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

130s Central Nervous System Tumors
2060 General Poster Session (Board #14G), Sat, 1:15 PM-5:15 PM
Tolerance and feasibility of chemotherapy by procarbazine, lomustine, and
vincristine (PCV) for oligodendroglial anaplastic gliomas (OAG). Presenting
Author: Marine Davos, University Hospital Timone, Marseille, France
Background: Chemosensitivity of OAG has been documented although their
role as part of adjuvant treatment combined to radiotherapy is debated.
Beside temozolomide still under investigation, several studies have underlined
activity of PCV regimen in this setting. However, significant toxicity
has been described and dose intensity and schedule duration are not
clearly reported. Methods: This monocentric retrospective analysis included
all pts with OAG treated with at least 1 cycle of PVC (lomustine 110mg/m2
every 6 weeks) at our institution from August 2007 to August 2011
(pharmacy charter). Toxicities data were collected from clinical observations
and blood investigations. Results: 40 pts were identified (M/F: 23/17).
Median age was 45y (20 – 72). At the time of analyses, 32 pts were still
alive. Histologies were oligodendroglioma (73%) or oligoastrocytoma (27%).
Codeletion 1p19q was observed in 30 % of pts. PCV was administered in
first or second line of chemotherapy for 60 % and 40 % of pts respectively.
Seventy five percent and 52.5% of pts completed at least of 4 and 6 cycles
respectively. Discontinuation of PCV occurred in 45% of pts for toxicity
(10%), progression (30%), or other reason (5%). Because of toxicity
38/196 (19%) PCV cycles were delayed. Dose was adapted for 73% of pts
and decreased under 60% of theoretical dose in 30% of pts at cycle 4 and
in 57% of pts at cycle 6 (table1). Grade III or IV toxicity occurred in 28% of
pts and only grade I-II in 50%. Neuropathies occurred in 43 % of pts.
Conclusions: Despite activity of PCV regimen, significant toxicity is associated
to this schedule, that impact feasibility and compliance. PVC
schedule should be redefined taking into account dose intensity applied in
toxicity observed.
Cycles
Cumulative number (nb)
of pts under PCV
Nb of pts per dose
% of theoretical dose of lomustine
90–100% 70–80% 50–60% < 50 %
Total nb of
pts per cycle
1 40 (100%) 23 (57.5%) 13 (32.5%) 3 (7.5%) 1 (2.5%) 6 (15%)
2 34 (85%) 18 (53%) 11 (32%) 4 (12%) 1 (3%) 2 (5%)
3 32 (80%) 12 (38%) 12 (38%) 6 (18%) 2 (6%) 2 (5%)
4 30 (75%) 10 (33%) 11 (37%) 6 (20%) 3 (10%) 3 (7.5%)
5 27 (32.5%) 8 (30%) 8 (30%) 6 (22%) 5 (18%) 6 (15%)
6 21 (52.5%) 4 (19%) 5 (24%) 7 (33%) 5 (24%) 21 (52.5%)
2062 General Poster Session (Board #15A), Sat, 1:15 PM-5:15 PM
The association of pretreatment neutrophil to lymphocyte ratio with overall
survival in patients with glioblastoma multiforme (GBM). Presenting
Author: Richard Martin Bambury, Department of Medical Oncology, Cork
University Hospital, Cork, Ireland
Background: GBM is the most common and aggressive primary brain tumor.
The neutrophil to lymphocyte ratio (NLR) gives a measure of systemic
inflammatory response and lymphopenia, both of which are poor prognostic
factors in many malignancies. No published study has assessed the
prognostic impact of NLR in GBM. Methods: Patients treated for GBM at our
regional referral centre with assessable complete blood count at first
presentation (prior to corticosteroid therapy or surgery) were identified.
Medical notes were reviewed to extract demographic and treatment data.
Survival curves were estimated via Kaplan-Meier method and compared via
log-rank method. Multivariate analysis was performed via Cox proportional
hazards regression modelling. Results: A total of 86 patients were identified,
of which 65(76%) were male. Median age at diagnosis was 58 years
(range: 18–76). At the time of analysis all patients still alive had � 2 years
follow-up. Median overall survival (OS) was 9.3 months (range: 1-82). 57%
completed the standard adjuvant Stupp protocol and 43% discontinued
early due to disease progression or treatment toxicity. Median OS was 11.2
months in patients with NLR�4 and 7.5 months in patients with NLR�4
(HR 0.59, p�.04). Other significant prognostic factors based on univariate
analysis were consistent with published data (Table). After correcting for
known prognostic factors NLR remained a significant predictor of survival
(Table). Conclusions: Recent advances in immunotherapy have highlighted
the importance of the immune system in the treatment and prognosis of
cancer patients. Many GBM patients are on corticosteroids for a significant
proportion of their disease course which may abrogate the effects of host
immunity on outcome. Nevertheless, we have shown that NLR at diagnosis
is an independent predictor of survival in GBM patients. Investigation of
therapies which harness the immune response are warranted in this
disease.
Univariate Multivariate
Hazard ratio p value p value
NLR (4) 0.59 0.01 0.01
Age (60) 0.47 �0.01 0.01
Surgery (debulking vs biopsy) 0.60 0.01 0.01
Stupp protocol (complete vs incomplete) 0.21 �0.01 �0.01
2061 General Poster Session (Board #14H), Sat, 1:15 PM-5:15 PM
Anaplastic gliomas at first recurrence: Outcome analysis. Presenting
Author: Enrico Franceschi, Medical Oncology Department, Bellaria-
Maggiore Hospital, Azienda USL of Bologna, Bologna, Italy
Background: Although anaplastic gliomas show a more favorable response
to postsurgical therapy than glioblastoma, when recurs, salvage therapies
offer only temporary benefit. Moreover, due to the rarity of these entities, no
study exists to evaluate the clinical outcomes of anaplastic gliomas at first
recurrence. Methods: A retrospective analysis was made using a database
on 249 anaplastic glioma patients (pts) followed prospectively between
01/2000 and 12/2011. Eligibility criteria: age �18 years; PS 0-2;
histological diagnosis at first surgery of anaplastic astrocytoma (AA),
anaplastic oligodendroglioma (AO), and anaplastic oligoastrocytoma (AOA);
first recurrence after postsurgical treatments. Results: 163 pts (recurrent
AA:52%, AOA:23%, AO: 25%, mean age: 45 years, range: 21–74) were
enrolled. 1p deletion and MGMT methylation were found in 23% and 56%
of evaluable specimens, respectively. At time progression, second surgery
was performed in 51 pts (31%). Chemotherapy was delivered in 128 pts:
temozolomide in 96 pts (75%), PCV regimen in 11 pts (9%), and other
cytotoxic treatments in 21 pts (16%). Median PFS was 7.1 months (95%
CI: 5.8–8.5), being PFS-6 57.8% (95%CI: 49.8%–65.8%), mOS: 18.3
months (95% CI: 13.9–22.8) and OS-12: 63% (95%CI: 55.4%-70.6%).
1p status was not significantly associated with PFS and OS measured from
first recurrence to second progression or death, respectively (p�0.12 and
p�0.08). In the Cox proportional hazard model, PFS at recurrence was
significantly correlated with OS measured at the first disease recurrence
(p�0.00001). Conclusions: our data represent the largest series that
evaluated the outcome of anaplastic gliomas at first recurrence. In this
setting, PFS should be considered as a worthy endpoint, being significantly
correlated with OS.
2063 General Poster Session (Board #15B), Sat, 1:15 PM-5:15 PM
Illness intrusiveness and subjective well-being in patients with glioblastoma
multiforme. Presenting Author: Linda Coate, Princess Margaret
Hospital, Toronto, ON, Canada
Background: Glioblastoma multiforme (GBM) is the most common adult
CNS malignancy. The quality-of-life (QOL) impact of its neurological
sequelae and poor prognosis is poorly understood. In this study we
examined relations between disease severity and mood in GBM patients.
Methods: GBM patients (n�73) completed validated questionnaires examining
depression (CESD), positive affect (ABS), illness intrusiveness (II),
and health-related QOL (EORTC-QLQ30, BN-20). Median age was 53 years
(range 26-75), median time since diagnosis was 1.1 years (range 0.1-
12.4). 88% were on temozolomide. Questionnaire scores were compared to
normative data from GI, GU, Breast, Head and Neck, Lymphoma, and Lung
cancer groups using t-tests. Hierarchical multiple regression analyses
tested the impact of disease severity indicators (ECOG; Symptoms, derived
from QLQ30, BN20) and potential moderators on mood and whether II
mediates those effects. Results: GBM patients reported less positive affect,
more depression and greater II than other cancer patients (p�.05).
Increase in symptoms correlated with greater II (��.59; 95% CI [.31, .87],
p�.0001) and depression (��.37; 95% CI [.20, .55], p�.0001) and less
positive affect (��-.04; 95% CI [-.08, -.01], p�.02). Surprisingly, higher
ECOG (i.e., poorer performance status) was associated with less II
(��-3.58; 95%CI [-7.06, -.10], p�.04) and depression (��-2.20; 95%CI
[-4.21, -.19], p�.03). II partially mediated the relations between disease
severity and mood, evidenced by the change in the disease severity
coefficient when II was added to the models (mean change measured by
bootstrap sampling: CESD�.23, 95% CI [.06, .43]; ABS�.21, 95%CI
[.02, .44]). The occurrence of other stressful life events was associated
with II (��2.73; 95% CI [.43, 5.02], p�.02), but there was no evidence of
a moderating effect on this or any other relationship (p�.05). Conclusions:
GBM patients are more distressed than other cancer patients. GBMinduced
lifestyle disruptions partially mediate the association between
disease severity and subjective well-being. Efforts to engage patients in
valued activities and interests, despite the constraints, can help to preserve
QOL.
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