: Length of treatment
�6 mo with Bev or Bev-containing regimen was associated with improved
PFS in both AG and GB but only the GB subgroup showed improved OS.
These results suggest equivocal survival benefit in patients with AG with
longer duration of bevacizumab treatment, which requires further study in
prospective trials.
2066 General Poster Session (Board #15E), Sat, 1:15 PM-5:15 PM
A preclinical study on the combined treatment of nimotuzumab and
sirolimus in glioblastoma. Presenting Author: Chee Kian Tham, National
Cancer Centre, Singapore
Background: The human epidermal growth factor receptor (EGFR) is an
ideal therapeutic target for inhibiting glioblastoma (GBM) growth as the
signaling pathway is highly dysregulated in GBM. However, trials so far with
EGFR inhibitors have not shown clinically meaningful improvement in
response rates and survival. One of the postulated mechanisms of resistance
is the constitutive activation of the downstream, PI3K/AKT/mTOR
pathway, independent of the upstream EGFR activation status. Hence, the
dual blockage of the pathways with an anti-EGFR agent and mTOR inhibitor
is postulated to have synergistic anti-tumour effects. We aim to investigate
the anti-tumour effect of combined nimotuzumab (anti-EGFR monoclonal
antibody) and sirolimus (mTOR inhibitor) in a GBM preclinical model.
Methods: Primary human GBM cells were derived from surgical GBM
specimens. The endogenous expressions of glial-fibrillary acidic proteins
and EGFR were determined by IHC staining and Western Blot analysis. Cell
viability assays were then carried out in these GBM cells and immortalized
human normal astrocytes (iHNA) using a range of concentrations of
nimotuzumab alone, sirolimus alone or combined treatment. Results: GBM
cells treated with nimotuzumab showed a dose- dependent cell kill and the
optimal concentration was determined to be 2 �g/ml. Treatment of the
GBM cells with sirolimus showed that the drug was capable of inducing cell
death at varying levels and the optimal level was determined to be 0.1 mM.
Combined treatment with nimotuzumab (2�g/ml) and rapamycin (0.1 mM)
showed a dose dependent cell kill in GBM cells which was not observed in
iNHA cells. The combined treatment resulted in only 10% of residual
gliomas at 24 h post treatment. Single treatment with rapamycin has no
cytotoxic effect whereas treatment with nimotuzumab alone exerts a
cytotoxicity effect of 33%. Taken together, we observed an additive effect
of cell kill when rapamycin is used together with nimotuzumab in human
glioma cells. Conclusions: In this study, combined treatment of nimotuzumab
and sirolimus resulted in a greater cytocidal effects in GBM cells
than either agent alone. We will further examine this combination regimen
in a subsequent phase I clinical trial.
Central Nervous System Tumors
131s
2065 General Poster Session (Board #15D), Sat, 1:15 PM-5:15 PM
Rising incidence of glioblastoma and meningioma in the United States:
Projections through 2050. Presenting Author: Derek Richard Johnson,
Mayo Clinic, Rochester, MN
Background: In the absence of proven environmental or behavioral risk
factors, patient age and sex remain the most important predictors of
primary brain tumor risk. In coming years, an increasing incidence of brain
tumors in the United States can be anticipated based on shifts in the
demographic structure of the population. This study provides estimates of
glioblastoma and meningioma incidence through 2050. Methods: Groupspecific
glioblastoma and meningioma incidence rates based on age
(eleven categories) and sex were calculated from National Cancer Institute
(NCI) Surveillance, Epidemiology, and End Results (SEER) data for the
period 2004-2008. United States Census projections based on data from
the 2000 census were used to compute the size of the twenty-two
demographic subpopulations of interest in 2010, 2020, 2030, 2040, and
2050. The estimated number of new glioblastoma and meningioma
diagnoses for each of these years was calculated from the defined
incidence rates and population size. Results: Crude annual tumor incidence
rates were 3.13 per 100,000 persons for glioblastoma and 6.81 per
100,000 persons for meningioma. While the overall size of the population
is expected to increase only 42% between 2010 and 2050, the number of
Americans over 65 years of age, the group at highest risk of glioblastoma
and meningioma, is expected to increase by 120%. We estimate that the
number of new glioblastoma diagnoses will rise from 10,688 in 2010 to
18,466 in 2050, a 72% increase. Likewise, the number of new meningioma
diagnoses will rise from 22,946 to 40,680 over the same period, a
77% increase. Conclusions: The number of new glioblastoma and meningioma
diagnoses will increase substantially in the future. This analysis, which
assumes a fixed incidence rate, may underestimate the true magnitude of
the coming change given reports suggesting that incidence rates of
glioblastoma and meningioma are rising over time.
2067 General Poster Session (Board #15F), Sat, 1:15 PM-5:15 PM
Bevacizumab failure in glioblastomas. Presenting Author: Ghazaleh Tabatabai,
Department of Neurology, University Hospital Zurich, Zurich, Switzerland
Background: Bevacizumab has been approved for the treatment of recurrent
glioblastoma in various countries. The phase III registration trial assessing
the addition of bevacizumab to standard chemoradiotherapy in newly
diagnosed glioblastomas has completed recruitment. Salvage treatment of
glioblastoma patients after bevacizumab failure, however, is commonly not
successful. In the present study, we aimed at characterizing histological
and molecular characteristics associated with glioma recurrence after
bevacizumab. Methods: Paired tissue samples from primary and recurrent
tumors obtained from 12 patients with glioblastoma (n�11) or anaplastic
astrocytoma (n�1) before and after bevacizumab treatment, and 14
non-bevacizumab-treated patients as a reference group, were analyzed for
histological features as well as molecular markers. Clinical records and
magnetic resonance images were reviewed. Results: Histologically, recurrent
tumors after bevacizumab showed more commonly a decreased blood
vessel density and reduced glomeroloid microvascular proliferations when
compared to recurrent tumors after conventional radiochemotherapy. In
contrast, tumor cellularity and proliferation rate were similar. Distant
relapse was more common in bevacizumab-treated patients. Molecular
genetic studies of the respective tissue specimens are currently under way.
Conclusions: Histological and molecular analyses of tumor tissue samples
from glioma patients before and after bevacizumab treatment, combined
with thorough clinical and radiological correlates, may provide hints for
therapy escape mechanisms that can then be validated in preclinical
models.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.