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

134s Central Nervous System Tumors
2077 General Poster Session (Board #16H), Sat, 1:15 PM-5:15 PM
Utility of iron oxide nanoparticles in the radiographic diagnosis of CNS
lymphoma and inflammatory diseases. Presenting Author: Brian T. Farrell,
Oregon Health & Science University, Portland, OR
Background: Ferumoxytol, an ultrasmall superparamagnetic iron oxide
nanoparticle (USPIO), is approved for intravenous treatment of iron
deficiency in chronic renal failure. The package insert warns of potential
alterations of magnetic resonance imaging (MRI). Our initial animal studies
provided evidence of USPIO uptake by macrophages and lymphoreticular
cells suggesting its potential in CNS lymphoma (CNSL), post transplant
lymphoproliferative disease, or CNS inflammation (i.e. multiple sclerosis).
The mechanism of USPIO enhancement differs from gadolinium-based
contrast agents (GBCA), which optimally image areas of increased vascular
permeability. Methods: USPIO was administered as an MRI contrast agent
to 20 patients with presumptive or de facto diagnosis of CNSL or CNS
inflammation. Seventeen of 20 patients underwent both USPIO- and
gadolinium-based MRI. Three patients received only USPIO due to risk of
nephrogenic systemic fibrosis (NSF) with GBCA exposure. In the pilot
phase of the study, patients were given the USPIO ferumoxtran-10 and
subsequent patients were given a successor USPIO (ferumoxytol) which
has improved pharmaceutical properties. All patients were monitored for
adverse reactions. MRI scans were subsequently reviewed by a neuroradiologist.
Results: No significant toxicities were seen. Thirteen of 17 patients
who received both contrast agents showed equal numbers of enhancing
lesions on postcontrast images. USPIO-based contrast revealed additional
areas of enhancement in three of 17 patients that were not visible when
GBCA was administered. In three patients more lesions were seen with
GBCA. Examples of ferumoxytol utility include 1) improved targeting for
surgical biopsy; 2) avoidance of NSF; 3) demonstrating enhancement
related to macrophages within lesions; 4) correlating cerebral blood volume
and CNS inflammation; 5) demonstrating pitfalls such as prolonged
imaging changes (3 months) in one case due to intensive inflammation,
which can simulate hemorrhage. Conclusions: These studies provide data
about the utility and value of USPIO-based contrast imaging in CNSL and
inflammatory CNS lesions that support a dual role for these agents beyond
iron replacement.
2079 General Poster Session (Board #17B), Sat, 1:15 PM-5:15 PM
Tegwondo-CCNU: A novel combination of protracted, near-continuous
temozolomide and CCNU with activity in recurrent malignant gliomas.
Presenting Author: Herwig Matthias Strik, University of Marburg, Marburg,
Germany
Background: Recent data have been raising doubt if dose-dense temozolomide
is more efficient against malignant gliomas than with conventional
dosing. We report here updated results of combined near-continuous
temozolomide, aimed at depleting anti-alkylating MGMT, with once weekly
application of low-dose lomustine (CCNU) at first or second relapse of
malignant gliomas. Methods: 25 consecutive patients with recurrent
malignant gliomas (12 anaplastic gliomas WHO III, 13 glioblastomas or
gliosarkomas WHO IV) were treated: 15 males (60%), 10 females (40%);
mean age at start of chemotherapy was 52 (20-78) years; Eight patients
were treated at first, 15 at second and two at third recurrence. All patients
were pretreated with temozolomide. Four patients received fractionated,
stereotactically guided re-irradiation (FSRT). The treatment regimen consisted
of near-continuous temozolomide 50mg/m2 day 1-5/7 and low-dose
CCNU 40mg absolute dose day 6/7. In cases of bone-marrow depression,
temozolomide was reduced in steps of 20mg total dose or – in more severe
cases – chemotherapy was interrupted until normalization of blood counts.
Results: In total, 89 cycles (months) of chemotherapy were applied. The
combination was well tolerated in terms of nausea and fatigue. Blood
counts usually decreased continuously, enabling a gradual dose adaptation.
Hematological WHO grade 3�4 toxicity occurred in 5/25 patients
(20%), two of them were symptomatic. Three patients had prolonged
elevation of liver enzymes. Best responses after � 3 months (23 patients)
were: 2 complete and 1 partial remissions (13%, ), 13 stable diseases
(57%), and 7 progressive diseases (30%). Progression-free survival at six
months from start of chemotherapy of the 16 patients treated � 6 months
or deceased (PFS 6) was 37%, median overall survival 6.3 months.
Conclusions: Although some hematotoxicity was observed, the regimen
presented here is well tolerated and safe if carefully controlled. The
objective responses and considerable rate of stable diseases indicate that
this combination is active in malignant gliomas after pretreatment with
temozolomide alone. The results have to be controlled in a prospective trial.
2078 General Poster Session (Board #17A), Sat, 1:15 PM-5:15 PM
MRI-based vessel function maps for high-resolution differentiation between
tumor and nontumoral tissues in brain tumor patients. Presenting
Author: Leor Zach, Sheba Medical Center, Ramat-Gan, Israel
Background: Changes in enhancement seen in post treatment brain MRIs in
primary and secondary brain malignancies often mimic tumor progression
(pseudoprogression, radiation necrosis). Conventional MRI cannot differentiate
tumor progression from treatment related effects resulting in suboptimal
patient management. Methods: The application of delayed contrast
extravasation MRI for depicting unique vessels characteristics with high
resolution and high sensitivity to subtle BBB disruption is demonstrated in
17 GBM and 15 brain metastases patients undergoing standard chemoradiation
and radiosurgery respectively. Results: 2 primary vessel function
populations were defined: a slow population where contrast clearance from
the tissue was slower than accumulation, and a fast population where
clearance was faster than accumulation. Ten stereotactic biopsies acquired
from GBM patients showed complete correlation with the maps, confirming
the discrimination between fast population regions, reflecting morphological
active tumor and slow regions reflecting necrosis/treatment-induced
changes. Typical fast population vessel morphology consisted of proliferating
endothelial cells, dilated lumen, peri vascular fibrosis and glumeroloid
vessels, while slow regions consisted of necrotic vessels, in agreement with
the observed MRI vessel function. The fast component volume 3 weeks post
treatment was significantly correlated with the fast volume 4 (r2�0.84, p�0.0005) and 6 months (r2�0.84, p�0.01) later, suggesting early
prediction of response. Brain metastases histology showed similar results:
5 brain metastases with a fast population component were confirmed
histologically to contain morphologically active tumor. One metastasis
consisting of the slow population only significantly decreased in volume in
the following MRIs. Conclusions: These results demonstrate the feasibility
of applying our delayed contrast extravasation high resolution function
vessel maps for improving patient management by clearly depicting tumor
and non-tumoral tissues in patients with primary and secondary brain
malignancies undergoing standard chemoradiation or radiosurgery.
2080 General Poster Session (Board #17C), Sat, 1:15 PM-5:15 PM
Retrospective analysis of glioblastoma patients treated with bevacizumab
who presented with multifocal disease at diagnosis. Presenting Author:
Jethro Lisien Hu, Cedars-Sinai Medical Center, Los Angeles, CA
Background: Glioblastoma patients who present with multifocal disease
have an extremely poor prognosis – a recent analysis at our institution
demonstrated a median survival of 6 months, versus 11 months for a cohort
of unifocal glioblastoma patients matched for age, extent of resection, and
KPS. Bevacizumab is frequently used to treat patients with recurrent or
progressive glioblastoma. However, its benefit in the setting of multifocal
disease is unproven, particularly in light of the concern that antiangiogenic
treatment may promote a more invasive, multifocal, and potentially
treatment-resistant phenotype. Methods: Between 2004 to 2010, 368
patients were diagnosed with glioblastoma at our institution. We identified
46 patients with multifocal disease on initial presentation, and retrospectively
reviewed their clinical course and treatment history. Kaplan-Meier
estimates and Wilcoxon tests were used to assess survival distribution.
Results: Of the 46 patients with multifocal disease, 12 were treated with
bevacizumab (7 upfront and 5 at first recurrence). All 12 bevacizumabtreated
patients received external beam radiation therapy, and 11 received
temozolomide. In the bevacizumab-treated cohort, median age at the time
of surgery was 59 years, and median KPS was 80. For the 34 patients with
multifocal disease who did not receive bevacizumab, median age was 69
years, and median KPS was 75. Median survival for the bevacizumabtreated
patients was 12.9 months, with 12-month survival of 58.3%. By
comparison, median survival for patients with multifocal disease who did
not receive bevacizumab was 5.8 months, with 12-month survival of
20.6%. The difference in survival between the two groups was statistically
significant, with p-value of 0.045 by the Wilcoxon test. Conclusions: This
single-institution retrospective analysis suggests that bevacizumab treatment
is associated with a survival benefit for glioblastoma patients who
present with multifocal disease. One can infer that the clinical benefit of
bevacizumab in this setting outweighs any potential concerns regarding the
ability of bevacizumab to promote an invasive, treatment-resistant tumor
phenotype.
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