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Annals of Oncology
hyponatremia (4.5%). Best tumor response rate and median survival time were 36.8%
and 6.6 months (m) for NSCLC, and 50% and 8.3 m for breast cancer.
Conclusion: Addition of veliparib up to 200 mg BID was well tolerated with
concurrent standard WBRT and dose escalation is ongoing. These encouraging safety
and preliminary efficacy data suggest that veliparib requires further evaluation as a
radiosensitizer with WBRT in pts with NSCLC and brain mets in a randomized trial.
Disclosure: M.P. Mehta: Consultant: Abbott, BMS, Elekta, Merck, Novartis, Novocure,
Tomotherapy, Vertex; Stock Options: Accuray, Pharmacyclics; DSMB: Apogenix;
Protocol Data Review: Adnexus; Board of Directors: Pharmacyclics. W.J. Curran: Dr.
Curran had served on the advisory board of Lilly, BMS, and Plexxikon. There are no
conflicts. D. Wang: As a clinical investigator, and the principle investigator at Henry
Ford Health System, I have conducted this clinical trial that is financially supported by
Abbott Oncology. I have no other conflict of interest to be disclosed, otherwise. L.
Kleinberg: I have received research funding from Abbott. J. Qian: Full-time Abbott
employee and stockholder. T. Leahy: Full-time Abbott employee and stockholder. B.
Desai: Full-time Abbott employee and stockholder. V.L. Giranda: Full-time Abbott
employee and stockholder. All other authors have declared no conflicts of interest.
429P NEUROLOGICAL (NEU) AND CYTOLOGICAL (CYT) RESPONSE
(R) AS EARLY PREDICTORS OF TIME-TO-PROGRESSION
(TTP) AND OVERALL SURVIVAL (OS) IN PATIENTS (PTS) WITH
LEPTOMENINGEAL CARCINOMATOSIS (LMC) TREATED WITH
INTRATHECAL (I.T) LIPOSOMAL CYTARABINE (LYC)
J.P. Fusco, E. Castanon Alvarez, L. Zubiri, P. Martín, O.E. Carranza Rua,
J. Espinos Jimenez, J. Rodriguez, M. Santisteban, J.M. Aramendia,
I. Gil-BazoDepartment of Oncology, Clínica Universidad de Navarra, Pamplona,
SPAIN
Background: The palliative treatment of LMC involves i.t chemotherapy or supportive
care. Lcy is a slow-releasing cytarabine formulation approved for leptomeningeal
involvement of hematological malignancies. In pts with LMC from solid tumors
interesting Neu and Cyt R rates after i.t Lcy have been observed. However, the potential
use of those responses as early predictors of TTP and OS has never been explored. Here
we show how both Neu and Cyt R can precociously predict a longer TTP and OS.
Patients and methods: Twenty-seven pts with LMC consecutively treated at our
institution with i.t Lcy under compassionate use (17/27 female), were studied. All pts
received i.t Lcy (50 mg) every 2 weeks (w) during induction and every 4 w during
maintenance. Neu and Cyt responses were assessed before every Lcy cycle.
Results: The predominant primary tumor origin was breast (15/27), followed by
gastrointestinal (3), lung (3), brain (2), and 4 other organs. A complete Neu R
(resolution of all Neu symptoms) was seen in 3/27 pts; partial R (improvement of
>50% of Neu symptoms for >2 w) in 6/27 pts; stable disease (no change in Neu
symptoms) in 8/27 pts and progressive disease (progression or appearance of new
Neu symptoms) in 10/27 pts. The Cyt assessment was available in 9/27 pts with a
Cyt complete R confirmed in 7/9 pts. The median time to Neu and Cyt R was 15
days (d) and 14 d, respectively. The overall median TTP was 22 d and the median
OS was 41 d. In a subgroup analysis regarding the type of R achieved with the
treatment, the median TTP and OS for pts showing a combined Neu and Cyt R were
significantly longer compared to those in pts showing both, Neu and Cyt progression
as shown in table 1. The most frequently reported adverse event was grade 2
headache with no grade 4 toxicities.
Conclusions: For the first time, Neu and Cyt R are shown to be early predictors of
TTP and OS in pts receiving i.t Lcy for LMC. This result could help to early select
patients most likely to benefit from i.t Lcy and to consider discontinuation when very
poor prognosis is estimated.
Neu R Cyt R TTP (d) OS (d) p
Yes Yes 122 141 0.001
Yes No 14 32 0.001
No Yes 42 72 0.001
No No 3 3 0.001
Disclosure: All authors have declared no conflicts of interest.
430P DEMOGRAPHIC DATA AND TREATMENT OUTCOME IN
RETINOBLASTOMA: RETROSPECTIVE REVIEW FROM
TERTIARY CENTRE IN INDIA
F.A. Ansari 1 , P. Shukla 2 , V. Roshan 1 , B. Mohanti 1
1 Radiotherapy, aiims, Delhi, INDIA, 2 Radiation Oncology, All India Institute of
Medical Sciences (AIIMS) Institute Rotary Cancer Hospital, New Delhi, INDIA
Purpose: To characterize the patient population and analyse treatment outcome in
patients with retinoblastoma.
Method and material: A retrospective study of 180 patients with retinoblastoma
affecting a total of 297 eyes. Demographic data, tumor features and outcome were
assessed.
Results: The mean age of diagnosis was 32 months (range 2-204 months) for
unilateral eyes and 26 months ( range 2-132months) for bilateral eyes. The male
to female ratio was 1.4:1. The most common symptoms was leukokoria (74%),
followed by proptosis of eye (11.5%), strabismus (8%) and poor vision (6.5%).
Out of 297 eyes 39 were Group I-II, 17 were Group III, 198 were group IV-V
and 43 had missing information. The mean basal diameter was 14mm (range
2–37mm). The mean interval between initial diagnosis and treatment was
7months ( range 1-36 months). Familial history was seen in eight patients (4.4%).
Out of 180 patients 64 patients received radiation. 144 patients underwent
enucleation. No children underwent bilateral enucleation. All patients were treated
with 6–12 cycles of chemotherapy vincristine, etoposide and carboplatin.
Chemotherapy offer satisfactory local control for Group I-III, with treatment
failure necessitating additional radiation and or enucleation in only 14% of
patients. The radiation doses were either 39Gy in 13 fraction, three fraction per
week or 40Gy in 20 fraction, five fraction per week. The mean duration of follow
up was 28 months (0-64months). The overall local control or freedom from
relapse was 55%. Local control in patients receiving radiation after enucleation
was 84%. Distant metastases were seen in 13 patients (preauricular node (5),
vertebrae (3), humerus (1), suprasellar (1), scalp (1), CSF(1), and meningeal
dissemination (1)). No case of second malignant neoplasm has been reported.
Conclusion: Lack of awareness leads to delay in diagnosis and treatment.
Multimodality treatment is required for management of retinoblastoma.
Chemoreduction offer satisfactory control retinoblastoma in group I-III, with
preservation of vision. There is significant improvement in local control with
radiation therapy in locally advance cases.
Disclosure: All authors have declared no conflicts of interest.
431 BLOOD VESSELS WITH DIFFERENT CHARACTERISTICS HAVE
DISTINCT IMPACT ON SURVIVAL OF GLIOBLASTOMA
MULTIFORME PATIENTS
M. Kase 1 , A. Minajeva 2 , K. Niinepuu 2 , S. Kase 3 , A. Adamson 2 , M. Saretok 2 ,
M. Vardja 4 , T. Asser 5 , J. Jaal 6
1 Dept. of Radiotherapy, North Estonia Medical Centre, Oncology and
Haematology Clinic, Tallinn, ESTONIA, 2 Faculty of Medicine, University of Tartu,
Tartu, ESTONIA, 3 Nursing, Health Care College, Tartu, ESTONIA, 4 Dept of
Radiotherapy and Oncological Therapy, Tartu University Hospital, Haematology
and Oncology Clinic, Tartu, ESTONIA, 5 Dept of Neurosurgery, Tartu University
Hospital, Tartu, ESTONIA, 6 Dept of Radiotherapy and Oncological Therapy, Tartu
University Hospital, Tartu, ESTONIA
Background: Glioblastoma multiforme (GBM) is the most aggressive type of brain
tumor in adults. GBMs are highly angiogenic: next to capillaries and bigger blood
vessels, microvascular proliferations (MP) forming glomeruloid structures can be
found. The aim of our study was to evaluate the prognostic significance of different
blood vessel types in GBM.
Methods: Between Jan 2006 and Dec 2008, 42 patients (30–77 years) received
postoperative radiotherapy and chemotherapy. Surgically excised GBM tissues were
histologically examined for overall proportion of MP (low, medium, high) and the
total number of blood vessels (per microscopic field). Also, immunohistochemical
staining intensity of CD133 and ICAM-1 were determined in endothelial cells
(arbitrary score 0–3). Finally, blood vessel parameters were correlated with patients
overall survival.
Results: The overall proportion of MP was low-medium in 39% and high in 61%
of GBM patients. The number of blood vessels per microscopic field was 2.5 ± 1.4
(mean ± SD). A positive association was found between the number of blood
vessels and endothelial CD133 staining intensity (p = 0.03). However, between the
number of blood vessels and endothelial ICAM-1 staining intensity, a negative
correlation was detected (p = 0.04). Median survival time of the study group was
10.0 months (95% CI 9.0–11.0). The proportion of MP did not significantly affect
survival (log rank test, p = 0.07). However, the survival time clearly depended on
the number of blood vessels in GBM tissue (log rank test, p = 0.03). Median
survival times for patients with low (