Annals of Oncology 17 (Supplement 9): ix262–ix264, 2006
material receive strictly personal usernames and passwords. Submitters have access to
neuro-oncology all their data and to summarized data from the whole database. Importantly, the actual
histological materials remain at the local Institutions. Access to all the data in the
virtual tissue bank is available only to the curators of the database (MP, FB) and to the
897P CLINICAL FEATURES, OUTCOME AND LATE EFFECTS IN IELSG data-managers. Investigators willing to perform research on PCNSL can submit
MALIGNANT INTRACRANIAL GERM CELL TUMORS. a research project to the IELSG; each project will be evaluated for material availability
and for scientiﬁc relevance.
Monica D. Dragomir1, Rodica M. Anghel2, Vlad Ciurea3, Eugen Gruber4, Codruta The possibility for any pathologist to submit their cases of PCNSL will make possible in
Radu4, Camelia Colichi1 the future to perform biologic studies, necessary to improve our knowledge on this
Institute of oncology, Medical oncology, Bucharest, Romania, 2Institute of lymphoma entity.
oncology, Radiotherapy, Bucharest, Romania, 3Bagdasar- Arseni Hospital,
Neurosurgery department, Bucharest, Romania, 4Institute of oncology,
Paediatric oncology, Bucharest, Romania 899P OUTCOME WITH CARBOPLATIN AND ETOPOSIDE
COMBINATION CHEMOTHERAPY IN MEDULLOBLASTOMA-
Purpose: to evaluate the clinical features, outcome and late effects in intracranial germ SINGLE INSTITUTION RETROSPECTIVE ANALYSIS
cell tumors (GCTs).
Methods and patients: We retrospectively analyzed 20 cases treated in our institute Tarun Puri, Monica Malik, Shikha Goyal, Gagan Saini, Pramod K. Julka,
between 1992- 2004. Patients’ characteristics: overt predominance of male cases (80%); Goura K. Rath
age limits: 8 and 30 years old; the most frequent sites: sellar and pineal region (70%). All India Institute of Medical Sciences, Radiotherapy and oncology, New Delhi,
The multidisciplinary treatment consisted in: surgery (S)+ radiation therapy(RT)+ India
chemotherapy(CT) in 40% of patients(pts); S+ RT in 31% of pts; RT+ CT in 1 pt.
Surgery was performed in 18 pts (33%-biopsies). 70% of pts underwent RT on different Introduction: The management of medulloblastoma (MB) includes surgery and
ﬁelds (cranial, localized or craniospinal) and in varied doses (2,000-5,600 cGy). CT craniospinal radiotherapy (CSRT). Different chemotherapy (CT) schedules have
comprised two types of protocols: BEP and ETO+ IFO+ DDP. Starting with 2002, the been tried with an aim to improve survival with variable results. We studied a
therapy approach was unitary: limited S with diagnostic purpose + CT (2-4 cycles)+ RT
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schedule of CT with carboplatin and etoposide in the adjuvant setting.
(cranial ﬁeld, 2,400-3,000 cGy in complete response or 3,000-3,600 cGy in partial Purpose: To study the outcome in patients with MB treated with surgery, CSRT and
response, + spinal irradiation in cases with malignant cells in cerebrospinal ﬂuid). The CT with carboplatin and etoposide.
deﬁnitive diagnosis was accepted without biopsy in pts with characteristic radiological Patients and Methods: We retrospectively reviewed the records of 50 patients with
aspects correlated with high-levels of tumour markers (CEA, AFP) in serum and/or MB treated at our institution from May 2001 to May 2005. These patients received
cerebrospinal ﬂuid. adjuvant CT in addition to surgery and CSRT. After surgery, CSRT was given (36
Discussions: 50% of pts were between 15-25 years old. The predominant symptoms: Gy in 20 fractions over 4 weeks to whole brain, 30 Gy in 20 fractions over 4 weeks
headaches- 75% of pts, visual disturbances (diplopya, strabismus, poor vision)- 75% of to spine, followed by 20 Gy boost to the posterior fossa). All patients were planned
pts, diabetes insipidus- 40%. Increased intracranial pressure urged the installing of for 6 cycles of CT with carboplatin (AUC 5 iv D1) and etoposide (100 mg/m2/day
ventriculo-peritoneal shunts in 11 pts. The long-term sequelae were: endocrine iv D1-D3) given 3-weekly after completing CSRT, except in patients under 5 years
disturbances -diabetes insipidus (7 pts), global hypophysis impairment (1 pt), of age who were given CT upfront in order to delay RT. Patients were followed
hypothyroidism (1 pt); ophthalmologic impairments (8 pts); equilibrium deﬁciencies up with clinical examination every 3 months and MRI of brain and spine every
(2 pts); hearing disturbances (1 pt). 6 months.
Results: Overall survival evaluated by Kaplan-Meier method: 84%. Median survival:137 Results: 70% (35) patients were male and 30% (15) were female. Mean age was
months. We registered recurrences in 5 pts and cerebral and/or bone marrow 16.22 ± 11.83 years with a median of 11.5 years (range 3-55). MRI showed
metastases in 2 pts. 33 (66%) patients having midline lesions and 17 (34%) patients having lateralized
Conclusions: 1. The current multidisciplinary therapeutic approach entails a minimize lesions. 30 patients (60%) underwent gross total excision, 12 (24%) near total
of the late side-effects by reducing the cranial irradiation efﬁcient dose. 2. The surgical excision and 8 (16%) tumor decompression. Histopathology showed classic
approach limited to a diagnostic purpose obviate important endocrine and histology in 41 (82%) patients, desmoplastic variant in 7 (14%) patients and
ophthalmologic long-term sequelae. anaplastic variant in 2 (4%) patients. All patients received CSRT as per the
planned protocol. A total of 242 cycles of CT were given, median number of cycles
per patient being 6. The patients were followed up for a median duration of
59 weeks (range 13-230 weeks). At last follow up, 34 (68%) patients were
898P THE INTERNATIONAL EXTRANODAL LYMPHOMA STUDY disease-free, 3 (6%) had local progression, 1 (2%) had residual disease. Disease
GROUP (IELSG) VIRTUAL TISSUE BANK FOR PRIMARY status was not available for 12 (24%) patients. No grade 3 or 4 CT or RT induced
CENTRAL NERVOUS SYSTEM LYMPHOMA toxicities were seen.
Conclusion: CT with carboplatin and etoposide is an effective combination to be used
Francesco Bertoni1, Ivo Kwee1, Emanuele Zucca1, Andre J. Ferreri2, Franco
´ in the adjuvant treatment of MB following surgery and CSRT.
Cavalli1, Maurilio Ponzoni3
Oncology Institute of Southern Switzerland, Laboratory of Experimental
Oncology & Lymphoma Unit, Bellinzona, Switzerland, 2San Raffaele H Scientiﬁc
Institute, Dept. of Radiochemotherapy, Milan, Italy, 3San Raffaele H Scientiﬁc 900P MEDULLOBLASTOMA WITH EXTRA-CENTRAL NERVOUS
Institute, Pathology Unit, Milan, Italy SYSTEM METASTASES: CLINICAL PRESENTATION AND
Objective. The availability of material for Primary Central Nervous System
Lymphomas (PCNSL) is extremely limited. To overcome this problem, multi- Kochbati lotﬁ1, Hamouda Boussen2, Olfa Daldoul2, Nesrine Chraiet2, Chiraz Nasr1,
institutional collaborations are mandatory. Within the International Extranodal Noureddine Bouaouina3, Farouk Benna1, Amel Mezlini2, Mongi Maalej1
Lymphoma Study Group (IELSG), and in collaboration with the International PCNSL Salah Azaiz, Radiotherapy, Tunis, Tunisia, 2Salah Azaiz, Medical Oncology,
Collaborative Group (IPCG), we set up a virtual tissue bank for residual PCNSL tissue, Tunis, Tunisia, 3Farhat Hahed Hospital, Radiotherapy, Sousse, Tunisia
which could be used for forthcoming biological studies on PCNSL.
Methods: The database backend runs Filemaker Server Advanced 7 (FileMaker Inc., Purpose: Extra-central nervous system (extra-CNS) metastases are relatively unknown
Santa Clara, USA) on a dedicated server within the IELSG premises and can serve up to failure patterns in medulloblastoma. The aim of this study is to analyse
100 users simultaneously. Security has been enforced by placing the server on an epidemiological, clinical and aetiopathological aspects of these extra-CNS localisations.
isolated subnet behind a double ﬁrewall, while additional security using SSL data Methods and material: Extra-CNS metastases were retrospectively, identiﬁed in
encryption is planned. Records consist of 24 data ﬁelds describing (anonymous) ¨
patients treated in the department of radiation therapy at Salah-Azız Istitute (ISA) for
patient, pathology and availability of samples. For privacy reasons, we do not record medulloblastoma. Diagnosis of these metastases was retained for all extra-CNS
the patient information except for the date of birth and sex. The patient is identiﬁed by localisation not related to other tumour aetiology. Aetiopathological aspects are
a local histology number that only the pathologist has access to. Database access discussed with a literature review.
restrictions have been set according to different user types. Results: Among 103 patients treated and followed up in the department of radiation
Results And Conclusion: The virtual tissue bank is accessible via the IELSG website therapy of ISA from 1970 to 1992, 8 developed extra-CNS metastases (7.7%). Age at
(www.ielsg.org) with any web-browser and any operating system. After having read diagnosis of primitive tumour varied from 3 to 23 years. Sex ratio was 1. Primitive
and signed the virtual tissue bank policies, Pathologists willing to share their archival tumour treatment was: complete surgical resection in 4 patients with preoperative
ª 2006 European Society for Medical Oncology
Annals of Oncology abstracts
cerebrospinal ﬂuid shunting in two, cerebrospinal axis irradiation in 7 patients and one month after treatment. We conclude that follow-up studies of G207 in these
a cerebral-limited irradiation in 1. Two patients received chemotherapy for their initial patients are warranted.
treatment (systemic in one case and intrathecal in the other). The mean free-interval
from diagnosis of primitive tumour to extra-CNS metastases was 23 months, varying
from 8 to 53 months. These metastases were located in the liver (1 case), cervical lymph
nodes (2 cases), bone marrow (1 case) and bone (2 cases). Two patients had multiple 903P PHASE I/II TRIAL (UKT-03) OF CCNU PLUS TEMOZOLOMIDE
metastases: bone and bone marrow (in one), lung, pleura, cervical lymph node and CHEMOTHERAPY IN ADDITION TO RADIOTHERAPY AS
bone localisations (in one). Treatment of these metastases was: chemotherapy in 5 FIRST-LINE THERAPY FOR GLIOBLASTOMA
cases, chemotherapy and radiation in one, radiation therapy in one and 2 patients were
given only supportive care treatment. All patients died or are in progressive disease in Ulrich Herrlinger1, Johannes Rieger2, Dorothee Koch3, Simon Loeser4, Britta
less than one year from the diagnosis of extra-CNS metastases. Blaschke4, Rolf-Dieter Kortmann5, Thomas Hundsberger6, Julius Schuth7, Guido
Reifenberger4, Michael Weller8
University of Bonn, Department of Neurology, Bonn, Germany, 2University of
901P PEDIATRIC BRAIN STEM GLIOMAS: AIIMS EXPERIENCE Tu ¨bingen, Department of Neurology, Tu¨bingen, Germany, 3University of Mainz,
Department of Neurosurgery, Mainz, Germany, 4University of Duesseldorf,
Monica Malik, Tarun Puri, Pramod K. Julka, Goura K. Rath Department of Neuropathology, Duesseldorf, Germany, 5University of
All India Institute of Medical Sciences, Radiation Oncology, New Delhi, India Tuebingen, Department of Radiation Oncology, Tuebingen, Germany,
University of Mainz, Department of Neurology, Mainz, Germany, 7Schering
Purpose: Pediatric brain stem gliomas continue to represent a formidable challenge to Plough, Essex Pharma Germany, Munich, Germany, 8University of Tuebingen,
the oncologist. Optimal therapeutic approaches are yet to be determined. Department of Neurology, Tuebingen, Germany
Patients and Methods: Patients of brain stem gliomas aged less that 20 years diagnosed
from September 2002 to October 2005 were retrospectively analyzed. The clinical The UKT-03 trial evaluated the toxicity and efﬁcacy of a combination therapy with
proﬁle, imaging ﬁndings, histological details when available, were obtained. CCNU, temozolomide (TMZ) and involved-ﬁeld radiotherapy in patients with newly
Progression free survival and overall survival were obtained using Kaplan-Mier diagnosed glioblastoma (GBM). Thirty-one adult patients (median Karnofsky score
estimates. 90%, median age 51 years) accrued in two centers received involved-ﬁeld radiotherapy
Results: 42 patients were available for analysis. There were 23 males and 19 females. (60 Gy in 2 Gy fractions) and chemotherapy with CCNU 100 mg/m2 (day 1) and TMZ
Median age was 10 years (range 3-20). The commonest site of involvement was the 100 mg/m2/d (days 2-6) with individual dose adjustments according to hematotoxicity.
pons (30/42) followed by the midbrain (20/42) and medulla (19/42). 25 had A median of 5 courses (range 1-6 courses) were applied. WHO grade 4 hematotoxicity
morphologically diffuse lesions, 17 had well deﬁned lesions of which 10 were exophytic. was observed in 5 patients (16%). One patient died from myelosuppression-associated
17 patients underwent insertion of a ventriculoperitoneal shunt. The 10 patients with septicemia. Non-hematological toxicity included one patient with WHO grade 4 drug-
exophytic tumors underwent surgical decompression (6-subtotal excision, 1-near total induced hepatitis leading to discontinuation of CCNU/TMZ and one patient with
excision, 2-gross total excision, 1-biopsy). Histological details: pilocytic astrocytoma-4, WHO grade 2 lung ﬁbrosis leading to discontinuation of CCNU. The median
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ependymoma- 4, low grade astrocytoma-1 and glioblastome multiforme- 1. The progression-free survival (PFS) was 9 months (95% CI 5.3 - 11.7 months), the median
remaining cases were diagnosed on basis of imaging ﬁndings. 37 patients received overall survival time (MST) was 22.6 months (95% CI 12.5 - NA) with a 2-year survival
external beam radiotherapy (RT) of which 34 completed the entire course of RT as rate of 44.7%. Patients with a methylated O6-methylguanine-DNA methyltransferase
scheduled. 21 patients received a dose of 56 Gy and 13 patients received 60 Gy. 12 (MGMT) gene promoter in tumor tissue showed a longer PFS (p=0.014, logrank test)
patients received concomitant chemotherapy with carboplatin (3 cases), paclitaxel (4 and MST (p=0.037) than patients with a non-methylated MGMT promoter. CCNU/
cases) or temozolomide (5 cases). 17 patients received adjuvant chemotherapy with TMZ therapy was feasible with acceptable toxicity. CCNU/TMZ therapy was highly
carboplatin and etoposide for a median of 4 cycles. At a median follow up of 13 effective in GBM with substantially prolonged survival times compared with the
months, the progression free (PFS) and overall survival (OS) were 40.5% and 54.8% EORTC NCIC standard regimen of TMZ radiochemotherapy. The CCNU/TMZ
respectively. The median PFS was 12 months. Patients who received RT dose of 60 Gy regimen improved survival only in patients with MGMT gene promoter methylation.
tended to have a better PFS (54% vs 45%) and OS (77% vs 55%). Similarly, patients
with exophytic lesions fared better than those with diffuse tumors (OS-72% vs 50%).
Conclusions: Brain stem gliomas are associated with signiﬁcant mortality and
morbidity and novel therapeutic strategies are strongly warranted. 904P IMATINIB PLUS HYDROXYUREA IN PRETREATED NON-
PROGRESSIVE GLIOBLASTOMA (GBM) - A SINGLE CENTER
PHASE II STUDY
902P LOCAL TREATMENT OF MALIGNANT GLIOMA WITH G207,
A GENETICALLY ENGINEERED HSV-1: RESULTS OF A Gregor Dresemann1, Christian Hosius2, Zariana Nikolova3
PHASE 1B STUDY Franz-Hospital, Onkologische Abteilung, Du¨lmen, Germany, 2Novartis
Deutschland, Onkologie, Nu ¨rnberg, Germany, 3Novartis Pharma, Onkology,
Jim Markert1, Matthias Karrasch2, Eunice Braz2, Axel Mescheder2, Yancey Basel, Switzerland
The University of Alabama at Birmingham, Department of Neurosurgery, Introduction:
Alabama, AL, 2MediGene, Clinical Research & Development, Martinsried, GBM iis a platelet derived growth factor receptor (PDGF-R) positive malignant brain
Germany tumor with a median survival of less than 15 months. While single agent Imatinib (I)
did not show signiﬁcant activity the combination of I plus Hydroxyurea (HU) could
G207 is a modiﬁed oncolytic herpes simplex virus (oHSV) type 1 that has been demonstrate efﬁcacy in a group of 30 progressive pretreated GBM. Stable disease (SD)
genetically engineered to replicate in and kill cancer cells while sparing normal cells. was an important and potentially long lasting event. GBM usually shows a short period
G207’s unique construction allows it to be inoculated directly into malignant gliomas. of SD after primary treatment or effective treatment of relapse. Therefore the efﬁcacy of
Prior to this study, G207 was evaluated in a phase 1 dose-escalating study, where 21 I plus HU was analysed in a phase II study in GBM pts with SD for at least 6 weeks. As
patients with malignant glioma were stereotactically inoculated with G207. The present the role of enzyme-inducing anticonvulsives in this setting is not clear these drugs were
study was designed to test G207 in combination with surgical resection for recurrent not allowed in this study.
glioma. G207 was administered twice to each subject. The ﬁrst administration (15% of Methods: From 2003, December up to 2005, June 30 GBM pts with SD after primary,
the dose) was by stereotatic intratumoral injection and the second was 2 to 5 days later, secondary or third treatment were included. 600 mg of I and 1000 mg of HU were given
at the time of tumor resection and consisted of multiple injections into the resected as a continuous daily dosage, all pts were followed up by blood cell count weekly and
tumor bed. The total quantity of G207 administered was 1.15 x 109 pfu. Three of the 6 magnetic resonance imaging every 6 weeks.
participating patients (50%) had demonstrated an improved Karnofsky performance Results: All pts are eligible for toxicity and 12 months progression free survival (PFS)
score following G207 injection. One month after viral G207 injection all patients were and overall survival (OS). 25 pts are male, 5 pts female, the median age is 44 years (32 to
alive and 4 patients still showed stable disease according to the WHO response criteria 71). All 30 pts had prior radiotherapy, 21 pts had temozolomide containing
(decrease of less than 50% or increase of less than 25% in the sum of the products of chemotherapy and 9 pts not temozolomide containing regimens only. 8 pts were free
perpendicular diameters of all lesions). The median survival from date of diagnosis was from relapse, 17 pts after ﬁrst and 5 pts after second relapse. The median observation
23 months and the median progression-free survival was 1 month. The deaths of the 6 time is 20 months. Hematotoxicity grade 2 and 3 occurred in 11 out of 30 pts and
study patients were attributed to disease progression. One patient developed a transient required dose reduction of HU in 8 pts, dose reduction of I in 1 pt and G-CSF
hyperthermia and decreased responsiveness probably related to G207 which resolved subcutaniously in 8 pts. No febrile neutropenia, no study interruption due to toxicity
within 12 hours on steroid therapy. and no treatment related death occurred. 6/12 months PFS was 57% (17/30) / 40% (12/
This study conﬁrmed that G207 can be inoculated safely into malignant gliomas 30) and 6/12 months OS was 87% (26/30) / 60% (18/30).
without development of encephalitis or occurrence of toxicity related to herpes Conclusion: I 600 mg/day and HU 1000 mg/day was well tolerated, main toxicity was
virus. While patients did develop complications frequently associated with moderate hematotoxicity. The 6/12 months PFS and OS data indicate that the oral I
malignant glioma, including death, the only complication believed to be related to plus HU concept is able to substantially prolong time to progression. Although the
G207 appeared to be the result of an inadvertent ventricular injection and quickly study population was heterogeneous no difference could be seen according to the
resolved. G207 was generally well tolerated with no dose-limiting toxicity observed. relapse status. Further studies are necessary to ensure I plus HU as maintenance
67% of the patients experienced clinical beneﬁt as demonstrated by stable disease at treatment and to identify the pts qualiﬁed for treatment
Volume 17 | Supplement 9 | September 2006 doi:10.1093/annonc/mdl220 | ix263
abstracts Annals of Oncology
905P OUTCOMES OF YOUNGER GLIOBLASTOMA MULTIFORME 907 NEUROCUTANEOUS DISORDERS: CENTRAL NEURAL
PATIENTS SYSTEM AND ABDOMINAL VISCERAL MANIFESTATION.
Cuneyt Ulutin1, Okan Kuzhan2 David K. Miminoshvili, Fridon I. Todua, George B. Tsivtsivadze
GATA, Radiation Oncology, Ankara, Turkey, 2GATA, Medical Oncology, Institute of Radiology, CT department, Tbilisi, Georgia
PURPOSE: To review the results of complex radiological (Multi-slice CT,CT-
Aim: To demonstrate tratment outcome differences between younger and older angiography and MRI) examinations in cases of phacomatosis and estimate the role of
glioblastoma multiforme patients. Methods: Seventy patients with primary diagnostical imaging in revealing multisystemic lesions in case of this pathology.
glioblastoma multiforme (GBM) treated at our department between 1996 and 2004. MATERIALS AND METHODS: We examined 24 patients (14 male and 10 female)
The male-female ratio was 2.6:1. The median patient age was 53 (16-74). Sixty-eight with phacomatosis, age ranged from 6 to 43 years. CT and MRI of central neural system
patients (97%) were operated before radiotherapy and, two patients (%3) had only and abdominal organs were performed.
stereotactic biopsy. All patients received radiotherapy. Postoperative chemotherapy as RESULTS: In all patients (8 cases) with Bourneville’s disease multiple bilateral
an adjuvant to radiotherapy was given to 9 patients (12%). The patients were divided subependimal nodular non-enhancing calciﬁed lesions were found. In 3 cases on CT
into two groups according to their age (group A £35 n=21 vs. group B >35 n=49). The examinations similar lesions were revealed in cerebellum. In 5 cases out of them kidney
survivals were determined with Kaplan-Meier methods, and differences were compared volume mass were noted; angiomyolipoma (n=3) and in cyst (n=2).
with log-rank test. Cox-regression analyzes were also performed to ﬁnd out the In cases of Recklinghausen’s disease in 5 patients presence of cranial (VIII nerve)
independent prognostic factors. The Karnofsky performance status (‡70 vs. 35), schwanoma was noted. In 2 cases multiple bilateral meningiomas were detected. In 3
gender, tumor size (£4 cm vs. >4 cm), the number of involved brain lobes (uni vs. cases along with above mentioned optic nerve glioma was seen. In 1 patient spinal cord
multi), the operation type (total vs. subtotal), the preoperative history of seizure tumor of cervico-thoracic region was detected.
(present vs. absent), the radiotherapy ﬁeld (total cranium vs. partial), the total In patients with Hippel-Lindau syndrome (n=4) mostly cystic lesions of kidneys were
radiotherapy dose (60 Gy vs. 66 Gy) and adjuvant chemotherapy (present vs. absent) found, in 1 patient it was associated with liver and pancreatic cysts. In 2 cases renal cyst
were evaluated in univariate analyze. was non-homogenous, slightly enhancing after contrast injection. Postoperatively
Results: The median survival was 10.3 months in whole group, 19.5 months in the morphological study revealed renal cell carcinoma. In 2 patient cerebellum
younger age group and 5.7 months in older group. During the follow-up re- hemangioblastoma was seen.
craniotomy were performed in 2 patients, and 1 patient developed spinal seeding In patients with Sturge-Weber syndrome (n=3) on MR and CT angiography
metastases and received spinal radiotherapy. According to univariate analyze the examinations multiply pathological vessels and subcortical serpantine calciﬁcations
younger age vs. older age median 19.5 months vs. 5.27 months (P=0.0012); Karnofsky (‘‘tram-line’’) was seen. Facial ‘‘Port-Wine Nevus’’ along the distribution of the
performance status ‡70 vs. <70 median 15.3 months vs. 2.67 months (P<0.0001), and trigeminal nerve was also noted. In this case of hepatic hemangioma was revealed with
external radiotherapy dose 60 Gy vs. 66Gy median 11.6 months vs. 3 months (p=0.02) the typical appearance on CT-angiography.
were found as signiﬁcant prognostic factors on survival. In the regression analyze the CONCLUSION: Thus, knowledge of the CNS and abdominal visceral manifestations of
poorer performance status (KPS <70) found as an only independent factor on survival neurocutaneous diseases is very important for the diagnosis and determines selection
Downloaded from annonc.oxfordjournals.org by guest on September 25, 2011
[P=0.014 95% CI HR=0.0043 (0.0001-0.15)]. of appropriate treatment
Conclusion: The younger patients with primary glioblastoma multiforme had relatively
long survival rates (i.e. median 19.5 months and 2-year survival rate is 30%) in contrast
to older ones. This was particularly due to their better performance status.
908 COMBINED TREATMENT WITH RADIOTHERAPY AND
TEMOZOLOMIDE IN GLIOBLASTOMA MULTIFORME: A
906P ROLE OF P53, BCL-2 ONCOPROTEINS AND SURVIVIN IN THE RETROSPECTIVE SURVEY
PROGNOSIS OF GLIOMAS.
Teresa Jaraquemada1, Claudia Caeiro1, Isabel Augusto1, Lı´gia Osorio2, Paulo
Vanessa Medina Villaamil1, A. Alvarez1, D. Dopico2, M. Quindos2, I. Gallegos2, M.
´ Linhares3, Lı´gia Castro4, Margarida Damasceno1
Haz2, I. Santamarina2, S. Dı´az2, M. Valladares Ayerbes2, L. M. Anton Aparicio1
´ ˜o ˜o, ˜o
Hospital Sa Joa Medical Oncology, Porto, Portugal, Hospital Sa Joa ˜o,
Juan Canalejo University Hospital. UDC., Department of Oncology and Radiotherapy, Porto, Portugal, 3Hospital Sa Joa Neurosurgery, Porto,
Pathology., La Corun Spain, 2Juan Canalejo University Hospital.UDC.,
˜a, ˜o ˜o,
Portugal, Hospital Sa Joa Pathology, Porto, Portugal
Department of Oncology and Pathology., La Corun Spain
Background: Glioblastoma multiforme (GBM), the most common primary brain
Background: Prognostic factors in human malignant gliomas are not well deﬁned. The tumor in adults, carries a dismal prognosis. Combined approaches of surgical resection
biological behaviour of these tumours is somewhat unpredictable, ranging from rapid to the extent feasible followed by radiotherapy plus adjuvant temozolomide (TMZ)
progression to prolonged survival. A supplementary biological target is, therefore, have been improving survival.
desirable. This study investigated the pattern of apoptotic protein expression in brain Aim: To evaluate the overall survival (OS) and progression-free survival (PFS) in
tumour specimens using tissue array (TA) technology. patients with GBM.
Objective: To assess a possible correlation between the immunohistochemical (IHC) Methods: Retrospective analysis of a group of 22 patients with histologically
p53, Bcl-2 and survivin expression in relation to tumour grade and clinicopathologic conﬁrmed diagnosis of GBM treated at our institution between January 2003 and
outcome. December 2005. After surgical resection, patients were proposed to receive
Materials and Methods: We retrospectively analyzed primary and recurrent radiotherapy (daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total
astrocytomas (WHO grades I-IV) of 74 patients. 6x8 matrix was designed to construct of 60 Gy) plus TMZ (75 mg/m2/day, 7 days per week for the duration of
TA blocks. IHC staining was performed using anti-p53 (clone PAb 240), anti-Bcl-2 radiotherapy), followed by 6 cicles of adjuvant TMZ (200 mg/m2 for 5 days, every
(clone 124) and anti-survivin (clone D8) monoclonal antibodies. The reaction was 28 days).
visualized by the Dako EnVision system and diaminobenzidine according to the Results: The median age at diagnosis was 59.5 years. Seventeen patients were male.
manufacturers instructions. Fifty percent of patients had a performance status (ECOG) between 2 and 4.
Results: A preliminary analysis(n=33 patients) showed a tendency for anaplastic Temporal, followed by frontal and parietal lobes, were the most frequent locations;
tumours to have more nuclear survivin expression (15%) than the better differentiated 4 patients had basal nuclei and corpus callosum involvement. Complete resection
ones (<1%). Cytoplasmic expression wasnt seen. Survivin is a novel inhibitor of was only possible in 3 patients, with partial resection being undertaken in 15 patients
apoptosis via a pathway independent of Bcl-2. The correlation of Bcl-2 expression with and biopsy in 4 of them. The median OS was 8.9 months, with an estimated
histological grade is a point of disagreement. 70% of tumours were Bcl-2 positive. The survival rate of 46% at 17 months. The median PFS was 6.9 months. At the end of
reaction product was either diffuse or focal due to protein localization on cytoplasmic, this study, 6 patients were still undergoing adjuvant therapy with TMZ. Concomitant
nuclear and mitochondrial membranes. Nuclear p53 immunopositivity was observed treatment with radiotherapy plus TMZ resulted in grade 3 or 4 hematologic toxicity
in all cases, particulary high-grade lesions. in 18.2% of patients.
Conclusions: These results indicate that survivin may be useful in the future grading of Conclusions: Although our results are poorer than those achieved in recent studies
malignancy in gliomas. It seems unlikely that p53 and Bcl-2 IHC might have predicting using the same regimen, we have to consider that in most patients a complete resection
value in gliomas. Much larger glioma patient series are needed to validate the ﬁndings was not possible. Furthermore, the majority of patients had a poor performance status
of our approach. Correlation to clinical features is in progress. at the beginning of treatment.
ix264 | abstracts Volume 17 | Supplement 9 | September 2006