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432 GAMMA KNIFE RADIOSURGERY AS A MAIN MODALITY IN
TREATING INTRACRANIAL LESIONS OF NF II PATIENTS
K. Abdel Karim, 1 , N.M. Elmashad 2 ,W.Reda 1 , A. El Shehaby 1
1 Gamma Knife Center, Nasser Institute, Cairo, EGYPT, 2 Clinical Oncology
Department, Tanta University, Tanta, EGYPT
Objective: Gamma knife radiosurgery GKS was used for the treatment of the
patients with Neurofibromatosis type II (NFII) for years to achieve better tumor
control and to avoid the post operative neurological deficits. This study aimed at
exploring the effect of GKS on the tumor control rate, the avoidance of new
neurological deficits, and the associated morbidity.
Methods: We revised the data of 50 intracranial NFII patients (either vestibular
schwannomas or meningiomas) who were treated consequently between July 2001
and October 2009 in our center, the data of 43 patients were evaluable. The mean
follow up period was 43.7 months (range 6 to 96). We treated 22 females (51.2%)
and 21 males (48.8%) with a mean age of 27.6 years (range 9–53 years). Eight
patients (18.6%) had a family history of NFII, 29 patients (67.4%) had previous
surgeries. A hundred and seventy NFII lesions were treated in 169 treatment
procedures, 83/170 were vestibular schwannomas and 87 were meningiomas. The
mean number of treated lesions per patient was 3.97 (range 1–14). The mean
marginal dose was 11.9 Gy (range 8 to 13 Gy), with a mean isodose of 52.5%, mean
percent coverage was 95.7% (ranged 71-100%). The mean target volume was 11.1 cc
(range 0.1 to 26.11 cc).
Results: Regarding the overall radiological response, 16 lesions (9.4%) had
regressed, 146 (85.9%) remained stable, and 8 (4.7%) had progressed. For 83
schwannomas, 7 lesions (8.4%) had regression, 72 (86.7%) remained stable, and 4
(4.8%) developed progression. For the 87 meningiomas, 9 (10.3%) had regressed,
74 (85.1%) were stable, and 4 (4.6%) had progressed. The Overall survival rate
(OS) for all patients was 95.3% (only 2 died), the mean tumor control rate of
95.1%. The overall Freedom from neurological deficits was 97.7%. Only one patient
complained of Grade III facial palsy which was temporary and resolved after
medical treatment. Using a median dose of 12 Gy maintained serviceable hearing
in 56.6% of ears.
Conclusion: Gamma knife radiosurgery for NFII patients can achieve good tumor
control and preserved function with low risk of morbidity.
Disclosure: All authors have declared no conflicts of interest.
433 PEMETREXED AND WHOLE-BRAIN RADIATION THERAPY
FOR TREATMENT OF BRAIN METASTASES FROM NON
SMALL-CELL LUNG ADENOCARCINOMA: A SINGLE
INSTITUTON ANALYSIS
C. Chargari 1 , Y. Moussaid 2 , C. Helissey 1 , J. Jacob 1 , O. Bauduceau 1 ,
B. Ceccaldi 1 , L. Védrine 1 , S. Le Moulec 1
1 Oncology and Radiation Oncology, Hôpital d’Instruction des Armées du
Val-de-Grâce, Paris, FRANCE, 2 Rabat, Hopital d’Instruction des Armées
Mohamed V, Rabat, MOROCCO
Background: Folate antimetabolite pemetrexed was approved for treatment of
patients with metastatic non small-cell lung carcinoma (NSCLC). Its activity on brain
metastases makes it attractive in combination with whole brain radiation therapy
(WBRT), but this regimen could also potentially increase toxicity.
Patients and treatment: We retrospectively assessed the use of pemetrexed
concurrently with WBRT in 12 consecutive patients with brain metastases from
NSCLC. Patients received pemetrexed 500 mg/m2, either alone (n = 4) or combined
with cisplatin 75mg/m2 (n = 6) or carboplatin AUC5 (n = 2). Median total number of
pemetrexed-based chemotherapy cycles was 3.5 (range: 1–8). In the course of
chemotherapy, patients received WBRT delivering 30 Gy in 10 fractions (n = 8) or 20
Gy in 5 fractions (n = 4).
Results: Six patients improved neurologically with treatment (five complete and one
partial responses). Four patients had their neurological symptoms stable. Best
radiological response was complete response lasting until last follow-up in one
patient. Five patients experienced partial response. One patient had stable disease.
Progressions were identified in four patients, within a median time interval of 17
weeks (range: 6–58 weeks). Three patients were not analyzable for tumor response
because of rapid systemic progression leading to death. Two of them had improved
neurologically. No high-grade WBRT-toxicity was reported but one patient
developed symptoms suggestive of a limbic encephalopathy five weeks after WBRT
completion.
Conclusion: The combination of pemetrexed with WBRT was associated with a
substantial improvement of neurological deficits and tumor responses in most
patients. However, survival remained disappointing and there were concerns
about toxicity in one patient. A clinical trial is required for better analyzing the
potential synergistic effects of drug with radiation and evaluating neurological
toxicity.
Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
434 LIMITED PREDICTIVE VALUE OF SCORING SYSTEMS FOR
METASTATIC SPINAL CORD COMPRESSION (MSCC):
RESTROSPECTIVE MONOCENTRIC STUDY
E. Tabouret 1 , C. Cauvin 2 , S. Fuentes 3 , B. Esterni 4 , T. Adetchessi 3 , N. Salem 5 ,
A. Madroszyk 2 , A. Gonçalves 1 ,P.Viens 6 , G. Gravis-Mescam 1
1 Medical Oncology, Paoli Calmettes, Marseille, FRANCE, 2 Medical Oncology,
Institut Paoli Calmettes, Marseille, FRANCE, 3 Neuro-surgery, AP HM, Marseille,
FRANCE, 4 Biostatistic, Paoli Calmette, Marseille, FRANCE, 5 Radiotherapy, Paoli
Calmettes, Marseille, FRANCE, 6 Cancer Center, Institute Paoli Calmettes,
Marseille Cedex, FRANCE
Background: Incidence of MSCC is increasing, paralleling increasing life expectancy
of patients (pts). We analyzed pts referred for surgery for MSCC to evaluate scoring
system relevance, prognosis factors, efficiency and safety.
Methods: From 2004 to 2010 148 pts (77 men) with oncologic (84%) and
hematological (16 %) diseases had surgery for MSCC. Patients and tumoral
characteristics were recorded. Prognostic value of Tomita, Tokuhashi scores, ASA
score, Frankel score (FS) and pain was investigated.
Results: Median age was 60 y (22–87). Lung (17%) and breast cancer (18%), were
mainly represented. Multiple extra-bone metastases were observed in 39% of pts.
Pain was present in 96% of pts and 66% were hyperalgic (pain score > 6). FS was
decreased for 49% of pts and median Karnofsky Performance Scale (KPS) was 70%.
Majority had laminectomy with spinal fixation: 73 %. Radiotherapy was done for
68%. Median overall survival (OS) was 8.9 months (IC95: 4.4–13). Tokuhashi but not
Tomita score was relevant. Survival predictive accuracy of TS was only 51%. By
univariate analyses, moderate pain (p = 0.001), primary breast (p = 0.02) or
hematological (p < 0.001) diseases are associated with higher OS than lung cancer
(p = 0.004). Absence of extra-bone metastase (p < 0.001), KPS > 70 (p < 0.001), ASA
score (p < 0.001), FS (p = 0.01), type of surgery (p = 0.03), post surgery
chemotherapy (p < 0.001) presented prognostic value. By multivariate analysis
extra-bone metastases (p = 0.004), KPS (p = 0.001) and ASA score (p = 0.007)
remained significant. Pain decrease was observed for 75% of pts. After surgery, 92%
of pts were ambulatory and FS was improved for 31%. Surgery complications
occurred in 16.8% and only 7% of pts died within 30 days.
Conclusion: Surgery for MSCC is associated with limited morbidity, improvement of
patients’ autonomy and remission of pain. In our study, usual scores seem not
relevant, whereas ASA score, KPS and extra-bone metastases are significant survival
prognostic factors.
Disclosure: All authors have declared no conflicts of interest.
435TiP A DUAL PHASE I/II STUDY OF TH-302 AND BEVACIZUMAB
IN RESECTABLE RECURRENT GLIOBLASTOMA FOLLOWING
BEVACIZUMAB FAILURE
R.M. Zuniga 1 , J. Sun 2 , J.R. Floyd 1 , S.R. Yerragudi 1 , C. Hart 2 , C. Eng 2 ,
A.J. Brenner 1
1 Cancer Therapy and Research Center, University of Texas Health Sceince
Center at San Antonio, San Antonio, TX, UNITED STATES OF AMERICA,
2 Clinical Operations, Threshold Pharmaceuticals, South San Francisco, CA,
UNITED STATES OF AMERICA
Introduction: Bevacizumab, a recombinant human monoclonal anti-VEGF antibody,
exhibits anti-tumor activity in recurrent glioblastoma; however, the median progression
free survival (PFS) of patients who progress on bevacizumab and are subsequently
started on a non-bevacizumab containing regimen is only 1.6 months. Pre-clinical
studies have shown that anti-angiogenic treatment leads to an increase in hypoxia in
the tumor microenvironment leading to increased invasiveness. Hypoxia upregulates
survival mechanisms, inhibits apoptosis, and stimulates invasiveness. TH-302 is a
hypoxia-activated prodrug that once activated releases the alkylating agent Br-IPM.
This drug has shown to potentiate, in vivo, the anti-tumor efficacy of other
anti-angiogenic agents. This dual phase I/II study enrolled subjects with recurrent
glioblastoma following bevacizumab failure that were planned for repeat craniotomy.
Methods: Single center, dose-escalation, prospective study with TH-302 single dose at
575 mg/m2 or placebo administered pre-operatively, followed by postoperative
combination therapy of bevacizumab at 10 mg/kg every 2 weeks and TH-302 dose
escalated 240–480 mg/m2 every 2 weeks (4 week cycle) until disease progression.
Resected tumor tissue was evaluated for hypoxia induced pimonidazole adducts,
endogenous CAIX staining, double-strand DNA damage by gamma-H2AX and MGMT
expression.
Results: Five patients underwent craniotomy and initiated TH-302 plus bevacizumab.
No dose limiting toxicity was reported. There were no grade 3 or 4 adverse events
(AEs) observed at 240mg/m2, and one grade 3 (skin ulceration) and no grade 4 AEs
observed thus far in the second cohort at 340mg/m2. Of the initial 5 patients treated,
one patient had a partial response (PR) and 3 patients had stable disease (SD) per
RANO criteria. Histological assessment of resected tumors demonstrated extensive
areas of hypoxia as measured by pimonidazole and a heterogeneous distribution of
gamma-H2AX staining.
ix150 | Abstracts Volume 23 | Supplement 9 | September 2012