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

132s Central Nervous System Tumors
2069 General Poster Session (Board #15H), Sat, 1:15 PM-5:15 PM
Effect of electrochemotherapy with IV bleomycin on complete response in a
preclinical brain tumor study. Presenting Author: Birgit Agerholm-Larsen,
Department of Oncology, C*EDGE at Glostrup Research Institute, Glostrup,
Denmark
Background: Electrochemotherapy (ECT) describes enhanced chemotherapeutic
drug uptake after cell membranes have been made transiently
permeable due to application of an electric field to the tumor. ECT is
routinely used to treat skin metastases, with high response rates after
once-only treatment. We have developed an electrode for use in the brain,
both a rodent model and an electrode for clinical use. The aim of the
present study was to evaluate ECT using intravenous (iv) bleomycin in a rat
brain tumor model. Methods: Sprague Dawley male rats (7-11 week old)
were inoculated with rat glial cell derived tumor cells (N32) through a burr
hole in the skull. When tumors appeared on MRI, animals were allocated to
ECT (iv bleomycin and local electric pulses), iv bleomycin only, iv
bleomycin with placement of electrodes (no pulses), or no treatment.
Bleomycin was injected iv in the tail vein (600�L, 3 IU/�L) and electrode
deployment was made through the burr hole into the brain tissue.
Electrochemotherapy parameters were 32 pulses, 100V, 100�s, 1Hz.
Tumor size was determined based on contrast enhanced area from MR
scans. Kaplan-Meyer events were defined as termination due to extensive
tumor progression prior to end of the three independent experiments
performed. Immuno-histo-pathology was performed after termination to
verify MRI findings. Results: In 88% of the animals (14 of 16) treated with
electrochemotherapy we found complete response (no tumor), validated by
MRI and immuno-histo-pathology, whereas bleomycin only, bleomycin and
electrodes, and no treatment showed progression in 11 out of 13 control
animals. A Kaplan-Meier plot showed a pronounced improved survival for
the ECT group as compared to controls within 3 weeks from treatment
(p�0.001). Treatment was well tolerated. Conclusions: The present data
suggest that electrochemotherapy with iv injection of bleomycin is a new
promising treatment for brain tumors. In a clinical study using iv bleomycin
and electrochemotherapy for brain metastases (www.clinicaltrials.gov,
ID:NCT01322100) the first patient has just been treated successfully with
ECT, indicating feasibility of the approach in the clinical setting.
2071 General Poster Session (Board #16B), Sat, 1:15 PM-5:15 PM
Health-related quality of life (HRQOL) in patients with glioblastoma (GBM)
and their caregivers in the end-of-life phase: A retrospective study.
Presenting Author: Birgit Flechl, Medical University of Vienna, Vienna,
Austria
Background: Glioblastoma multiforme (GBM) still harbours an inevitably
fatal prognosis. The specially course of this disease poses unique challenges
in care provision to the relatives. We still lack data about the
end-of-life phase of GBM patients to improve counseling and supporting
GBM patients and their proxies. Methods: In this retrospecitve study we
included 52 caregivers of deceased GBM patients treated in two hospitals
in Vienna, Austria. We used a specially developed questionnaire by the
Medical University of Amsterdam to explore and document the last three
months of living of GBM patients. Results: Most of the included caregivers
were the partners of the patients (88%) and two thirds were female. The
most common symptom in GBM patients was fatigue (87%), followed by
reduced consciousness (81%) and aphasia (77%). 22% of the patients
were bedbound during their last three months increasing to 80% in the last
week of life. 30% of the caregivers told that they felt incompletely informed
for their task and about the illness of their loved one. They stated the quality
of life (QOL) of the patients with 2.2 and their own with 2.8 on a scale of 1
to 7 whereas 7 displays the best possible answer. The majority of the
patients (46%) died in hospitals and 38% at home, which was the most
often expressed wish for place of death (45%)by patients. Regarding the
caregivers´ symptoms, sadness (90%), fear (69%), burnout (60%), less
interest in others (54%) and irritation (42%) were the leading ones and did
not differ significantly in-between the places of death. Conclusions: The
end-of-life phase of GBM patients is different from that of patients dying
from other cancers. Most alarmingly, one thirds of their caregivers feels
poorly informed. About two thirds of the caregivers fell overstrained and
stresses thereby the urgent need for support and dedicated educational
programs.
2070 General Poster Session (Board #16A), Sat, 1:15 PM-5:15 PM
Prospective follow-up of a cohort of 112 patients with leptomeningeal
metastases of breast cancer recruited from 2007 to 2011: Prognostic
factors. Presenting Author: Fahed Zairi, CHRU, Lille, France
Background: Around 5% of patients with breast cancers (BC) will develop
leptomeningeal metastasis (LM). The incidence may increase. Methods: We
reported the description and outcome of 112 consecutive BC patients
diagnosed with LM in our institution from 2007 to 2011. Correlations
between characteristics and overall survival (OS) were analyzed using usual
statistical methods (Kaplan Meier, Log-rank, Cox model). Results: BC were
invasive ductal carcinoma in 69.7%. Estrogen and progesterone receptors
were detected in respectively 61.6 and 44.6%. HER2 expression was
observed in 26%. 23% were triple negative. Median time between BC
diagnosis and LM diagnosis was 44 months. At LM diagnosis, median age
was 54 and median Performance Status (PS) was 2. CSF cytology and
cerebrospinal MRI were positive in respectively 72,5% and 87%. 103
(92%) LM patients received IT liposomal cytarabine as 1st line of
treatment (ventricular device in 47%). IT therapy could be associated with
systemic treatment in 58% of the cases and cerebral radiotherapy for LM in
14% of the cases. Clinical response after 1st line treatment was observed
in 57%, CSF response in 30,5%, MRI response in 62,5%. 24 patients
received a 2nd line of IT thiotepa, 6 a 3rd line of IT methotrexate. The more
significant prognostic factors (p�0,0001) were initial PS, associated
systemic treatment and triple negative BC status. Other significant predictors
of OS were thiotepa as 2nd line treatment (p�0,0004), intracranial
hypertension at LM diagnosis (p�0,019), associated cerebral radiotherapy
(p�0,02), progesterone receptor status (p�0,04). Median OS of the 103
treated patients was 3,8 months (4,75 months for 0-2 PS and 1,6 months
for 3-4 PS patients). Conclusions: Median OS was consistent those of other
recent cohorts of BC LM. Our results confirm the role of a very early
diagnosis, before the degradation of the general status. The association
with systemic treatment or cerebral radiotherapy is indicated when possible.
2072 General Poster Session (Board #16C), Sat, 1:15 PM-5:15 PM
Pediatric glioblastoma: Results with adjuvant chemoradiation using temozolomide.
Presenting Author: Nikhil Purushottam Joshi, All India Institute
of Medical Sciences, New Delhi, India
Background: Paediatric glioblastoma patients are underrepresented in
major trials for this disease. The value of concurrent and adjuvant
temozolomide is not known in this subset of patients. Methods: We
retrospectively analysed our database between 2004 and 2010. All
patients were treated with maximally safe surgical resection. This was
followed by a uniform treatment schedule of post-operative radiation
according to RTOG guidelines with concurrent daily temozolomide at 75
mg per meter square. The radiation dose was 60 Gy in 30 fractions planned
by 3 dimensional conformal radiotherapy. 4 weeks later, adjuvant temozolomide
was started at 150 mg per meter square, day 1 to 5 every 28 days
and escalated to 200 mg per meter square if well tolerated. Log-rank test
was used to compare survival distribution. The data was analysed using
SPSS 16. Results: 23 patients were analysed. The median age was 11 years
(range: 5 to 19 years). 15 males and 8 females were noted. 4 patients had
seizures at presentation while 19 did not. 13 patients underwent a gross
total resection while 10 underwent a subtotal resection. 5 patients received
only concurrent temozolomide while 18 received concurrent and adjuvant
temozolomide. The median number of adjuvant temozolomide cycles were
6 (range 2 to 12). The median follow up was 11.9 months (range: 1.6 to
30.1 months). 6 patients were dead and 17 were alive at the time of
analysis. The median overall survival was not reached. The median survival
for patients receiving only concurrent temozolomide was 13 months while
that for patients receiving concurrent and adjuvant temozolomide was not
reached and the difference was statistically significant (p�0.0009). The
overall survival was not statistically different for age less or more than 10
years, gender, and type of surgery or the number of adjuvant cycles of
temozolomide (less or more than 6). Conclusions: Temozolomide may have
a role in paediatric Glioblastoma. Both concurrent and adjuvant temozolomide
seem to be important for superior overall survival in this group of
patients.
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