ESTRO 36 Abstract Book

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S326 ESTRO 36 2017
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whereas patients with AC/CC genotypes had a median PFS
of 13.7 months (P=0.0088). No significant differences in
PFS and OS for the other genotypes of the investigated
MC4R polymorphisms were found.
Conclusion
The rs489693 AA genotype is significantly associated with
a shorter PFS in GBM patients treated with radiotherapy
and temozolomide schedule.
The present, pilot study may represent the stimulus to
prospectively investigate the role of MC4R polymorphisms
as a predictive pharmacogenetic marker or as a target for
new drug therapies for GBM patients.
PO-0631 Molecular subtypes of glioblastoma:
immunohistochemical approach and clinical
correlations
L. Triggiani1, M. Cominelli2, E. Tratta2, P. Ghirardelli 1, S.
Pedretti1, N. Pasinetti1, M. Buglione1, R. Galli3, S.
Magrini1 , P.L. Poliani2
1 Spedali Civili di Brescia, Radiation Oncology, Brescia,
Italy
2 Pathology Unit, Department of Molecular and
Translational Medicine- University of Brescia-, Brescia,
Italy
3 San Raffaele Scientific Institute, Neural Stem Cell
Biology Unit- Division of Regenerative Medicine- Stem
Cells & Gene Therapy, Milano, Italy
Purpose or Objective
It is currently accepted that Glioblastomas (GBMs) can be
classified according to their transcriptional profile in three
major molecular subtypes (classic (CL), proneural/neural
(PN/N) and mesenchymal (MES)) associated with different
gene signature, specific molecular alterations and
different prognosis. However, molecular approach is not
routinely feasible in daily clinical practice. Thus,
assessment of simple tools for GBMs sub-classification is
stringently required, particularly for the development of
personalized therapeutic strategies. Goal of our study is
to investigate the possibility of classifying GBMs by an
immunohistochemical approach and correlate the data
with clinical information in a large cohort of patients.
Material and Methods
We evaluated a wide panel of biomarkers, recognized as
subgroup-specific gene classifiers, by IHC on FFPE tissue
samples from a large cohort of GBMs (n=151). EGFR
amplification and 1p/19q deletion were assayed by FISH.
Correlation with histological and prognostic features
(including MGMT promoter methylation) were also
performed. EGFR status and expression of TP53, IDH1,
ASCL1, OLIG2, PDGFRa, PTEN, MET, YKL40 and CD44 were
semi-quantitative assayed based on percentage and
intensity of expression in immunoreactive cells. Data were
also validated at molecular level by mean of RNAseq
technology. For statistical analysis, to identify distinct
GBM subclasses, we applied consensus clustering to our
immunohistochemical data. For clinico-pathological
correlations, we retrospectively collected all clinical data,
including adjuvant treatment (radiotherapy -
chemotherapy).
Results
By cluster analysis we identified EGFR, MET, YKL40 and
ASCL1 as the most sensitive and specific markers. Their
combination allowed to recognize GBM subtypes in 78.8%
of cases. Moreover, pleomorphism and epithelioid
features were found to be strongly associated to MES
subtype (46.2% and 25.7% of MES cases respectively) and
small cell component to CL subtype (65.1%). Notably,
survival analysis showed that MES GBMs were associated
with worst prognosis (p=0.079) and CL GBMs is related to
a better radio-chemotherapy response.
Conclusion
Although GBMs are morphologically defined as unique
entity, they are extremely heterogeneous tumours
associated with great variability in term of response to
treatment (radiotherapy-chemotherapy) and clinical
outcome Our results indicates that using a restricted panel
of highly sensitive markers we can identify GBM subgroups
with protein expression profiles strongly related to the
transcriptional profile.
PO-0632 Phase I/II Trial on Intraoperative Radiotherapy
(IORT) in Glioblastoma Multiforme (INTRAGO I/II)
F. Giordano1, S. Brehmer 2, B. Mürle3, G. Welzel1, E.
Sperk1, A. Keller 1, Y. Abo-Madyan 1, S. Clausen1, F.
Schneider1, C. Herskind1, M. Seiz-Rosenhagen2, C.
Groden3, P. Schmiedek2, M. Glas4, D. Hänggi2, K.
Petrecca5
1Universitätsmedizin Mannheim- Medical Faculty
Mannheim- Heidelberg University, Department of
Radiation Oncology, Mannheim, Germany
2Universitätsmedizin Mannheim- Medical Faculty
Mannheim- Heidelberg University, Department of
Neurosurgery, Mannheim, Germany
3Universitätsmedizin Mannheim- Medical Faculty
Mannheim- Heidelberg University, Department of
Neuroradiology, Mannheim, Germany
4University of Bonn Medical Center, Divison of Clinical
Neurooncology and Clinical Cooperation Unit
Neurooncology MediClin Robert Janker Klinik, Bonn,
Germany
5Montreal Neurological Institute and Hospital,
Department of Neurology and Neurosurgery, Montreal,
Canada
Purpose or Objective
The median progression-free survival time after standard-
of care therapy for glioblastoma multiforme (GBM) is
about 7 months. Most GBM recur locally, suggesting that
augmenting local treatments may improve outcomes. We
here present the results of a phase I/II trial testing local
radiation dose escalation to the resection cavity.
Material and Methods
INTRAGO I/II was a monocentric phase 1/2 trial that
included patients with resectable GBM. Patients received
intraoperative radiotherapy (IORT) with low-energy
photons (50 kV) at three dose levels, whereas dosing
started at 20 Gy (prescribed to the cavity margin) and was
escalated in 10 Gy increments up to 40 Gy. After surgery